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Two-Layered Biomimetic Flexible Self-Powered Electrical Stimulator for Promoting Wound Healing
用于促进伤口愈合的两层仿生柔性自供电电刺激器Click to copy article link
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- Yining ChenYining ChenKey Laboratory of Leather Chemistry and Engineering (Ministry of Education), Sichuan University, Chengdu 610065, ChinaResearch Center of Biomedical Engineering, Sichuan University, Chengdu, Sichuan 610065, ChinaMore by Yining Chen
- Wenxin XuWenxin XuKey Laboratory of Leather Chemistry and Engineering (Ministry of Education), Sichuan University, Chengdu 610065, ChinaResearch Center of Biomedical Engineering, Sichuan University, Chengdu, Sichuan 610065, ChinaMore by Wenxin Xu
- Xin ZhengXin ZhengKey Laboratory of Leather Chemistry and Engineering (Ministry of Education), Sichuan University, Chengdu 610065, ChinaResearch Center of Biomedical Engineering, Sichuan University, Chengdu, Sichuan 610065, ChinaMore by Xin Zheng
- Xuantao HuangXuantao HuangKey Laboratory of Leather Chemistry and Engineering (Ministry of Education), Sichuan University, Chengdu 610065, ChinaResearch Center of Biomedical Engineering, Sichuan University, Chengdu, Sichuan 610065, ChinaMore by Xuantao Huang
- Nianhua Dan*Nianhua Dan*Email: dannianhua@scu.edu.cnKey Laboratory of Leather Chemistry and Engineering (Ministry of Education), Sichuan University, Chengdu 610065, ChinaResearch Center of Biomedical Engineering, Sichuan University, Chengdu, Sichuan 610065, ChinaMore by Nianhua Dan
- Meng WangMeng WangDepartment of Orthopaedics, Strategic Support Force Medical Center, Beijing 100101, P. R. ChinaMore by Meng Wang
- Yuwen LiYuwen LiDepartment of Pharmacy, West China Hospital, Sichuan University, Chengdu 610041, ChinaMore by Yuwen Li
- Zhengjun LiZhengjun LiKey Laboratory of Leather Chemistry and Engineering (Ministry of Education), Sichuan University, Chengdu 610065, ChinaResearch Center of Biomedical Engineering, Sichuan University, Chengdu, Sichuan 610065, ChinaMore by Zhengjun Li
- Weihua DanWeihua DanKey Laboratory of Leather Chemistry and Engineering (Ministry of Education), Sichuan University, Chengdu 610065, ChinaResearch Center of Biomedical Engineering, Sichuan University, Chengdu, Sichuan 610065, ChinaMore by Weihua Dan
- Yunbing WangYunbing WangNational Engineering Research Center for Biomaterials, Sichuan University, 29 Wang Jiang Road, Chengdu 610065, ChinaMore by Yunbing Wang
Abstract 抽象的
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The repair of wound damage has been a common problem in clinic for a long time. Inspired by the electroactive nature of tissues and the electrical stimulation of wounds in clinical practice, the next generation of wound therapy with self-powered electrical stimulator is expected to achieve the desired therapeutic effect. In this work, a two-layered self-powered electrical-stimulator-based wound dressing (SEWD) was designed through the on-demand integration of the bionic tree-like piezoelectric nanofiber and the adhesive hydrogel with biomimetic electrical activity. SEWD has good mechanical properties, adhesion properties, self-powered properties, high sensitivity, and biocompatibility. The interface between the two layers was well integrated and relatively independent. Herein, the piezoelectric nanofibers were prepared by P(VDF-TrFE) electrospinning, and the morphology of the nanofibers was controlled by adjusting the electrical conductivity of the electrospinning solution. Benefiting from its bionic dendritic structure, the prepared piezoelectric nanofibers had better mechanical properties and piezoelectric sensitivity than native P(VDF-TrFE) nanofibers, which can convert tiny forces into electrical signals as a power source for tissue repair. At the same time, the designed conductive adhesive hydrogel was inspired by the adhesive properties of natural mussels and the redox electron pairs formed by catechol and metal ions. It has bionic electrical activity matching with the tissue and can conduct the electrical signal generated by the piezoelectric effect to the wound site so as to facilitate the electrical stimulation treatment of tissue repair. In addition, in vitro and in vivo experiments demonstrated that SEWD converts mechanical energy into electricity to stimulate cell proliferation and wound healing. The proposed healing strategy for the effective treatment of skin injury was provided by developing self-powered wound dressing, which is of great significance to the rapid, safe, and effective promotion of wound healing.
伤口损伤的修复长期以来一直是临床上的常见问题。受临床实践中组织的电活性性质和伤口电刺激的启发，下一代自供电电刺激器伤口治疗有望达到预期的治疗效果。在这项工作中，通过按需集成仿生树状压电纳米纤维和具有仿生电活性的粘合水凝胶，设计了一种基于自供电电刺激器的伤口敷料（SEWD）。 SEWD具有良好的机械性能、粘附性能、自供电性能、高灵敏度和生物相容性。两层之间的接口融合良好且相对独立。本文通过P(VDF-TrFE)静电纺丝制备了压电纳米纤维，并通过调节静电纺丝溶液的电导率来控制纳米纤维的形貌。得益于其仿生树枝状结构，所制备的压电纳米纤维比天然P(VDF-TrFE)纳米纤维具有更好的机械性能和压电敏感性，可以将微小的力转化为电信号作为组织修复的动力源。同时，设计的导电粘合水凝胶的灵感来自天然贻贝的粘合特性以及儿茶酚和金属离子形成的氧化还原电子对。它具有与组织相匹配的仿生电活动，可以将压电效应产生的电信号传导到伤口部位，以利于组织修复的电刺激治疗。 此外，体外和体内实验表明SEWD可将机械能转化为电能，从而刺激细胞增殖和伤口愈合。通过开发自供电伤口敷料，提出了有效治疗皮肤损伤的愈合策略，对于快速、安全、有效促进伤口愈合具有重要意义。
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Copyright © 2023 American Chemical Society
版权所有 © 2023 美国化学会
版权所有 © 2023 美国化学会
1. Introduction 一、简介
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As a natural protective barrier, the skin plays an important role in protecting the body from foreign matter and pathogens, extreme temperature, water loss, ultraviolet radiation, microbial and chemical insults, and injury. Therefore, it is required to maintain skin integrity. (1) The protective ability of skin could be damaged by surgical trauma, burns, and various chronic skin ulcers. The treatment of skin injuries can be traced back to the early stages of human civilization since human beings had mastered the dressing of wounds. More effective wound dressing and treatment strategies have emerged, owing to the rapid development of modern medicine and materials science. (2) Currently, wound healing methods, such as advanced growth factor-mediated therapy, (3) structure imitation of the natural extracellular matrix, (4) optimization of the cell-growing environment, (5) and use of bioactive materials, (6) are effective for skin regeneration; however, these methods still have the challenges of inaccurate control and biological activity loss. With the elucidation of wound healing, both wound dressing and treatment strategies have been constantly developing. (7) In the field of wound healing, researches have focused on methods to rapidly, safely, and effectively treat skin wounds, accelerate healing, and improve healing quality. (8)
作为天然的保护屏障，皮肤在保护身体免受异物和病原体、极端温度、水分流失、紫外线辐射、微生物和化学侵害以及伤害方面发挥着重要作用。因此，需要保持皮肤的完整性。 (1)手术创伤、烧伤、各种慢性皮肤溃疡等都会损害皮肤的保护能力。皮肤损伤的治疗可以追溯到人类文明早期，人类就已经掌握了伤口的包扎。由于现代医学和材料科学的快速发展，更有效的伤口敷料和治疗策略已经出现。 (2)目前的伤口愈合方法，如先进的生长因子介导疗法，(3)天然细胞外基质的结构模仿，(4)细胞生长环境的优化，(5)生物活性材料的使用，( 6）有效促进皮肤再生；然而，这些方法仍然面临控制不准确和生物活性损失的挑战。随着伤口愈合的阐明，伤口敷料和治疗策略都在不断发展。 (7)在伤口愈合领域，研究重点是快速、安全、有效治疗皮肤伤口、加速愈合、提高愈合质量的方法。 (8)
作为天然的保护屏障，皮肤在保护身体免受异物和病原体、极端温度、水分流失、紫外线辐射、微生物和化学侵害以及伤害方面发挥着重要作用。因此，需要保持皮肤的完整性。 (1)手术创伤、烧伤、各种慢性皮肤溃疡等都会损害皮肤的保护能力。皮肤损伤的治疗可以追溯到人类文明早期，人类就已经掌握了伤口的包扎。由于现代医学和材料科学的快速发展，更有效的伤口敷料和治疗策略已经出现。 (2)目前的伤口愈合方法，如先进的生长因子介导疗法，(3)天然细胞外基质的结构模仿，(4)细胞生长环境的优化，(5)生物活性材料的使用，( 6）有效促进皮肤再生；然而，这些方法仍然面临控制不准确和生物活性损失的挑战。随着伤口愈合的阐明，伤口敷料和治疗策略都在不断发展。 (7)在伤口愈合领域，研究重点是快速、安全、有效治疗皮肤伤口、加速愈合、提高愈合质量的方法。 (8)
The physiological microcurrent, whose effect on the human body has been studied for numerous years, universally exists in human tissues. There are endogenous potential and transcutaneous current potential of 10–60 mV in the human skin. (9,10) When the current flows through the skin wound, an electric field known as “injury current” is generated as an important factor for wound initiation and repair. (11) The potential difference disappears when the epithelial cells decompose, owing to the injury. This disappearance is the earliest stimulation signal to initiate cell migration and re-epithelialization. Many epithelial cells, including human keratinocytes, can detect electric fields as well as directional migration, (12) and electrical stimulation has been demonstrated by numerous studies to be an effective treatment method to promote wound healing. (13,14) As non-pharmacological biophysical energy, electrical stimulation (ES) can promote the skin healing rate and prevent the formation of ischemic and necrotic tissues. (14,15) In 2002, ES equipment was approved for use in the clinical treatment of certain chronic wounds (e.g., diabetes, stasis, and arterial ulcer) by the U.S. Food and Drug Administration. (16) Currently, numerous clinical studies have reported that ES positively affects wound healing and has been used to accelerate wound closure in clinical practice. (17,18)
生理微电流普遍存在于人体组织中，其对人体的影响已被研究多年。人体皮肤存在10-60 mV的内源电位和经皮电流电位。 (9,10) 当电流流过皮肤伤口时，会产生一种称为“损伤电流”的电场，这是伤口发生和修复的重要因素。 (11)当上皮细胞因损伤而分解时，电位差消失。这种消失是启动细胞迁移和再上皮化的最早刺激信号。许多上皮细胞，包括人类角质形成细胞，可以检测电场以及定向迁移（12），并且大量研究已证明电刺激是促进伤口愈合的有效治疗方法。 (13,14)作为非药物生物物理能量，电刺激(ES)可以促进皮肤愈合速度并防止缺血和坏死组织的形成。 (14,15) 2002年，美国食品和药物管理局批准ES设备用于某些慢性伤口（例如糖尿病、瘀血和动脉溃疡）的临床治疗。 (16) 目前，大量临床研究表明ES对伤口愈合有积极影响，并已在临床实践中用于加速伤口闭合。 (17,18)
生理微电流普遍存在于人体组织中，其对人体的影响已被研究多年。人体皮肤存在10-60 mV的内源电位和经皮电流电位。 (9,10) 当电流流过皮肤伤口时，会产生一种称为“损伤电流”的电场，这是伤口发生和修复的重要因素。 (11)当上皮细胞因损伤而分解时，电位差消失。这种消失是启动细胞迁移和再上皮化的最早刺激信号。许多上皮细胞，包括人类角质形成细胞，可以检测电场以及定向迁移（12），并且大量研究已证明电刺激是促进伤口愈合的有效治疗方法。 (13,14)作为非药物生物物理能量，电刺激(ES)可以促进皮肤愈合速度并防止缺血和坏死组织的形成。 (14,15) 2002年，美国食品和药物管理局批准ES设备用于某些慢性伤口（例如糖尿病、瘀血和动脉溃疡）的临床治疗。 (16) 目前，大量临床研究表明ES对伤口愈合有积极影响，并已在临床实践中用于加速伤口闭合。 (17,18)
However, the large-scale application of microcurrent stimulation is significantly limited, as it generally depends on the equipment and requires to be operated by qualified personnel. Consequently, bioelectric dressings were introduced and are an effective method for ES application in wound treatment. For instance, including a microcircuit, PosiFect RD (Biofisica UK Ltd., Basingstoke, UK) of the first batch to the market, can continuously deliver the microcurrent generated by two non-rechargeable batteries to the wound for a minimum of 48 h. (19) Procellera is a bioelectric bandage wound dressing, which can continuously generate ES of 2–10 mV through the metal microcells of silver and zinc in the woven material when wetted by wound exudate or normal saline. (20) Additionally, piezoelectric materials have potential for application in microcurrent dressing. (21) Because of this self-electric-generating feature, piezoelectric materials are suitable for preparing wireless, simple, and flexible microcurrent dressing. Long et al. accelerated wound healing using an effective electronic bandage fabricated using a wearable nanogenerator based on piezoelectric and triboelectric effects to generate an alternating discrete electric field via the conversion of mechanical displacement from skin movement into electric energy. (22) Although these dressings enable the convenient use of ES in wound treatments by overcoming the aforementioned limitations, a disadvantage remains: the intrinsic advantages of numerous advanced dressings, such as the bionic extracellular matrix structure, material surface characteristics that can regulate cell behavior, and hydrophilic and moisturizing characteristics that provide a wet healing environment, are lost by introducing and strengthening the functions of ES therapy. A multiplier effect may be achieved if ES therapy can be introduced to the dressings without hindering the advantages of advanced dressings.
然而，微电流刺激的大规模应用受到很大限制，因为它通常依赖于设备并且需要由合格的人员操作。因此，生物电敷料应运而生，是 ES 在伤口治疗中应用的有效方法。例如，第一批上市的PosiFect RD（Biofisica UK Ltd.，Basingstoke，UK）包含一个微电路，可以将两节不可充电电池产生的微电流连续输送到伤口至少48小时。 (19) Procellera是一种生物电绷带伤口敷料，当被伤口渗出液或生理盐水润湿时，它可以通过编织材料中的银和锌金属微电池连续产生2-10 mV的ES。 (20) 此外，压电材料在微电流敷料方面具有应用潜力。 (21)由于压电材料的这种自发电特性，适合制备无线、简单、灵活的微电流敷料。龙等人。使用有效的电子绷带加速伤口愈合，该绷带使用基于压电和摩擦电效应的可穿戴纳米发电机制造，通过将皮肤运动的机械位移转换为电能来产生交变离散电场。 (22) 虽然这些敷料克服了上述限制，使得 ES 能够方便地用于伤口治疗，但仍然存在一个缺点：众多先进敷料的固有优点，如仿生细胞外基质结构、可以调节细胞行为的材料表面特性、通过引入和强化ES疗法的功能，提供湿润愈合环境的亲水性和保湿特性会丧失。如果能够将 ES 疗法引入敷料中而不妨碍先进敷料的优点，可能会取得事半功倍的效果。
然而，微电流刺激的大规模应用受到很大限制，因为它通常依赖于设备并且需要由合格的人员操作。因此，生物电敷料应运而生，是 ES 在伤口治疗中应用的有效方法。例如，第一批上市的PosiFect RD（Biofisica UK Ltd.，Basingstoke，UK）包含一个微电路，可以将两节不可充电电池产生的微电流连续输送到伤口至少48小时。 (19) Procellera是一种生物电绷带伤口敷料，当被伤口渗出液或生理盐水润湿时，它可以通过编织材料中的银和锌金属微电池连续产生2-10 mV的ES。 (20) 此外，压电材料在微电流敷料方面具有应用潜力。 (21)由于压电材料的这种自发电特性，适合制备无线、简单、灵活的微电流敷料。龙等人。使用有效的电子绷带加速伤口愈合，该绷带使用基于压电和摩擦电效应的可穿戴纳米发电机制造，通过将皮肤运动的机械位移转换为电能来产生交变离散电场。 (22) 虽然这些敷料克服了上述限制，使得 ES 能够方便地用于伤口治疗，但仍然存在一个缺点：众多先进敷料的固有优点，如仿生细胞外基质结构、可以调节细胞行为的材料表面特性、通过引入和强化ES疗法的功能，提供湿润愈合环境的亲水性和保湿特性会丧失。如果能够将 ES 疗法引入敷料中而不妨碍先进敷料的优点，可能会取得事半功倍的效果。
In this work, a smart electronic scaffold was designed by integrating a self-powered generator based on piezoelectric materials and a bioactive porous scaffold based on conductive adhesive hydrogels. The obtained self-powered electrical-stimulator-based wound dressing (SEWD) was used in the treatment of wound for introducing ES therapy. As shown in Figure 1, the SEWD material comprised two functional layers: the upper piezoelectric layer is a tree-like P(VDF-TrFE) nanofiber (P(VDF-TrFE) NF), used for ES generation during force deformation, prepared via electrospinning; the lower layer is an iron ion and catechol group-based conductive adhesive polyacrylamide-gelatin double-network hydrogel, which can bond the piezoelectric film and fix the SEWD material to the wound to effectively transmit ES to the wound. The fiber structure of P(VDF-TrFE) NFs was biomimetically designed as a dendritic structure for better electrical signal generation and better mechanical properties; then, conductive adhesive hydrogels were prepared and integrated with P(VDF-TrFE) NFs, and the key properties were characterized; finally, the healing-promoting functionality of the SEWD was demonstrated using in vivo and in vitro tests to comprehensively investigate its safety and effectiveness.
在这项工作中，通过集成基于压电材料的自供电发电机和基于导电粘合剂水凝胶的生物活性多孔支架，设计了一种智能电子支架。所获得的自供电电刺激伤口敷料（SEWD）用于伤口治疗，引入ES疗法。如图1所示，SEWD材料由两个功能层组成：上压电层是树状P(VDF-TrFE)纳米纤维(P(VDF-TrFE) NF)，用于在力变形过程中产生ES，通过静电纺丝；下层是基于铁离子和儿茶酚基团的导电粘合剂聚丙烯酰胺-明胶双网络水凝胶，可以粘合压电薄膜并将SEWD材料固定在伤口上，有效地将ES传输到伤口。 P(VDF-TrFE) NFs的纤维结构被仿生设计为树枝状结构，以实现更好的电信号生成和更好的机械性能；然后，制备导电粘合剂水凝胶并将其与P(VDF-TrFE) NFs集成，并表征其关键性能；最后，通过体内和体外测试证明了SEWD的促进愈合功能，以全面研究其安全性和有效性。
在这项工作中，通过集成基于压电材料的自供电发电机和基于导电粘合剂水凝胶的生物活性多孔支架，设计了一种智能电子支架。所获得的自供电电刺激伤口敷料（SEWD）用于伤口治疗，引入ES疗法。如图1所示，SEWD材料由两个功能层组成：上压电层是树状P(VDF-TrFE)纳米纤维(P(VDF-TrFE) NF)，用于在力变形过程中产生ES，通过静电纺丝；下层是基于铁离子和儿茶酚基团的导电粘合剂聚丙烯酰胺-明胶双网络水凝胶，可以粘合压电薄膜并将SEWD材料固定在伤口上，有效地将ES传输到伤口。 P(VDF-TrFE) NFs的纤维结构被仿生设计为树枝状结构，以实现更好的电信号生成和更好的机械性能；然后，制备导电粘合剂水凝胶并将其与P(VDF-TrFE) NFs集成，并表征其关键性能；最后，通过体内和体外测试证明了SEWD的促进愈合功能，以全面研究其安全性和有效性。
Figure 1 图1
Figure 1. Schematic diagram of the two-layered SEWD.
图 1. 两层 SEWD 示意图。
2. Materials and Methods 2。材料和方法
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2.1. Materials 2.1.材料
P(VDF-TrFE) (75/25) was purchased from Piezotech Inc. (France). Tetrabutylammonium chloride (TBAC), N-dimethylformamide (DMF), acetone, and dimethyl sulfoxide were purchased from Kelong Chemical Co., Ltd. (China). Fe3O4 nanoparticles (Fe3O4 NPs), acrylamide (AM), and ammonium persulfate were purchased from Dekedaojin Co., Ltd. (China). Gelatin, DAPI, and rhodamine cyclopeptide were purchased from Beijing Solarbio Science & Technology Co., Ltd. (China). Dopamine hydrochloride was purchased from Sigma-Aldrich (St. Louis, MO, USA). RPMI-1640 medium, methyltetrazolium (MTT), penicillin–streptomycin, and pancreatin were purchased from Thermo Fisher Biochemical Products Co., Ltd.
P(VDF-TrFE) (75/25) 购自 Piezotech Inc.（法国）。四丁基氯化铵（TBAC）、N-二甲基甲酰胺（DMF）、丙酮和二甲亚砜购自科龙化学有限公司（中国）。 Fe3O4 纳米粒子（Fe3O4 NPs）、丙烯酰胺（AM）和过硫酸铵购自德科道金有限公司（中国）。明胶、DAPI 和罗丹明环肽购自北京索拉宝科技有限公司（中国）。盐酸多巴胺购自 Sigma-Aldrich（美国密苏里州圣路易斯）。 RPMI-1640培养基、甲基四唑(MTT)、青霉素-链霉素、胰酶购自赛默飞生化产品有限公司。
P(VDF-TrFE) (75/25) 购自 Piezotech Inc.（法国）。四丁基氯化铵（TBAC）、N-二甲基甲酰胺（DMF）、丙酮和二甲亚砜购自科龙化学有限公司（中国）。 Fe3O4 纳米粒子（Fe3O4 NPs）、丙烯酰胺（AM）和过硫酸铵购自德科道金有限公司（中国）。明胶、DAPI 和罗丹明环肽购自北京索拉宝科技有限公司（中国）。盐酸多巴胺购自 Sigma-Aldrich（美国密苏里州圣路易斯）。 RPMI-1640培养基、甲基四唑(MTT)、青霉素-链霉素、胰酶购自赛默飞生化产品有限公司。
2.2. Preparation of SEWD 2.2. SEWD的准备
First, 1.08 g of P(VDF-TrFE), 0.096 g of TBAC, and 0.004 g of Fe3O4 NPs were added in a mixed solvent containing 4 mL of acetone and 6 mL of DMF. The solution was stirred overnight under the action of a magnetic stirrer at room temperature. The bubbles were removed by ultrasonication before use. The electrospinning solution after ultrasonic defoaming was carefully loaded into the syringe without bubbles, then the conductive needle was connected, and the syringe was loaded into the injector, and the high-voltage power supply was connected to the conductive needle; a layer of aluminum foil was wrapped on the receiving roller with a speed of 500 rpm. Then, the high-voltage power supply was turned on, and the voltage was adjusted to 28.6 kV. The obtained electrospun nanofibers were dried in an oven to remove the solvent completely. Second, P(VDF-TrFE) NFs were laid flat on the bottom of a mold containing the catechol-grafted oxidized sodium alginate (COA; dopamine was grafted onto dialdehyde sodium alginate by a carbodiimide-assisted amidation reaction; Figure S1), iron ions, gelatin, and acrylamide (AM) solution (refer to line 5 of Table S1 for specific dosage). Catechol groups and iron ions could form redox pairs to initiate free radical polymerization of acrylamide (PAM) and crosslinking of gelatin to form double-network hydrogels grown on the P(VDF-TrFE) NFs with conductive and adhesive functions. The detailed methods and the contents of the hydrogels are listed in Table S1. The obtained hydrogel was labeled as CF-Gel-PAM. The whole scaffold composed of two layers was SEWD.
首先，将1.08g P(VDF-TrFE)、0.096g TBAC和0.004g Fe3O4 NP添加到含有4mL丙酮和6mL DMF的混合溶剂中。将溶液在磁力搅拌器的作用下于室温搅拌过夜。使用前通过超声波去除气泡。将超声波消泡后的静电纺丝溶液小心地装入注射器中，无气泡，然后连接导电针，将注射器装入注射器中，将高压电源连接到导电针上；在接收辊上包裹一层铝箔，转速为500转/分钟。然后，打开高压电源，将电压调整至28.6 kV。将所得静电纺丝纳米纤维在烘箱中干燥以完全除去溶剂。其次，将 P(VDF-TrFE) NF 平放在含有儿茶酚接枝的氧化海藻酸钠（COA；通过碳二亚胺辅助酰胺化反应将多巴胺接枝到二醛海藻酸钠上；图 S1）的模具底部，铁离子、明胶、丙烯酰胺（AM）溶液（具体用量参见表S1第5行）。儿茶酚基团和铁离子可以形成氧化还原对，引发丙烯酰胺（PAM）的自由基聚合和明胶的交联，形成在 P(VDF-TrFE) NF 上生长的双网络水凝胶，具有导电和粘合功能。详细方法和水凝胶的含量列于表S1。获得的水凝胶被标记为CF-Gel-PAM。整个支架由两层组成，为SEWD。
首先，将1.08g P(VDF-TrFE)、0.096g TBAC和0.004g Fe3O4 NP添加到含有4mL丙酮和6mL DMF的混合溶剂中。将溶液在磁力搅拌器的作用下于室温搅拌过夜。使用前通过超声波去除气泡。将超声波消泡后的静电纺丝溶液小心地装入注射器中，无气泡，然后连接导电针，将注射器装入注射器中，将高压电源连接到导电针上；在接收辊上包裹一层铝箔，转速为500转/分钟。然后，打开高压电源，将电压调整至28.6 kV。将所得静电纺丝纳米纤维在烘箱中干燥以完全除去溶剂。其次，将 P(VDF-TrFE) NF 平放在含有儿茶酚接枝的氧化海藻酸钠（COA；通过碳二亚胺辅助酰胺化反应将多巴胺接枝到二醛海藻酸钠上；图 S1）的模具底部，铁离子、明胶、丙烯酰胺（AM）溶液（具体用量参见表S1第5行）。儿茶酚基团和铁离子可以形成氧化还原对，引发丙烯酰胺（PAM）的自由基聚合和明胶的交联，形成在 P(VDF-TrFE) NF 上生长的双网络水凝胶，具有导电和粘合功能。详细方法和水凝胶的含量列于表S1。获得的水凝胶被标记为CF-Gel-PAM。整个支架由两层组成，为SEWD。
2.3. Scanning Electron Microscopy (SEM)
2.3.扫描电子显微镜 (SEM)
The morphology of the SEWD samples was observed by SEM (S3000N, Hitachi, Japan). The samples were broken in liquid nitrogen and sprayed with gold on the surface. Then, the software ImageJ was used to measure the diameters of the nanofibers of P(VDF-TrFE) NFs (100 trunk fibers in the SEM image magnified by 5000 times were selected) and pores of the hydrogel, and the diameter distribution statistics were carried out in the software Origin.
SEWD 样品的形貌通过 SEM（S3000N，日立，日本）观察。将样品在液氮中破碎并在表面喷金。然后使用ImageJ软件测量P(VDF-TrFE) NFs纳米纤维（选取放大5000倍SEM图像中的100根主干纤维）和水凝胶的孔隙直径，并进行直径分布统计出在软件Origin中。
SEWD 样品的形貌通过 SEM（S3000N，日立，日本）观察。将样品在液氮中破碎并在表面喷金。然后使用ImageJ软件测量P(VDF-TrFE) NFs纳米纤维（选取放大5000倍SEM图像中的100根主干纤维）和水凝胶的孔隙直径，并进行直径分布统计出在软件Origin中。
2.4. Measurement of Mechanical Properties
2.4.机械性能的测量
The mechanical properties, including tensile strength and elongation at break, were determined at a strain rate of 100 mm/min using a universal testing machine (AI-7000S, Gotech, China). The samples were cut into bone-shaped specimens with dimensions of length × width = 20 mm × 4 mm. The measurements were carried out at 25 °C using five specimens of each sample type; the values were averaged and expressed as mean ± standard deviation.
使用万能试验机（AI-7000S，Gotech，中国）在 100 mm/min 的应变速率下测定机械性能，包括拉伸强度和断裂伸长率。将样品切成长×宽=20mm×4mm的骨状标本。测量是在 25°C 下使用每种样品类型的五个样本进行的；对值进行平均并表示为平均值±标准差。
使用万能试验机（AI-7000S，Gotech，中国）在 100 mm/min 的应变速率下测定机械性能，包括拉伸强度和断裂伸长率。将样品切成长×宽=20mm×4mm的骨状标本。测量是在 25°C 下使用每种样品类型的五个样本进行的；对值进行平均并表示为平均值±标准差。
2.5. Measurement of Adhesive Properties
2.5.粘合性能的测量
The pigskin was selected to represent the biological tissue, and the adhesion of SEWD to the biological tissue was tested. The adhesion strength of SEWD on the surface of the pigskin was tested by using the lap shear adhesion test. The fresh skin (40 mm × 10 mm) from the pigskin was soaked in cold water for 2 h, and then the two pieces of the pigskin were glued together by SEWD with an adhesive area of 1 cm × 1 cm. The samples were pulled to the failure state by a universal testing machine at a strain rate of 5 mm/min. The tissue adhesion properties of the hydrogels were characterized according to the shear strength.
选择猪皮作为生物组织，测试SEWD对生物组织的粘附力。采用搭接剪切粘合试验测试SEWD在猪皮表面的粘合强度。将猪皮上的鲜皮（40毫米×10毫米）用冷水浸泡2小时，然后将两块猪皮用SEWD粘合在一起，粘合面积为1厘米×1厘米。通过万能试验机以 5 mm/min 的应变速率将样品拉至失效状态。根据剪切强度表征水凝胶的组织粘附特性。
选择猪皮作为生物组织，测试SEWD对生物组织的粘附力。采用搭接剪切粘合试验测试SEWD在猪皮表面的粘合强度。将猪皮上的鲜皮（40毫米×10毫米）用冷水浸泡2小时，然后将两块猪皮用SEWD粘合在一起，粘合面积为1厘米×1厘米。通过万能试验机以 5 mm/min 的应变速率将样品拉至失效状态。根据剪切强度表征水凝胶的组织粘附特性。
The adhesive strength between the two layers of SEWD was also evaluated. Both sides of P(VDF-TrFE) NFs were bonded with hydrogels, respectively, and the bonding area was 1 cm × 1 cm. Then, a universal testing machine was used to pull the sample to the failure state at a strain rate of 1 mm/min, and the bond strength between the two layers of SEWD materials was characterized according to the shear strength.
还评估了两层 SEWD 之间的粘合强度。 P(VDF-TrFE) NFs的两侧分别与水凝胶粘合，粘合面积为1 cm×1 cm。然后使用万能试验机以1 mm/min的应变速率将样品拉至破坏状态，根据剪切强度表征两层SEWD材料之间的粘结强度。
还评估了两层 SEWD 之间的粘合强度。 P(VDF-TrFE) NFs的两侧分别与水凝胶粘合，粘合面积为1 cm×1 cm。然后使用万能试验机以1 mm/min的应变速率将样品拉至破坏状态，根据剪切强度表征两层SEWD材料之间的粘结强度。
2.6. Evaluation of the Piezoelectric and Conductive Properties
2.6。压电和导电性能的评估
The piezoelectric properties of P(VDF-TrFE) NFs were tested by a CHI660E electrochemical workstation (CH Instruments, Inc., China) and an ESM303-COMP mechanical measurement system (Mark-10 Corporation, USA). The samples of 4 cm × 2 cm were cut, and the high purity copper foil with 0.01 mm thickness was bonded to both ends with conductive silver adhesive and dried for 24 h, as shown in Figure S2. The downward pressure velocity of the mechanical measurement system was set to 10 mm/s, and the lifting speed was 200 mm/s. The open circuit voltage (OCV) was measured and recorded by an electrochemical workstation under 1 N pressure. In addition, the OCV of the optimized P(VDF-TrFE) NFs was measured at 0.1, 1, 2, and 5 N cyclic pressures, respectively. The electric domain structure of P(VDF-TrFE) NFs was measured by piezoresponse force microscopy (PFM; MFP-3D Infinity, Oxford Instruments, UK) with a voltage of 4 V.
P(VDF-TrFE) NFs的压电性能通过CHI660E电化学工作站（CH Instruments，Inc.，中国）和ESM303-COMP机械测量系统（Mark-10 Corporation，美国）进行测试。切割4 cm×2 cm的样品，两端用导电银胶粘合0.01 mm厚的高纯铜箔，干燥24 h，如图S2所示。机械测量系统的向下压力速度设置为10 mm/s，提升速度为200 mm/s。通过电化学工作站在1 N压力下测量并记录开路电压（OCV）。此外，分别在 0.1、1、2 和 5 N 循环压力下测量了优化的 P(VDF-TrFE) NF 的 OCV。 P(VDF-TrFE) NF 的电域结构通过压敏力显微镜（PFM；MFP-3D Infinity，Oxford Instruments，UK）在 4 V 电压下测量。
P(VDF-TrFE) NFs的压电性能通过CHI660E电化学工作站（CH Instruments，Inc.，中国）和ESM303-COMP机械测量系统（Mark-10 Corporation，美国）进行测试。切割4 cm×2 cm的样品，两端用导电银胶粘合0.01 mm厚的高纯铜箔，干燥24 h，如图S2所示。机械测量系统的向下压力速度设置为10 mm/s，提升速度为200 mm/s。通过电化学工作站在1 N压力下测量并记录开路电压（OCV）。此外，分别在 0.1、1、2 和 5 N 循环压力下测量了优化的 P(VDF-TrFE) NF 的 OCV。 P(VDF-TrFE) NF 的电域结构通过压敏力显微镜（PFM；MFP-3D Infinity，Oxford Instruments，UK）在 4 V 电压下测量。
The electrochemical workstation (CHI660E, CH Instruments, Inc., China) was used to detect the conductivity of the hydrogel. First, the hydrogel was processed into a diameter of 20 × 20 mm and a thickness of 1 mm, and the sample was sandwiched between the copper electrode sheets. The current and voltage curve of the hydrogel was tested, and the conductivity of the material was calculated by the following equation: (23)
采用电化学工作站（CHI660E，CH Instruments，Inc.，中国）检测水凝胶的电导率。首先，将水凝胶加工成直径20×20mm、厚度1mm，并将样品夹在铜电极片之间。测试水凝胶的电流电压曲线，并通过以下公式计算材料的电导率： (23)where σ is the conductivity, V is the measurement voltage, I is the measurement current, L is the distance between the two electrodes, and S is the sample cross-sectional area.
其中σ是电导率，V是测量电压，I是测量电流，L是两个电极之间的距离，S是样品横截面积。
采用电化学工作站（CHI660E，CH Instruments，Inc.，中国）检测水凝胶的电导率。首先，将水凝胶加工成直径20×20mm、厚度1mm，并将样品夹在铜电极片之间。测试水凝胶的电流电压曲线，并通过以下公式计算材料的电导率： (23)
其中σ是电导率，V是测量电压，I是测量电流，L是两个电极之间的距离，S是样品横截面积。
2.7. Evaluation of In Vitro Cytocompatibility
2.7.体外细胞相容性评价
The cytocompatibility of the individual layers of SEWD was evaluated in vitro with an MTT assay. Proliferation of cells cultured in extracts of samples was assessed. In brief, the samples were sealed before 60Co irradiation sterilization. Then, the 40 mm × 70 mm film samples were soaked in 9.3 mL of cell culture medium for 24 h to obtain the extracts, while the hydrogel samples were added to the extract liquid volume per 0.1 g/mL. The cell culture medium was 1640 medium supplemented with 10% (v/v) calf serum and 1% (v/v) antibiotics. Cells (the cell concentration was 1 × 104 per milliliter) were cultured with 0.1 mL of the extract in a humidified atmosphere containing 5% CO2 at 37 °C in 96-well plastic tissue culture plates, while the fresh cell culture medium was used for the blank control group. Cell viability was assessed after 1, 3, and 5 days of culture. At each time point, 20 μL/well of a solution of 5 mg/mL MTT was added to the culture and incubated at 37 °C for 4 h to form formazan crystals. Subsequently, DMSO (200 μL/well) was added to dissolve the formazan crystals and the optical density (OD) at 570 nm measured with a microplate reader (Model 550, Bio-Rad Corp., USA) to evaluate the degree of cytotoxicity.
SEWD 各层的细胞相容性通过 MTT 测定进行体外评估。评估了样品提取物中培养的细胞的增殖。简而言之，在 60Co 辐照灭菌之前将样品密封。然后将40 mm×70 mm薄膜样品在9.3 mL细胞培养基中浸泡24 h，得到提取物，同时将水凝胶样品按0.1 g/mL加入提取液体积中。细胞培养基是补充有10%（v/v）小牛血清和1%（v/v）抗生素的1640培养基。将细胞（细胞浓度为1×104/毫升）与0.1 mL提取物在37℃、含5%CO2的湿润气氛中于96孔塑料组织培养板中培养，同时使用新鲜的细胞培养基空白对照组。培养 1、3 和 5 天后评估细胞活力。在每个时间点，将20μL/孔的5mg/mL MTT溶液添加到培养物中，并在37℃下孵育4小时以形成甲臜晶体。随后加入DMSO（200 μL/孔）溶解甲臜晶体，用酶标仪（型号550，Bio-Rad Corp.，USA）测量570 nm处的光密度（OD）以评估细胞毒性程度。
SEWD 各层的细胞相容性通过 MTT 测定进行体外评估。评估了样品提取物中培养的细胞的增殖。简而言之，在 60Co 辐照灭菌之前将样品密封。然后将40 mm×70 mm薄膜样品在9.3 mL细胞培养基中浸泡24 h，得到提取物，同时将水凝胶样品按0.1 g/mL加入提取液体积中。细胞培养基是补充有10%（v/v）小牛血清和1%（v/v）抗生素的1640培养基。将细胞（细胞浓度为1×104/毫升）与0.1 mL提取物在37℃、含5%CO2的湿润气氛中于96孔塑料组织培养板中培养，同时使用新鲜的细胞培养基空白对照组。培养 1、3 和 5 天后评估细胞活力。在每个时间点，将20μL/孔的5mg/mL MTT溶液添加到培养物中，并在37℃下孵育4小时以形成甲臜晶体。随后加入DMSO（200 μL/孔）溶解甲臜晶体，用酶标仪（型号550，Bio-Rad Corp.，USA）测量570 nm处的光密度（OD）以评估细胞毒性程度。
2.8. Evaluation of Healing-Promoting Performance of SEWD In Vitro
2.8. SEWD 促愈合性能的体外评价
PLLA (1 g) and 1,4-dioxane (20 mL) were mixed well at room temperature to be used as glue. SEWD was cut into a circle with a diameter of 35 mm and fixed to a 6-well BioFlex culture plate (BF-3001U, Flexcell Co., USA) with a soft bottom with PLLA glue. BioFlex culture plates were sealed and sterilized by 60Co irradiation. L929 fibroblasts were inoculated on SEWD samples in a BioFlex culture plate and cultured at 37 °C in an atmosphere containing 5% CO2. The culture medium was changed every 2 days. The plates were divided into two groups. The first group was cultured normally without any treatment. The second group received mechanical stimulation by a small vibrating blender (XK96-A, Xinkang Medical Instrument Co., Ltd.) once a day for 1 h. The culture plates were guarded and supervised during the whole process to ensure that the soft bottom could accept mechanical stimulation and the culture plates do not shift. On days 1, 3, and 5, L929 fibroblasts on the material were digested and transferred to a new plate, and the proliferation was determined by an MTT method after dilution. In addition, the L929 fibroblasts on SEWD samples were observed by SEM and confocal laser scanning microscopy (CLSM), respectively. Briefly, cells (the cell concentration was 5 × 104 per milliliter) were seeded on the samples and cultured in the cell culture medium at 37 °C in an atmosphere containing 5% CO2 for 3 days. Subsequently, the cells attached on the samples were fixed with 4% paraformaldehyde in PBS for 30 min at room temperature. The samples were dehydrated using different gradients of ethanol (30, 50, 75, 90, 95, and 100%) and dried with a critical-point drier before SEM (S3000N, Hitachi, Japan) observation. Moreover, the samples were rinsed with PBS (pH 7.4) and stained with tetraethyl rhodamine isothiocyanate-phalloidin and 4,6-diamidino-2-phenylindole (DAPI) prior to analysis by CLSM (N-SIM, Nikon, Japan).
将 PLLA (1 g) 和 1,4-二恶烷 (20 mL) 在室温下充分混合，用作胶水。将 SEWD 切成直径 35 mm 的圆形，并用 PLLA 胶固定于软底 6 孔 BioFlex 培养板（BF-3001U，Flexcell Co.，USA）上。 BioFlex 培养板密封并通过 60Co 辐照灭菌。 L929 成纤维细胞接种在 BioFlex 培养板中的 SEWD 样品上，并在 37°C、含 5% CO2 的气氛中培养。每2天更换一次培养基。将板分为两组。第一组正常培养，不做任何处理。第二组采用小型振动搅拌器（XK96-A，信康医疗器械有限公司）进行机械刺激，每天一次，持续1 h。培养板全程有人看守和监督，保证软底能接受机械刺激，培养板不移位。第1、3、5天，将材料上的L929成纤维细胞消化并转移到新的平板上，稀释后通过MTT法测定增殖情况。此外，分别通过SEM和共焦激光扫描显微镜（CLSM）观察SEWD样品上的L929成纤维细胞。简而言之，将细胞（细胞浓度为每毫升5×104）接种到样品上，并在37℃、含5%CO2的气氛下的细胞培养基中培养3天。随后，将附着在样品上的细胞用4%多聚甲醛的PBS溶液在室温下固定30分钟。使用不同梯度的乙醇（30%、50%、75%、90%、95%和100%）对样品进行脱水，并在SEM（S3000N，日立，日本）观察之前用临界点干燥器干燥。此外，用 PBS (pH 7.4) 并在 CLSM（N-SIM，尼康，日本）分析之前用四乙基罗丹明异硫氰酸酯-鬼笔环肽和 4,6-二脒基-2-苯基吲哚 (DAPI) 染色。
将 PLLA (1 g) 和 1,4-二恶烷 (20 mL) 在室温下充分混合，用作胶水。将 SEWD 切成直径 35 mm 的圆形，并用 PLLA 胶固定于软底 6 孔 BioFlex 培养板（BF-3001U，Flexcell Co.，USA）上。 BioFlex 培养板密封并通过 60Co 辐照灭菌。 L929 成纤维细胞接种在 BioFlex 培养板中的 SEWD 样品上，并在 37°C、含 5% CO2 的气氛中培养。每2天更换一次培养基。将板分为两组。第一组正常培养，不做任何处理。第二组采用小型振动搅拌器（XK96-A，信康医疗器械有限公司）进行机械刺激，每天一次，持续1 h。培养板全程有人看守和监督，保证软底能接受机械刺激，培养板不移位。第1、3、5天，将材料上的L929成纤维细胞消化并转移到新的平板上，稀释后通过MTT法测定增殖情况。此外，分别通过SEM和共焦激光扫描显微镜（CLSM）观察SEWD样品上的L929成纤维细胞。简而言之，将细胞（细胞浓度为每毫升5×104）接种到样品上，并在37℃、含5%CO2的气氛下的细胞培养基中培养3天。随后，将附着在样品上的细胞用4%多聚甲醛的PBS溶液在室温下固定30分钟。使用不同梯度的乙醇（30%、50%、75%、90%、95%和100%）对样品进行脱水，并在SEM（S3000N，日立，日本）观察之前用临界点干燥器干燥。此外，用 PBS (pH 7.4) 并在 CLSM（N-SIM，尼康，日本）分析之前用四乙基罗丹明异硫氰酸酯-鬼笔环肽和 4,6-二脒基-2-苯基吲哚 (DAPI) 染色。
The protein expression levels of the target collagen I genes were analyzed by Western blotting. Briefly, L929 fibroblasts cultured on SEWD with or without mechanical stimulation were lysed, and the proteins were separated by electrophoresis and transferred onto nitrocellulose filter films. The films were incubated with Rabbit Anti-Collagen I (Bioss, China) and Anti-Beta Actin (control) (Shenggong, China), followed by incubation with Goat-Anti-Rabbit IgG-HRP (Bioss, Beijing, China). The proteins were detected with electrogenerated chemiluminescence in X-ray film darkroom. The protein levels were normalized to that of the housekeeping gene actin. The relative intensities of the bands were quantified by Quantity One software.
通过蛋白质印迹分析目标胶原 I 基因的蛋白质表达水平。简而言之，在有或没有机械刺激的SEWD上培养的L929成纤维细胞被裂解，通过电泳分离蛋白质并转移到硝酸纤维素滤膜上。将膜与兔抗胶原蛋白 I（Bioss，中国）和抗 Beta 肌动蛋白（对照）（胜工，中国）一起孵育，然后与山羊抗兔 IgG-HRP（Bioss，北京，中国）一起孵育。在 X 射线胶片暗室中用电化学发光法检测蛋白质。将蛋白质水平标准化为管家基因肌动蛋白的水平。通过Quantity One 软件对条带的相对强度进行量化。
通过蛋白质印迹分析目标胶原 I 基因的蛋白质表达水平。简而言之，在有或没有机械刺激的SEWD上培养的L929成纤维细胞被裂解，通过电泳分离蛋白质并转移到硝酸纤维素滤膜上。将膜与兔抗胶原蛋白 I（Bioss，中国）和抗 Beta 肌动蛋白（对照）（胜工，中国）一起孵育，然后与山羊抗兔 IgG-HRP（Bioss，北京，中国）一起孵育。在 X 射线胶片暗室中用电化学发光法检测蛋白质。将蛋白质水平标准化为管家基因肌动蛋白的水平。通过Quantity One 软件对条带的相对强度进行量化。
2.9. Evaluation of Healing-Promoting Performance of SEWD In Vivo
2.9. SEWD 体内促愈合性能评价
Sprague–Dawley (SD) rats with weights around 300 g were anesthetized by intraperitoneal injection of 10% chloral hydrate (300 mg/kg). Under an aseptic condition, approximately 10 mm × 20 mm full-thickness skin excision wounds were created on both sides (left and right) of the dorsal surface of the rats (two injuries/rat). The samples were cut into 10 mm × 20 mm rectangles and then sterilized with 60Co irradiation. The hydrogel was implanted on rat’s left-sided wound, while the SEWD was implanted on rat’s right-sided wound. Penicillin was injected intramuscularly for 3 days to prevent the wound from infection. Each rat was kept in a separate space so that it had a free range of motion and mechanical stimulation through daily movement or daily activities. The animals were sacrificed at 3-, 7-, and 14-day post-surgery. The wound and surrounding tissues were removed from animals for further analysis. The samples were fixed in 10% buffered formalin, dehydrated using a gradient of ethanol, and then cleared with xylene. Paraffin-embedded tissue samples were sectioned into 5 μm thick slides. In histological studies, hematoxylin and eosin (H&E) staining and immunohistological staining were used according to standard protocols. The studies were carried out to observe the expressions of basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), and platelet-derived growth factor (PDGF). All experimental animals were handled according to the guidelines for human use and care of laboratory animals, set out by the National Institutes of Health (NIH). The procedures performed on animals were approved by the Animal Care and Use Committee of Sichuan University. The images of the wound were analyzed by ImageJ software to calculate the wound area.
体重约 300 g 的 Sprague-Dawley (SD) 大鼠通过腹腔注射 10% 水合氯醛 (300 mg/kg) 进行麻醉。在无菌条件下，在大鼠背侧两侧（左、右）制作约10mm×20mm的全层皮肤切除伤口（每只大鼠2处）。将样品切成10 mm×20 mm的矩形，然后用60Co辐照灭菌。将水凝胶植入大鼠的左侧伤口，而SEWD则植入大鼠的右侧伤口。肌注青霉素3天，防止伤口感染。将每只大鼠饲养在单独的空间中，使其通过日常运动或日常活动获得自由的运动范围和机械刺激。手术后3、7和14天处死动物。从动物身上取出伤口和周围组织以进行进一步分析。将样品固定在 10% 缓冲福尔马林中，使用乙醇梯度脱水，然后用二甲苯澄清。将石蜡包埋的组织样本切成 5 μm 厚的载玻片。在组织学研究中，根据标准方案使用苏木精和伊红（H&E）染色和免疫组织学染色。观察碱性成纤维细胞生长因子（bFGF）、血管内皮生长因子（VEGF）、血小板源性生长因子（PDGF）的表达。所有实验动物均按照美国国立卫生研究院 (NIH) 制定的人类使用和实验动物护理指南进行处理。对动物进行的程序得到了四川大学动物护理和使用委员会的批准。通过ImageJ软件分析伤口图像，计算伤口面积。
体重约 300 g 的 Sprague-Dawley (SD) 大鼠通过腹腔注射 10% 水合氯醛 (300 mg/kg) 进行麻醉。在无菌条件下，在大鼠背侧两侧（左、右）制作约10mm×20mm的全层皮肤切除伤口（每只大鼠2处）。将样品切成10 mm×20 mm的矩形，然后用60Co辐照灭菌。将水凝胶植入大鼠的左侧伤口，而SEWD则植入大鼠的右侧伤口。肌注青霉素3天，防止伤口感染。将每只大鼠饲养在单独的空间中，使其通过日常运动或日常活动获得自由的运动范围和机械刺激。手术后3、7和14天处死动物。从动物身上取出伤口和周围组织以进行进一步分析。将样品固定在 10% 缓冲福尔马林中，使用乙醇梯度脱水，然后用二甲苯澄清。将石蜡包埋的组织样本切成 5 μm 厚的载玻片。在组织学研究中，根据标准方案使用苏木精和伊红（H&E）染色和免疫组织学染色。观察碱性成纤维细胞生长因子（bFGF）、血管内皮生长因子（VEGF）、血小板源性生长因子（PDGF）的表达。所有实验动物均按照美国国立卫生研究院 (NIH) 制定的人类使用和实验动物护理指南进行处理。对动物进行的程序得到了四川大学动物护理和使用委员会的批准。通过ImageJ软件分析伤口图像，计算伤口面积。
2.10. Statistical Analysis
2.10.统计分析
The data were expressed as the mean ± standard deviation (SD). Each experiment was repeated at least three times. Statistically significant differences (p < 0.05) were measured using one-way analysis of variance (ANOVA) combined with the Student–Newman–Keuls (SNK) multiple comparison post hoc test. Statistical analysis was performed using SPSS-23 (International Business Machines Corporation (IBM), USA) software.
数据表示为平均值±标准差（SD）。每个实验至少重复三次。使用单因素方差分析 (ANOVA) 结合 Student-Newman-Keuls (SNK) 多重比较事后检验来测量统计显着性差异 (p < 0.05)。使用SPSS-23（国际商业机器公司（IBM），美国）软件进行统计分析。
数据表示为平均值±标准差（SD）。每个实验至少重复三次。使用单因素方差分析 (ANOVA) 结合 Student-Newman-Keuls (SNK) 多重比较事后检验来测量统计显着性差异 (p < 0.05)。使用SPSS-23（国际商业机器公司（IBM），美国）软件进行统计分析。
3. Results and Discussion
3。结果与讨论
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3.1. Characteristics of the SEWD Material
3.1. SEWD材料的特性
Skin injury is a common problem in clinical practice. How to accelerate tissue repair safely and effectively and improve wound healing quality is an eternal topic. To introduce the safe and effective wound ES therapy into the convenient wound treatment, in this work, a novel wound dressing SEWD with self-powered capability based on the piezoelectric effect was developed. The dressing was composed of a double-layer structure, of which a hydrogel material with a conductive adhesion function was grown on the dendritic nanofiber film with a bionic structure, as shown in Figure 2A. Inspired by the large motion amplitude at the end of branches when trees are blown by the wind in nature, the P(VDF-TrFE) nanofiber microstructure is controlled by regulating the electrical conductivity of the electrospinning solution, and the nanofiber with a tree-like bionic structure is obtained, which has better piezoelectric properties and mechanical properties than the traditional P(VDF-TrFE) electrospinning film. It can sensitize the mechanical stimulation brought by small activities into electrical signals, which are transmitted to the wound surface through the conductive adhesive hydrogel and play the role of ES therapy (Figure 2B). The conductive adhesive hydrogel was inspired by marine mussels, and its preparation mechanism is shown in Figure 2C. Acrylamide (AM) was introduced to the gelatin network and polymerized, wherein the gelatin (Gel) molecules could form chain entanglement to form Gel-PAM. When COA was added, the COA aldehyde groups reacted with gelatin to promote network formation. Moreover, the catechol structures on the COA molecular chain reacted with PAM as well as the active groups of gelatins, such as the amino group, and there are also hydrogen bonds. Additionally, the addition of Fe3+ could avoid the adverse effects of catechol reducibility on AM radical polymerization, as it induces redox reaction and chelation with the COA catechol structure. In this process, notably, Fe3+ and the catechol structure formed redox pairs that can activate ammonium persulfate (APS) to generate free radicals, consequently leading to the gentle and rapid promotion of hydrogel network formation from AM (high temperature is not required). (24) Without introducing Fe3+, a high catechol concentration affects the APS activity to a certain extent, thereby affecting PAM polymerization. (25) The addition of Fe3+ can increase the catechol group content in the system, which benefits the structure and hydrogel properties. Furthermore, Fe3+ can improve the conductivity of hydrogels as a carrier of electron conduction. The prepared SEWD improves the defect that traditional piezoelectric dressing is not conducive to direct contact with the wound, and also solves the problem of inconvenient use of clinical ES equipment.
皮肤损伤是临床上常见的问题。如何安全有效地加速组织修复，提高伤口愈合质量是一个永恒的话题。为了将安全有效的伤口ES治疗引入到方便的伤口治疗中，本工作开发了一种基于压电效应的具有自供电能力的新型伤口敷料SEWD。该敷料由双层结构组成，其中具有导电粘附功能的水凝胶材料生长在具有仿生结构的树枝状纳米纤维薄膜上，如图2A所示。受自然界树木被风吹动时树枝末端的大运动幅度的启发，通过调节静电纺丝溶液的电导率来控制P(VDF-TrFE)纳米纤维的微观结构，获得了具有树状结构的纳米纤维。获得了仿生结构，比传统的P(VDF-TrFE)静电纺丝薄膜具有更好的压电性能和力学性能。它可以将微小活动带来的机械刺激敏化为电信号，通过导电粘合水凝胶传输到创面，起到ES治疗的作用（图2B）。导电粘合剂水凝胶的灵感来自于海洋贻贝，其制备机制如图2C所示。将丙烯酰胺（AM）引入到明胶网络中并聚合，其中明胶（Gel）分子可以形成链缠结，形成Gel-PAM。添加 COA 后，COA 醛基与明胶反应，促进网络形成。而且COA分子链上的儿茶酚结构与PAM以及明胶的活性基团如氨基发生反应，也存在氢键。 此外，Fe3+的添加可以避免儿茶酚还原性对AM自由基聚合的不利影响，因为它会引发氧化还原反应并与COA儿茶酚结构发生螯合。值得注意的是，在此过程中，Fe3+和儿茶酚结构形成氧化还原对，可以激活过硫酸铵（APS）产生自由基，从而温和而快速地促进AM水凝胶网络的形成（不需要高温）。 (24)在不引入Fe3+的情况下，较高的儿茶酚浓度会在一定程度上影响APS活性，从而影响PAM聚合。 (25) Fe3+的添加可以增加体系中儿茶酚基团的含量，有利于水凝胶的结构和性能。此外，Fe3+作为电子传导的载体可以提高水凝胶的电导率。制备的SEWD改善了传统压电敷料不利于直接接触创面的缺陷，也解决了临床ES设备使用不方便的问题。
皮肤损伤是临床上常见的问题。如何安全有效地加速组织修复，提高伤口愈合质量是一个永恒的话题。为了将安全有效的伤口ES治疗引入到方便的伤口治疗中，本工作开发了一种基于压电效应的具有自供电能力的新型伤口敷料SEWD。该敷料由双层结构组成，其中具有导电粘附功能的水凝胶材料生长在具有仿生结构的树枝状纳米纤维薄膜上，如图2A所示。受自然界树木被风吹动时树枝末端的大运动幅度的启发，通过调节静电纺丝溶液的电导率来控制P(VDF-TrFE)纳米纤维的微观结构，获得了具有树状结构的纳米纤维。获得了仿生结构，比传统的P(VDF-TrFE)静电纺丝薄膜具有更好的压电性能和力学性能。它可以将微小活动带来的机械刺激敏化为电信号，通过导电粘合水凝胶传输到创面，起到ES治疗的作用（图2B）。导电粘合剂水凝胶的灵感来自于海洋贻贝，其制备机制如图2C所示。将丙烯酰胺（AM）引入到明胶网络中并聚合，其中明胶（Gel）分子可以形成链缠结，形成Gel-PAM。添加 COA 后，COA 醛基与明胶反应，促进网络形成。而且COA分子链上的儿茶酚结构与PAM以及明胶的活性基团如氨基发生反应，也存在氢键。 此外，Fe3+的添加可以避免儿茶酚还原性对AM自由基聚合的不利影响，因为它会引发氧化还原反应并与COA儿茶酚结构发生螯合。值得注意的是，在此过程中，Fe3+和儿茶酚结构形成氧化还原对，可以激活过硫酸铵（APS）产生自由基，从而温和而快速地促进AM水凝胶网络的形成（不需要高温）。 (24)在不引入Fe3+的情况下，较高的儿茶酚浓度会在一定程度上影响APS活性，从而影响PAM聚合。 (25) Fe3+的添加可以增加体系中儿茶酚基团的含量，有利于水凝胶的结构和性能。此外，Fe3+作为电子传导的载体可以提高水凝胶的电导率。制备的SEWD改善了传统压电敷料不利于直接接触创面的缺陷，也解决了临床ES设备使用不方便的问题。
Figure 2 图2
Figure 2. (A) Schematic diagram of the preparation of the two-layered SEWD. (B) Mussel-inspired adhesion mechanism inside SEWD and the properties of SEWD. (C) Main chemical reactions in the formation of the CF-Gel-PAM hydrogel.
图2.(A)两层SEWD的制备示意图。 (B) SEWD 内部受贻贝启发的粘附机制以及 SEWD 的特性。 (C) CF-Gel-PAM 水凝胶形成过程中的主要化学反应。
3.2. Microtopography of the SEWD Material
3.2. SEWD 材料的微观形貌
The photo and macroscopic morphology of SEWD are shown in Figure 3A,B, in which the two layers can be distinguished; the first layer is P(VDF-TrFE) NFs, while the second is CF-Gel-PAM hydrogel. Although the two layers of materials have completely different microstructures, their interfaces are well integrated with each other, and they are independent of each other. The unique structure of SEWD ensures that it can exist as a complete material when applied. For the first layer of SEWD, inspired by nature that the tree is rooted in the soil, the breeze is able to make the end of the branch move much more than the trunk. Piezoelectric materials can convert mechanical stimulation into electrical signals, and the tree-like nanofibers help capture more motion, laying the foundation for subsequent applications. By adding different substances to P(VDF-TrFE) electrospinning solution to adjust the electrical conductivity, the fiber morphology can be regulated. The morphology of nanofibers was observed using SEM. As shown in Figure S3, it can be seen that the samples with TBAC and Fe3O4 NPs added have a more vivid dendritic structure and thinner trunk fibers. Therefore, this group of samples was selected for the follow-up experiment. Detailedly, it can be seen from Figure 3C,D that the fibers are disorderly close-packed with numerous dendritic structures, because when the charge density of the solution exceeded a certain threshold (Figure S4), the electric field force overcame the surface tension, subsequently causing jet splitting, thereby resulting in the formation of a dendritic structure, corresponding with the observed morphology (Figure 3F–H). (26) Through the diameter analysis of the sample fiber at 5000× zoom, the trunk fiber distribution was moderately concentrated with an average diameter of 0.1943 ± 0.0389 μm, and the average diameter of the branch fibers was 0.028 ± 0.0011 μm. In addition, the favorable water and air permeability (7610 ± 1252 mg/10 cm2·24 h) of the P(VDF-TrFE) NFs was secured by its favorable pore structure. The internal morphology and the pore analysis of the hydrogel are shown in Figure 3I–K and Figure S5. The self-crosslinked network from the PAM polymerization interpenetrated with the gelatin and COA network, resulting in the formation of a compact three-dimensional network structure. The hydrogel structure crosslinked using COA is more compact. In contrast, the hydrogel pore size is nonuniform with less COA content, and the average pore size and porosity after crosslinking both show a decreasing trend. This may be attributable to the sufficient chemical reactions, such as crosslinking between various components in the hydrogel, including the Schiff base reaction, Michael addition, and hydrogen bonding. (27)
SEWD的照片和宏观形貌如图3A、B所示，其中可以区分两层；第一层是P(VDF-TrFE) NFs，第二层是CF-Gel-PAM水凝胶。尽管两层材料的微观结构完全不同，但它们的界面相互融合良好，并且相互独立。 SEWD独特的结构保证了它在应用时能够作为完整的材料存在。对于SEWD的第一层，受到树木扎根于土壤的大自然的启发，微风能够使树枝末端比树干移动更多。压电材料可以将机械刺激转化为电信号，树状纳米纤维有助于捕捉更多运动，为后续应用奠定基础。通过在P(VDF-TrFE)静电纺丝溶液中添加不同的物质来调节电导率，可以调控纤维的形貌。使用SEM观察纳米纤维的形貌。如图S3所示，可以看出添加TBAC和Fe3O4 NPs的样品具有更鲜艳的树枝状结构和更细的主干纤维。因此，选取该组样品进行后续实验。具体来说，从图3C、D可以看出，纤维是无序密堆积的，具有大量的树枝状结构，因为当溶液的电荷密度超过一定阈值时（图S4），电场力克服了表面张力，随后引起射流分裂，从而形成树枝状结构，与观察到的形态相对应（图3F-H）。 (26)通过5000倍变焦下对样品纤维直径分析，主干纤维分布适度集中，平均直径为0.1943±0.0389μm，分支纤维平均直径为0.028±0.0011μm。此外，P(VDF-TrFE) NFs良好的孔结构保证了其良好的透水性和透气性（7610±1252 mg/10 cm2·24 h）。水凝胶的内部形态和孔隙分析如图3I-K和图S5所示。 PAM聚合产生的自交联网络与明胶和COA网络相互渗透，形成致密的三维网络结构。使用COA交联的水凝胶结构更加致密。相比之下，COA含量较少的水凝胶孔径不均匀，交联后的平均孔径和孔隙率均呈现下降趋势。这可能归因于充分的化学反应，例如水凝胶中各组分之间的交联，包括席夫碱反应、迈克尔加成和氢键。 (27)
SEWD的照片和宏观形貌如图3A、B所示，其中可以区分两层；第一层是P(VDF-TrFE) NFs，第二层是CF-Gel-PAM水凝胶。尽管两层材料的微观结构完全不同，但它们的界面相互融合良好，并且相互独立。 SEWD独特的结构保证了它在应用时能够作为完整的材料存在。对于SEWD的第一层，受到树木扎根于土壤的大自然的启发，微风能够使树枝末端比树干移动更多。压电材料可以将机械刺激转化为电信号，树状纳米纤维有助于捕捉更多运动，为后续应用奠定基础。通过在P(VDF-TrFE)静电纺丝溶液中添加不同的物质来调节电导率，可以调控纤维的形貌。使用SEM观察纳米纤维的形貌。如图S3所示，可以看出添加TBAC和Fe3O4 NPs的样品具有更鲜艳的树枝状结构和更细的主干纤维。因此，选取该组样品进行后续实验。具体来说，从图3C、D可以看出，纤维是无序密堆积的，具有大量的树枝状结构，因为当溶液的电荷密度超过一定阈值时（图S4），电场力克服了表面张力，随后引起射流分裂，从而形成树枝状结构，与观察到的形态相对应（图3F-H）。 (26)通过5000倍变焦下对样品纤维直径分析，主干纤维分布适度集中，平均直径为0.1943±0.0389μm，分支纤维平均直径为0.028±0.0011μm。此外，P(VDF-TrFE) NFs良好的孔结构保证了其良好的透水性和透气性（7610±1252 mg/10 cm2·24 h）。水凝胶的内部形态和孔隙分析如图3I-K和图S5所示。 PAM聚合产生的自交联网络与明胶和COA网络相互渗透，形成致密的三维网络结构。使用COA交联的水凝胶结构更加致密。相比之下，COA含量较少的水凝胶孔径不均匀，交联后的平均孔径和孔隙率均呈现下降趋势。这可能归因于充分的化学反应，例如水凝胶中各组分之间的交联，包括席夫碱反应、迈克尔加成和氢键。 (27)
Figure 3 图3
Figure 3. (A) Photo of the two-layered SEWD ((I) P(VDF-TrFE) NFs and (II) CF-Gel-PAM hydrogel). (B) SEM image of the two-layered SEWD. (C) SEM image of P(VDF-TrFE) NFs, ×1000. (D) SEM image of P(VDF-TrFE) NFs, ×10,000. (E) Diameter distribution of P(VDF-TrFE) NFs. (F) Magnifying SEM image of P(VDF-TrFE) NFs. (G) Diagrammatic drawing of the tree-like nanofiber of P(VDF-TrFE) NFs. (H) Photo of a tree. (I) SEM image of the CF-Gel-PAM hydrogel, ×200. (J) SEM image of the CF-Gel-PAM hydrogel, ×500. (K) Pore size analysis of the CF-Gel-PAM hydrogel.
图 3. (A) 两层 SEWD 的照片（(I) P(VDF-TrFE) NF 和 (II) CF-Gel-PAM 水凝胶）。 (B) 两层 SEWD 的 SEM 图像。 (C) P(VDF-TrFE) NF 的 SEM 图像，×1000。 (D) P(VDF-TrFE) NF 的 SEM 图像，×10,000。 (E) P(VDF-TrFE) NF 的直径分布。 (F) P(VDF-TrFE) NF 的放大 SEM 图像。 (G) P(VDF-TrFE) NF 树状纳米纤维的示意图。 (H) 一棵树的照片。 (I) CF-Gel-PAM水凝胶的SEM图像，×200。 (J) CF-Gel-PAM 水凝胶的 SEM 图像，×500。 (K) CF-Gel-PAM 水凝胶的孔径分析。
3.3. Properties of the SEWD Material
3.3. SEWD 材料的特性
The mechanical properties of SEWD were measured (Figure 4A,B). The double-layer structure can maintain consistent deformation in a large range under test conditions, and its tensile strength was 46.6 ± 2.3 KPa. The adhesive strength between two independent structures was measured by the lap shear test, which was 8.7 ± 0.83 KPa. Subsequently, the mechanical properties of the materials with two independent structures were measured, respectively. The tensile strength and elongation at break of the electrospun samples were tested, and the results are shown in Figure S6. In general, the mechanical properties are strongly dependent on the morphology of the electrospun film and the interaction between nanofibers. Comparing the samples with native P(VDF-TrFE) NFs, it can be seen that the prepared sample with a tree-like structure could promote the increase of its mechanical properties. The trunk fiber can be used as the skeleton support, and the branch fiber can be used as the connecting pillar. The strong interaction of the joint points and entanglement between the fibers could improve the tensile strength. (28) The storage modulus (elastic modulus, G′) and loss modulus (viscosity modulus, G″) of the hydrogels were evaluated using rheological tests. The mechanical properties of the hydrogels depend on the polymer chain rigidity and crosslinking degree in the hydrogel network as well as the gel swelling rate. Figure S7a,b shows the modulus–frequency curve of the hydrogel, indicating the stable viscoelastic solid properties of and effective crosslinking within the hydrogels. (29) In addition, the stability of the hydrogel structure was positively affected by the combined physical and chemical crosslinking of COA. (30) The hydrophilic properties of SEWD were measured. The contact angle of layer I indicated that it is a hydrophobic layer (Figure S8). Since layer II is directly in contact with the wound, the hydrophobic property of layer I may play a role of waterproof, antifouling, and wound protection to a certain extent. The swelling performance of the hydrogel of layer II is shown in Figure S7c. The equilibrium swelling rate and water content of a set of hydrogels exhibited little differences. The ability to swell and retain a large portion of water is due to hydrophilic functional groups attached to the backbone of the hydrogel polymer, while the resistance to solubility can be attributed to the crosslinked hydrogel network. In addition, the swelling rate of SEWD was 1589 ± 147%, which was not much different from that of the hydrogels. The degradation property test results showed that the degradation rate of SEWD in PBS buffer solution was less than 5% (Figure S7) in 7 days, which was mainly attributed to the degradation of gelatin in the material components.
测量了 SEWD 的机械性能（图 4A、B）。双层结构在试验条件下能在大范围内保持一致的变形，其抗拉强度为46.6±2.3 KPa。通过搭接剪切试验测量两个独立结构之间的粘合强度，结果为8.7±0.83 KPa。随后，分别测量了具有两个独立结构的材料的力学性能。对静电纺丝样品的拉伸强度和断裂伸长率进行了测试，结果如图S6所示。一般来说，机械性能很大程度上取决于电纺薄膜的形态和纳米纤维之间的相互作用。将样品与天然P(VDF-TrFE) NFs进行比较，可以看出制备的树状结构样品可以促进其力学性能的提高。主干纤维可作为骨架支撑，分支纤维可作为连接支柱。接头点的强相互作用和纤维之间的缠结可以提高拉伸强度。 (28)通过流变测试评估水凝胶的储能模量（弹性模量，G'）和损耗模量（粘度模量，G''）。水凝胶的机械性能取决于水凝胶网络中聚合物链的刚性和交联度以及凝胶溶胀速率。图S7a、b显示了水凝胶的模量-频率曲线，表明水凝胶具有稳定的粘弹性固体特性和水凝胶内的有效交联。 (29) 此外，COA 的物理和化学交联相结合对水凝胶结构的稳定性产生积极影响。 (30)测量SEWD的亲水性。 I层的接触角表明它是疏水层（图S8）。由于第二层直接与伤口接触，第一层的疏水性可以在一定程度上起到防水、防污、保护伤口的作用。第二层水凝胶的溶胀性能如图S7c所示。一组水凝胶的平衡溶胀率和含水量几乎没有差异。溶胀和保留大部分水的能力归因于连接到水凝胶聚合物主链上的亲水官能团，而抗溶解性可归因于交联的水凝胶网络。此外，SEWD的溶胀率为1589±147%，与水凝胶的溶胀率没有太大差异。降解性能测试结果显示，7天内SEWD在PBS缓冲溶液中的降解率小于5%（图S7），这主要归因于材料成分中明胶的降解。
测量了 SEWD 的机械性能（图 4A、B）。双层结构在试验条件下能在大范围内保持一致的变形，其抗拉强度为46.6±2.3 KPa。通过搭接剪切试验测量两个独立结构之间的粘合强度，结果为8.7±0.83 KPa。随后，分别测量了具有两个独立结构的材料的力学性能。对静电纺丝样品的拉伸强度和断裂伸长率进行了测试，结果如图S6所示。一般来说，机械性能很大程度上取决于电纺薄膜的形态和纳米纤维之间的相互作用。将样品与天然P(VDF-TrFE) NFs进行比较，可以看出制备的树状结构样品可以促进其力学性能的提高。主干纤维可作为骨架支撑，分支纤维可作为连接支柱。接头点的强相互作用和纤维之间的缠结可以提高拉伸强度。 (28)通过流变测试评估水凝胶的储能模量（弹性模量，G'）和损耗模量（粘度模量，G''）。水凝胶的机械性能取决于水凝胶网络中聚合物链的刚性和交联度以及凝胶溶胀速率。图S7a、b显示了水凝胶的模量-频率曲线，表明水凝胶具有稳定的粘弹性固体特性和水凝胶内的有效交联。 (29) 此外，COA 的物理和化学交联相结合对水凝胶结构的稳定性产生积极影响。 (30)测量SEWD的亲水性。 I层的接触角表明它是疏水层（图S8）。由于第二层直接与伤口接触，第一层的疏水性可以在一定程度上起到防水、防污、保护伤口的作用。第二层水凝胶的溶胀性能如图S7c所示。一组水凝胶的平衡溶胀率和含水量几乎没有差异。溶胀和保留大部分水的能力归因于连接到水凝胶聚合物主链上的亲水官能团，而抗溶解性可归因于交联的水凝胶网络。此外，SEWD的溶胀率为1589±147%，与水凝胶的溶胀率没有太大差异。降解性能测试结果显示，7天内SEWD在PBS缓冲溶液中的降解率小于5%（图S7），这主要归因于材料成分中明胶的降解。
Figure 4 图4
Figure 4. (A) Typical stretch curve of SEWD. (B) Adhesion strength of SEWD. (C) Schematic diagram of the piezoelectric effect. (D) OCV output curve under different pressures. (E) PFM scanning phase diagram. (F) Micro-piezoelectric response curves of the P(VDF-TrFE) film. (G) Pictures of the SEWD making the bulb glow (left, not connected; right, connected).
图 4. (A) SEWD 的典型拉伸曲线。 (B) SEWD 的粘合强度。 (C) 压电效应示意图。 (D) 不同压力下的OCV输出曲线。 (E) PFM 扫描相图。 (F) P(VDF-TrFE) 薄膜的微压电响应曲线。 (G) SEWD 使灯泡发光的图片（左，未连接；右，已连接）。
Figure 4C shows the schematic diagram of the piezoelectric effect. The OCV value of P(VDF-TrFE) NFs was measured under different pressures, as shown in Figure 4D, different OCV signals were output by the P(VDF-TrFE) NFs under different forces, and a voltage of approximately 0.3 V was detected under a 0.1 N force, indicating a stable response to small forces. Herein, the OCV was 2.7 V under a 2 N force. For comparison, Habibur et al. (31) improved the P(VDF-TrFE) properties under unpolarized conditions, wherein the piezoelectric output is 2.4 V under a 2 V force. Figure S9 shows the piezoelectric properties of electrospinning films with and without a dendritic fiber structure, and it can be seen that dendritic fibers have obvious advantages. Through FTIR and XRD analysis of several samples with different structures, as shown in Figure S10, dendritic fibers had higher crystallinity, which is due to the greater mechanical stretching required to form dendritic fibers in the electrospinning process, which is favorable for the crystallization of P(VDF-TrFE). And this is why dendritic fibers had better piezoelectric properties. The results indicate that the prepared tree-like nanofibers demonstrated good application ability. Furthermore, piezoelectric force microscopy (PFM) was used to characterize the piezoelectric properties of the P(VDF-TrFE) NFs, and the PFM scanning phase diagram and micro-piezoelectric response curves, namely, the loop curves showing the dependences of amplitude and phase on bias, are shown in Figure 4E,F, exhibiting the ferroelectric and piezoelectric response of the electrospun fibers. Ferroelectric domains, defined as small regions with the same spontaneous polarization direction, exist in ferroelectrics and can be observed in the phase diagram. The chiaroscuro in the phase diagram proved different domain orientations in the fiber. (32) A voltage bias was applied to the needle tip, and the corresponding PFM phase and amplitude were measured. The film surfaces deformed, owing to the response and reversal of the domain structure caused by applied voltage, and the deformations were recorded. (33) The relationship between amplitude and bias voltage and the relationship between phase and bias voltage were illustrated using a black (triangle point) and blue curve (square point), respectively. Characteristics, such as the strain butterfly curve and hysteresis curve, were respectively observed in these two curves. The transition illustrated in the phase bias diagram corresponds to the change in the polarization direction. Herein, the domain phase shows a switching characteristic of 180° domain under the reversal of the applied electric field, elucidating the ferroelectric properties of the P(VDF-TrFE) NFs. (34) This is because the piezoelectric and spontaneous polarization properties of the crystal are determined by its symmetry. The spontaneous polarization of the ferroelectrics can be reversed by an external electric field. The amplitude curve is an electric-field-inducing strain behavior, because it is a strain change under the action of an external field. In addition, it can also be found that the phase and amplitude of P(VDF-TrFE) NFs were asymmetrical, that is, along the voltage axis that has been shifted. This might be because there was a certain space charge at the interface between the film and the electrode. When the external force load was applied, due to the piezoelectric effect inside the film, a large number of electrons generated might cause a certain amount of negative space charge to accumulate on the upper surface of the film. When PFM was used for the loop test, the negative charge would shield the positive test voltage, resulting in the shift of the piezoelectric loop. The asymmetry of the butterfly curve was related to the internal field generated by nonuniformly distributed charged defects. It has been confirmed that the piezoelectric property of layer I could convert mechanical energy into electrical energy, and these generated electrical signals could be transmitted by layer II to the wound site. Performing as a conductor when connected in a bulb electric circuit, the CF-Gel-PAM hydrogel enabled the lighting of the bulb (Figure 4G). This is because Fe3+ formed a network of electron carriers within the hydrogel network and formed redox pairs by coordinating with the catechol groups in COA. The COA helped stabilize Fe3+, crosslinked and hydrogen bonded with gelatin as well as PAM; thus, an effective conductive network was formed in the hydrogel. Then, the hydrogel conductivity was tested and calculated (Figure S11a).The skin conductivity range has been reported to be 0.26–1 × 10–5 S/m. The conductivity of CF-Ge-PAM is in the range of the conductivity of skin tissue, (35) indicating that the enhanced electrical conductivity will potentially facilitate the possible transmission of bioelectrical signals and promote the wound healing process.
图4C显示了压电效应的示意图。在不同压力下测量P(VDF-TrFE) NFs的OCV值，如图4D所示，不同力下P(VDF-TrFE) NFs输出不同的OCV信号，检测到约0.3 V的电压在 0.1 N 的力作用下，表明对小力的稳定响应。这里，在2N力下OCV为2.7V。为了进行比较，Habibur 等人。 (31)改善了非极化条件下的P(VDF-TrFE)性能，其中在2V力下压电输出为2.4V。图S9显示了具有和不具有树枝状纤维结构的静电纺丝薄膜的压电性能，可以看出树枝状纤维具有明显的优势。通过对几种不同结构的样品进行FTIR和XRD分析，如图S10所示，树枝状纤维具有较高的结晶度，这是由于静电纺丝过程中形成树枝状纤维需要更大的机械拉伸，有利于P的结晶。 (VDF-TrFE)。这就是为什么树枝状纤维具有更好的压电性能。结果表明，所制备的树状纳米纤维表现出良好的应用能力。此外，利用压电力显微镜（PFM）表征了P(VDF-TrFE) NF的压电特性，以及PFM扫描相图和微压电响应曲线，即显示振幅和相位依赖性的环路曲线在偏压下，如图 4E、F 所示，展示了电纺纤维的铁电和压电响应。铁电畴定义为具有相同自发极化方向的小区域，存在于铁电体中并且可以在相图中观察到。 相图中的明暗对比证明了纤维中不同的磁畴取向。 (32)向针尖施加偏压，测量相应的PFM相位和幅度。由于施加电压引起的域结构的响应和反转，薄膜表面发生变形，并记录变形。 (33)分别使用黑色（三角点）和蓝色曲线（方形点）来说明幅度和偏置电压之间的关系以及相位和偏置电压之间的关系。在这两条曲线中分别观察到应变蝶形曲线和磁滞曲线等特性。相位偏置图中所示的转变对应于偏振方向的变化。在此，域相在施加电场反转下显示出180°域的切换特性，阐明了P(VDF-TrFE) NF的铁电特性。 (34) 这是因为晶体的压电和自发极化特性是由其对称性决定的。铁电体的自发极化可以通过外部电场逆转。振幅曲线是电场诱发应变行为，因为它是在外场作用下的应变变化。此外，还可以发现P(VDF-TrFE) NF的相位和幅度是不对称的，即沿着已经偏移的电压轴。这可能是因为薄膜和电极之间的界面处存在一定的空间电荷。 当施加外力载荷时，由于薄膜内部的压电效应，产生大量电子，可能会导致薄膜上表面积累一定量的负空间电荷。当使用PFM进行回路测试时，负电荷会屏蔽正测试电压，导致压电回路发生偏移。蝴蝶曲线的不对称性与不均匀分布的带电缺陷产生的内场有关。已经证实，第一层的压电特性可以将机械能转化为电能，产生的电信号可以通过第二层传输到伤口部位。当连接到灯泡电路中时，CF-Gel-PAM 水凝胶充当导体，使灯泡发光（图 4G）。这是因为 Fe3+ 在水凝胶网络内形成了电子载体网络，并通过与 COA 中的儿茶酚基团配位形成氧化还原对。 COA 有助于稳定 Fe3+，与明胶以及 PAM 交联并形成氢键；因此，在水凝胶中形成了有效的导电网络。然后，测试并计算了水凝胶电导率（图S11a）。据报道，皮肤电导率范围为0.26–1 × 10–5 S/m。 CF-Ge-PAM的电导率在皮肤组织的电导率范围内，（35）表明增强的电导率将潜在地促进生物电信号的可能传输并促进伤口愈合过程。
图4C显示了压电效应的示意图。在不同压力下测量P(VDF-TrFE) NFs的OCV值，如图4D所示，不同力下P(VDF-TrFE) NFs输出不同的OCV信号，检测到约0.3 V的电压在 0.1 N 的力作用下，表明对小力的稳定响应。这里，在2N力下OCV为2.7V。为了进行比较，Habibur 等人。 (31)改善了非极化条件下的P(VDF-TrFE)性能，其中在2V力下压电输出为2.4V。图S9显示了具有和不具有树枝状纤维结构的静电纺丝薄膜的压电性能，可以看出树枝状纤维具有明显的优势。通过对几种不同结构的样品进行FTIR和XRD分析，如图S10所示，树枝状纤维具有较高的结晶度，这是由于静电纺丝过程中形成树枝状纤维需要更大的机械拉伸，有利于P的结晶。 (VDF-TrFE)。这就是为什么树枝状纤维具有更好的压电性能。结果表明，所制备的树状纳米纤维表现出良好的应用能力。此外，利用压电力显微镜（PFM）表征了P(VDF-TrFE) NF的压电特性，以及PFM扫描相图和微压电响应曲线，即显示振幅和相位依赖性的环路曲线在偏压下，如图 4E、F 所示，展示了电纺纤维的铁电和压电响应。铁电畴定义为具有相同自发极化方向的小区域，存在于铁电体中并且可以在相图中观察到。 相图中的明暗对比证明了纤维中不同的磁畴取向。 (32)向针尖施加偏压，测量相应的PFM相位和幅度。由于施加电压引起的域结构的响应和反转，薄膜表面发生变形，并记录变形。 (33)分别使用黑色（三角点）和蓝色曲线（方形点）来说明幅度和偏置电压之间的关系以及相位和偏置电压之间的关系。在这两条曲线中分别观察到应变蝶形曲线和磁滞曲线等特性。相位偏置图中所示的转变对应于偏振方向的变化。在此，域相在施加电场反转下显示出180°域的切换特性，阐明了P(VDF-TrFE) NF的铁电特性。 (34) 这是因为晶体的压电和自发极化特性是由其对称性决定的。铁电体的自发极化可以通过外部电场逆转。振幅曲线是电场诱发应变行为，因为它是在外场作用下的应变变化。此外，还可以发现P(VDF-TrFE) NF的相位和幅度是不对称的，即沿着已经偏移的电压轴。这可能是因为薄膜和电极之间的界面处存在一定的空间电荷。 当施加外力载荷时，由于薄膜内部的压电效应，产生大量电子，可能会导致薄膜上表面积累一定量的负空间电荷。当使用PFM进行回路测试时，负电荷会屏蔽正测试电压，导致压电回路发生偏移。蝴蝶曲线的不对称性与不均匀分布的带电缺陷产生的内场有关。已经证实，第一层的压电特性可以将机械能转化为电能，产生的电信号可以通过第二层传输到伤口部位。当连接到灯泡电路中时，CF-Gel-PAM 水凝胶充当导体，使灯泡发光（图 4G）。这是因为 Fe3+ 在水凝胶网络内形成了电子载体网络，并通过与 COA 中的儿茶酚基团配位形成氧化还原对。 COA 有助于稳定 Fe3+，与明胶以及 PAM 交联并形成氢键；因此，在水凝胶中形成了有效的导电网络。然后，测试并计算了水凝胶电导率（图S11a）。据报道，皮肤电导率范围为0.26–1 × 10–5 S/m。 CF-Ge-PAM的电导率在皮肤组织的电导率范围内，（35）表明增强的电导率将潜在地促进生物电信号的可能传输并促进伤口愈合过程。
The adhesion performance of the SEWD was tested, and Figure 5 demonstrates that the COA introduction enables the adhesion of the SEWD to the object surface. SEWD was adhered to the pigskin for the lap shear strength test, and the adhesion strength was about 8.5 KPa (Figure 4B). Furthermore, SEWD can be well adhered to the surfaces of various articles and can be painlessly pasted and removed on the human skin (Figure 5). In addition, it was observed that the lap shear strength increased (better adhesion to the pigskin) with increasing COA content, because the increase in COA introduced more active catechol groups (Figure S11b). The studies demonstrate that catechol groups can form a reversible coordination interaction of high intensity on inorganic surfaces, whereas the oxidized o-quinone groups can attach to organic surfaces via immediate covalent crosslinking. (36) The favorable adhesion to the pigskin indicates the capability of SEWD for use as conductive materials for the skin tissue.
对SEWD的粘附性能进行了测试，图5表明COA的引入使得SEWD能够粘附到物体表面。将SEWD粘附在猪皮上进行搭接剪切强度测试，粘附强度约为8.5 KPa（图4B）。此外，SEWD可以很好地粘附在各种物品的表面，并且可以在人体皮肤上无痛地粘贴和去除（图5）。此外，还观察到，随着 COA 含量的增加，搭接剪切强度也随之增加（与猪皮的粘合性更好），因为 COA 的增加引入了更多活性儿茶酚基团（图 S11b）。研究表明，儿茶酚基团可以在无机表面上形成高强度的可逆配位相互作用，而氧化的邻醌基团可以通过直接共价交联附着到有机表面。 (36) 对猪皮的良好粘附性表明 SEWD 能够用作皮肤组织的导电材料。
对SEWD的粘附性能进行了测试，图5表明COA的引入使得SEWD能够粘附到物体表面。将SEWD粘附在猪皮上进行搭接剪切强度测试，粘附强度约为8.5 KPa（图4B）。此外，SEWD可以很好地粘附在各种物品的表面，并且可以在人体皮肤上无痛地粘贴和去除（图5）。此外，还观察到，随着 COA 含量的增加，搭接剪切强度也随之增加（与猪皮的粘合性更好），因为 COA 的增加引入了更多活性儿茶酚基团（图 S11b）。研究表明，儿茶酚基团可以在无机表面上形成高强度的可逆配位相互作用，而氧化的邻醌基团可以通过直接共价交联附着到有机表面。 (36) 对猪皮的良好粘附性表明 SEWD 能够用作皮肤组织的导电材料。
Figure 5 图5
Figure 5. Adhesion ability of SEWD (A) PE, (B) plastic, (C) porcine skin, (D) rubber, (E) stainless steel, (F) leather, (G) leaf, and (H) spume. (I) SEWD adheres to the author’s skin and peels off without residue. (J) Mussel-inspired adhesion mechanism of the hydrogel: (I) hydrogen bond, (II) coordination bond, (III) cation−π interaction, (IV) π–π interaction, and (V) covalent linkage.
图 5. SEWD 的粘附能力 (A) PE、(B) 塑料、(C) 猪皮、(D) 橡胶、(E) 不锈钢、(F) 皮革、(G) 树叶和 (H) 泡沫。 (I) SEWD 粘附在作者的皮肤上并且剥离无残留。 （J）受贻贝启发的水凝胶粘附机制：（I）氢键，（II）配位键，（III）阳离子-π相互作用，（IV）π-π相互作用，（V）共价键。
3.4. Cytotoxicity In Vitro
3.4.体外细胞毒性
Before the scaffolds were evaluated for in vitro cytocompatibility evaluation, the samples were all sterilized by 60Co irradiation, which did not have a significant effect on the appearance and properties of the samples. A favorable biocompatibility is required for biomedical materials. Figure 6A–C and Figure S12 show the absorbance values of L929 SEWD, P(VDF-TrFE) NFs, and CF-Gel-PAM hydrogel measured using the MTT method at different time intervals of cell culturing inside. No significant difference between the absorbance value of samples and that of the control was observed, demonstrating that the material has no potential cytotoxicity. Although the as-prepared P(VDF-TrFE) NFs do not directly come in contact with the wound, contact with human body fluid is inevitable in practical applications. Therefore, the safety of every layer of SEWD is ensured, as the cells are protected from dissolved substances’ affection. Figure 6D shows the absorbance values measured by the MTT method after co-culture of SEWD and L929 cells before and after the addition of mechanical stimulation. It can be seen that the number of cells increased significantly after the action of mechanical stimulation. This was mainly attributed to the positive effect of ES brought by mechanical stimulation on cell growth. Research has shown that ES promotes cell growth and differentiation via manipulating transfilm potential, (37) particularly for nerve regeneration, wherein the ES effects of improving nerve differentiation and directional growth of nerve processes were confirmed. In addition, studies demonstrated that cell migration can be controlled via the potential difference. This phenomenon is known as electrotaxis and can be produced in most mammalian cells by placing them in an external electric field. ES can activate the signal pathway of phosphatidylinositol-3-kinase (PI3K), thereby explaining the cell migration mechanism guided by ES. (38) It has been widely reported that the human skin, corneal epithelial cells, fibroblasts, lymphocytes, macrophages, endothelial cells, and nerve cells all respond to the applied electric field. (10) Herein, compared with ordinary ES, effective ES can be provided using piezoelectric materials without requiring electrodes, external power supplies, or battery implantation. A piezoelectric support can generate electric pulses through instantaneous deformation, which can easily be realized in daily activities. Moreover, the advantages of being light weight, flexible, and tailorable endow the material with considerable application potential. The expression level of collagen in the scaffold cell layer was detected using the Western blot. Figure 6E confirms that the protein expression level of the experimental group was higher than that of the control group, indicating that the cell function on SEWD is enhanced, owing to ES, under the assistance of piezoelectricity. Figure 6F,G shows cell growth on separate P(VDF-TrFE) NFs and CF-Gel-PAM hydrogel, respectively. The SEM and CLSM images of the cells grown on SEWD for 3 days are shown in Figure 6H–K, respectively, and both confirm that the cells grow better on the mechanically stimulated materials. The cells adhered to and grew on the SEWD as fusiform in the action of stimulation, and the cells were more dynamic with the pseudopodia extending to the adjacent cell. And this was also confirmed via the CLSM image: the connection between the cells was tighter, pseudopodia were more distinct with overlaps, and cells exhibited a trend of growing into the fiber pores. Live/Dead staining of cells showed less apoptosis of cells cultured on SEWD with or without mechanical stimulation and more living cells in the group treated with mechanical stimulation, as shown in Figure 6L,M. Numerous studies have demonstrated that ES can effectively regulate the cell growth behavior. (39) The cell migration mechanism, proliferation, and differentiation induced by ES are considered as effects of the electric field, which can be directly affected by intracellular ions, growth factors, and receptors or indirectly affected through the aggregation or conformational change in extracellular ions and proteins. Reports have confirmed that ES can promote and regulate the secretion of a few active factors, such as bone morphogenetic protein 6 (BMP6), (40) which can regulate cell proliferation, and VEGF, (41) which can regulate the growth of endothelial cells, that are conducive to cell growth. It can also inhibit the nuclear transcription factor (NF-κB) activity to regulate immune and inflammatory responses. (42) Furthermore, ES can enhance mitochondrial function and promote energy supply. (19) It was observed that free calcium is the primary factor in both direct and indirect mechanisms of ES when the simulation comes into effect. (43) In addition, it has been reported that ES can lead to more conducive conformational changes in fibronectin, owing to the connection between the materials and protein, to promote protein adsorption to biomaterials. More adhesion protein on the cell surfaces can promote cell adhesion and growth, because a few extracellular matrix proteins are crucial for cell adhesion. (44)
支架进行体外细胞相容性评价前，样品均经过60Co辐照灭菌，对样品的外观和性能没有明显影响。生物医用材料需要良好的生物相容性。图6A-C和图S12显示了使用MTT方法在内部细胞培养的不同时间间隔测量的L929 SEWD、P(VDF-TrFE) NF和CF-Gel-PAM水凝胶的吸光度值。样品的吸光度值与对照品的吸光度值没有观察到显着差异，表明该材料不具有潜在的细胞毒性。虽然所制备的P(VDF-TrFE) NFs不直接与伤口接触，但在实际应用中与人体体液的接触是不可避免的。因此，SEWD每一层的安全性都得到了保证，因为细胞免受溶解物质的影响。图6D显示了在加入机械刺激之前和之后SEWD和L929细胞共培养后通过MTT方法测量的吸光度值。可见机械刺激作用后细胞数量明显增加。这主要归因于ES机械刺激对细胞生长带来的积极作用。研究表明，ES 通过操纵跨膜电位来促进细胞生长和分化，(37) 特别是对于神经再生，其中证实了 ES 改善神经分化和神经突起定向生长的作用。此外，研究表明细胞迁移可以通过电位差来控制。 这种现象被称为趋电性，可以通过将大多数哺乳动物细胞置于外部电场中来产生。 ES可以激活磷脂酰肌醇3激酶（PI3K）信号通路，从而解释ES引导的细胞迁移机制。 (38) 据广泛报道，人体皮肤、角膜上皮细胞、成纤维细胞、淋巴细胞、巨噬细胞、内皮细胞和神经细胞都会对所施加的电场做出反应。 (10)这里，与普通ES相比，可以使用压电材料提供有效的ES，而不需要电极、外部电源或电池植入。压电支架可以通过瞬时变形产生电脉冲，这在日常活动中很容易实现。此外，轻质、灵活、可定制等优点赋予该材料巨大的应用潜力。采用Western blot检测支架细胞层中胶原蛋白的表达水平。图6E证实实验组的蛋白表达水平高于对照组，表明SEWD上的细胞功能在压电的辅助下由于ES而增强。图6F、G分别显示了单独的P(VDF-TrFE) NF和CF-Gel-PAM水凝胶上的细胞生长。在 SEWD 上生长 3 天的细胞的 SEM 和 CLSM 图像分别如图 6H-K 所示，两者均证实细胞在机械刺激的材料上生长得更好。细胞在刺激作用下呈梭形贴壁生长在SEWD上，且伪足延伸至邻近细胞，细胞更具活力。 CLSM图像也证实了这一点：细胞之间的连接更加紧密，伪足更加清晰且重叠，细胞呈现出向纤维孔内生长的趋势。细胞的活/死染色显示，在有或没有机械刺激的SEWD上培养的细胞凋亡较少，而机械刺激处理组中的活细胞较多，如图6L、M所示。大量研究表明ES可以有效调节细胞生长行为。 (39) ES诱导的细胞迁移机制、增殖和分化被认为是电场的作用，可以直接受细胞内离子、生长因子和受体的影响，也可以通过细胞外离子的聚集或构象变化间接影响和蛋白质。有报道证实ES可以促进和调节一些活性因子的分泌，如调节细胞增殖的骨形态发生蛋白6（BMP6），（40）和调节内皮细胞生长的VEGF，（41） ，有利于细胞生长。它还可以抑制核转录因子（NF-κB）活性来调节免疫和炎症反应。 (42) 此外，ES可以增强线粒体功能并促进能量供应。 (19) 结果表明，当模拟生效时，游离钙是 ES 直接和间接机制的主要因素。 (43) 此外，据报道，由于材料和蛋白质之间的连接，ES 可以导致纤连蛋白发生更有利的构象变化，从而促进蛋白质吸附到生物材料上。 细胞表面更多的粘附蛋白可以促进细胞粘附和生长，因为一些细胞外基质蛋白对于细胞粘附至关重要。 (44)
支架进行体外细胞相容性评价前，样品均经过60Co辐照灭菌，对样品的外观和性能没有明显影响。生物医用材料需要良好的生物相容性。图6A-C和图S12显示了使用MTT方法在内部细胞培养的不同时间间隔测量的L929 SEWD、P(VDF-TrFE) NF和CF-Gel-PAM水凝胶的吸光度值。样品的吸光度值与对照品的吸光度值没有观察到显着差异，表明该材料不具有潜在的细胞毒性。虽然所制备的P(VDF-TrFE) NFs不直接与伤口接触，但在实际应用中与人体体液的接触是不可避免的。因此，SEWD每一层的安全性都得到了保证，因为细胞免受溶解物质的影响。图6D显示了在加入机械刺激之前和之后SEWD和L929细胞共培养后通过MTT方法测量的吸光度值。可见机械刺激作用后细胞数量明显增加。这主要归因于ES机械刺激对细胞生长带来的积极作用。研究表明，ES 通过操纵跨膜电位来促进细胞生长和分化，(37) 特别是对于神经再生，其中证实了 ES 改善神经分化和神经突起定向生长的作用。此外，研究表明细胞迁移可以通过电位差来控制。 这种现象被称为趋电性，可以通过将大多数哺乳动物细胞置于外部电场中来产生。 ES可以激活磷脂酰肌醇3激酶（PI3K）信号通路，从而解释ES引导的细胞迁移机制。 (38) 据广泛报道，人体皮肤、角膜上皮细胞、成纤维细胞、淋巴细胞、巨噬细胞、内皮细胞和神经细胞都会对所施加的电场做出反应。 (10)这里，与普通ES相比，可以使用压电材料提供有效的ES，而不需要电极、外部电源或电池植入。压电支架可以通过瞬时变形产生电脉冲，这在日常活动中很容易实现。此外，轻质、灵活、可定制等优点赋予该材料巨大的应用潜力。采用Western blot检测支架细胞层中胶原蛋白的表达水平。图6E证实实验组的蛋白表达水平高于对照组，表明SEWD上的细胞功能在压电的辅助下由于ES而增强。图6F、G分别显示了单独的P(VDF-TrFE) NF和CF-Gel-PAM水凝胶上的细胞生长。在 SEWD 上生长 3 天的细胞的 SEM 和 CLSM 图像分别如图 6H-K 所示，两者均证实细胞在机械刺激的材料上生长得更好。细胞在刺激作用下呈梭形贴壁生长在SEWD上，且伪足延伸至邻近细胞，细胞更具活力。 CLSM图像也证实了这一点：细胞之间的连接更加紧密，伪足更加清晰且重叠，细胞呈现出向纤维孔内生长的趋势。细胞的活/死染色显示，在有或没有机械刺激的SEWD上培养的细胞凋亡较少，而机械刺激处理组中的活细胞较多，如图6L、M所示。大量研究表明ES可以有效调节细胞生长行为。 (39) ES诱导的细胞迁移机制、增殖和分化被认为是电场的作用，可以直接受细胞内离子、生长因子和受体的影响，也可以通过细胞外离子的聚集或构象变化间接影响和蛋白质。有报道证实ES可以促进和调节一些活性因子的分泌，如调节细胞增殖的骨形态发生蛋白6（BMP6），（40）和调节内皮细胞生长的VEGF，（41） ，有利于细胞生长。它还可以抑制核转录因子（NF-κB）活性来调节免疫和炎症反应。 (42) 此外，ES可以增强线粒体功能并促进能量供应。 (19) 结果表明，当模拟生效时，游离钙是 ES 直接和间接机制的主要因素。 (43) 此外，据报道，由于材料和蛋白质之间的连接，ES 可以导致纤连蛋白发生更有利的构象变化，从而促进蛋白质吸附到生物材料上。 细胞表面更多的粘附蛋白可以促进细胞粘附和生长，因为一些细胞外基质蛋白对于细胞粘附至关重要。 (44)
Figure 6 图6
Figure 6. (A) OD values of SEWD extracts. (B) OD values of P(VDF-TrFE) NFs extracts. (C) OD values of extracts. (D) Cell proliferation on SEWD under different stimulation. (E) Protein level of SEWD under different stimulation. (F) SEM images (×2000) of L929 fibroblasts cultured on P(VDF-TrFE) NFs. (G) SEM images (×2000) of L929 fibroblasts cultured on the CF-Gel-PAM hydrogel. (H) SEM images (×2000) of L929 fibroblasts cultured on SEWD. (I) SEM images (×2000) of L929 fibroblasts cultured on SEWD with mechanical stimulation. (J) CLSM images of L929 fibroblasts cultured on SEWD. (K) CLSM images of L929 fibroblasts cultured on SEWD with mechanical stimulation. (L) Live/Dead staining of L929 fibroblasts cultured on SEWD. (M) Live/Dead staining of L929 fibroblasts cultured on SEWD with mechanical stimulation.
图 6.(A) SEWD 提取物的 OD 值。 (B) P(VDF-TrFE) NF 提取物的 OD 值。 (C) 提取物的 OD 值。 (D) 不同刺激下 SEWD 上的细胞增殖。 (E)不同刺激下SEWD的蛋白水平。 (F) 在 P(VDF-TrFE) NF 上培养的 L929 成纤维细胞的 SEM 图像 (×2000)。 (G) CF-Gel-PAM 水凝胶上培养的 L929 成纤维细胞的 SEM 图像 (×2000)。 (H) SEWD 上培养的 L929 成纤维细胞的 SEM 图像 (×2000)。 (I) SEWD 机械刺激下培养的 L929 成纤维细胞的 SEM 图像（×2000）。 (J) SEWD 上培养的 L929 成纤维细胞的 CLSM 图像。 (K) 在 SEWD 上机械刺激下培养的 L929 成纤维细胞的 CLSM 图像。 (L) SEWD 上培养的 L929 成纤维细胞的活/死染色。 (M) 在 SEWD 上机械刺激下培养的 L929 成纤维细胞的活/死染色。
3.5. In Vivo Performance Verification of Healing Promotion for SEWD
3.5. SEWD 愈合促进的体内性能验证
The healing-promoting effect of full-thickness skin defects in SD rats was evaluated with SEWD. Since the side of SEWD directly in contact with the wound was hydrogel, the hydrogel was selected as the control group for the experiment. The results are shown in Figure 7. The wound image of SD rats and the wound contour plotted on identical scales demonstrate that the wound has a higher healing rate with the aid of SEWD: in the first week, the wound closure in the SEWD group was nearly 80%, much higher than that in the hydrogel control group (53%) and the gauze control group (36%); in the second week, the wound in the SEWD group had healed; however, the wound in the control group and hydrogel group did not heal, and the wound closure was only 60 and 81%, respectively. On the one hand, the SEWD dressing exhibits an excellent healing-promoting of the hydrogel, which predominantly comprises biomass and has a bionic structure, facilitating a favorable healing environment for the wound. On the other hand, the excellent healing-promoting of the SEWD is also attributable to the ES generated by the piezoelectric layer. Rats generate effective mechanical stimulation to the piezoelectric layer via free activities after operation, and consequently, electrical signals were generated in the piezoelectric layer and were subsequently transmitted to the skin tissue around the wound through the conductive hydrogel to electrically stimulate the wound. Therefore, cell proliferation was promoted, and wound healing was accelerated. Changes in the wound were observed using H&E staining. The wound was in the proliferation stage 7 days after operation, as the fibroblasts migrated to the injured area, resulting in capillary growth, collagen synthesis, new tissue formation, and epithelial cell migration. As shown in Figure 8, new and small collagen fibers are observed to be disorderly arranged. Compared with the hydrogel group, more fibers were observed, and the dermal tissue began gradually recovering in the SEWD group. Notably, for the SEWD group, the tissue continuously remolded 14 days after operation, with strong collagen fibers, formation of the skin appendages, and the favorable wound repair. The collagen fibers in the hydrogel group were relatively scattered. However, the hydrogel group still performed better than the gauze control group. Figure S13 shows the staining results of the control groups. To characterize the expression of bFGF, PDGF, and VEGF, immunohistochemical analysis was performed for the wound tissue. The results are shown in Figure 8, demonstrating that the positive expression of the SEWD was stronger than that of the hydrogel, indicating that more secretion of growth factors at the wound can be promoted using the SEWD, which is effective and important for wound healing. The skin possesses endogenous potential, which changes during wound healing. The small deformation caused by daily activities of the rats after operation potentially led to electrical signals generated by SEWD, and the electrical signals were subsequently transmitted to the vicinity of the wound, consequently providing the wound with ES, which is considered as physical therapy, thereby promoting wound healing via imitating the natural current generated during injury. Capable of accelerating cell proliferation and promoting tissue growth, ES is a natural healing mechanism for promoting wound healing, as there is an inherent potential difference around the wound tissue. Compared with other treatments, ES is suitable for various wounds, owing to the advantages of requiring no foreign objects and minimal side effects. Exogenous ES can promote the directional migration of cells and signal molecules through chemotaxis, (10) promote the secretion of relevant growth factors, (45) enhance the mitochondrial function, (16) and promote various intracellular ways; (18) thus, collagen fiber synthesis increased, the wound epithelization was accelerated, and the wound closed faster in an endogenous manner. The effectiveness of ES therapy has been confirmed on several animal and clinical studies, (18,46) and this therapy predominantly relied on specialized equipment or batteries, thereby inconveniencing medical staff and patients. This disadvantage can be well overcome by the spontaneous electricity generation of piezoelectric materials under deformation. Moreover, no power depletion problem arises in comparison with using batteries. Materials without cytotoxicity can be accurately tailored to the size and shape of the wound in practical applications. The healing-promoting effect of using SEWD was confirmed to be superior to that of the pure hydrogel dressing through the repair experiment on the full-thickness skin defect in SD rats. Hydrogels had been widely applied in the treatment of burns, as it can promote wound healing. SEWD inherits the property of the hydrogel and also possesses a piezoelectric layer to promote healing with ES therapy, so the original dressing is endowed with a dual and synergistic healing ability.
采用SEWD评价SD大鼠全层皮肤缺损的促愈合作用。由于SEWD直接接触伤口的一侧是水凝胶，因此选择水凝胶作为实验的对照组。结果如图7所示。SD大鼠的伤口图像和相同比例绘制的伤口轮廓表明，在SEWD的帮助下，伤口具有较高的愈合率：第一周，SEWD组的伤口闭合率近80%，远高于水凝胶对照组（53%）和纱布对照组（36%）；第二周，SEWD组伤口愈合；然而，对照组和水凝胶组的伤口并未愈合，伤口闭合率分别仅为60%和81%。一方面，SEWD敷料表现出优异的水凝胶促进愈合作用，水凝胶主要由生物质组成，具有仿生结构，有利于伤口的愈合环境。另一方面，SEWD优异的促进愈合效果也归功于压电层产生的ES。大鼠术后通过自由活动对压电层产生有效的机械刺激，压电层中产生电信号，随后通过导电水凝胶传输到伤口周围的皮肤组织，对伤口进行电刺激。因此，促进细胞增殖，加速伤口愈合。使用H&E染色观察伤口的变化。 术后7天伤口处于增殖阶段，成纤维细胞迁移至受伤部位，导致毛细血管生长、胶原蛋白合成、新组织形成和上皮细胞迁移。如图8所示，观察到新的小胶原纤维排列紊乱。与水凝胶组相比，SEWD组观察到更多的纤维，并且真皮组织开始逐渐恢复。值得注意的是，SEWD组术后14天组织持续重塑，胶原纤维强健，皮肤附属器形成，伤口修复良好。水凝胶组的胶原纤维相对分散。然而，水凝胶组的表现仍然优于纱布对照组。图S13显示了对照组的染色结果。为了表征 bFGF、PDGF 和 VEGF 的表达，对伤口组织进行了免疫组织化学分析。结果如图8所示，表明SEWD的阳性表达强于水凝胶，表明SEWD可以促进伤口处更多生长因子的分泌，这对于伤口愈合是有效且重要的。皮肤具有内源性潜力，在伤口愈合过程中会发生变化。手术后大鼠日常活动造成的微小变形可能导致SEWD产生电信号，电信号随后传输到伤口附近，从而为伤口提供ES，这被认为是物理治疗，从而通过模仿受伤时产生的自然电流来促进伤口愈合。 ES能够加速细胞增殖并促进组织生长，是一种促进伤口愈合的自然愈合机制，因为伤口组织周围存在固有的电位差。与其他治疗方法相比，ES具有不需要异物、副作用小的优点，适用于各种伤口。外源ES可以通过趋化作用促进细胞和信号分子的定向迁移，（10）促进相关生长因子的分泌，（45）增强线粒体功能，（16）促进多种细胞内途径； (18)因此，胶原纤维合成增加，伤口上皮化加速，伤口以内源性方式更快闭合。 ES疗法的有效性已在多项动物和临床研究中得到证实(18,46)，并且该疗法主要依赖于专用设备或电池，从而给医务人员和患者带来不便。压电材料在形变下自发发电可以很好地克服这一缺点。此外，与使用电池相比，不会出现电力耗尽的问题。无细胞毒性的材料在实际应用中可以根据伤口的大小和形状精确定制。通过SD大鼠全层皮肤缺损的修复实验，证实SEWD的促愈合效果优于纯水凝胶敷料。水凝胶已广泛应用于烧伤治疗，因为它可以促进伤口愈合。 SEWD继承了水凝胶的特性，同时还拥有压电层，可以促进ES治疗的愈合，因此赋予了原有敷料双重协同的愈合能力。
采用SEWD评价SD大鼠全层皮肤缺损的促愈合作用。由于SEWD直接接触伤口的一侧是水凝胶，因此选择水凝胶作为实验的对照组。结果如图7所示。SD大鼠的伤口图像和相同比例绘制的伤口轮廓表明，在SEWD的帮助下，伤口具有较高的愈合率：第一周，SEWD组的伤口闭合率近80%，远高于水凝胶对照组（53%）和纱布对照组（36%）；第二周，SEWD组伤口愈合；然而，对照组和水凝胶组的伤口并未愈合，伤口闭合率分别仅为60%和81%。一方面，SEWD敷料表现出优异的水凝胶促进愈合作用，水凝胶主要由生物质组成，具有仿生结构，有利于伤口的愈合环境。另一方面，SEWD优异的促进愈合效果也归功于压电层产生的ES。大鼠术后通过自由活动对压电层产生有效的机械刺激，压电层中产生电信号，随后通过导电水凝胶传输到伤口周围的皮肤组织，对伤口进行电刺激。因此，促进细胞增殖，加速伤口愈合。使用H&E染色观察伤口的变化。 术后7天伤口处于增殖阶段，成纤维细胞迁移至受伤部位，导致毛细血管生长、胶原蛋白合成、新组织形成和上皮细胞迁移。如图8所示，观察到新的小胶原纤维排列紊乱。与水凝胶组相比，SEWD组观察到更多的纤维，并且真皮组织开始逐渐恢复。值得注意的是，SEWD组术后14天组织持续重塑，胶原纤维强健，皮肤附属器形成，伤口修复良好。水凝胶组的胶原纤维相对分散。然而，水凝胶组的表现仍然优于纱布对照组。图S13显示了对照组的染色结果。为了表征 bFGF、PDGF 和 VEGF 的表达，对伤口组织进行了免疫组织化学分析。结果如图8所示，表明SEWD的阳性表达强于水凝胶，表明SEWD可以促进伤口处更多生长因子的分泌，这对于伤口愈合是有效且重要的。皮肤具有内源性潜力，在伤口愈合过程中会发生变化。手术后大鼠日常活动造成的微小变形可能导致SEWD产生电信号，电信号随后传输到伤口附近，从而为伤口提供ES，这被认为是物理治疗，从而通过模仿受伤时产生的自然电流来促进伤口愈合。 ES能够加速细胞增殖并促进组织生长，是一种促进伤口愈合的自然愈合机制，因为伤口组织周围存在固有的电位差。与其他治疗方法相比，ES具有不需要异物、副作用小的优点，适用于各种伤口。外源ES可以通过趋化作用促进细胞和信号分子的定向迁移，（10）促进相关生长因子的分泌，（45）增强线粒体功能，（16）促进多种细胞内途径； (18)因此，胶原纤维合成增加，伤口上皮化加速，伤口以内源性方式更快闭合。 ES疗法的有效性已在多项动物和临床研究中得到证实(18,46)，并且该疗法主要依赖于专用设备或电池，从而给医务人员和患者带来不便。压电材料在形变下自发发电可以很好地克服这一缺点。此外，与使用电池相比，不会出现电力耗尽的问题。无细胞毒性的材料在实际应用中可以根据伤口的大小和形状精确定制。通过SD大鼠全层皮肤缺损的修复实验，证实SEWD的促愈合效果优于纯水凝胶敷料。水凝胶已广泛应用于烧伤治疗，因为它可以促进伤口愈合。 SEWD继承了水凝胶的特性，同时还拥有压电层，可以促进ES治疗的愈合，因此赋予了原有敷料双重协同的愈合能力。
Figure 7 图7
Figure 7. (A) Photos of the healing process of the full-thickness wounds. (B) Images of wounds at different time points. (C) Quantitative results of wounds. (D) Regional traces of skin wound tissue in each group of rats during 14 days postoperatively.
图 7. (A) 全层伤口愈合过程的照片。 (B) 不同时间点的伤口图像。 (C) 伤口的定量结果。 (D)术后14天内各组大鼠皮肤伤口组织的区域痕迹。
Figure 8 图8
Figure 8. H&E staining, bFGF immunohistochemical analysis, PDGF immunohistochemical analysis, and VEGF immunohistochemical analysis of wound areas treated by SEWD and CF-Gel-PAM hydrogel.
图 8. SEWD 和 CF-Gel-PAM 水凝胶处理的伤口区域的 H&E 染色、bFGF 免疫组织化学分析、PDGF 免疫组织化学分析和 VEGF 免疫组织化学分析。
The as-prepared novel two-layered dressing for wound repair composed of a biomimetic tree-like piezoelectric nanofiber and a conductive adhesive hydrogel in this study can adhere to the piezoelectric layer with a healing-promoting function on other dressings. As a universal material for wound dressings, this material effectively combines ES therapy with various dressings to improve the healing-promoting ability of the hydrogel dressings. This strategy helps overcome the limitation that the currently used ES therapy depends on additional equipment as well as qualified personnel, broadening the application scope and mode of ES therapy in the field of wound repair. In addition, the as-prepared piezoelectric material for wound healing can be tailored according to the sizes and shapes of the wounds.
本研究制备的新型两层伤口修复敷料由仿生树状压电纳米纤维和导电粘合水凝胶组成，可以粘附在其他敷料上具有促进愈合功能的压电层上。作为伤口敷料的通用材料，该材料将ES疗法与各种敷料有效结合，提高水凝胶敷料的促愈合能力。这一策略有助于克服目前使用的ES疗法依赖额外设备和合格人员的限制，拓宽了ES疗法在伤口修复领域的应用范围和模式。此外，所制备的用于伤口愈合的压电材料可以根据伤口的大小和形状进行定制。
本研究制备的新型两层伤口修复敷料由仿生树状压电纳米纤维和导电粘合水凝胶组成，可以粘附在其他敷料上具有促进愈合功能的压电层上。作为伤口敷料的通用材料，该材料将ES疗法与各种敷料有效结合，提高水凝胶敷料的促愈合能力。这一策略有助于克服目前使用的ES疗法依赖额外设备和合格人员的限制，拓宽了ES疗法在伤口修复领域的应用范围和模式。此外，所制备的用于伤口愈合的压电材料可以根据伤口的大小和形状进行定制。
4. Conclusions 4。结论
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The current ES therapy is inconvenient, as it depends on equipment and hinders intrinsic advantages of dressings. It requires the consideration of reasonably and effectively applying various healing-promoting methods to wound dressings according to the wound features and healing process to improve the healing-promoting ability. Thus, in this study, a healing-promoting material combining a piezoelectric layer and a conductive adhesive layer with favorable physical and chemical properties as well as biocompatibility was developed. The piezoelectric layer is a dendritic nanofiber scaffold with a bionic structure, which has better piezoelectric and physicochemical properties than the conventional nanofiber scaffold. The hydrogel layer has biomimetic electrical activity and controllable adhesion ability. The results of experiments in vitro and in vivo demonstrated that the SEWD can promote cell migration, proliferation, and expression. Moreover, as a healing-promoting material, SEWD is suitable for irregular surfaces and edges of the wounds, because it can be tailored to the different wound sizes and shapes. Moreover, this material can minimize inconveniencing patients, owing to the following advantages: wireless, easy application and replacement, no requirement of external power supply or specialized operators trained by ES, and rapid healing with reasonable costs. A new method for the application of ES in wound dressing was developed, and a novel healing strategy for the effective treatment of skin injury was provided by developing self-powered wound dressing, which is of great significance to the rapid, safe, and effective promotion of wound healing.
目前的ES治疗不方便，因为它依赖于设备并且阻碍了敷料的固有优势。需要根据伤口特点和愈合过程，考虑合理、有效地对伤口敷料应用各种促愈合方法，以提高促愈合能力。因此，在这项研究中，开发了一种结合压电层和导电粘合层的促进愈合材料，具有良好的物理和化学性能以及生物相容性。压电层是具有仿生结构的树枝状纳米纤维支架，比传统纳米纤维支架具有更好的压电和物理化学性能。水凝胶层具有仿生电活性和可控的粘附能力。体外和体内实验结果表明SEWD可以促进细胞迁移、增殖和表达。此外，作为一种促进愈合的材料，SEWD适用于伤口的不规则表面和边缘，因为它可以根据不同的伤口大小和形状进行定制。此外，这种材料可以最大程度地减少给患者带来的不便，因为它具有以下优点：无线、易于使用和更换、不需要外部电源或经过 ES 培训的专业操作人员、快速愈合且成本合理。提出了ES在伤口敷料中应用的新方法，通过开发自供电伤口敷料，为皮肤损伤的有效治疗提供了新的治疗策略，对于快速、安全、有效的推广具有重要意义。伤口愈合。
目前的ES治疗不方便，因为它依赖于设备并且阻碍了敷料的固有优势。需要根据伤口特点和愈合过程，考虑合理、有效地对伤口敷料应用各种促愈合方法，以提高促愈合能力。因此，在这项研究中，开发了一种结合压电层和导电粘合层的促进愈合材料，具有良好的物理和化学性能以及生物相容性。压电层是具有仿生结构的树枝状纳米纤维支架，比传统纳米纤维支架具有更好的压电和物理化学性能。水凝胶层具有仿生电活性和可控的粘附能力。体外和体内实验结果表明SEWD可以促进细胞迁移、增殖和表达。此外，作为一种促进愈合的材料，SEWD适用于伤口的不规则表面和边缘，因为它可以根据不同的伤口大小和形状进行定制。此外，这种材料可以最大程度地减少给患者带来的不便，因为它具有以下优点：无线、易于使用和更换、不需要外部电源或经过 ES 培训的专业操作人员、快速愈合且成本合理。提出了ES在伤口敷料中应用的新方法，通过开发自供电伤口敷料，为皮肤损伤的有效治疗提供了新的治疗策略，对于快速、安全、有效的推广具有重要意义。伤口愈合。
Supporting Information 支持信息
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The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acs.biomac.2c01520.
支持信息可在 https://pubs.acs.org/doi/10.1021/acs.biomac.2c01520 免费获取。
SEM images, diameter distribution, typical stretch curves, tensile strength, elongation at break, contact angle, open circuit voltage output curves, FTIR spectra, XRD patterns of P(VDF-TrFE) NFs with different additives; conductivity of P(VDF-TrFE) electrospinning solution; SEM images, pore size distribution, mean pore size, and porosity, rheological properties, water content, swelling rate, conductivity, and adhesion strength of hydrogels; the H&E staining, bFGF immunohistochemical analysis, PDGF immunohistochemical analysis, and VEGF immunohistochemical analysis of wound areas treated by the CF-Gel-PAM hydrogel and gauze control group (PDF)
不同添加剂的P(VDF-TrFE) NFs的SEM图像、直径分布、典型拉伸曲线、拉伸强度、断裂伸长率、接触角、开路电压输出曲线、FTIR光谱、XRD图谱； P(VDF-TrFE)静电纺丝溶液的电导率；水凝胶的SEM图像、孔径分布、平均孔径、孔隙率、流变性能、含水量、溶胀率、电导率和粘附强度； CF-Gel-PAM水凝胶和纱布对照组治疗伤口区域的H&E染色、bFGF免疫组化分析、PDGF免疫组化分析和VEGF免疫组化分析(PDF)
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Author Information 作者信息
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- Nianhua Dan - Key Laboratory of Leather Chemistry and Engineering (Ministry of Education), Sichuan University, Chengdu 610065, China; Research Center of Biomedical Engineering, Sichuan University, Chengdu, Sichuan 610065, China;
https://orcid.org/0000-0001-9819-1439;
年华蛋-四川大学皮革化学与工程教育部重点实验室，成都 610065；四川大学生物医学工程研究中心, 四川 成都 610065; https://orcid.org/0000-0001-9819-1439；邮箱：dannianhua@scu.edu.cn
- Yining Chen - Key Laboratory of Leather Chemistry and Engineering (Ministry of Education), Sichuan University, Chengdu 610065, China; Research Center of Biomedical Engineering, Sichuan University, Chengdu, Sichuan 610065, China;https://orcid.org/0000-0002-9501-5293
陈一宁 - 四川大学皮革化学与工程教育部重点实验室, 成都 610065;四川大学生物医学工程研究中心, 四川 成都 610065; https://orcid.org/0000-0002-9501-5293
This research was supported by the National Natural Science Foundation of China, nos. 32101081 and 81673631; the Fundamental Research Funds for the Central Universities, no. 20826041E4156; the Opening Project of Key Laboratory of Leather Chemistry and Engineering (Sichuan University), Ministry of Education, no. SCU2021D005; and the Sichuan University Postdoctoral Interdisciplinary Innovation Fund.
该研究得到国家自然科学基金项目的资助，编号： 32101081和81673631；中央高校基本科研业务费专项资金，No. 20826041E4156;皮革化学与工程教育部重点实验室（四川大学）开放项目，No. SCU2021D005；四川大学博士后跨学科创新基金。
Acknowledgments 致谢
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We would like to thank Dr. Yanping Huang from the Center of Engineering Experimental Teaching, School of Chemical Engineering, Sichuan University, for SEM images and Dr. Ying Song at the College of Biomass Science and Engineering, Sichuan University, for the technical assistance.
感谢四川大学化工学院工程实验教学中心黄艳平博士提供的扫描电镜图像，感谢四川大学生物质科学与工程学院宋英博士提供的技术帮助。
References 参考
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This article references
46 other publications.
本文引用了 46 篇其他出版物。
- 1Huang, B.; Hu, D.; Dong, A.; Tian, J.; Zhang, W. Highly Antibacterial and Adhesive Hyaluronic Acid Hydrogel for Wound Repair. Biomacromolecules 2022, 23, 4766– 4777, DOI: 10.1021/acs.biomac.2c00950Google Scholar 谷歌学术1https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB38XislKgtb3J&md5=78c9229a996f2001b1072c2c448089c1Highly Antibacterial and Adhesive Hyaluronic Acid Hydrogel for Wound RepairHuang, Baoxuan; Hu, Dan; Dong, Alideertu; Tian, Jia; Zhang, WeianBiomacromolecules (2022), 23 (11), 4766-4777CODEN: BOMAF6; ISSN:1525-7797. (American Chemical Society)Bacterial infections accompanied with wound healing often lead to more serious health hazards to patients. Therefore, it is urgent to explore a wound dressing that can promote wound repair while possessing antibacterial capability. Here, we constructed a multifunctional hydrogel dressing by a redox-initiated crosslinking reaction of methacrylated hyaluronic acid (HAMA), 5,10,15,20-tetra (4-methacrylate phenyl) porphyrin (TPP), and dopamine methacrylamide (DMA), named HAMA-TPP-DMA, with broad-spectrum photodynamic antibacterial capability, where the aggregation of TPP photosensitizer units could be greatly inhibited to produce more singlet oxygen. The hydrogel has excellent biodegradability and biocompatibility, providing favorable conditions for wound healing. Furthermore, the incorporation of dopamine into the hydrogel gives the wound dressing with enhanced adhesiveness, benefiting for the wound repair. More importantly, the antibacterial expts. in vitro and mice wound models in vivo showed that the HAMA-TPP-DMA hydrogel can significantly resist bacteria and accelerate the wound healing in mice (the closure rate > 98% after 15 days). Thus, this hydrogel dressing with superior antibacterial infection and wound healing capability provides a promising strategy in wound repair.
1黄B.；胡，D。董，A.；田，J。张，W.用于伤口修复的高抗菌和粘附透明质酸水凝胶。生物大分子 2022, 23, 4766–4777, DOI: 10.1021/acs.biomac.2c00950 - 2Sun, B. K.; Siprashvili, Z.; Khavari, P. A. Advances in skin grafting and treatment of cutaneous wounds. Science 2014, 346, 941– 945, DOI: 10.1126/science.1253836Google Scholar 谷歌学术2https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhvFehurbN&md5=70a9ddca37068672ce2f77328cb2e892Advances in skin grafting and treatment of cutaneous woundsSun, Bryan K.; Siprashvili, Zurab; Khavari, Paul A.Science (Washington, DC, United States) (2014), 346 (6212), 941-945CODEN: SCIEAS; ISSN:0036-8075. (American Association for the Advancement of Science)The ability of the skin to repair itself after injury is vital to human survival and is disrupted in a spectrum of disorders. The process of cutaneous wound healing is complex, requiring a coordinated response by immune cells, hematopoietic cells, and resident cells of the skin. We review the classic paradigms of wound healing and evaluate how recent discoveries have enriched our understanding of this process. We evaluate current and exptl. approaches to treating cutaneous wounds, with an emphasis on cell-based therapies and skin transplantation.
2Sun，B.K.；西普拉什维利，Z.； Khavari, P. A. 皮肤移植和皮肤伤口治疗的进展。科学 2014, 346, 941–945, DOI: 10.1126/science.1253836 - 3Yamakawa, S.; Hayashida, K. Advances in surgical applications of growth factors for wound healing. Burns Trauma 2019, 7, 10, DOI: 10.1186/s41038-019-0148-1Google Scholar 谷歌学术3https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB3M%252Fmt1Cntw%253D%253D&md5=4b4c16bcc1d729c5318eb678edc67400Advances in surgical applications of growth factors for wound healingYamakawa Sho; Hayashida KenjiBurns & trauma (2019), 7 (), 10 ISSN:2321-3868.Growth factors have recently gained clinical importance for wound management. Application of recombinant growth factors has been shown to mimic cell migration, proliferation, and differentiation in vivo, allowing for external modulation of the healing process. Perioperative drug delivery systems can enhance the biological activity of these growth factors, which have a very short in vivo half-life after topical administration. Although the basic mechanisms of these growth factors are well understood, most have yet to demonstrate a significant impact in animal studies or small-sized clinical trials. In this review, we emphasized currently approved growth factor therapies, including a sustained release system for growth factors, emerging therapies, and future research possibilities combined with surgical procedures. Approaches seeking to understand wound healing at a systemic level are currently ongoing. However, further research and consideration in surgery will be needed to provide definitive confirmation of the efficacy of growth factor therapies for intractable wounds.
3山川，S.； Hayashida, K.生长因子在伤口愈合中的外科应用进展。烧伤创伤 2019, 7, 10, DOI: 10.1186/s41038-019-0148-1 - 4Hofer, M.; Lutolf, M. P. Engineering organoids. Nat. Rev. Mater. 2021, 6, 402– 420, DOI: 10.1038/s41578-021-00279-yGoogle Scholar 谷歌学术4https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3MXhsFegtbfM&md5=de6d2cf83898c666fd2bca595a93ed48Engineering organoidsHofer, Moritz; Lutolf, Matthias P.Nature Reviews Materials (2021), 6 (5), 402-420CODEN: NRMADL; ISSN:2058-8437. (Nature Portfolio)A review. Abstr.: Organoids are in vitro miniaturized and simplified model systems of organs that have gained enormous interest for modeling tissue development and disease, and for personalized medicine, drug screening and cell therapy. Despite considerable success in culturing physiol. relevant organoids, challenges remain to achieve real-life applications. In particular, the high variability of self-organizing growth and restricted exptl. and anal. access hamper the translatability of organoid systems. In this Review, we argue that many limitations of traditional organoid culture can be addressed by engineering approaches at all levels of organoid systems. We investigate cell surface and genetic engineering approaches, and discuss stem cell niche engineering based on the design of matrixes that allow spatiotemporal control of organoid growth and shape-guided morphogenesis. We examine how microfluidic approaches and lessons learnt from organs-on-a-chip enable the integration of mechano-physiol. parameters and increase accessibility of organoids to improve functional readouts. Applying engineering principles to organoids increases reproducibility and provides exptl. control, which will, ultimately, be required to enable clin. translation.
4霍弗，M.； Lutolf，M.P.工程类器官。纳特。马特牧师。 2021, 6, 402–420, DOI: 10.1038/s41578-021-00279-y - 5Hu, C.; Chu, C.; Liu, L.; Wang, C.; Jin, S.; Yang, R.; Rung, S.; Li, J.; Qu, Y.; Man, Y. Dissecting the microenvironment around biosynthetic scaffolds in murine skin wound healing. Sci. Adv. 2021, 7, eabf0787 DOI: 10.1126/sciadv.abf0787Google Scholar 谷歌学术There is no corresponding record for this reference.
5Hu，C.；楚，C.；刘，L。王，C.；金，S。杨，R。朗格，S.；李，J。曲，Y。 Man，Y.剖析小鼠皮肤伤口愈合中生物合成支架周围的微环境。科学。副词。 2021, 7, eabf0787 DOI: 10.1126/sciadv.abf0787 - 6Krishnan, K. A.; Thomas, S. Recent advances on herb-derived constituents-incorporated wound-dressing materials: A review. Polym. Adv. Technol. 2019, 30, 823– 838, DOI: 10.1002/pat.4540Google Scholar 谷歌学术6https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXhtFSgtL0%253D&md5=0555ceacdb57c719756c8b4f5429c3beRecent advances on herb-derived constituents-incorporated wound-dressing materials: A reviewKrishnan K, Asha; Thomas, SabuPolymers for Advanced Technologies (2019), 30 (4), 823-838CODEN: PADTE5; ISSN:1042-7147. (John Wiley & Sons Ltd.)A review. Since ancient times, wound dressings have evolved with persistent and substantial changes. Several efforts have been made toward the development of new dressing materials, which can meet the demanding conditions for the treatment of skin wounds. Currently, many studies have been focused on the prodn. and designing of herb-incorporated wound dressings. Herb-derived constituents are more effective than conventional medicines because of their nontoxic nature and can be administered over long periods. Herbal medicines in wound healing provide a suitable environment for aiding the natural course of healing. This review mainly focuses on the diverse approaches that have been developed to produce a wound dressing material, which can deliver herb-derived bioactive constituents in a controlled manner. This review also discusses the common wound-dressing materials available, basic principles of wound healing, and wound-healing agents from medicinal plants.
6Krishnan，K.A.； Thomas, S. 草药衍生成分掺入伤口敷料材料的最新进展：综述。聚合物。副词。技术。 2019, 30, 823–838, DOI: 10.1002/pat.4540 - 7(a) Zeng, Q.; Qi, X.; Shi, G.; Zhang, M.; Haick, H. Wound Dressing: From Nanomaterials to Diagnostic Dressings and Healing Evaluations. ACS Nano 2022, 16, 1708– 1733, DOI: 10.1021/acsnano.1c08411Google Scholar 谷歌学术7ahttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB38XhsFertbc%253D&md5=2c1fbf3a27094ee51808f474da1dbd78Wound Dressing: From Nanomaterials to Diagnostic Dressings and Healing EvaluationsZeng, Qiankun; Qi, Xiaoliang; Shi, Guoyue; Zhang, Min; Haick, HossamACS Nano (2022), 16 (2), 1708-1733CODEN: ANCAC3; ISSN:1936-0851. (American Chemical Society)A review. Wound dressings based on nanomaterials play a crucial role in wound treatment and are widely used in a whole range of medical settings, from minor to life-threatening tissue injuries. This article presents an educational review on the accumulating knowledge in this multidisciplinary area to lay out the challenges and opportunities that lie ahead and ignite the further and faster development of clin. valuable technologies. The review analyzes the functional advantages of nanomaterial-based gauzes and hydrogels as well as hybrid structures thereof. On this basis, the review presents state-of-the-art advances to transfer the (semi)blind approaches to the evaluation of a wound state to smart wound dressings that enable real-time monitoring and diagnostic functions that could help in wound evaluation during healing. This review explores the translation of nanomaterial-based wound dressings and related medical aspects into real-world use. The ongoing challenges and future opportunities assocd. with nanomaterial-based wound dressings and related clin. decisions are presented and reviewed.
7(a) 曾Q.；齐，X。石，G。张，M。 Haick, H.《伤口敷料：从纳米材料到诊断敷料和愈合评估》。 ACS 纳米 2022, 16, 1708–1733, DOI: 10.1021/acsnano.1c08411(b) Zhang, X. Y.; Liu, C.; Fan, P. S.; Zhang, X. H.; Hou, D. Y.; Wang, J. Q.; Yang, H.; Wang, H.; Qiao, Z. Y. Skin-like wound dressings with on-demand administration based on in situ peptide self-assembly for skin regeneration. J. Mater. Chem. B 2022, 10, 3624– 3636, DOI: 10.1039/d2tb00348a
(b) 张X.Y.；刘，C.；范，PS；张X.H.；侯德勇；王J.Q.；杨，H。王，H。乔，Z.Y.基于原位肽自组装的按需给药的类皮肤伤口敷料用于皮肤再生。 J.马特。化学。 B 2022, 10, 3624–3636, DOI: 10.1039/d2tb00348aGoogle Scholar 谷歌学术7bhttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB38XpvVant7o%253D&md5=2c4ad7f27700e86992f8c6f800534d2cSkin-like wound dressings with on-demand administration based on in situ peptide self-assembly for skin regenerationZhang, Xiao-Ying; Liu, Cong; Fan, Peng-Sheng; Zhang, Xue-Hao; Hou, Da-Yong; Wang, Jia-Qi; Yang, Hui; Wang, Hao; Qiao, Zeng-YingJournal of Materials Chemistry B: Materials for Biology and Medicine (2022), 10 (19), 3624-3636CODEN: JMCBDV; ISSN:2050-7518. (Royal Society of Chemistry)Burn injuries without the normal skin barrier usually cause skin wound infections, and wound dressings are necessary. Although various dressings with antibacterial ability have already been developed, the biosafety and administration mode are still bottleneck problems for further application. Herein, we designed skin-like wound dressings based on silk fibroin (SF), which are modified with the gelatinase-cleavable self-assembled/antibacterial peptide (GPLK) and epidermal growth factor (EGF). When a skin wound is infected, the gelatinase over-secreted by bacteria can cut the GPLK peptides, leading to the in situ self-assembly of peptides and the resultant high-efficiency sterilization. Compared with the com. antibacterial dressing, the SF-GPLK displayed a faster wound healing rate. When a skin wound is not infected, the GPLK peptides remain in the SF, realizing good biosafety. Generally, the EGF can be released to promote wound healing and skin regeneration in both cases. Therefore, skin-like SF-GPLK wound dressings with on-demand release of antibacterial peptides provide a smart administration mode for clin. wound management and skin regeneration. - 8(a) Krawetz, R. J.; Abubacker, S.; Leonard, C.; Masson, A. O.; Shah, S.; Narendran, N.; Tailor, P.; Regmi, S. C.; Labit, E.; Ninkovic, N. Proteoglycan 4 (PRG4) treatment enhances wound closure and tissue regeneration. NPJ Regen. Med. 2022, 7, 32, DOI: 10.1038/s41536-022-00228-5Google Scholar 谷歌学术8ahttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB38Xit1Smt7zL&md5=be78d129f0dbe736467c05e67f700a82Proteoglycan 4 (PRG4) treatment enhances wound closure and tissue regenerationKrawetz, Roman J.; Abubacker, Saleem; Leonard, Catherine; Masson, Anand O.; Shah, Sophia; Narendran, Nadia; Tailor, Pankaj; Regmi, Suresh C.; Labit, Elodie; Ninkovic, Nicoletta; Corpuz, Jessica May; Ito, Kenichi; Underhill, T. Michael; Salo, Paul T.; Schmidt, Tannin A.; Biernaskie, Jeff A.npj Regenerative Medicine (2022), 7 (1), 32CODEN: RMEED2; ISSN:2057-3995. (Nature Portfolio)Abstr.: The wound healing response is one of most primitive and conserved physiol. responses in the animal kingdom, as restoring tissue integrity/homeostasis can be the difference between life and death. Wound healing in mammals is mediated by immune cells and inflammatory signaling mols. that regulate tissue resident cells, including local progenitor cells, to mediate closure of the wound through formation of a scar. Proteoglycan 4 (PRG4), a protein found throughout the animal kingdom from fish to elephants, is best known as a glycoprotein that reduces friction between articulating surfaces (e.g. cartilage). Previously, PRG4 was also shown to regulate the inflammatory and fibrotic response. Based on this, we asked whether PRG4 plays a role in the wound healing response. Using an ear wound model, topical application of exogenous recombinant human (rh)PRG4 hastened wound closure and enhanced tissue regeneration. Our results also suggest that rhPRG4 may impact the fibrotic response, angiogenesis/blood flow to the injury site, macrophage inflammatory dynamics, recruitment of immune and increased proliferation of adult mesenchymal progenitor cells (MPCs) and promoting chondrogenic differentiation of MPCs to form the auricular cartilage scaffold of the injured ear. These results suggest that PRG4 has the potential to suppress scar formation while enhancing connective tissue regeneration post-injury by modulating aspects of each wound healing stage (blood clotting, inflammation, tissue generation and tissue remodeling). Therefore, we propose that rhPRG4 may represent a potential therapy to mitigate scar and improve wound healing.
8(a) 克拉维茨，R.J.；阿布巴克，S.；伦纳德，C.；马森，A.O.；沙阿，S.；纳伦德兰，N.；裁缝，P.；雷格米，南卡罗来纳州；拉比特，E.； Ninkovic, N. 蛋白聚糖 4 (PRG4) 治疗可增强伤口闭合和组织再生。 NPJ 再生。医学。 2022 年 7 月 32 日，DOI：10.1038/s41536-022-00228-5(b) Zhu, Y.; Jung, J.; Anilkumar, S.; Ethiraj, S.; Madira, S.; Tran, N. A.; Mullis, D. M.; Casey, K. M.; Walsh, S. K.; Stark, C. J. A novel photosynthetic biologic topical gel for enhanced localized hyperoxygenation augments wound healing in peripheral artery disease. Sci. Rep. 2022, 12, 10028, DOI: 10.1038/s41598-022-14085-1
(b) 朱宇；荣格，J。阿尼尔库马尔，S.；埃蒂拉吉，S.；马德拉，S.；特兰，N.A.；穆利斯，D.M.；凯西，K.M.；沃尔什，S.K.； Stark, C. J. 一种新型光合生物局部凝胶，可增强局部高氧合，增强外周动脉疾病的伤口愈合。科学。报告 2022, 12, 10028, DOI: 10.1038/s41598-022-14085-1Google Scholar 谷歌学术8bhttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB38Xhs1SksLzF&md5=76a472d0cf2587f80a3d4c2f790ce2c5A novel photosynthetic biologic topical gel for enhanced localized hyperoxygenation augments wound healing in peripheral artery diseaseZhu, Yuanjia; Jung, Jinsuh; Anilkumar, Shreya; Ethiraj, Sidarth; Madira, Sarah; Tran, Nicholas A.; Mullis, Danielle M.; Casey, Kerriann M.; Walsh, Sabrina K.; Stark, Charles J.; Venkatesh, Akshay; Boakye, Alexander; Wang, Hanjay; Woo, Y. JosephScientific Reports (2022), 12 (1), 10028CODEN: SRCEC3; ISSN:2045-2322. (Nature Portfolio)Peripheral artery disease and the assocd. ischemic wounds are substantial causes of global morbidity and mortality, affecting over 200 million people worldwide. Although advancements have been made in preventive, pharmacol., and surgical strategies to treat this disease, ischemic wounds, a consequence of end-stage peripheral artery disease, remain a significant clin. and economic challenge. Synechococcus elongatus is a cyanobacterium that grows photoautotrophically and converts carbon dioxide and water into oxygen. We present a novel topical biol. gel contg. S. elongatus that provides oxygen via photosynthesis to augment wound healing by rescuing ischemic tissues caused by peripheral artery disease. By using light rather than blood as a source of energy, our novel topical therapy significantly accelerated wound healing in two rodent ischemic wound models. This novel topical gel can be directly translated to clin. practise by using a localized, portable light source without interfering with patients' daily activities, demonstrating potential to generate a paradigm shift in treating ischemic wounds from peripheral artery disease. Its novelty, low prodn. cost, and ease of clin. translatability can potentially impact the clin. care for millions of patients suffering from peripheral arterial disease.(c) Yu, R.; Li, M.; Li, Z.; Pan, G.; Liang, Y.; Guo, B. Supramolecular Thermo-Contracting Adhesive Hydrogel with Self-Removability Simultaneously Enhancing Noninvasive Wound Closure and MRSA-Infected Wound Healing. Adv. Healthcare Mater. 2022, 11, e2102749 DOI: 10.1002/adhm.202102749
(c) 于 R.；李，M。李，Z。潘，G.；梁，Y。郭，B.具有自移除性的超分子热收缩粘合水凝胶，同时增强非侵入性伤口闭合和 MRSA 感染的伤口愈合。副词。医疗保健材料。 2022, 11, e2102749 DOI: 10.1002/adhm.202102749Google Scholar 谷歌学术8chttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB38XhtFWitL3O&md5=ce57657a2f132dea059b45d659414882Supramolecular Thermo-Contracting Adhesive Hydrogel with Self-Removability Simultaneously Enhancing Noninvasive Wound Closure and MRSA-Infected Wound HealingYu, Rui; Li, Meng; Li, Zhenlong; Pan, Guoying; Liang, Yuqing; Guo, BaolinAdvanced Healthcare Materials (2022), 11 (13), 2102749CODEN: AHMDBJ; ISSN:2192-2640. (Wiley-VCH Verlag GmbH & Co. KGaA)Conventional wound closure and dressing are two crucial, time-consuming but isolated principles in wound care. Even though tissue adhesive opens a new era for wound closure, the method and biomaterial that can simultaneously achieve noninvasive wound closure and promote wound healing are highly appreciated. Herein, a novel supramol. poly(N-isopropylacrylamide) hybrid hydrogel dressing composed of quaternized chitosan-graft-β-cyclodextrin, adenine, and polypyrrole nanotubes via host-guest interaction and hydrogen bonds is developed. The hydrogel demonstrates thermal contraction of 47% remaining area after 2 h at 37°C and tissue adhesion of 5.74 kPa, which are essential for noninvasive wound closure, and multiple mech. and biol. properties including suitable mech. properties, self-healing, on-demand removal, antioxidant, hemostasis, and photothermal/intrinsic antibacterial activity (higher 99% killing ratio within 5 min after irradn.). In both full-thickness skin incision and excision wound models, the hydrogel reveals significant wound closure after 24 h post-surgery. In acute and methicillin-resistant Staphylococcus aureus-infected wound and photothermal/intrinsic antibacterial activity assays, wounds treated with the hydrogel demonstrate enhanced wound healing with rapid wound closure rate, mild inflammatory response, advanced angiogenesis, and well-arranged collagen fibers. Altogether, the results indicate the hydrogel is promising in synchronously noninvasive wound closure and enhanced wound healing.(d) Huang, Y.; Mu, L.; Zhao, X.; Han, Y.; Guo, B. Bacterial Growth-Induced Tobramycin Smart Release Self-Healing Hydrogel for Pseudomonas aeruginosa-Infected Burn Wound Healing. ACS Nano 2022, 16, 13022– 13036, DOI: 10.1021/acsnano.2c05557
(d) 黄Y.；穆，L。赵X。韩，Y。郭，B.细菌生长诱导妥布霉素智能释放自愈水凝胶，用于铜绿假单胞菌感染的烧伤创面愈合。 ACS 纳米 2022, 16, 13022–13036, DOI: 10.1021/acsnano.2c05557Google Scholar 谷歌学术8dhttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB38XitVSisLjJ&md5=173c595ccb786734fdf8aaa1d9f6895aBacterial growth-induced tobramycin smart release self-healing hydrogel for Pseudomonas aeruginosa-infected burn wound healingHuang, Ying; Mu, Lei; Zhao, Xin; Han, Yong; Guo, BaolinACS Nano (2022), 16 (8), 13022-13036CODEN: ANCAC3; ISSN:1936-0851. (American Chemical Society)Burns are a common health problem worldwide and are highly susceptible to bacterial infections that are difficult to handle with ordinary wound dressings. Therefore, burn wound repair is extremely challenging in clin. practice. Herein, a series of self-healing hydrogels (QCS/OD/TOB/PPY@PDA) with good elec. cond. and antioxidant activity were prepd. on the basis of quaternized chitosan (QCS), oxidized dextran (OD), tobramycin (TOB), and polydopamine-coated polypyrrole nanowires (PPY@PDA NWs). These Schiff base cross-links between the aminoglycoside antibiotic TOB and OD enable TOB to be slowly released and responsive to pH. Interestingly, the acidic substances during the bacteria growth process can induce the on-demand release of TOB, avoiding the abuse of antibiotics. The antibacterial results showed that the QCS/OD/TOB/PPY@PDA9 hydrogel could kill high concns. of Pseudomonas aeruginosa (PA), Staphylococcus aureus, and Escherichia coli in a short time and showed a bactericidal effect for up to 11 days in an agar plate diffusion expt., while showing good in vivo antibacterial activity. Excellent and long-lasting antibacterial properties make it suitable for severely infected wounds. Furthermore, the incorporation of PPY@PDA endowed the hydrogel with near-IR (NIR) irradn. assisted bactericidal activity of drug-resistant bacteria, cond., and antioxidant activity. Most importantly, in the PA-infected burn wound model, the QCS/OD/TOB/PPY@PDA9 hydrogel more effectively controlled wound inflammation levels and promoted collagen deposition, vascular generation, and earlier wound closure compared to Tegaderm dressings. Therefore, the TOB smart release hydrogels with on-demand delivery are extremely advantageous for bacterial-infected burn wound healing. - 9Foulds, I. S.; Barker, A. T. Human Skin Battery Potentials and Their Possible Role in Wound Healing. Br. J. Dermatol. 1983, 109, 515– 522, DOI: 10.1111/j.1365-2133.1983.tb07673.xGoogle Scholar 谷歌学术9https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADyaL2c%252FltlahsQ%253D%253D&md5=bffc07d0afb9a16b37f6db0c6f26d3edHuman skin battery potentials and their possible role in wound healingFoulds I S; Barker A TThe British journal of dermatology (1983), 109 (5), 515-22 ISSN:0007-0963.Measurements of transcutaneous voltage have been made on seventeen normal volunteers. The results show the presence of 'skin battery' voltages comparable in size to those previously reported for amphibian and mammalian skin. No correlation was found between battery voltage and age or sex in the group studied, but consistent anatomical variations were observed. The possible role of these voltages in the natural wound healing process is discussed.
9Folds，I.S.； Barker，A.T.人类皮肤电池潜力及其在伤口愈合中的可能作用。 Br。 J.德马托尔。 1983, 109, 515–522, DOI: 10.1111/j.1365-2133.1983.tb07673.x - 10Tai, G.; Tai, M.; Zhao, M. Electrically stimulated cell migration and its contribution to wound healing. Burns Trauma 2018, 6, 20, DOI: 10.1186/s41038-018-0123-2Google Scholar 谷歌学术10https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB3c%252Fns12nug%253D%253D&md5=9095be644c9eccd8ef1c3ed01121713aElectrically stimulated cell migration and its contribution to wound healingTai Guangping; Tai Michael; Zhao MinBurns & trauma (2018), 6 (), 20 ISSN:2321-3868.Naturally occurring electric fields are known to be morphogenetic cues and associated with growth and healing throughout mammalian and amphibian animals and the plant kingdom. Electricity in animals was discovered in the eighteenth century. Electric fields activate multiple cellular signaling pathways such as PI3K/PTEN, the membrane channel of KCNJ15/Kir4.2 and intracellular polyamines. These pathways are involved in the sensing of physiological electric fields, directional cell migration (galvanotaxis, also known as electrotaxis), and possibly other cellular responses. Importantly, electric fields provide a dominant and over-riding signal that directs cell migration. Electrical stimulation could be a promising therapeutic method in promoting wound healing and activating regeneration of chronic and non-healing wounds. This review provides an update of the physiological role of electric fields, its cellular and molecular mechanisms, its potential therapeutic value, and questions that still await answers.
10Tai，G.；泰，M.；赵，M.电刺激细胞迁移及其对伤口愈合的贡献。烧伤创伤 2018, 6, 20, DOI: 10.1186/s41038-018-0123-2 - 11Barker, A. T.; Jaffe, L. F.; Vanable, J. W., Jr. The glabrous epidermis of cavies contains a powerful battery. Am. J. Physiol. 1982, 242, R358– R366, DOI: 10.1152/ajpregu.1982.242.3.R358Google Scholar 谷歌学术There is no corresponding record for this reference.
11 巴克，A.T.；贾菲，L.F.； Vanable, J. W., Jr. 豚鼠无毛的表皮含有强大的电池。是。 J.生理学。 1982, 242, R358–R366, DOI: 10.1152/ajpregu.1982.242.3.R358 - 12Liu, H.; Feng, Y.; Che, S.; Guan, L.; Yang, X.; Zhao, Y.; Fang, L.; Zvyagin, A. V.; Lin, Q. An Electroconductive Hydrogel Scaffold with Injectability and Biodegradability to Manipulate Neural Stem Cells for Enhancing Spinal Cord Injury Repair. Biomacromolecules 2023, 24, 86– 97, DOI: 10.1021/acs.biomac.2c00920Google Scholar 谷歌学术12https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB38XjtVygsrjM&md5=e0b7bf8d704305a5dab22ac86b980fccAn Electroconductive Hydrogel Scaffold with Injectability and Biodegradability to Manipulate Neural Stem Cells for Enhancing Spinal Cord Injury RepairLiu, Hou; Feng, Yubin; Che, Songtian; Guan, Lin; Yang, Xinting; Zhao, Yue; Fang, Linan; Zvyagin, Andrei V.; Lin, QuanBiomacromolecules (2023), 24 (1), 86-97CODEN: BOMAF6; ISSN:1525-7797. (American Chemical Society)Spinal cord injury (SCI) generally leads to long-term functional deficits and is difficult to repair spontaneously. Many biol. scaffold materials and stem cell treatment strategies have been explored, but very few researches focused on the method of combining exogenous neural stem cells (NSCs) with biodegradable conductive hydrogel scaffold. Here, NSCs loaded conductive hydrogel scaffold (named ICH/NSCs) was assembled by amino-modified gelatin (NH2-Gelatin) and aniline tetramer grafted oxidized hyaluronic acid (AT-OHA). Desirably, the well-conducting ICH/NSCs can be simply injected into the target site of SCI for establishing a good elec. signal pathway of cells, and the proper degrdn. cycle facilitates new nerve growth. In vitro expts. indicated that the inherent electroactive microenvironment of hydrogel could better manipulate the differentiation of NSCs into neurons, and inhibit the formation of glial cells and scars. Collectively, the ICH/NSCs scaffold has successfully stimulated the recovery of SCI and may provide a promising treatment strategy for SCI repair.
12刘，H.；冯，Y。车，S。关，L。杨X.；赵，Y。方，L.；兹维亚金，A.V.； Lin，Q.一种具有可注射性和生物降解性的导电水凝胶支架，可操纵神经干细胞以增强脊髓损伤修复。生物大分子 2023, 24, 86–97, DOI: 10.1021/acs.biomac.2c00920 - 13Nishimura, K. Y.; Isseroff, R. R.; Nuccitelli, R. Human Keratinocytes Migrate to the Negative Pole in Direct Current Electric Fields Comparable to those Measured in Mammalian Wounds. J. Cell Sci. 1996, 109, 199– 207, DOI: 10.1242/jcs.109.1.199Google Scholar 谷歌学术13https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK28XosVagug%253D%253D&md5=fa81e6113d569529269c09cce99798e2Human keratinocytes migrate to the negative pole in direct current electric fields comparable to those measured in mammalian woundsNishimura, Karen Y.; isseroff, R. Rivkah; Nuccitelli, RichardJournal of Cell Science (1996), 109 (1), 199-207CODEN: JNCSAI; ISSN:0021-9533. (Company of Biologists)Previous measurements of the lateral elec. fields near skin wounds in guinea pigs have detected DC fields between 100-200 mV/mm near the edge of the wound. We have studied the translocation response of motile primary human keratinocytes migrating on a collagen substrate while exposed to similar physiol. DC elec. fields. We find that keratinocytes migrate randomly on collage in fields of 5 mV/mm or less, but in larger fields they migrate towards the neg. pole of the field, exhibiting galvanotaxis. Since these cells have an av. cell length of 50 μm, this implies that they are able to detect a voltage gradient as low as 0.5 mV along their length. This cath-odally-directed movement exhibits increased directedness with increasing field strengths between 10 and 100 mV/mm. We observe a maximally directed response at 100 mV/mm with half of the cells responding to the field within 14 min. The av. speed of migration tended to be greater in fields above 50 mV/mm than in smaller fields. We conclude that human keratinocytes migrate towards the neg. pole in DC elec. fields that are of the same magnitude as measured in vivo near wounds in mammalian skin.
13西村K.Y.；伊瑟罗夫，R.R.； Nuccitelli，R.人类角质形成细胞在直流电场中迁移到负极，与在哺乳动物伤口中测量的结果相当。 J.细胞科学。 1996, 109, 199–207, DOI: 10.1242/jcs.109.1.199 - 14Zhang, J.; Wu, C.; Xu, Y.; Chen, J.; Ning, N.; Yang, Z.; Guo, Y.; Hu, X.; Wang, Y. Highly Stretchable and Conductive Self-Healing Hydrogels for Temperature and Strain Sensing and Chronic Wound Treatment. ACS Appl. Mater. Interfaces 2020, 12, 40990– 40999, DOI: 10.1021/acsami.0c08291Google Scholar 谷歌学术14https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhs1aqs7jF&md5=67f3a00d3e7840e68205e971e785fcd9Highly Stretchable and Conductive Self-Healing Hydrogels for Temperature and Strain Sensing and Chronic Wound TreatmentZhang, Jieyu; Wu, Can; Xu, Yuanyuan; Chen, Jiali; Ning, Ning; Yang, Zeyu; Guo, Yi; Hu, Xuefeng; Wang, YunbingACS Applied Materials & Interfaces (2020), 12 (37), 40990-40999CODEN: AAMICK; ISSN:1944-8244. (American Chemical Society)Flexible bioelectronics for biomedical applications requires a stretchable, conductive, self-healable, and biocompatible material that can be obtained by cost-effective chems. and strategies. Herein, we synthesized polypyrrole or Zn-functionalized chitosan mols., which are cross-linked with poly(vinyl alc.) to form a hydrogel through dynamic di-diol complexations, hydrogen bonding, and zinc-based coordination bonds. These multiple dynamic interactions endow the material with excellent stretchability and autonomous self-healing ability. The choice of Food and Drug Administration (FDA)-approved materials (poly(vinyl alc.) and chitosan) as the matrix materials ensures the good biocompatibility of the hydrogel. The cond. contributed by the polypyrrole allowed the hydrogel to sense strain and temp., and the coordinated Zn significantly enhanced the antibacterial activity of the hydrogel. Moreover, using a diabetic rat model, we have proved that this hydrogel is capable of promoting the healing of the infected chronic wounds with elec. stimulation.
14张杰；吴，C.；徐，Y。陈，J。宁，N。杨，Z。郭，Y。胡，X。 Wang, Y. 用于温度和应变传感以及慢性伤口治疗的高拉伸性和导电性自愈水凝胶。 ACS 应用马特。接口 2020, 12, 40990–40999, DOI: 10.1021/acsami.0c08291 - 15Lu, Y.; Wang, Y.; Zhang, J.; Hu, X.; Yang, Z.; Guo, Y.; Wang, Y. In-situ doping of a conductive hydrogel with low protein absorption and bacterial adhesion for electrical stimulation of chronic wounds. Acta Biomater. 2019, 89, 217– 226, DOI: 10.1016/j.actbio.2019.03.018Google Scholar 谷歌学术15https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXltFCqtrg%253D&md5=879fc1f1771d1a6ddd1971ea999f04adIn-situ doping of a conductive hydrogel with low protein absorption and bacterial adhesion for electrical stimulation of chronic woundsLu, Yuhui; Wang, Yanan; Zhang, Jieyu; Hu, Xuefeng; Yang, Zeyu; Guo, Yi; Wang, YunbingActa Biomaterialia (2019), 89 (), 217-226CODEN: ABCICB; ISSN:1742-7061. (Elsevier Ltd.)Elec. stimulation (ES) via electrodes is promising for treating chronic wounds, but this electrode-based strategy is unable to stimulate the whole wound area and the therapeutic outcome may be compromised. In this study, a conductive poly(2-hydroxyethyl methacrylate) (polyHEMA)/polypyrrole (PPY) hydrogel was developed, and 3-sulfopropyl methacrylate was covalently incorporated in the hydrogel's network to in-situ dope the PPY and maintain the hydrogel's cond. in the weak alk. physiol. environment. The obtained hydrogel was superior to the com. Hydrosorb dressing for preventing bacterial adhesion and protein absorption, and this is helpful to reduce the possibilities of infection and secondary damage during dressing replacement. The in vitro scratch assay demonstrates that ES through the hydrogel enhanced fibroblast migration, and this enhancement effect remained even after the ES was ended. The in vivo assay using diabetic rats shows that when ES was conducted with this polyHEMA/PPY hydrogel, the healing rate was faster than that achieved by the electrode-based ES strategy. Therefore, this polyHEMA/PPY hydrogel shows a great potential for developing the next generation of ES treatment for chronic wounds. Elec. stimulation (ES) via sepd. electrodes is promising for treating chronic wounds, but this electrode-based strategy is unable to stimulate the whole wound area, compromising the therapeutic outcome. Herein, a hydrogel was developed with stable elec. cond. in the physiol. environment and strong resistance to protein absorption and bacterial adhesion. The in vitro and in vivo tests proved that ES applied through the flexible and conductive hydrogel that covered the wound was superior to ES through electrodes for promoting the healing of the chronic wound. This hydrogel-based ES strategy combines the advantages of ES and hydrogel dressing and will pave the way for the next generation of ES treatment for chronic wounds.
15卢，Y.；王，Y。张，J。胡，X。杨，Z。郭，Y。 Wang，Y.具有低蛋白质吸收和细菌粘附的导电水凝胶的原位掺杂用于慢性伤口的电刺激。生物材料学报。 2019, 89, 217–226, DOI: 10.1016/j.actbio.2019.03.018 - 16Yu, C.; Hu, Z. Q.; Peng, R. Y. Effects and mechanisms of a microcurrent dressing on skin wound healing: a review. Mil. Med. Res. 2014, 1, 1– 8, DOI: 10.1186/2054-9369-1-24Google Scholar 谷歌学术There is no corresponding record for this reference.
16Yu，C.；胡志强； Peng，R. Y.微电流敷料对皮肤伤口愈合的影响和机制：综述。米尔。医学。资源。 2014, 1, 1–8, DOI: 10.1186/2054-9369-1-24 - 17(a) Isseroff, R. R.; Dahle, S. E. Electrical Stimulation Therapy and Wound Healing: Where Are We Now?. Adv. Wound Care 2012, 1, 238– 243, DOI: 10.1089/wound.2011.0351Google Scholar 谷歌学术17ahttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC2sbps12isQ%253D%253D&md5=8a1a37d35b6d66405c9132be4f3d243cElectrical Stimulation Therapy and Wound Healing: Where Are We Now?Isseroff R Rivkah; Dahle Sara EAdvances in wound care (2012), 1 (6), 238-243 ISSN:2162-1918.BACKGROUND: Healing chronic wounds is an ongoing challenge for clinicians and poses a serious public health burden. Electrical stimulation (ES), broadly defined as the application of electrical current via electrodes placed on the skin adjacent to or directly within the wound, has been proposed as a therapeutic modality over a century ago, and recent advances in understanding the biology of electrical phenomena in the skin have rekindled an interest in this modality. THE PROBLEM: Despite evidence that has shown ES to be effective for wound healing, it has been slow to gain acceptance in the United States. Also, there has been no consensus in terms of standardization of parameters to devise a systematic protocol for implementation of this technology. BASIC/CLINICAL SCIENCE ADVANCES: The epidermis maintains a "skin battery" that generates an endogenous electric field and current flow when wounded. Experimental models have demonstrated that most of the cell types within the wound can sense an electric field in the range of that endogenously generated in the wound, and respond with a variety of biological and functional responses that can contribute to healing. Multiple animal wound models have demonstrated enhancement of a number of parameters of healing when ES is exogenously supplied. CLINICAL CARE RELEVANCE: Clinical trials have investigated the efficacy of multiple forms of ES for improving healing in a wide variety of human chronic wounds. In 2002 the Centers for Medicare and Medicaid Services approved reimbursement for use of ES in a clinical setting for certain chronic wounds. CONCLUSION: THERE REMAIN MANY VOIDS IN OUR KNOWLEDGE BASE: clinical evidence is limited by deficiencies in the design of many of the trials, a multiplicity of ES application modes and waveforms used in trials prevent selection of an optimal modality, and lack of uniformity in reporting ES dosages leave us not much advanced from our clinical knowledge base a decade ago.
17(a) 伊瑟罗夫，R.R.； Dahle, S. E. 电刺激疗法和伤口愈合：我们现在在哪里？副词。伤口护理 2012, 1, 238–243, DOI: 10.1089/wound.2011.0351(b) Whitcomb, E.; Monroe, N.; Hope-Higman, J.; Campbell, P. Demonstration of a microcurrent-generating wound care device for wound healing within a rehabilitation center patient population. J. Am. Coll. Clin. Wound Spec. 2012, 4, 32– 39, DOI: 10.1016/j.jccw.2013.07.001
(b) 惠特科姆，E.；门罗，N.；霍普-希格曼，J.； Campbell, P. 演示用于康复中心患者群体伤口愈合的微电流伤口护理装置。 J. Am.科尔。临床。伤口规格2012, 4, 32–39, DOI: 10.1016/j.jccw.2013.07.001Google Scholar 谷歌学术17bhttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC2cvltFaruw%253D%253D&md5=c2c094612e9bbd6bf65213506a024d0cDemonstration of a microcurrent-generating wound care device for wound healing within a rehabilitation center patient populationWhitcomb Emily; Monroe Nina; Hope-Higman Jennifer; Campbell PennyThe journal of the American College of Clinical Wound Specialists (2012), 4 (2), 32-9 ISSN:2213-5103.PURPOSE: Wound care in a rehabilitation environment is a costly and difficult problem. The goal of this retrospective study is to evaluate differences in wound closure outcomes in acute and chronic wounds when treated with a microcurrent-generating wound care device as compared to standard wound care methods. METHODS: Data files of 38 patients who received either standard wound treatment (SOC; n = 20), or were treated with a microcurrent-generating wound device (MCD, n = 18), were retrospectively reviewed. Wounds were assessed until deemed clinically to have closed or healed with up to 100% epithelialization. All patients (18-99 years) with single wounds were included. The number of days to wound closure and the rate of wound volume reduction were compared across groups. Persistent reduction of wound size improvement was also examined. RESULTS: The wounds in the SOC group closed on average at 36.25 days (SD = 28.89), while the MCD group closed significantly faster in 19.78 days (SD = 14.45), p = 0.036. The rate of volume reduction per day was -3.83% for SOC vs. -9.82% volume reduction per day (p = 0.013) for the MCD group. The SOC group had 50% of its wounds close monotonically vs. 83.3% in the MCD group (p = 0.018). CONCLUSION: This two-center retrospective study demonstrated a 45.4% faster, and more robust healing of wounds with the use of the MCD, when compared to SOC in a rehabilitation center environment. This translates into improved patient care, and potentially significant cost savings. Economic benefits for the use of MCD compared to other wound care methods are planned for future research. - 18Ud-Din, S.; Bayat, A. Electrical Stimulation and Cutaneous Wound Healing: A Review of Clinical Evidence. Healthcare 2014, 2, 445– 467, DOI: 10.3390/healthcare2040445Google Scholar 谷歌学术18https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC2s3hvVCnug%253D%253D&md5=c15b8dc4f8ecc043db58370925c5ab00Electrical Stimulation and Cutaneous Wound Healing: A Review of Clinical EvidenceUd-Din Sara; Bayat Ardeshir; Ud-Din Sara; Bayat ArdeshirHealthcare (Basel, Switzerland) (2014), 2 (4), 445-67 ISSN:2227-9032.Electrical stimulation (ES) has been shown to have beneficial effects in wound healing. It is important to assess the effects of ES on cutaneous wound healing in order to ensure optimization for clinical practice. Several different applications as well as modalities of ES have been described, including direct current (DC), alternating current (AC), high-voltage pulsed current (HVPC), low-intensity direct current (LIDC) and electrobiofeedback ES. However, no one method has been advocated as the most optimal for the treatment of cutaneous wound healing. Therefore, this review aims to examine the level of evidence (LOE) for the application of different types of ES to enhance cutaneous wound healing in the skin. An extensive search was conducted to identify relevant clinical studies utilising ES for cutaneous wound healing since 1980 using PubMed, Medline and EMBASE. A total of 48 studies were evaluated and assigned LOE. All types of ES demonstrated positive effects on cutaneous wound healing in the majority of studies. However, the reported studies demonstrate contrasting differences in the parameters and types of ES application, leading to an inability to generate sufficient evidence to support any one standard therapeutic approach. Despite variations in the type of current, duration, and dosing of ES, the majority of studies showed a significant improvement in wound area reduction or accelerated wound healing compared to the standard of care or sham therapy as well as improved local perfusion. The limited number of LOE-1 trials for investigating the effects of ES in wound healing make critical evaluation and assessment somewhat difficult. Further, better-designed clinical trials are needed to improve our understanding of the optimal dosing, timing and type of ES to be used.
18Ud-Din，S.； Bayat, A. 电刺激和皮肤伤口愈合：临床证据回顾。医疗保健 2014 年，2，445–467，DOI：10.3390/healthcare2040445 - 19Banerjee, J.; Das Ghatak, P.; Roy, S.; Khanna, S.; Sequin, E. K.; Bellman, K.; Dickinson, B. C.; Suri, P.; Subramaniam, V. V.; Chang, C. J.; Sen, C. K. Improvement of Human Keratinocyte Migration by a Redox Active Bioelectric Dressing. PLoS One 2014, 9, e89239 DOI: 10.1371/journal.pone.0089239Google Scholar 谷歌学术19https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhsVWgu7fK&md5=74aeabf0da3b8d78b5bd558029a0d8d1Improvement of human keratinocyte migration by a redox active bioelectric dressingBanerjee, Jaideep; Ghatak, Piya Das; Roy, Sashwati; Khanna, Savita; Sequin, Emily K.; Bellman, Karen; Dickinson, Bryan C.; Suri, Prerna; Subramaniam, Vish V.; Chang, Christopher J.; Sen, Chandan K.PLoS One (2014), 9 (3), e89239/1-e89239/14, 14 pp.CODEN: POLNCL; ISSN:1932-6203. (Public Library of Science)Exogenous application of an elec. field can direct cell migration and improve wound healing; however clin. application of the therapy remains elusive due to lack of a suitable device and hence, limitations in understanding the mol. mechanisms. Here we report on a novel FDA approved redox-active Ag/Zn bioelec. dressing (BED) which generates elec. fields. To develop a mechanistic understanding of how the BED may potentially influence wound re-epithelialization, we direct emphasis on understanding the influence of BED on human keratinocyte cell migration. Mapping of the elec. field generated by BED led to the observation that BED increases keratinocyte migration by three mechanisms: (i) generating hydrogen peroxide, known to be a potent driver of redox signaling, (ii) phosphorylation of redox-sensitive IGF1R directly implicated in cell migration, and (iii) redn. of protein thiols and increase in integrin αv expression, both of which are known to be drivers of cell migration. BED also increased keratinocyte mitochondrial membrane potential consistent with its ability to fuel an energy demanding migration process. Elec. fields generated by a Ag/Zn BED can cross-talk with keratinocytes via redox-dependent processes improving keratinocyte migration, a crit. event in wound re-epithelialization.
19班纳吉，J.；达斯·加塔克，P.；罗伊，S.；卡纳，S.；亮片，E.K.；贝尔曼，K.；不列颠哥伦比亚省迪金森；苏里，P。苏布拉马尼亚姆 (Subramaniam)，V.V.；张，C.J.； Sen，C.K.通过氧化还原活性生物电敷料改善人类角质形成细胞迁移。 PLoS One 2014, 9, e89239 DOI: 10.1371/journal.pone.0089239 - 20Blount, A. L.; Foster, S.; Rapp, D. A.; Wilcox, R. The use of bioelectric dressings in skin graft harvest sites: a prospective case series. J. Burn Care Res. 2012, 33, 354– 357, DOI: 10.1097/BCR.0b013e31823356e4Google Scholar 谷歌学术20https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC38zmtlWjsg%253D%253D&md5=9f6af7a4bfabf827e87a6dc4ec82a41eThe use of bioelectric dressings in skin graft harvest sites: a prospective case seriesBlount Andrew L; Foster Sarah; Rapp Derek A; Wilcox RichardJournal of burn care & research : official publication of the American Burn Association (2012), 33 (3), 354-7 ISSN:.Despite advances in wound care treatments for the management of acute and chronic wounds, there remains an unmet need for interventions that accelerate epithelialization. Many authors in the past have advocated the use of electric currents to accelerate wound healing. Novel wound dressings with inherent electric activity are emerging, and studies of these specific modalities are lacking. The principal aim of this study is to evaluate the impact of a bioelectric dressing on acute wound healing. Thirteen patients who underwent skin grafting were enrolled. One half of all skin graft donor sites were treated with the bioelectric dressing and semi-occlusive dressing (SOD) and the other half using solely a SOD. Epithelialization was rated by a blinded burn surgeon attending. Participants also provided a self-assessment of their scar appearance. At week 1 postprocedure, average epithelialization of 71.8% was noted on the bioelectric dressing-treated side, compared with 46.9% on the SOD side, representing an average 34.62% faster wound healing (P = .015). At 1 month, patients rated the bioelectric dressing-treated half as superior in terms of scar color (P = .198), stiffness (P = .088), thickness (P = .038), and overall quality (P = .028). These early data show promise in terms of faster healing, improved scarring, and improved patient subjective outcome with the use of the bioelectric dressing on acute wounds. With fulfillment of an extended study population, the authors hope to provide a solid foundation for extrapolating their data beyond skin graft donor sites to all areas of wound care.
20 布朗特，A.L.；福斯特，S.；拉普，D.A.； Wilcox, R.在皮肤移植收获部位使用生物电敷料：前瞻性病例系列。 J.烧伤护理研究中心。 2012, 33, 354–357, DOI: 10.1097/BCR.0b013e31823356e4 - 21Tandon, B.; Blaker, J. J.; Cartmell, S. H. Piezoelectric materials as stimulatory biomedical materials and scaffolds for bone repair. Acta Biomater. 2018, 73, 1– 20, DOI: 10.1016/j.actbio.2018.04.026Google Scholar 谷歌学术21https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXoslyrs7c%253D&md5=216ce623e06c494a56ae47b1cb7c2bcbPiezoelectric materials as stimulatory biomedical materials and scaffolds for bone repairTandon, Biranche; Blaker, Jonny J.; Cartmell, Sarah H.Acta Biomaterialia (2018), 73 (), 1-20CODEN: ABCICB; ISSN:1742-7061. (Elsevier Ltd.)The process of bone repair and regeneration requires multiple physiol. cues including biochem., elec. and mech. - that act together to ensure functional recovery. Myriad materials have been explored as bioactive scaffolds to deliver these cues locally to the damage site, amongst these piezoelec. materials have demonstrated significant potential for tissue engineering and regeneration, esp. for bone repair. Piezoelec. materials have been widely explored for power generation and harvesting, structural health monitoring, and use in biomedical devices. They have the ability to deform with physiol. movements and consequently deliver elec. stimulation to cells or damaged tissue without the need of an external power source. Bone itself is piezoelec. and the charges/potentials it generates in response to mech. activity are capable of enhancing bone growth. Piezoelec. materials are capable of stimulating the physiol. elec. microenvironment, and can play a vital role to stimulate regeneration and repair. This review gives an overview of the assocn. of piezoelec. effect with bone repair, and focuses on state-of-the-art piezoelec. materials (polymers, ceramics and their composites), the fabrication routes to produce piezoelec. scaffolds, and their application in bone repair. Important characteristics of these materials from the perspective of bone tissue engineering are highlighted. Promising upcoming strategies and new piezoelec. materials for this application are presented. Elec. stimulation/elec. microenvironment are known effect the process of bone regeneration by altering the cellular response and are crucial in maintaining tissue functionality. Piezoelec. materials, owing to their capability of generating charges/potentials in response to mech. deformations, have displayed great potential for fabricating smart stimulatory scaffolds for bone tissue engineering. The growing interest of the scientific community and compelling results of the published research articles has been the motivation of this review article. This article summarizes the significant progress in the field with a focus on the fabrication aspects of piezoelec. materials. The review of both material and cellular aspects on this topic ensures that this paper appeals to both material scientists and tissue engineers.
21坦登，B.；布莱克，J.J.； Cartmell, S. H. 压电材料作为刺激生物医学材料和骨修复支架。生物材料学报。 2018, 73, 1–20, DOI: 10.1016/j.actbio.2018.04.026 - 22Long, Y.; Wei, H.; Li, J.; Yao, G.; Yu, B.; Ni, D.; Gibson, A. L.; Lan, X.; Jiang, Y.; Cai, W. Effective Wound Healing Enabled by Discrete Alternative Electric Fields from Wearable Nanogenerators. ACS Nano 2018, 12, 12533– 12540, DOI: 10.1021/acsnano.8b07038Google Scholar 谷歌学术22https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXitlaktbbE&md5=80104e6fdb34474303a42fafa30c3c63Effective Wound Healing Enabled by Discrete Alternative Electric Fields from Wearable NanogeneratorsLong, Yin; Wei, Hao; Li, Jun; Yao, Guang; Yu, Bo; Ni, Dalong; Gibson, Angela LF; Lan, Xiaoli; Jiang, Yadong; Cai, Weibo; Wang, XudongACS Nano (2018), 12 (12), 12533-12540CODEN: ANCAC3; ISSN:1936-0851. (American Chemical Society)Skin wound healing is a major health care issue. While elec. stimulations have been known for decades to be effective for facilitating skin wound recovery, practical applications are still largely limited by the clumsy elec. systems. Here, we report an efficient elec. bandage for accelerated skin wound healing. On the bandage, an alternating discrete elec. field is generated by a wearable nanogenerator by converting mech. displacement from skin movements into electricity. Rat studies demonstrated rapid closure of a full-thickness rectangular skin wound within 3 days as compared to 12 days of usual contraction-based healing processes in rodents. From in vitro studies, the accelerated skin wound healing was attributed to elec. field-facilitated fibroblast migration, proliferation, and transdifferentiation. This self-powered elec.-dressing modality could lead to a facile therapeutic strategy for nonhealing skin wound treatment.
22Long，Y.；魏，H。李，J。姚，G。于，B.；尼，D。吉布森，A.L.；兰，X。蒋，Y。 Cai, W.可穿戴纳米发电机的离散替代电场实现有效的伤口愈合。 ACS 纳米 2018, 12, 12533–12540, DOI: 10.1021/acsnano.8b07038 - 23Yang, B.; Yao, F.; Hao, T.; Fang, W.; Ye, L.; Zhang, Y.; Wang, Y.; Li, J.; Wang, C. Development of Electrically Conductive Double-Network Hydrogels via One-Step Facile Strategy for Cardiac Tissue Engineering. Adv. Healthcare Mater. 2016, 5, 474– 488, DOI: 10.1002/adhm.201500520Google Scholar 谷歌学术23https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhvFaltbjK&md5=59ca6c2c957e039a7c6295117311dd76Development of Electrically Conductive Double-Network Hydrogels via One-Step Facile Strategy for Cardiac Tissue EngineeringYang, Boguang; Yao, Fanglian; Hao, Tong; Fang, Wancai; Ye, Lei; Zhang, Yabin; Wang, Yan; Li, Junjie; Wang, ChangyongAdvanced Healthcare Materials (2016), 5 (4), 474-488CODEN: AHMDBJ; ISSN:2192-2640. (Wiley-VCH Verlag GmbH & Co. KGaA)Cardiac tissue engineering is an effective method to treat the myocardial infarction. However, the lack of elec. cond. of biomaterials limits their applications. In this work, a homogeneous electronically conductive double network (HEDN) hydrogel via one-step facile strategy is developed, consisting of a rigid/hydrophobic/conductive network of chem. crosslinked poly(thiophene-3-acetic acid) (PTAA) and a flexible/hydrophilic/biocompatible network of photo-crosslinking methacrylated aminated gelatin (MAAG). Results suggest that the swelling, mech., and conductive properties of HEDN hydrogel can be modulated via adjusting the ratio of PTAA network to MAAG network. HEDN hydrogel has Young's moduli ranging from 22.7 to 493.1 kPa, and its cond. (≈10-4 S cm-1) falls in the range of reported conductivities for native myocardium tissue. To assess their biol. activity, the brown adipose-derived stem cells (BADSCs) are seeded on the surface of HEDN hydrogel with or without elec. stimulation. Our data show that the HEDN hydrogel can support the survival and proliferation of BADSCs, and that it can improve the cardiac differentiation efficiency of BADSCs and upregulate the expression of connexin 43. Moreover, elec. stimulation can further improve this effect. Overall, it is concluded that the HEDN hydrogel may represent an ideal scaffold for cardiac tissue engineering.
23杨，B.；姚，F。郝，T。方，W。叶，L。张，Y。王，Y。李，J。 Wang, C.通过心脏组织工程的一步简便策略开发导电双网络水凝胶。副词。医疗保健材料。 2016, 5, 474–488, DOI: 10.1002/adhm.201500520 - 24Han, L.; Yan, L.; Wang, M.; Wang, K.; Fang, L.; Zhou, J.; Fang, J.; Ren, F.; Lu, X. Transparent, Adhesive, and Conductive Hydrogel for Soft Bioelectronics Based on Light-Transmitting Polydopamine-Doped Polypyrrole Nanofibrils. Chem. Mater. 2018, 30, 5561– 5572, DOI: 10.1021/acs.chemmater.8b01446Google Scholar 谷歌学术24https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXhtlKqur%252FE&md5=3540dc40df8fe8ab558943e057e98938Transparent, Adhesive, and Conductive Hydrogel for Soft Bioelectronics Based on Light-Transmitting Polydopamine-Doped Polypyrrole NanofibrilsHan, Lu; Yan, Liwei; Wang, Menghao; Wang, Kefeng; Fang, Liming; Zhou, Jie; Fang, Ju; Ren, Fuzeng; Lu, XiongChemistry of Materials (2018), 30 (16), 5561-5572CODEN: CMATEX; ISSN:0897-4756. (American Chemical Society)Conductive hydrogels are promising materials for soft electronic devices. To satisfy the diverse requirement of bioelectronic devices, esp. those for human-machine interfaces, hydrogels are required to be transparent, conductive, highly stretchable, and skin-adhesive. However, fabrication of a conductive-polymer-incorporated hydrogel with high performance is a challenge because of the hydrophobic nature of conductive polymers making processing difficult. Here, we report a transparent, conductive, stretchable, and self-adhesive hydrogel by in situ formation of polydopamine (PDA)-doped polypyrrole (PPy) nanofibrils in the polymer network. The in situ formed nanofibrils with good hydrophilicity were well-integrated with the hydrophilic polymer phase and interwoven into a nanomesh, which created a complete conductive path and allowed visible light to pass through for transparency. Catechol groups from the PDA-PPy nanofibrils imparted the hydrogel with self-adhesiveness. Reinforcement by the nanofibrils made the hydrogel tough and stretchable. The proposed simple and smart strategy of in situ formation of conductive nanofillers opens a new route to incorporate hydrophobic and undissolvable conductive polymers into hydrogels. The fabricated multifunctional hydrogel shows promise in a range of applications, such as transparent electronic skins, wound dressings, and bioelectrodes for see-through body-adhered signal detection.
24Han，L.；严，L。王，M。王，K。方，L.；周，J。方，J。任，F.； Lu，X.基于透光聚多巴胺掺杂聚吡咯纳米纤维的软生物电子学透明、粘合和导电水凝胶。化学。马特。 2018, 30, 5561–5572, DOI: 10.1021/acs.chemmater.8b01446 - 25Han, L.; Yan, L.; Wang, K.; Fang, L.; Zhang, H.; Tang, Y.; Ding, Y.; Weng, L.-T.; Xu, J.; Weng, J. Tough, self-healable and tissue-adhesive hydrogel with tunable multifunctionality. NPG Asia Mater. 2017, 9, e372– e372, DOI: 10.1038/am.2017.33Google Scholar 谷歌学术25https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXlslegsbY%253D&md5=af4c4c6366d5be4e9fdb7097b18fcbdeTough, self-healable and tissue-adhesive hydrogel with tunable multifunctionalityHan, Lu; Yan, Liwei; Wang, Kefeng; Fang, Liming; Zhang, Hongping; Tang, Youhong; Ding, Yonghui; Weng, Lu-Tao; Xu, Jielong; Weng, Jie; Liu, Yujie; Ren, Fuzeng; Lu, XiongNPG Asia Materials (2017), 9 (4), e372CODEN: NAMPCE; ISSN:1884-4057. (Nature Publishing Group)An ideal hydrogel for biomedical engineering should mimic the intrinsic properties of natural tissue, esp. high toughness and self-healing ability, in order to withstand cyclic loading and repair skin and muscle damage. In addn., excellent cell affinity and tissue adhesiveness enable integration with the surrounding tissue after implantation. Inspired by the natural mussel adhesive mechanism, we designed a polydopamine-polyacrylamide (PDA-PAM) single network hydrogel by preventing the overoxidn. of dopamine to maintain enough free catechol groups in the hydrogel. Therefore, the hydrogel possesses super stretchability, high toughness, stimuli-free self-healing ability, cell affinity and tissue adhesiveness. More remarkably, the current hydrogel can repeatedly be adhered on/stripped from a variety of surfaces for many cycles without loss of adhesion strength. Furthermore, the hydrogel can serve as an excellent platform to host various nano-building blocks, in which multiple functionalities are integrated to achieve versatile potential applications, such as magnetic and elec. therapies.
25Han，L.；严，L。王，K。方，L.；张，H。唐，Y。丁，Y。翁L.-T.；徐，J。 Weng，J.具有可调节多功能性的坚韧、可自愈和组织粘附水凝胶。 NPG亚洲材料。 2017, 9, e372– e372, DOI: 10.1038/am.2017.33 - 26Ju, J.; Shi, Z.; Deng, N.; Liang, Y.; Kang, W.; Cheng, B. Designing waterproof breathable material with moisture unidirectional transport characteristics based on a TPU/TBAC tree-like and TPU nanofiber double-layer membrane fabricated by electrospinning. RSC Adv. 2017, 7, 32155– 32163, DOI: 10.1039/c7ra04843bGoogle Scholar 谷歌学术26https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXhtVGnsbzM&md5=a17dcf986e4277da9ae1183a576ee32dDesigning waterproof breathable material with moisture unidirectional transport characteristics based on a TPU/TBAC tree-like and TPU nanofiber double-layer membrane fabricated by electrospinningJu, Jingge; Shi, Zhijie; Deng, Nanping; Liang, Yueyao; Kang, Weimin; Cheng, BowenRSC Advances (2017), 7 (51), 32155-32163CODEN: RSCACL; ISSN:2046-2069. (Royal Society of Chemistry)In this study, a thermoplastic polyurethane (TPU) tree-like nanofiber membrane was fabricated via one-step electrospinning by adding a small amt. of tetrabutylammonium chloride (TBAC). On the basis of the "push and pull" effect, double-layer membranes composed of pure TPU nanofiber membranes (hydrophobic) and TPU/TBAC tree-like nanofiber membranes (hydrophilic) were prepd. by the direct electrospinning compounding method. The double-layer membranes were used as waterproof breathable materials with moisture unidirectional transport properties and good shielding properties. The water resistance, mech., waterproof, moisture permeability, air permeability, air filtration and moisture unidirectional transport performances of the double-layer membranes were tested. The results showed that the double-layer TPU membranes displayed good performances compared with the existing products on the market; they provide a new approach for the development of waterproof breathable materials.
26朱，J.；石，Z。邓，N.；梁，Y。康，W.； Cheng B.基于静电纺丝制备的TPU/TBAC树状和TPU纳米纤维双层膜，设计具有水分单向传输特性的防水透气材料。 RSC 高级2017, 7, 32155–32163, DOI: 10.1039/c7ra04843b - 27(a) Sedó, J.; Saiz-Poseu, J.; Busqué, F.; Ruiz-Molina, D. Catechol-based biomimetic functional materials. Adv. Mater. 2013, 25, 653– 701, DOI: 10.1002/adma.201202343Google Scholar 谷歌学术27ahttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XhslejtL7F&md5=9f8a316acb87614fd7da40d87b750f4bCatechol-Based Biomimetic Functional MaterialsSedo, Josep; Saiz-Poseu, Javier; Busque, Felix; Ruiz-Molina, DanielAdvanced Materials (Weinheim, Germany) (2013), 25 (5), 653-701CODEN: ADVMEW; ISSN:0935-9648. (Wiley-VCH Verlag GmbH & Co. KGaA)A review. Catechols are found in nature taking part in a remarkably broad scope of biochem. processes and functions. Though not exclusively, such versatility may be traced back to several properties uniquely found together in the o-dihydroxyaryl chem. function; namely, its ability to establish reversible equil. at moderate redox potentials and pHs and to irreversibly cross-link through complex oxidn. mechanisms; its excellent chelating properties, greatly exemplified by, but by no means exclusive, to the binding of Fe3+; and the diverse modes of interaction of the vicinal hydroxyl groups with all kinds of surfaces of remarkably different chem. and phys. nature. Thanks to this diversity, catechols can be found either as simple mol. systems, forming part of supramol. structures, coordinated to different metal ions or as macromols. mostly arising from polymn. mechanisms through covalent bonds. Such versatility has allowed catechols to participate in several natural processes and functions that range from the adhesive properties of marine organisms to the storage of some transition metal ions. As a result of such an astonishing range of functionalities, catechol-based systems have in recent years been subject to intense research, aimed at mimicking these natural systems in order to develop new functional materials and coatings. A comprehensive review of these studies is discussed in this paper.
27(a) 塞多，J.；赛兹-波修，J.；布斯克，F.； Ruiz-Molina, D.基于儿茶酚的仿生功能材料。副词。马特。 2013, 25, 653–701, DOI: 10.1002/adma.201202343(b) Ryu, J. H.; Hong, S.; Lee, H. Bio-inspired adhesive catechol-conjugated chitosan for biomedical applications: A mini review. Acta Biomater. 2015, 27, 101– 115, DOI: 10.1016/j.actbio.2015.08.043
(b) Ryu，J.H.；洪，S。 Lee, H.用于生物医学应用的仿生粘合剂儿茶酚缀合壳聚糖：小型回顾。生物材料学报。 2015, 27, 101–115, DOI: 10.1016/j.actbio.2015.08.043Google Scholar 谷歌学术27bhttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhsFWmtLzJ&md5=b1f4e3d23d20e08ca08398b1388de0f1Bio-inspired adhesive catechol-conjugated chitosan for biomedical applications: A mini reviewRyu, Ji Hyun; Hong, Seonki; Lee, HaeshinActa Biomaterialia (2015), 27 (), 101-115CODEN: ABCICB; ISSN:1742-7061. (Elsevier Ltd.)The development of adhesive materials, such as cyanoacrylate derivs., fibrin glues, and gelatin-based adhesives, has been an emerging topic in biomaterial science because of the many uses of these materials, including in wound healing patches, tissue sealants, and hemostatic materials. However, most bio-adhesives exhibit poor adhesion to tissue and related surfaces due to the presence of body fluid. For a decade, studies have aimed at addressing this issue by developing wet-resistant adhesives. Mussels demonstrate robust wet-resistant adhesion despite the ceaseless waves at seashores, and mussel adhesive proteins play a key role in this adhesion. Adhesive proteins located at the distal end (i.e., those that directly contact surfaces) are composed of nearly 60% of amino acids called 3,4-dihydroxy-L-phenylalanine (DOPA), lysine, and histidine, which contain side chains of catechol, primary amines, and secondary amines, resp. Inspired by the abundant catecholamine in mussel adhesive proteins, researchers have developed various types of polymeric mimics, such as polyethylenimine-catechol, chitosan-catechol, and other related catecholic polymers. Among them, chitosan-catechol is a promising adhesive polymer for biomedical applications. The conjugation of catechol onto chitosan dramatically increases its soly. from zero to nearly 60 mg/mL (i.e., 6% w/v) in pH 7 aq. solns. The enhanced soly. maximizes the ability of catecholamine to behave similar to mussel adhesive proteins. Chitosan-catechol is biocompatible and exhibits excellent hemostatic ability and tissue adhesion, and thus, chitosan-catechol will be widely used in a variety of medical settings in the future. This review focuses on the various aspects of chitosan-catechol, including its (1) prepn. methods, (2) physicochem. properties, and (3) current applications. - 28Li, Z.; Xu, Y.; Fan, L.; Kang, W.; Cheng, B. Fabrication of polyvinylidene fluoride tree-like nanofiber via one-step electrospinning. Mater. Des. 2016, 92, 95– 101, DOI: 10.1016/j.matdes.2015.12.037Google Scholar 谷歌学术28https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XksVSrsbs%253D&md5=dc259ad5b0a876ca1d2c03e93769e136Fabrication of polyvinylidene fluoride tree-like nanofiber via one-step electrospinningLi, Zongjie; Xu, Yongzheng; Fan, Lanlan; Kang, Weimin; Cheng, BowenMaterials & Design (2016), 92 (), 95-101CODEN: MADSD2; ISSN:0264-1275. (Elsevier Ltd.)A novel polyvinylidene fluoride (PVDF) tree-like nanofiber was controllably fabricated via one-step electrospinning by adding certain amt. of salt into PVDF soln. A possible mechanism for the formation of the tree-like nanofibers was proposed by analyzing high speed camera photos of the spin jet and the result showed that the formation of tree-like nanofibers was due to the splitting of jets. The effects of salt type, salt content and processing parameter on the content of tree-like branches were investigated. The electrospun nanofibers were characterized by field emission SEM(FE-SEM), energy disperse spectroscopy (EDS), X-ray diffraction (XRD), pore size meter and mech. properties measurement. It was found that the PVDF/TBAC tree-like nanofibers with improved crystallinity and mech. strength. The decreased av. pore size caused by the tree-like structure and the resistance to org. solvent, can make it as a potential candidate for membrane sepn.
28Li，Z.；徐，Y。范，L.；康，W.； Cheng，B.通过一步静电纺丝制造聚偏二氟乙烯树状纳米纤维。马特。德斯。 2016, 92, 95–101, DOI: 10.1016/j.matdes.2015.12.037 - 29Hu, C.; Zhang, F.; Long, L.; Kong, Q.; Luo, R.; Wang, Y. Dual-responsive injectable hydrogels encapsulating drug-loaded micelles for on-demand antimicrobial activity and accelerated wound healing. J. Controlled Release 2020, 324, 204– 217, DOI: 10.1016/j.jconrel.2020.05.010Google Scholar 谷歌学术29https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXpvVKjtLY%253D&md5=d284004a6bca463f0ff87006c3e396eeDual-responsive injectable hydrogels encapsulating drug-loaded micelles for on-demand antimicrobial activity and accelerated wound healingHu, Cheng; Zhang, Fanjun; Long, Linyu; Kong, Qunshou; Luo, Rifang; Wang, YunbingJournal of Controlled Release (2020), 324 (), 204-217CODEN: JCREEC; ISSN:0168-3659. (Elsevier B.V.)Disease microenvironment stimuli-responsive hydrogels are of special interests in enhancing the drug delivery specificity for biomedical applications. In order to achieve specific drug release characteristic at the inflammation region, a smart pH- and reactive oxygen species (ROS)-responsive injectable hydrogel with self-healing and remodeling capability was designed in our present work. Such hydrogel formulation not only preserved the structural integrity and excellent rheol. properties of the hydrogel but also allowed for a controllable drug release rate at inflammation sites. The antibacterial expt. results in vitro demonstrated that the hydrogel could effectively kill bacteria by amikacin release, with the inhibitive rate reached to 90% for S. aureus and 98% for P.aeruginosa. In addn., it efficiently reduced the levels of TNF-a (the pro-inflammatory cytokine) by 2.80 times, and increased IL-10 (anti-inflammatory cytokine) by 2.41 times than the hydrogel control without antibiotic and anti-inflammatory drug. Within the dual-responsiveness of pH and ROS, the hydrogel reduced the inflammation response of the surrounding tissues significantly and accelerated the healing process of the infected area. Collectively, this smart hydrogel formula contg. antibiotic and drug-loaded micelles is very promising to be applied topically against various microbial infections. We believe that this strategy can also be applied to various disease treatments.
29Hu，C.；张，F。朗，L.；孔，Q。罗，R。 Wang, Y. 封装载药胶束的双响应可注射水凝胶，可实现按需抗菌活性并加速伤口愈合。 J. 受控发布 2020, 324, 204–217, DOI: 10.1016/j.jconrel.2020.05.010 - 30Yu, G.; Dan, N.; Dan, W.; Chen, Y. Wearable Tissue Adhesive Ternary Hydrogel of N-(2-Hydroxyl) Propyl-3-trimethyl Ammonium Chitosan, Tannic Acid, and Polyacrylamide. Ind. Eng. Chem. Res. 2022, 61, 5502– 5513, DOI: 10.1021/acs.iecr.2c00055Google Scholar 谷歌学术30https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB38XpvVGhsbk%253D&md5=ac7d53ab3175d530715fbbc2a704e34bWearable Tissue Adhesive Ternary Hydrogel of N-(2-Hydroxyl) Propyl-3-trimethyl Ammonium Chitosan, Tannic Acid, and PolyacrylamideYu, Guofei; Dan, Nianhua; Dan, Weihua; Chen, YiningIndustrial & Engineering Chemistry Research (2022), 61 (16), 5502-5513CODEN: IECRED; ISSN:0888-5885. (American Chemical Society)Bionic electronic skin has aroused widespread attention in intelligent robots, health detection, and other aspects. To improve the inherent fragility and adhesion of the hydrogel, a multifunctional electronic skin mediated by tannic acid and chitosan quaternary ammonium salt was manufd. In this work, by simply mixing chitosan quaternary ammonium salt, tannic acid, and acrylamide without further treatment, a flexible, conductive, and antibacterial adhesive hydrogel was directly prepd. The chitosan quaternary ammonium salt plays a leading role in the electromech. properties and antibacterial properties of the hydrogel. Tannic acid gives the hydrogel good and reproducible adhesion and oxidn. resistance. More importantly, the obtained hydrogel has good sensing properties and can detect mech. conduction signals of human body motion. This work provides a feasible method to prep. hydrogel sensors with high antibacterial efficiency, excellent mech. properties, and good adhesion for broad-range application in human motion detection and intelligence skins.
30Yu，G.；丹，N.；丹，W.； Chen，Y.N-(2-羟基)丙基-3-三甲基铵壳聚糖、单宁酸和聚丙烯酰胺的可穿戴组织粘合剂三元水凝胶。工业。工程师。化学。资源。 2022, 61, 5502–5513, DOI: 10.1021/acs.iecr.2c00055 - 31Habibur, R. M.; Yaqoob, U.; Muhammad, S.; Uddin, A. S. M. I.; Kim, H. C. The effect of RGO on dielectric and energy harvesting properties of P(VDF-TrFE) matrix by optimizing electroactive β phase without traditional polling process. Mater. Chem. Phys. 2018, 215, 46– 55, DOI: 10.1016/j.matchemphys.2018.05.010Google Scholar 谷歌学术31https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXps1Oiu7k%253D&md5=aca44bf9bf94c39e43007527a49af6fcThe effect of RGO on dielectric and energy harvesting properties of P(VDF-TrFE) matrix by optimizing electroactive β phase without traditional polling processHabibur, Rahaman Md.; Yaqoob, Usman; Muhammad, Sheeraz; Uddin, A. S. M. Iftekhar; Kim, Hyeon CheolMaterials Chemistry and Physics (2018), 215 (), 46-55CODEN: MCHPDR; ISSN:0254-0584. (Elsevier B.V.)This study explores the role of RGO in improving the energy harvesting potentiality of P(VDF-TrFE) matrix without applying the conventional polling process. Five different piezoelec. sheets were prepd. by varying the RGO contents in P(VDF-TrFE) matrix to realize its optimum concn. in the matrix. The effect of RGO on the electroactive polar beta (β) phase of P(VDF-TrFE) was investigated through the X-ray diffraction (XRD) pattern and the Fourier transform IR spectroscopy (FT-IR). To elaborate the RGO role, dielec. properties of the as-prepd. piezoelec. sheets were also checked over the frequency range of kHz-100 kHz at room temp. Finally, these piezoelec. sheets were used to fabricate the piezoelec. nanogenerators (PENGs) devices. Among the fabricated PENGs, the PENG with 0.1% RGO contents reveals the max. open circuit voltage of 2.4 V and highest peak of short-circuit current around 0.8 μA at an applied force of 2 N. Moreover, it exhibits the highest output power of 3.2 μW at 1.8 MΩ load resistance, all the outputs were recorded without applying polling process. It was estd. that our fabricated self-poled, flexible piezoelec. nanogenerator can be a useful candidate to powering futuristic nanodevices.
31哈比布尔，R.M.；雅各布，美国；穆罕默德，S.；乌丁，A.S.M.I.； Kim, H. C.通过优化电活性 β 相（无需传统的轮询过程）来研究 RGO 对 P(VDF-TrFE) 基质的介电和能量收集特性的影响。马特。化学。物理。 2018, 215, 46–55, DOI: 10.1016/j.matchemphys.2018.05.010 - 32Sharma, P.; Reece, T.; Wu, D.; Fridkin, V. M.; Ducharme, S.; Gruverman, A. Nanoscale domain patterns in ultrathin polymer ferroelectric films. J. Phys. Condens. Matter 2009, 21, 485902 DOI: 10.1088/0953-8984/21/48/485902Google Scholar 谷歌学术32https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXnvV2itQ%253D%253D&md5=b463fa0aec4014469b615445926a10ffNanoscale domain patterns in ultrathin polymer ferroelectric filmsSharma, P.; Reece, T.; Wu, D.; Fridkin, V. M.; Ducharme, S.; Gruverman, A.Journal of Physics: Condensed Matter (2009), 21 (48), 485902/1-485902/6CODEN: JCOMEL; ISSN:0953-8984. (Institute of Physics Publishing)High-resoln. studies of domain configurations in Langmuir-Blodgett films of ferroelec. polymer poly(vinylidene fluoride-trifluoroethylene), P(VDF-TrFE), have been carried out by means of piezoresponse force microscopy (PFM). Changes in film thickness and morphol. cause significant variations in polarization patterns. In continuous films and nanomesas with relatively low thickness/grain aspect ratio (<1/10), the relationship between the av. domain size and thickness follows the Kittel law. Nanomesas with high aspect ratio (>1/5) exhibit significant deviations from this law, suggesting addnl. surface-energy-related mechanisms affecting the domain patterns. Polarization reversal within a single crystallite has been demonstrated and local switching parameters (coercive voltage and remnant piezoresponse) have been measured by monitoring the local hysteresis loops. Reliable control of polarization at the sub-grain level demonstrates a possibility of studying the mechanism of the intrinsic switching behavior down to the mol. scale.
32夏尔马，P.；里斯，T.；吴，D。弗里德金，V.M.；杜查尔姆，S.； Gruverman，A.超薄聚合物铁电薄膜中的纳米级域图案。 J. Phys。凝结。事项 2009, 21, 485902 DOI: 10.1088/0953-8984/21/48/485902 - 33Baji, A.; Mai, Y. W.; Li, Q.; Liu, Y. Electrospinning induced ferroelectricity in poly(vinylidene fluoride) fibers. Nanoscale 2011, 3, 3068– 3071, DOI: 10.1039/c1nr10467eGoogle Scholar 谷歌学术33https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXhtValtLzI&md5=c62b96967953b1df00e7ddbee84759a0Electrospinning induced ferroelectricity in poly(vinylidene fluoride) fibersBaji, Avinash; Mai, Yiu-Wing; Li, Qian; Liu, YunNanoscale (2011), 3 (8), 3068-3071CODEN: NANOHL; ISSN:2040-3372. (Royal Society of Chemistry)Poly(vinylidene fluoride) (PVDF) fibers with diams. ranging from 70-400 nm are produced by electrospinning and the effect of fiber size on the ferroelec. β-cryst. phase is detd. Domain switching and assocd. ferro-/piezoelec. properties of the electrospun PVDF fibers were also detd. The fibers showed well-defined ferroelec. and piezoelec. properties.
33 巴吉，A.；麦，Y.W.；李，Q。聚偏二氟乙烯纤维中的静电纺丝诱导铁电性。纳米尺度 2011, 3, 3068–3071, DOI: 10.1039/c1nr10467e - 34Ji, S.; Yun, J. Fabrication and Characterization of Aligned Flexible Lead-Free Piezoelectric Nanofibers for Wearable Device Applications. Nanomater 2018, 8, 206, DOI: 10.3390/nano8040206Google Scholar 谷歌学术34https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXpsFSqs78%253D&md5=d217029710b3455ead854e64256bacefFabrication and characterization of aligned flexible lead-free piezoelectric nanofibers for wearable device applicationsJi, Sang Hyun; Yun, Ji SunNanomaterials (2018), 8 (4), 206/1-206/9CODEN: NANOKO; ISSN:2079-4991. (MDPI AG)Flexible lead-free piezoelec. nanofibers, based on BNT-ST (0.78Bi0.5Na0.5TiO3-0.22SrTiO3) ceramic and poly(vinylidene fluoride-trifluoroethylene) (PVDF-TrFE) copolymers, were fabricated by an electrospinning method and the effects of the degree of alignment in the nanofibers on the piezoelec. characteristics were investigated. The microstructure of the lead-free piezoelec. nanofibers was obsd. by field emission scanning electron microscope (FE-SEM) and the orientation was analyzed by fast Fourier transform (FFT) images. X-ray diffraction (XRD) anal. confirmed that the phase was not changed by the electrospinning process and maintained a perovskite phase. Polarization-elec. field (P-E) loops and piezoresponse force microscopy (PFM) were used to investigate the piezoelec. properties of the piezoelec. nanofibers, according to the degree of alignment-the well aligned piezoelec. nanofibers had higher piezoelec. properties. Furthermore, the output voltage of the aligned lead-free piezoelec. nanofibers was measured according to the vibration frequency and the bending motion and the aligned piezoelec. nanofibers with a collector rotation speed of 1500 rpm performed the best.
34Ji，S.； Yun, J. 用于可穿戴设备应用的对齐柔性无铅压电纳米纤维的制造和表征。纳米材料 2018, 8, 206, DOI: 10.3390/nano8040206 - 35Zhang, B.; He, J.; Shi, M.; Liang, Y.; Guo, B. Injectable self-healing supramolecular hydrogels with conductivity and photo-thermal antibacterial activity to enhance complete skin regeneration. Chem. Eng. J. 2020, 400, 125994 DOI: 10.1016/j.cej.2020.125994Google Scholar 谷歌学术35https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhtlCqtLrM&md5=91f2c8963cbc21ebb022fbd9e2745339Injectable self-healing supramolecular hydrogels with conductivity and photo-thermal antibacterial activity to enhance complete skin regenerationZhang, Beilin; He, Jiahui; Shi, Mengting; Liang, Yuqing; Guo, BaolinChemical Engineering Journal (Amsterdam, Netherlands) (2020), 400 (), 125994CODEN: CMEJAJ; ISSN:1385-8947. (Elsevier B.V.)Hydrogel dressings with good biocompatibility and the ability to maintain a moist environment at the wound site have great potential for clin. application. Multifunctional injectable self-healing supramol. hydrogel with cond. and photo-thermal property as wound dressing to promote wound healing has been not reported. Herein, a series of antibacterial, injectable self-healing and conductive supramol. hydrogels were fabricated through host-guest interaction based on quaternized chitosan-graft-cyclodextrin (QCS-CD), quaternized chitosan-graft-adamantane (QCS-AD) and graphene oxide-graft-cyclodextrin (GO-CD) polymer solns. which combined the good antibacterial activity of QCS and photo-thermal property of reduced graphene oxide (rGO). These supramol. hydrogels wound dressings have a cond. value similar to that of the skin and a rapid self-healing behavior, and have great antibacterial property against E. coli (gram-neg.), S. aureus (gram-pos.), and multi-drug resistant bacteria (such as Methicillin-resistant Staphylococcus aureus, MRSA). Furthermore, QCS-CD-AD/GO4 (0.4 wt% of rGO in the sample) shows a good balance between antibacterial activity, cell proliferation and hemocompatibility. Compared with com. dressings (Tegaderm film) and QCS-CD-AD/GO0, the hydrogel QCS-CD-AD/GO4 significantly accelerated the in vivo healing process of full-thickness wounds with promoted epidermis and granulation tissue thickness, increased area coverage of collagen, and up-regulated VEGF expression. In short, these antibacterial, conductive self-healing supramol. hydrogels are promising biomaterials as wound dressings for full-thickness skin repair.
35张，B.；他，J。石，M。梁，Y。郭，B.具有导电性和光热抗菌活性的可注射自愈超分子水凝胶可增强皮肤的完全再生。化学。工程师。 J. 2020, 400, 125994 DOI: 10.1016/j.cej.2020.125994 - 36(a) Correia, C.; Sousa, R. O.; Vale, A. C.; Peixoto, D.; Silva, T. H.; Reis, R. L.; Pashkuleva, I.; Alves, N. M. Adhesive and biodegradable membranes made of sustainable catechol-functionalized marine collagen and chitosan. Colloids Surf., B 2022, 213, 112409 DOI: 10.1016/j.colsurfb.2022.112409Google Scholar 谷歌学术36ahttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB38XjvFWqu7s%253D&md5=1f66bbb3cbea51fe91bcf044ca2517c3Adhesive and biodegradable membranes made of sustainable catechol-functionalized marine collagen and chitosanCorreia, Catia; Sousa, Rita O.; Vale, A. Catarina; Peixoto, Daniela; Silva, Tiago H.; Reis, Rui L.; Pashkuleva, Iva; Alves, Natalia M.Colloids and Surfaces, B: Biointerfaces (2022), 213 (), 112409CODEN: CSBBEQ; ISSN:0927-7765. (Elsevier B.V.)We describe bioadhesive membranes developed from marine renewable biomaterials, namely chitosan and collagen extd. from fish skins. Collagen was functionalized with catechol groups (Coll-Cat) to provide the membranes with superior adhesive properties in a wet environment and blended with chitosan to improve the mech. properties. The blended membranes were compared to chitosan and chitosan blended with unmodified collagen in terms of surface morphol., wettability, wt. loss, water uptake, mech. and adhesive properties. The metabolic activity, the viability and the morphol. of L929 fibroblastic cells seeded on these membranes were also assessed. Our results show that the functionalization with catechol groups improves the adhesive and mech. properties of the membranes and enhances cell attachment and proliferation. These data suggest that the developed marine origin-raw membranes present a potential towards the restoration of the structural and functional properties of damaged soft tissues.
36(a) 科雷亚，C.；苏萨，R.O.；淡水河谷，A.C.；佩肖托，D.；席尔瓦，T.H.；雷斯，R.L.；帕什库列娃，I.； Alves，N. M.由可持续儿茶酚功能化海洋胶原蛋白和壳聚糖制成的粘合和可生物降解膜。高莱冲浪，B 2022, 213, 112409 DOI: 10.1016/j.colsurfb.2022.112409(b) Chi, J.; Li, A.; Zou, M.; Wang, S.; Liu, C.; Hu, R.; Jiang, Z.; Liu, W.; Sun, R.; Han, B. Novel dopamine-modified oxidized sodium alginate hydrogels promote angiogenesis and accelerate healing of chronic diabetic wounds. Int. J. Biol. Macromol. 2022, 203, 492– 504, DOI: 10.1016/j.ijbiomac.2022.01.153
(b) Chi, J.；李，A。邹，M。王S.；刘，C.；胡，R。蒋Z.；刘，W.；孙，R。 Han，B.新型多巴胺修饰的氧化海藻酸钠水凝胶促进血管生成并加速慢性糖尿病伤口的愈合。国际。 J.Biol。大分子。 2022, 203, 492–504, DOI: 10.1016/j.ijbiomac.2022.01.153Google Scholar 谷歌学术36bhttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB38Xislyrsr0%253D&md5=bf634b781c6b64d4a113bd0b2c1dff2bNovel dopamine-modified oxidized sodium alginate hydrogels promote angiogenesis and accelerate healing of chronic diabetic woundsChi, Jinhua; Li, Ai; Zou, Mingyu; Wang, Shuo; Liu, Chenqi; Hu, Rui; Jiang, Zhiwen; Liu, Wanshun; Sun, Rongju; Han, BaoqinInternational Journal of Biological Macromolecules (2022), 203 (), 492-504CODEN: IJBMDR; ISSN:0141-8130. (Elsevier B.V.)Herein, the dopamine (DA) was grafted with oxidized sodium alginate (OSA) via Schiff base redn. reaction, aiming to fabricate novel DA-grafted OSA (OSA-DA) hydrogels with enhanced biocompatibility and suitable adhesion for clin. applications. The chem. structures of OSA-DA were characterized via UV-Vis, FTIR and 1H NMR spectroscopy anal. The hydrogel characteristics, biocompatibility, as well as the chronic diabetic wound healing efficacy were investigated. Our results demonstrated that DA was grafted with OSA successfully with highest grafting rate of 7.50%. Besides, OSA-DA hydrogels possessed suitable swelling ratio and appropriate adhesion characteristics. Addnl., OSA-DA exhibited satisfactory cytocompatibility and cell affinity in L-929 cells, and superior biocompatibility in SD rats. Moreover, OSA-DA exerted remarkable promoting effects on migration and tube formation of human umbilical vein endothelial cells (HUVECs). Studies on full-thickness excision chronic diabetic wounds further revealed that OSA-DA hydrogels could accelerate healing via promoting angiogenesis, reducing inflammation response, and stimulating collagen deposition. Overall, our studies would provide basis for SA-based hydrogels as clin. wound dressings. - 37(a) Lee, J. Y.; Bashur, C. A.; Goldstein, A. S.; Schmidt, C. E. Polypyrrole-coated electrospun PLGA nanofibers for neural tissue applications. Biomaterials 2009, 30, 4325– 4335, DOI: 10.1016/j.biomaterials.2009.04.042Google Scholar 谷歌学术37ahttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXos1OrtLg%253D&md5=28226b514cd5a834e842c9c0ba8c2f66Polypyrrole-coated electrospun PLGA nanofibers for neural tissue applicationsLee, Jae Y.; Bashur, Chris A.; Goldstein, Aaron S.; Schmidt, Christine E.Biomaterials (2009), 30 (26), 4325-4335CODEN: BIMADU; ISSN:0142-9612. (Elsevier Ltd.)Electrospinning is a promising approach to create nanofiber structures that are capable of supporting adhesion and guiding extension of neurons for nerve regeneration. Concurrently, elec. stimulation of neurons in the absence of topog. features also has been shown to guide axonal extension. Therefore, the goal of this study was to form elec. conductive nanofiber structures and to examine the combined effect of nanofiber structures and elec. stimulation. Conductive meshes were produced by growing polypyrrole (PPy) on random and aligned electrospun poly(lactic-co-glycolic acid) (PLGA) nanofibers, as confirmed by scanning electron micrographs and X-ray photon spectroscopy. PPy-PLGA electrospun meshes supported the growth and differentiation of rat pheochromocytoma 12 (PC12) cells and hippocampal neurons comparable to non-coated PLGA control meshes, suggesting that PPy-PLGA may be suitable as conductive nanofibers for neuronal tissue scaffolds. Elec. stimulation studies showed that PC12 cells, stimulated with a potential of 10 mV/cm on PPy-PLGA scaffolds, exhibited 40-50% longer neurites and 40-90% more neurite formation compared to unstimulated cells on the same scaffolds. In addn., stimulation of the cells on aligned PPy-PLGA fibers resulted in longer neurites and more neurite-bearing cells than stimulation on random PPy-PLGA fibers, suggesting a combined effect of elec. stimulation and topog. guidance and the potential use of these scaffolds for neural tissue applications.
37(a) 李 J. Y.；巴舒尔，C.A.；戈德斯坦，A.S.； Schmidt, C. E. 用于神经组织应用的聚吡咯涂层电纺 PLGA 纳米纤维。生物材料 2009, 30, 4325–4335, DOI: 10.1016/j.biomaterials.2009.04.042(b) Ghasemi-Mobarakeh, L.; Prabhakaran, M. P.; Morshed, M.; Nasr-Esfahani, M. H.; Ramakrishna, S. Electrical Stimulation of Nerve Cells Using Conductive Nanofibrous Scaffolds for Nerve Tissue Engineering. Tissue Eng., Part A 2009, 15, 3605– 3619, DOI: 10.1089/ten.tea.2008.0689
(b) Ghasemi-Mobarakeh，L.；普拉巴卡兰，M.P.；莫希德，M.；纳斯尔-伊斯法哈尼，M. H.； Ramakrishna，S.使用导电纳米纤维支架进行神经组织工程的神经细胞电刺激。组织工程，A 部分 2009, 15, 3605–3619, DOI: 10.1089/ten.tea.2008.0689Google Scholar 谷歌学术37bhttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXhsF2hsr%252FE&md5=fb25ba696faa9d2fbcda0a3f55029a6fElectrical stimulation of nerve cells using conductive nanofibrous scaffolds for nerve tissue engineeringGhasemi-Mobarakeh, Laleh; Prabhakaran, Molamma P.; Morshed, Mohammad; Nasr-Esfahani, Mohammad Hossein; Ramakrishna, SeeramTissue Engineering, Part A (2009), 15 (11), 3605-3619CODEN: TEPAB9; ISSN:1937-3341. (Mary Ann Liebert, Inc.)Fabrication of scaffolds with suitable chem., mech., and elec. properties is crit. for the success of nerve tissue engineering. Elec. stimulation was directly applied to electrospun conductive nanofibrous scaffolds to enhance the nerve regeneration process. In the present study, electrospun conductive nanofibers were prepd. by mixing 10 and 15 wt% doped polyaniline (PANI) with poly (ε-caprolactone)/gelatin (PG) (70:30) soln. (PANI/PG) by electrospinning. The fiber diam., pore size, hydrophilicity, tensile properties, cond., Fourier transform IR (FTIR), and XPS spectra of nanofibers were detd., and the in vitro biodegradability of the different nanofibrous scaffolds was also evaluated. Nanofibrous scaffolds contg. 15% PANI was found to exhibit the most balanced properties to meet all the required specifications for elec. stimulation for its enhanced cond. and is used for in vitro culture and elec. stimulation of nerve stem cells. 3-(4,5-Dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay and SEM results showed that conductive nanofibrous scaffolds are suitable substrates for the attachment and proliferation of nerve stem cells. Elec. stimulation through conductive nanofibrous PANI/PG scaffolds showed enhanced cell proliferation and neurite outgrowth compared to the PANI/PG scaffolds that were not subjected to elec. stimulation. - 38Zhao, M.; Song, B.; Pu, J.; Wada, T.; Reid, B.; Tai, G.; Wang, F.; Guo, A.; Walczysko, P.; Gu, Y. Electrical signals control wound healing through phosphatidylinositol-3-OH kinase-gamma and PTEN. Nature 2006, 442, 457– 460, DOI: 10.1038/nature04925Google Scholar 谷歌学术38https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD28XnsVajurs%253D&md5=b606066a5d16ed8efecabc75f18c8ef9Electrical signals control wound healing through phosphatidylinositol-3-OH kinase-γ and PTENZhao, Min; Song, Bing; Pu, Jin; Wada, Teiji; Reid, Brian; Tai, Guangping; Wang, Fei; Guo, Aihua; Walczysko, Petr; Gu, Yu; Sasaki, Takehiko; Suzuki, Akira; Forrester, John V.; Bourne, Henry R.; Devreotes, Peter N.; McCaig, Colin D.; Penninger, Josef M.Nature (London, United Kingdom) (2006), 442 (7101), 457-460CODEN: NATUAS; ISSN:0028-0836. (Nature Publishing Group)Wound healing is essential for maintaining the integrity of multi-cellular organisms. In every species studied, disruption of an epithelial layer instantaneously generates endogenous elec. fields, which have been proposed to be important in wound healing. The identity of signaling pathways that guide both cell migration to elec. cues and elec.-field-induced wound healing have not been elucidated at a genetic level. Here we show that elec. fields, of a strength equal to those detected endogenously, direct cell migration during wound healing as a prime directional cue. Manipulation of endogenous wound elec. fields affects wound healing in vivo. Elec. stimulation triggers activation of Src and inositol-phospholipid signaling, which polarizes in the direction of cell migration. Notably, genetic disruption of phosphatidylinositol-3-OH kinase-γ (PI(3)Kγ) decreases elec.-field-induced signaling and abolishes directed movements of healing epithelium in response to elec. signals. Deletion of the tumor suppressor phosphatase and tensin homolog (PTEN) enhances signaling and electrotactic responses. These data identify genes essential for elec.-signal-induced wound healing and show that PI(3)Kγ and PTEN control electrotaxis.
38赵，M.；宋，B.；濮，J.；和田，T.；里德，B.；泰，G.；王，F。郭，A。瓦尔奇斯科，P.； Gu，Y.电信号通过磷脂酰肌醇-3-OH激酶-γ和PTEN控制伤口愈合。自然 2006, 442, 457–460, DOI: 10.1038/nature04925 - 39(a) Damaraju, S. M.; Shen, Y.; Elele, E.; Khusid, B.; Eshghinejad, A.; Li, J.; Jaffe, M.; Arinzeh, T. L. Three-dimensional piezoelectric fibrous scaffolds selectively promote mesenchymal stem cell differentiation. Biomaterials 2017, 149, 51– 62, DOI: 10.1016/j.biomaterials.2017.09.024Google Scholar 谷歌学术39ahttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXhs1WqtrrI&md5=863330da32a573fe18f542f112e38189Three-dimensional piezoelectric fibrous scaffolds selectively promote mesenchymal stem cell differentiationDamaraju, Sita M.; Shen, Yueyang; Elele, Ezinwa; Khusid, Boris; Eshghinejad, Ahmad; Li, Jiangyu; Jaffe, Michael; Arinzeh, Treena LivingstonBiomaterials (2017), 149 (), 51-62CODEN: BIMADU; ISSN:0142-9612. (Elsevier Ltd.)The discovery of elec. fields in biol. tissues has led to efforts in developing technologies utilizing elec. stimulation for therapeutic applications. Native tissues, such as cartilage and bone, exhibit piezoelec. behavior, wherein elec. activity can be generated due to mech. deformation. Yet, the use of piezoelec. materials have largely been unexplored as a potential strategy in tissue engineering, wherein a piezoelec. biomaterial acts as a scaffold to promote cell behavior and the formation of large tissues. Here we show, for the first time, that piezoelec. materials can be fabricated into flexible, three-dimensional fibrous scaffolds and can be used to stimulate human mesenchymal stem cell differentiation and corresponding extracellular matrix/tissue formation in physiol. loading conditions. Piezoelec. scaffolds that exhibit low voltage output, or streaming potential, promoted chondrogenic differentiation and piezoelec. scaffolds with a high voltage output promoted osteogenic differentiation. Electromech. stimulus promoted greater differentiation than mech. loading alone. Results demonstrate the additive effect of electromech. stimulus on stem cell differentiation, which is an important design consideration for tissue engineering scaffolds. Piezoelec., smart materials are attractive as scaffolds for regenerative medicine strategies due to their inherent elec. properties without the need for external power sources for elec. stimulation.
39(a) 达马拉朱，S.M.；沉，Y。埃莱勒，E.；库西德，B.；埃什吉内贾德，A.；李，J。贾菲，M.； Arinzeh，T. L.三维压电纤维支架选择性促进间充质干细胞分化。生物材料 2017, 149, 51–62, DOI: 10.1016/j.biomaterials.2017.09.024(b) Jeong, S. I.; Jun, I. D.; Choi, M. J.; Nho, Y. C.; Lee, Y. M.; Shin, H. Development of electroactive and elastic nanofibers that contain polyaniline and poly(L-lactide-co-epsilon-caprolactone) for the control of cell adhesion. Macromol. Biosci. 2008, 8, 627– 637, DOI: 10.1002/mabi.200800005
(b) Jeong, S.I.； Jun，I.D.；崔，M.J.； Nho，Y.C.；李，Y.M.； Shin, H.开发含有聚苯胺和聚(L-丙交酯-共-ε-己内酯)的电活性和弹性纳米纤维，用于控制细胞粘附。大分子。生物科学。 2008, 8, 627–637, DOI: 10.1002/mabi.200800005Google Scholar 谷歌学术39bhttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1cXovFWgs7g%253D&md5=c74c199a7502323f4340a54acb6368e2Development of electroactive and elastic nanofibers that contain polyaniline and poly(L-lactide-co-ε-caprolactone) for the control of cell adhesionJeong, Sung In; Jun, In Dong; Choi, Moon Jae; Nho, Young Chang; Lee, Young Moo; Shin, HeungsooMacromolecular Bioscience (2008), 8 (7), 627-637CODEN: MBAIBU; ISSN:1616-5187. (Wiley-VCH Verlag GmbH & Co. KGaA)Elec. conductive polyaniline (PAni) doped with camphorsulfonic acid (CPSA) is blended with poly(L-lactide-co-ε-caprolactone) (PLCL), and then electrospun to prep. uniform nanofibers. The CPSA-PAni/PLCL nanofibers show a smooth fiber structure without coarse lumps or beads and consistent fiber diams. (which range from 100 to 700 nm) even with an increase in the amt. of CPSA-PAni (from 0 to 30 wt.-%). However, the elongation at break decreases from 391.54% to 207.85% when 30% of CPSA-PAni is incorporated. Anal. of the surface of the nanofibers demonstrates the presence of homogeneously blended CPSA-PAni. Most importantly, a four-point probe anal. reveals that elec. properties are maintained in the nanofibers where the cond. is significantly increased from 0.0015 to 0.0138 S/cm when the nanofibers are prepd. with 30% CPSA-PAni. The cell adhesion tests using human dermal fibroblasts, NIH-3T3 fibroblasts, and C2C12 myoblasts demonstrate significantly higher adhesion on the CPSA-PAni/PLCL nanofibers than pure PLCL nanofibers. In addn., the growth of NIH-3T3 fibroblasts is enhanced under the stimulation of various d.c. flows. The CPSA-PAni/PLCL nanofibers with elec. conductive properties may potentially be used as a platform substrate to study the effect of elec. signals on cell activities and to direct desirable cell function for tissue engineering applications. - 40Tandon, N.; Cimetta, E.; Villasante, A.; Kupferstein, N.; Southall, M. D.; Fassih, A.; Xie, J.; Sun, Y.; Vunjak-Novakovic, G. Galvanic microparticles increase migration of human dermal fibroblasts in a wound-healing model via reactive oxygen species pathway. Exp. Cell Res. 2014, 320, 79– 91, DOI: 10.1016/j.yexcr.2013.09.016Google Scholar 谷歌学术40https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhs1Clt7vO&md5=458bc6fe0d6a99f0ab71e46ca31e0823Galvanic microparticles increase migration of human dermal fibroblasts in a wound-healing model via reactive oxygen species pathwayTandon, Nina; Cimetta, Elisa; Villasante, Aranzazu; Kupferstein, Nicolette; Southall, Michael D.; Fassih, Ali; Xie, Junxia; Sun, Ying; Vunjak-Novakovic, GordanaExperimental Cell Research (2014), 320 (1), 79-91CODEN: ECREAL; ISSN:0014-4827. (Elsevier B.V.)Elec. signals have been implied in many biol. mechanisms, including wound healing, which has been assocd. with transient elec. currents not present in intact skin. One method to generate elec. signals similar to those naturally occurring in wounds is by supplementation of galvanic particles dispersed in a cream or gel. We constructed a three-layered model of skin consisting of human dermal fibroblasts in hydrogel (mimic of dermis), a hydrogel barrier layer (mimic of epidermis) and galvanic microparticles in hydrogel (mimic of a cream contg. galvanic particles applied to skin). Using this model, we investigated the effects of the properties and amts. of Cu/Zn galvanic particles on adult human dermal fibroblasts in terms of the speed of wound closing and gene expression. The collected data suggest that the effects on wound closing are due to the ROS-mediated enhancement of fibroblast migration, which is in turn mediated by the BMP/SMAD signaling pathway. These results imply that topical low-grade elec. currents via microparticles could enhance wound healing.
40 坦登，北卡罗来纳州；西米塔，E.；维拉桑特，A.；库普弗斯坦，N.；索撒尔，医学博士；法西赫，A.；谢，J。孙，Y。 Vunjak-Novakovic，G.G.Galvanic 微粒通过活性氧途径增加伤口愈合模型中人类真皮成纤维细胞的迁移。过期。细胞研究。 2014, 320, 79–91, DOI: 10.1016/j.yexcr.2013.09.016 - 41Bai, H.; Forrester, J. V.; Zhao, M. DC electric stimulation upregulates angiogenic factors in endothelial cells through activation of VEGF receptors. Cytokine+ 2011, 55, 110– 115, DOI: 10.1016/j.cyto.2011.03.003Google Scholar 谷歌学术41https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXmvFWmu7Y%253D&md5=0e33000e6838dec1fe199d1b58f94a3bDC electric stimulation upregulates angiogenic factors in endothelial cells through activation of VEGF receptorsBai, Huai; Forrester, John V.; Zhao, MinCytokine+ (2011), 55 (1), 110-115CODEN: CYTIE9; ISSN:1043-4666. (Elsevier Ltd.)Small d.c. (DC) elec. fields direct some important angiogenic responses of vascular endothelial cells. Those responses indicate promising use of elec. fields to modulate angiogenesis. We sought to det. the regulation of elec. fields on transcription and expression of a serial of import angiogenic factors by endothelial cells themselves. Using semi-quant. PCR and ELISA we found that elec. stimulation upregulates the levels of mRNAs and proteins of a no. of angiogenic proteins, most importantly VEGF165, VEGF121 and IL-8 in human endothelial cells. The up-regulation of mRNA levels might be specific, as the mRNA encoding bFGF, TGF-beta and eNOS are not affected by d.c. elec. stimulation at 24 h time-point. Inhibition of VEGF receptor (VEGFR1 or VEGFR2) signaling significantly decreased VEGF prodn. and completely abolished IL-8 prodn. D.c. elec. stimulation selectively regulates prodn. of some growth factors and cytokines important for angiogenesis through a feed-back loop mediated by VEGF receptors.
41白，H.；福雷斯特，J.V.；赵，M.DC电刺激通过激活VEGF受体上调内皮细胞中的血管生成因子。细胞因子+ 2011, 55, 110–115, DOI: 10.1016/j.cyto.2011.03.003 - 42Kaur, S.; Lyte, P.; Garay, M.; Liebel, F.; Sun, Y.; Liu, J.-C.; Southall, M. D. Galvanic zinc–copper microparticles produce electrical stimulation that reduces the inflammatory and immune responses in skin. Arch. Dermatol. Res. 2011, 303, 551– 562, DOI: 10.1007/s00403-011-1145-9Google Scholar 谷歌学术42https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXht1Siur%252FK&md5=c84d8ab24b66c54979dba862d1708eaaGalvanic zinc-copper microparticles produce electrical stimulation that reduces the inflammatory and immune responses in skinKaur, Simarna; Lyte, Peter; Garay, Michelle; Liebel, Frank; Sun, Ying; Liu, Jue-Chen; Southall, Michael D.Archives of Dermatological Research (2011), 303 (8), 551-562CODEN: ADREDL; ISSN:0340-3696. (Springer)The human body has its own innate elec. system that regulates the body's functions via communications among organs through the well-known neural system. While the effect of low-level elec. stimulation on wound repair has been reported, few studies have examd. the effect of elec. potential on non-wounded, intact skin. A galvanic couple comprised of elemental zinc and copper was used to det. the effects of low-level elec. stimulation on intact skin physiol. using a Dermacorder device. Zn-Cu induced the elec. potential recorded on intact skin, enhanced H2O2 prodn. and activated p38 MAPK and Hsp27 in primary keratinocytes. Treatment with Zn-Cu was also found to reduce pro-inflammatory cytokines, such as IL-1α, IL-2, NO and TNF-α in multiple cell types after stimulation with PHA or Propionibacterium acnes bacteria. The Zn-Cu complex led to a dose-dependent inhibition of TNF-α-induced NF-κB levels in keratinocytes as measured by a dual-luciferase promoter assay, and prevented p65 translocation to the nucleus obsd. via immunofluorescence. Suppression of NF-κB activity via crosstalk with p38 MAPK might be one of the potential pathways by which Zn-Cu exerted its inflammatory effects. Topical application of Zn-Cu successfully mitigated TPA-induced dermatitis and oxazolone-induced hypersensitivity in mice models of ear edema. Anti-inflammatory activity induced by the Zn-Cu galvanic couple appears to be mediated, at least in part, by prodn. of low level of hydrogen peroxide since this activity is reversed by the addn. of Catalase enzyme. Collectively, these results show that a galvanic couple contg. Zn-Cu strongly reduces the inflammatory and immune responses in intact skin, providing evidence for the role of elec. stimulation in non-wounded skin.
42考尔，S.；莱特，P.；加雷，M.；利贝尔，F.；孙，Y。刘，J.-C.； Southall，M.D.Galvanic 锌铜微粒产生电刺激，减少皮肤的炎症和免疫反应。拱。德玛托。资源。 2011, 303, 551–562, DOI: 10.1007/s00403-011-1145-9 - 43Mycielska, M. E.; Djamgoz, M. B. Cellular mechanisms of direct-current electric field effects: galvanotaxis and metastatic disease. J. Cell Sci. 2004, 117, 1631– 1639, DOI: 10.1242/jcs.01125Google Scholar 谷歌学术43https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2cXjvFCitLs%253D&md5=619afb5bc29369723b3641037d9af85eCellular mechanisms of direct-current electric field effects: Galvanotaxis and metastatic diseaseMycielska, Maria E.; Djamgoz, Mustafa B. A.Journal of Cell Science (2004), 117 (9), 1631-1639CODEN: JNCSAI; ISSN:0021-9533. (Company of Biologists Ltd.)A review. Endogenous direct-current elec. fields (dcEFs) occur in vivo in the form of epithelial transcellular potentials or neuronal field potentials, and a variety of cells respond to dcEFs in vitro by directional movement. This is termed galvanotaxis. The passive influx of Ca2+ on the anodal side should increase the local intracellular Ca2+ concn., whereas passive efflux and/or intracellular redistribution decrease the local intracellular Ca2+ concn. on the cathodal side. These changes could give rise to "push-pull" effects, causing net movement of cells towards the cathode. However, such effects would be complicated in cells that possess voltage-gated Ca2+ channels and/or intracellular Ca2+ stores. Moreover, voltage-gated Na+ channels, protein kinases, growth factors, surface charge and electrophoresis of proteins have been found to be involved in galvanotaxis. Galvanotactic mechanisms might operate in both the short term (seconds to minutes) and the long term (minutes to hours), and recent work has shown that they might be involved in metastatic disease. The galvanotactic responses of strongly metastatic prostate and breast cancer cells are much more prominent, and the cells move in the opposite direction compared with corresponding weakly metastatic cells. This could have important implications for the metastatic process and has clin. implications. Galvanotaxis could thus play a significant role in both cellular physiol. and pathophysiol.
43Mycielska，M.E.； Djamgoz，M. B.直流电场效应的细胞机制：趋电性和转移性疾病。 J.细胞科学。 2004, 117, 1631–1639, DOI: 10.1242/jcs.01125 - 44Kotwal, A. Electrical stimulation alters protein adsorption and nerve cell interactions with electrically conducting biomaterials. Biomaterials 2001, 22, 1055– 1064, DOI: 10.1016/S0142-9612(00)00344-6Google Scholar 谷歌学术44https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3MXisVWjurY%253D&md5=5a346be5925b5e8c2097c8cdc081f7dcElectrical stimulation alters protein adsorption and nerve cell interactions with electrically conducting biomaterialsKotwal, A.; Schmidt, C. E.Biomaterials (2001), 22 (10), 1055-1064CODEN: BIMADU; ISSN:0142-9612. (Elsevier Science Ltd.)Elec. charges have been shown to enhance nerve regeneration; however, the mechanisms for this effect are unclear. One hypothesis is that an elec. stimulus alters the local elec. fields of extracellular matrix mols., changing protein adsorption. We have investigated this hypothesis - that elec. stimulation increases the adsorption of serum proteins, specifically fibronectin (FN), to the elec. conducting polymer polypyrrole (PP), thereby, increasing neurite extension. PP was used because elec. stimulation of PP has been shown to significantly enhance neurite outgrowth, and more importantly, PP can be formed into conduits to guide nerve regeneration in vivo. Here, we looked at the effects of elec. stimulation on protein adsorption when an elec. current was applied to PP (1) during protein adsorption (immediate stimulation) and (2) several hours after protein adsorption (delayed stimulation). We found that immediate stimulation of PP increases FN adsorption from purified FN and serum-contg. solns. Correspondingly, PC-12 cells grown on PP films that had been previously adsorbed with FN during immediate stimulation expressed longer neurites. However, for delayed stimulation, no significant differences in adsorption or neurite outgrowth were obsd. These studies suggest that increased FN adsorption with immediate elec. stimulation may explain enhanced neurite extension on elec. stimulated PP.
44Kotwal, A. 电刺激改变蛋白质吸附以及神经细胞与导电生物材料的相互作用。生物材料 2001, 22, 1055–1064, DOI: 10.1016/S0142-9612(00)00344-6 - 45Balakatounis, K. Electrical stimulation for wound healing. In Advanced Wound Repair Therapies; Woodhead Publishing Limited, 2011; pp. 571– 586.
45Balakatounis, K. 电刺激促进伤口愈合。在先进的伤口修复疗法中；伍德海德出版有限公司，2011；第 571–586 页。 - 46Torkaman, G. Electrical Stimulation of Wound Healing: A Review of Animal Experimental Evidence. Adv. Wound Care 2014, 3, 202– 218, DOI: 10.1089/wound.2012.0409Google Scholar 谷歌学术46https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC2sbpvVWltQ%253D%253D&md5=16d6acf7e898551707219dfc9427b1cfElectrical Stimulation of Wound Healing: A Review of Animal Experimental EvidenceTorkaman GitiAdvances in wound care (2014), 3 (2), 202-218 ISSN:2162-1918.Significance: Electrical stimulation (ES) is a therapeutic intervention that may help specialists facilitate wound healing rates. The purpose of this section is to compile the available animal research regarding the effectiveness of ES on the injury potential, healing rate, cellular and molecular proliferation, mechanical properties, and survival rate of skin flaps. Recent Advances: Regardless of the type of ES current and polarity used, most of the animal experimental evidence suggests that application of ES can facilitate wound healing. However, treatment time should be sufficiently long to attain good mechanical strength of regenerated tissue, because tensile strength is not consistent with augmented collagen deposition. ES improves the survival rate and skin blood flow of animal flaps, but clinical studies are needed to substantiate the findings from these animal experiments. Critical Issues: Impaired or delayed healing is a major clinical problem that can lead to wound chronicity. ES with various strategies has been used to facilitate the healing process, but many aspects remain controversial. Despite much research, no consensus exists regarding the detailed effects of ES on wound healing. Nevertheless, ES has been approved by the Center for Medicare and Medicine Services for reimbursement of the treatment of some chronic ulcers. Future Directions: Exogenous ES may promote the directional migration of cells and signaling molecules via electrotaxis; however, its underlying mechanism is still poorly understood. Future studies that further elucidate the mechanisms regulating electrotaxis will be necessary to optimize the use of ES in different wound states.
46Torkaman, G. 伤口愈合的电刺激：动物实验证据回顾。副词。伤口护理 2014, 3, 202–218, DOI: 10.1089/wound.2012.0409
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Abstract
Figure 1
Figure 1. Schematic diagram of the two-layered SEWD.
Figure 2
Figure 2. (A) Schematic diagram of the preparation of the two-layered SEWD. (B) Mussel-inspired adhesion mechanism inside SEWD and the properties of SEWD. (C) Main chemical reactions in the formation of the CF-Gel-PAM hydrogel.
Figure 3
Figure 3. (A) Photo of the two-layered SEWD ((I) P(VDF-TrFE) NFs and (II) CF-Gel-PAM hydrogel). (B) SEM image of the two-layered SEWD. (C) SEM image of P(VDF-TrFE) NFs, ×1000. (D) SEM image of P(VDF-TrFE) NFs, ×10,000. (E) Diameter distribution of P(VDF-TrFE) NFs. (F) Magnifying SEM image of P(VDF-TrFE) NFs. (G) Diagrammatic drawing of the tree-like nanofiber of P(VDF-TrFE) NFs. (H) Photo of a tree. (I) SEM image of the CF-Gel-PAM hydrogel, ×200. (J) SEM image of the CF-Gel-PAM hydrogel, ×500. (K) Pore size analysis of the CF-Gel-PAM hydrogel.
Figure 4
Figure 4. (A) Typical stretch curve of SEWD. (B) Adhesion strength of SEWD. (C) Schematic diagram of the piezoelectric effect. (D) OCV output curve under different pressures. (E) PFM scanning phase diagram. (F) Micro-piezoelectric response curves of the P(VDF-TrFE) film. (G) Pictures of the SEWD making the bulb glow (left, not connected; right, connected).
Figure 5
Figure 5. Adhesion ability of SEWD (A) PE, (B) plastic, (C) porcine skin, (D) rubber, (E) stainless steel, (F) leather, (G) leaf, and (H) spume. (I) SEWD adheres to the author’s skin and peels off without residue. (J) Mussel-inspired adhesion mechanism of the hydrogel: (I) hydrogen bond, (II) coordination bond, (III) cation−π interaction, (IV) π–π interaction, and (V) covalent linkage.
Figure 6
Figure 6. (A) OD values of SEWD extracts. (B) OD values of P(VDF-TrFE) NFs extracts. (C) OD values of extracts. (D) Cell proliferation on SEWD under different stimulation. (E) Protein level of SEWD under different stimulation. (F) SEM images (×2000) of L929 fibroblasts cultured on P(VDF-TrFE) NFs. (G) SEM images (×2000) of L929 fibroblasts cultured on the CF-Gel-PAM hydrogel. (H) SEM images (×2000) of L929 fibroblasts cultured on SEWD. (I) SEM images (×2000) of L929 fibroblasts cultured on SEWD with mechanical stimulation. (J) CLSM images of L929 fibroblasts cultured on SEWD. (K) CLSM images of L929 fibroblasts cultured on SEWD with mechanical stimulation. (L) Live/Dead staining of L929 fibroblasts cultured on SEWD. (M) Live/Dead staining of L929 fibroblasts cultured on SEWD with mechanical stimulation.
Figure 7
Figure 7. (A) Photos of the healing process of the full-thickness wounds. (B) Images of wounds at different time points. (C) Quantitative results of wounds. (D) Regional traces of skin wound tissue in each group of rats during 14 days postoperatively.
Figure 8
Figure 8. H&E staining, bFGF immunohistochemical analysis, PDGF immunohistochemical analysis, and VEGF immunohistochemical analysis of wound areas treated by SEWD and CF-Gel-PAM hydrogel.
References
This article references 46 other publications.
- 1Huang, B.; Hu, D.; Dong, A.; Tian, J.; Zhang, W. Highly Antibacterial and Adhesive Hyaluronic Acid Hydrogel for Wound Repair. Biomacromolecules 2022, 23, 4766– 4777, DOI: 10.1021/acs.biomac.2c009501https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB38XislKgtb3J&md5=78c9229a996f2001b1072c2c448089c1Highly Antibacterial and Adhesive Hyaluronic Acid Hydrogel for Wound RepairHuang, Baoxuan; Hu, Dan; Dong, Alideertu; Tian, Jia; Zhang, WeianBiomacromolecules (2022), 23 (11), 4766-4777CODEN: BOMAF6; ISSN:1525-7797. (American Chemical Society)Bacterial infections accompanied with wound healing often lead to more serious health hazards to patients. Therefore, it is urgent to explore a wound dressing that can promote wound repair while possessing antibacterial capability. Here, we constructed a multifunctional hydrogel dressing by a redox-initiated crosslinking reaction of methacrylated hyaluronic acid (HAMA), 5,10,15,20-tetra (4-methacrylate phenyl) porphyrin (TPP), and dopamine methacrylamide (DMA), named HAMA-TPP-DMA, with broad-spectrum photodynamic antibacterial capability, where the aggregation of TPP photosensitizer units could be greatly inhibited to produce more singlet oxygen. The hydrogel has excellent biodegradability and biocompatibility, providing favorable conditions for wound healing. Furthermore, the incorporation of dopamine into the hydrogel gives the wound dressing with enhanced adhesiveness, benefiting for the wound repair. More importantly, the antibacterial expts. in vitro and mice wound models in vivo showed that the HAMA-TPP-DMA hydrogel can significantly resist bacteria and accelerate the wound healing in mice (the closure rate > 98% after 15 days). Thus, this hydrogel dressing with superior antibacterial infection and wound healing capability provides a promising strategy in wound repair.
- 2Sun, B. K.; Siprashvili, Z.; Khavari, P. A. Advances in skin grafting and treatment of cutaneous wounds. Science 2014, 346, 941– 945, DOI: 10.1126/science.12538362https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhvFehurbN&md5=70a9ddca37068672ce2f77328cb2e892Advances in skin grafting and treatment of cutaneous woundsSun, Bryan K.; Siprashvili, Zurab; Khavari, Paul A.Science (Washington, DC, United States) (2014), 346 (6212), 941-945CODEN: SCIEAS; ISSN:0036-8075. (American Association for the Advancement of Science)The ability of the skin to repair itself after injury is vital to human survival and is disrupted in a spectrum of disorders. The process of cutaneous wound healing is complex, requiring a coordinated response by immune cells, hematopoietic cells, and resident cells of the skin. We review the classic paradigms of wound healing and evaluate how recent discoveries have enriched our understanding of this process. We evaluate current and exptl. approaches to treating cutaneous wounds, with an emphasis on cell-based therapies and skin transplantation.
- 3Yamakawa, S.; Hayashida, K. Advances in surgical applications of growth factors for wound healing. Burns Trauma 2019, 7, 10, DOI: 10.1186/s41038-019-0148-13https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB3M%252Fmt1Cntw%253D%253D&md5=4b4c16bcc1d729c5318eb678edc67400Advances in surgical applications of growth factors for wound healingYamakawa Sho; Hayashida KenjiBurns & trauma (2019), 7 (), 10 ISSN:2321-3868.Growth factors have recently gained clinical importance for wound management. Application of recombinant growth factors has been shown to mimic cell migration, proliferation, and differentiation in vivo, allowing for external modulation of the healing process. Perioperative drug delivery systems can enhance the biological activity of these growth factors, which have a very short in vivo half-life after topical administration. Although the basic mechanisms of these growth factors are well understood, most have yet to demonstrate a significant impact in animal studies or small-sized clinical trials. In this review, we emphasized currently approved growth factor therapies, including a sustained release system for growth factors, emerging therapies, and future research possibilities combined with surgical procedures. Approaches seeking to understand wound healing at a systemic level are currently ongoing. However, further research and consideration in surgery will be needed to provide definitive confirmation of the efficacy of growth factor therapies for intractable wounds.
- 4Hofer, M.; Lutolf, M. P. Engineering organoids. Nat. Rev. Mater. 2021, 6, 402– 420, DOI: 10.1038/s41578-021-00279-y4https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3MXhsFegtbfM&md5=de6d2cf83898c666fd2bca595a93ed48Engineering organoidsHofer, Moritz; Lutolf, Matthias P.Nature Reviews Materials (2021), 6 (5), 402-420CODEN: NRMADL; ISSN:2058-8437. (Nature Portfolio)A review. Abstr.: Organoids are in vitro miniaturized and simplified model systems of organs that have gained enormous interest for modeling tissue development and disease, and for personalized medicine, drug screening and cell therapy. Despite considerable success in culturing physiol. relevant organoids, challenges remain to achieve real-life applications. In particular, the high variability of self-organizing growth and restricted exptl. and anal. access hamper the translatability of organoid systems. In this Review, we argue that many limitations of traditional organoid culture can be addressed by engineering approaches at all levels of organoid systems. We investigate cell surface and genetic engineering approaches, and discuss stem cell niche engineering based on the design of matrixes that allow spatiotemporal control of organoid growth and shape-guided morphogenesis. We examine how microfluidic approaches and lessons learnt from organs-on-a-chip enable the integration of mechano-physiol. parameters and increase accessibility of organoids to improve functional readouts. Applying engineering principles to organoids increases reproducibility and provides exptl. control, which will, ultimately, be required to enable clin. translation.
- 5Hu, C.; Chu, C.; Liu, L.; Wang, C.; Jin, S.; Yang, R.; Rung, S.; Li, J.; Qu, Y.; Man, Y. Dissecting the microenvironment around biosynthetic scaffolds in murine skin wound healing. Sci. Adv. 2021, 7, eabf0787 DOI: 10.1126/sciadv.abf0787There is no corresponding record for this reference.
- 6Krishnan, K. A.; Thomas, S. Recent advances on herb-derived constituents-incorporated wound-dressing materials: A review. Polym. Adv. Technol. 2019, 30, 823– 838, DOI: 10.1002/pat.45406https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXhtFSgtL0%253D&md5=0555ceacdb57c719756c8b4f5429c3beRecent advances on herb-derived constituents-incorporated wound-dressing materials: A reviewKrishnan K, Asha; Thomas, SabuPolymers for Advanced Technologies (2019), 30 (4), 823-838CODEN: PADTE5; ISSN:1042-7147. (John Wiley & Sons Ltd.)A review. Since ancient times, wound dressings have evolved with persistent and substantial changes. Several efforts have been made toward the development of new dressing materials, which can meet the demanding conditions for the treatment of skin wounds. Currently, many studies have been focused on the prodn. and designing of herb-incorporated wound dressings. Herb-derived constituents are more effective than conventional medicines because of their nontoxic nature and can be administered over long periods. Herbal medicines in wound healing provide a suitable environment for aiding the natural course of healing. This review mainly focuses on the diverse approaches that have been developed to produce a wound dressing material, which can deliver herb-derived bioactive constituents in a controlled manner. This review also discusses the common wound-dressing materials available, basic principles of wound healing, and wound-healing agents from medicinal plants.
- 7(a) Zeng, Q.; Qi, X.; Shi, G.; Zhang, M.; Haick, H. Wound Dressing: From Nanomaterials to Diagnostic Dressings and Healing Evaluations. ACS Nano 2022, 16, 1708– 1733, DOI: 10.1021/acsnano.1c084117ahttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB38XhsFertbc%253D&md5=2c1fbf3a27094ee51808f474da1dbd78Wound Dressing: From Nanomaterials to Diagnostic Dressings and Healing EvaluationsZeng, Qiankun; Qi, Xiaoliang; Shi, Guoyue; Zhang, Min; Haick, HossamACS Nano (2022), 16 (2), 1708-1733CODEN: ANCAC3; ISSN:1936-0851. (American Chemical Society)A review. Wound dressings based on nanomaterials play a crucial role in wound treatment and are widely used in a whole range of medical settings, from minor to life-threatening tissue injuries. This article presents an educational review on the accumulating knowledge in this multidisciplinary area to lay out the challenges and opportunities that lie ahead and ignite the further and faster development of clin. valuable technologies. The review analyzes the functional advantages of nanomaterial-based gauzes and hydrogels as well as hybrid structures thereof. On this basis, the review presents state-of-the-art advances to transfer the (semi)blind approaches to the evaluation of a wound state to smart wound dressings that enable real-time monitoring and diagnostic functions that could help in wound evaluation during healing. This review explores the translation of nanomaterial-based wound dressings and related medical aspects into real-world use. The ongoing challenges and future opportunities assocd. with nanomaterial-based wound dressings and related clin. decisions are presented and reviewed.(b) Zhang, X. Y.; Liu, C.; Fan, P. S.; Zhang, X. H.; Hou, D. Y.; Wang, J. Q.; Yang, H.; Wang, H.; Qiao, Z. Y. Skin-like wound dressings with on-demand administration based on in situ peptide self-assembly for skin regeneration. J. Mater. Chem. B 2022, 10, 3624– 3636, DOI: 10.1039/d2tb00348a7bhttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB38XpvVant7o%253D&md5=2c4ad7f27700e86992f8c6f800534d2cSkin-like wound dressings with on-demand administration based on in situ peptide self-assembly for skin regenerationZhang, Xiao-Ying; Liu, Cong; Fan, Peng-Sheng; Zhang, Xue-Hao; Hou, Da-Yong; Wang, Jia-Qi; Yang, Hui; Wang, Hao; Qiao, Zeng-YingJournal of Materials Chemistry B: Materials for Biology and Medicine (2022), 10 (19), 3624-3636CODEN: JMCBDV; ISSN:2050-7518. (Royal Society of Chemistry)Burn injuries without the normal skin barrier usually cause skin wound infections, and wound dressings are necessary. Although various dressings with antibacterial ability have already been developed, the biosafety and administration mode are still bottleneck problems for further application. Herein, we designed skin-like wound dressings based on silk fibroin (SF), which are modified with the gelatinase-cleavable self-assembled/antibacterial peptide (GPLK) and epidermal growth factor (EGF). When a skin wound is infected, the gelatinase over-secreted by bacteria can cut the GPLK peptides, leading to the in situ self-assembly of peptides and the resultant high-efficiency sterilization. Compared with the com. antibacterial dressing, the SF-GPLK displayed a faster wound healing rate. When a skin wound is not infected, the GPLK peptides remain in the SF, realizing good biosafety. Generally, the EGF can be released to promote wound healing and skin regeneration in both cases. Therefore, skin-like SF-GPLK wound dressings with on-demand release of antibacterial peptides provide a smart administration mode for clin. wound management and skin regeneration.
- 8(a) Krawetz, R. J.; Abubacker, S.; Leonard, C.; Masson, A. O.; Shah, S.; Narendran, N.; Tailor, P.; Regmi, S. C.; Labit, E.; Ninkovic, N. Proteoglycan 4 (PRG4) treatment enhances wound closure and tissue regeneration. NPJ Regen. Med. 2022, 7, 32, DOI: 10.1038/s41536-022-00228-58ahttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB38Xit1Smt7zL&md5=be78d129f0dbe736467c05e67f700a82Proteoglycan 4 (PRG4) treatment enhances wound closure and tissue regenerationKrawetz, Roman J.; Abubacker, Saleem; Leonard, Catherine; Masson, Anand O.; Shah, Sophia; Narendran, Nadia; Tailor, Pankaj; Regmi, Suresh C.; Labit, Elodie; Ninkovic, Nicoletta; Corpuz, Jessica May; Ito, Kenichi; Underhill, T. Michael; Salo, Paul T.; Schmidt, Tannin A.; Biernaskie, Jeff A.npj Regenerative Medicine (2022), 7 (1), 32CODEN: RMEED2; ISSN:2057-3995. (Nature Portfolio)Abstr.: The wound healing response is one of most primitive and conserved physiol. responses in the animal kingdom, as restoring tissue integrity/homeostasis can be the difference between life and death. Wound healing in mammals is mediated by immune cells and inflammatory signaling mols. that regulate tissue resident cells, including local progenitor cells, to mediate closure of the wound through formation of a scar. Proteoglycan 4 (PRG4), a protein found throughout the animal kingdom from fish to elephants, is best known as a glycoprotein that reduces friction between articulating surfaces (e.g. cartilage). Previously, PRG4 was also shown to regulate the inflammatory and fibrotic response. Based on this, we asked whether PRG4 plays a role in the wound healing response. Using an ear wound model, topical application of exogenous recombinant human (rh)PRG4 hastened wound closure and enhanced tissue regeneration. Our results also suggest that rhPRG4 may impact the fibrotic response, angiogenesis/blood flow to the injury site, macrophage inflammatory dynamics, recruitment of immune and increased proliferation of adult mesenchymal progenitor cells (MPCs) and promoting chondrogenic differentiation of MPCs to form the auricular cartilage scaffold of the injured ear. These results suggest that PRG4 has the potential to suppress scar formation while enhancing connective tissue regeneration post-injury by modulating aspects of each wound healing stage (blood clotting, inflammation, tissue generation and tissue remodeling). Therefore, we propose that rhPRG4 may represent a potential therapy to mitigate scar and improve wound healing.(b) Zhu, Y.; Jung, J.; Anilkumar, S.; Ethiraj, S.; Madira, S.; Tran, N. A.; Mullis, D. M.; Casey, K. M.; Walsh, S. K.; Stark, C. J. A novel photosynthetic biologic topical gel for enhanced localized hyperoxygenation augments wound healing in peripheral artery disease. Sci. Rep. 2022, 12, 10028, DOI: 10.1038/s41598-022-14085-18bhttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB38Xhs1SksLzF&md5=76a472d0cf2587f80a3d4c2f790ce2c5A novel photosynthetic biologic topical gel for enhanced localized hyperoxygenation augments wound healing in peripheral artery diseaseZhu, Yuanjia; Jung, Jinsuh; Anilkumar, Shreya; Ethiraj, Sidarth; Madira, Sarah; Tran, Nicholas A.; Mullis, Danielle M.; Casey, Kerriann M.; Walsh, Sabrina K.; Stark, Charles J.; Venkatesh, Akshay; Boakye, Alexander; Wang, Hanjay; Woo, Y. JosephScientific Reports (2022), 12 (1), 10028CODEN: SRCEC3; ISSN:2045-2322. (Nature Portfolio)Peripheral artery disease and the assocd. ischemic wounds are substantial causes of global morbidity and mortality, affecting over 200 million people worldwide. Although advancements have been made in preventive, pharmacol., and surgical strategies to treat this disease, ischemic wounds, a consequence of end-stage peripheral artery disease, remain a significant clin. and economic challenge. Synechococcus elongatus is a cyanobacterium that grows photoautotrophically and converts carbon dioxide and water into oxygen. We present a novel topical biol. gel contg. S. elongatus that provides oxygen via photosynthesis to augment wound healing by rescuing ischemic tissues caused by peripheral artery disease. By using light rather than blood as a source of energy, our novel topical therapy significantly accelerated wound healing in two rodent ischemic wound models. This novel topical gel can be directly translated to clin. practise by using a localized, portable light source without interfering with patients' daily activities, demonstrating potential to generate a paradigm shift in treating ischemic wounds from peripheral artery disease. Its novelty, low prodn. cost, and ease of clin. translatability can potentially impact the clin. care for millions of patients suffering from peripheral arterial disease.(c) Yu, R.; Li, M.; Li, Z.; Pan, G.; Liang, Y.; Guo, B. Supramolecular Thermo-Contracting Adhesive Hydrogel with Self-Removability Simultaneously Enhancing Noninvasive Wound Closure and MRSA-Infected Wound Healing. Adv. Healthcare Mater. 2022, 11, e2102749 DOI: 10.1002/adhm.2021027498chttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB38XhtFWitL3O&md5=ce57657a2f132dea059b45d659414882Supramolecular Thermo-Contracting Adhesive Hydrogel with Self-Removability Simultaneously Enhancing Noninvasive Wound Closure and MRSA-Infected Wound HealingYu, Rui; Li, Meng; Li, Zhenlong; Pan, Guoying; Liang, Yuqing; Guo, BaolinAdvanced Healthcare Materials (2022), 11 (13), 2102749CODEN: AHMDBJ; ISSN:2192-2640. (Wiley-VCH Verlag GmbH & Co. KGaA)Conventional wound closure and dressing are two crucial, time-consuming but isolated principles in wound care. Even though tissue adhesive opens a new era for wound closure, the method and biomaterial that can simultaneously achieve noninvasive wound closure and promote wound healing are highly appreciated. Herein, a novel supramol. poly(N-isopropylacrylamide) hybrid hydrogel dressing composed of quaternized chitosan-graft-β-cyclodextrin, adenine, and polypyrrole nanotubes via host-guest interaction and hydrogen bonds is developed. The hydrogel demonstrates thermal contraction of 47% remaining area after 2 h at 37°C and tissue adhesion of 5.74 kPa, which are essential for noninvasive wound closure, and multiple mech. and biol. properties including suitable mech. properties, self-healing, on-demand removal, antioxidant, hemostasis, and photothermal/intrinsic antibacterial activity (higher 99% killing ratio within 5 min after irradn.). In both full-thickness skin incision and excision wound models, the hydrogel reveals significant wound closure after 24 h post-surgery. In acute and methicillin-resistant Staphylococcus aureus-infected wound and photothermal/intrinsic antibacterial activity assays, wounds treated with the hydrogel demonstrate enhanced wound healing with rapid wound closure rate, mild inflammatory response, advanced angiogenesis, and well-arranged collagen fibers. Altogether, the results indicate the hydrogel is promising in synchronously noninvasive wound closure and enhanced wound healing.(d) Huang, Y.; Mu, L.; Zhao, X.; Han, Y.; Guo, B. Bacterial Growth-Induced Tobramycin Smart Release Self-Healing Hydrogel for Pseudomonas aeruginosa-Infected Burn Wound Healing. ACS Nano 2022, 16, 13022– 13036, DOI: 10.1021/acsnano.2c055578dhttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB38XitVSisLjJ&md5=173c595ccb786734fdf8aaa1d9f6895aBacterial growth-induced tobramycin smart release self-healing hydrogel for Pseudomonas aeruginosa-infected burn wound healingHuang, Ying; Mu, Lei; Zhao, Xin; Han, Yong; Guo, BaolinACS Nano (2022), 16 (8), 13022-13036CODEN: ANCAC3; ISSN:1936-0851. (American Chemical Society)Burns are a common health problem worldwide and are highly susceptible to bacterial infections that are difficult to handle with ordinary wound dressings. Therefore, burn wound repair is extremely challenging in clin. practice. Herein, a series of self-healing hydrogels (QCS/OD/TOB/PPY@PDA) with good elec. cond. and antioxidant activity were prepd. on the basis of quaternized chitosan (QCS), oxidized dextran (OD), tobramycin (TOB), and polydopamine-coated polypyrrole nanowires (PPY@PDA NWs). These Schiff base cross-links between the aminoglycoside antibiotic TOB and OD enable TOB to be slowly released and responsive to pH. Interestingly, the acidic substances during the bacteria growth process can induce the on-demand release of TOB, avoiding the abuse of antibiotics. The antibacterial results showed that the QCS/OD/TOB/PPY@PDA9 hydrogel could kill high concns. of Pseudomonas aeruginosa (PA), Staphylococcus aureus, and Escherichia coli in a short time and showed a bactericidal effect for up to 11 days in an agar plate diffusion expt., while showing good in vivo antibacterial activity. Excellent and long-lasting antibacterial properties make it suitable for severely infected wounds. Furthermore, the incorporation of PPY@PDA endowed the hydrogel with near-IR (NIR) irradn. assisted bactericidal activity of drug-resistant bacteria, cond., and antioxidant activity. Most importantly, in the PA-infected burn wound model, the QCS/OD/TOB/PPY@PDA9 hydrogel more effectively controlled wound inflammation levels and promoted collagen deposition, vascular generation, and earlier wound closure compared to Tegaderm dressings. Therefore, the TOB smart release hydrogels with on-demand delivery are extremely advantageous for bacterial-infected burn wound healing.
- 9Foulds, I. S.; Barker, A. T. Human Skin Battery Potentials and Their Possible Role in Wound Healing. Br. J. Dermatol. 1983, 109, 515– 522, DOI: 10.1111/j.1365-2133.1983.tb07673.x9https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADyaL2c%252FltlahsQ%253D%253D&md5=bffc07d0afb9a16b37f6db0c6f26d3edHuman skin battery potentials and their possible role in wound healingFoulds I S; Barker A TThe British journal of dermatology (1983), 109 (5), 515-22 ISSN:0007-0963.Measurements of transcutaneous voltage have been made on seventeen normal volunteers. The results show the presence of 'skin battery' voltages comparable in size to those previously reported for amphibian and mammalian skin. No correlation was found between battery voltage and age or sex in the group studied, but consistent anatomical variations were observed. The possible role of these voltages in the natural wound healing process is discussed.
- 10Tai, G.; Tai, M.; Zhao, M. Electrically stimulated cell migration and its contribution to wound healing. Burns Trauma 2018, 6, 20, DOI: 10.1186/s41038-018-0123-210https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB3c%252Fns12nug%253D%253D&md5=9095be644c9eccd8ef1c3ed01121713aElectrically stimulated cell migration and its contribution to wound healingTai Guangping; Tai Michael; Zhao MinBurns & trauma (2018), 6 (), 20 ISSN:2321-3868.Naturally occurring electric fields are known to be morphogenetic cues and associated with growth and healing throughout mammalian and amphibian animals and the plant kingdom. Electricity in animals was discovered in the eighteenth century. Electric fields activate multiple cellular signaling pathways such as PI3K/PTEN, the membrane channel of KCNJ15/Kir4.2 and intracellular polyamines. These pathways are involved in the sensing of physiological electric fields, directional cell migration (galvanotaxis, also known as electrotaxis), and possibly other cellular responses. Importantly, electric fields provide a dominant and over-riding signal that directs cell migration. Electrical stimulation could be a promising therapeutic method in promoting wound healing and activating regeneration of chronic and non-healing wounds. This review provides an update of the physiological role of electric fields, its cellular and molecular mechanisms, its potential therapeutic value, and questions that still await answers.
- 11Barker, A. T.; Jaffe, L. F.; Vanable, J. W., Jr. The glabrous epidermis of cavies contains a powerful battery. Am. J. Physiol. 1982, 242, R358– R366, DOI: 10.1152/ajpregu.1982.242.3.R358There is no corresponding record for this reference.
- 12Liu, H.; Feng, Y.; Che, S.; Guan, L.; Yang, X.; Zhao, Y.; Fang, L.; Zvyagin, A. V.; Lin, Q. An Electroconductive Hydrogel Scaffold with Injectability and Biodegradability to Manipulate Neural Stem Cells for Enhancing Spinal Cord Injury Repair. Biomacromolecules 2023, 24, 86– 97, DOI: 10.1021/acs.biomac.2c0092012https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB38XjtVygsrjM&md5=e0b7bf8d704305a5dab22ac86b980fccAn Electroconductive Hydrogel Scaffold with Injectability and Biodegradability to Manipulate Neural Stem Cells for Enhancing Spinal Cord Injury RepairLiu, Hou; Feng, Yubin; Che, Songtian; Guan, Lin; Yang, Xinting; Zhao, Yue; Fang, Linan; Zvyagin, Andrei V.; Lin, QuanBiomacromolecules (2023), 24 (1), 86-97CODEN: BOMAF6; ISSN:1525-7797. (American Chemical Society)Spinal cord injury (SCI) generally leads to long-term functional deficits and is difficult to repair spontaneously. Many biol. scaffold materials and stem cell treatment strategies have been explored, but very few researches focused on the method of combining exogenous neural stem cells (NSCs) with biodegradable conductive hydrogel scaffold. Here, NSCs loaded conductive hydrogel scaffold (named ICH/NSCs) was assembled by amino-modified gelatin (NH2-Gelatin) and aniline tetramer grafted oxidized hyaluronic acid (AT-OHA). Desirably, the well-conducting ICH/NSCs can be simply injected into the target site of SCI for establishing a good elec. signal pathway of cells, and the proper degrdn. cycle facilitates new nerve growth. In vitro expts. indicated that the inherent electroactive microenvironment of hydrogel could better manipulate the differentiation of NSCs into neurons, and inhibit the formation of glial cells and scars. Collectively, the ICH/NSCs scaffold has successfully stimulated the recovery of SCI and may provide a promising treatment strategy for SCI repair.
- 13Nishimura, K. Y.; Isseroff, R. R.; Nuccitelli, R. Human Keratinocytes Migrate to the Negative Pole in Direct Current Electric Fields Comparable to those Measured in Mammalian Wounds. J. Cell Sci. 1996, 109, 199– 207, DOI: 10.1242/jcs.109.1.19913https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK28XosVagug%253D%253D&md5=fa81e6113d569529269c09cce99798e2Human keratinocytes migrate to the negative pole in direct current electric fields comparable to those measured in mammalian woundsNishimura, Karen Y.; isseroff, R. Rivkah; Nuccitelli, RichardJournal of Cell Science (1996), 109 (1), 199-207CODEN: JNCSAI; ISSN:0021-9533. (Company of Biologists)Previous measurements of the lateral elec. fields near skin wounds in guinea pigs have detected DC fields between 100-200 mV/mm near the edge of the wound. We have studied the translocation response of motile primary human keratinocytes migrating on a collagen substrate while exposed to similar physiol. DC elec. fields. We find that keratinocytes migrate randomly on collage in fields of 5 mV/mm or less, but in larger fields they migrate towards the neg. pole of the field, exhibiting galvanotaxis. Since these cells have an av. cell length of 50 μm, this implies that they are able to detect a voltage gradient as low as 0.5 mV along their length. This cath-odally-directed movement exhibits increased directedness with increasing field strengths between 10 and 100 mV/mm. We observe a maximally directed response at 100 mV/mm with half of the cells responding to the field within 14 min. The av. speed of migration tended to be greater in fields above 50 mV/mm than in smaller fields. We conclude that human keratinocytes migrate towards the neg. pole in DC elec. fields that are of the same magnitude as measured in vivo near wounds in mammalian skin.
- 14Zhang, J.; Wu, C.; Xu, Y.; Chen, J.; Ning, N.; Yang, Z.; Guo, Y.; Hu, X.; Wang, Y. Highly Stretchable and Conductive Self-Healing Hydrogels for Temperature and Strain Sensing and Chronic Wound Treatment. ACS Appl. Mater. Interfaces 2020, 12, 40990– 40999, DOI: 10.1021/acsami.0c0829114https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhs1aqs7jF&md5=67f3a00d3e7840e68205e971e785fcd9Highly Stretchable and Conductive Self-Healing Hydrogels for Temperature and Strain Sensing and Chronic Wound TreatmentZhang, Jieyu; Wu, Can; Xu, Yuanyuan; Chen, Jiali; Ning, Ning; Yang, Zeyu; Guo, Yi; Hu, Xuefeng; Wang, YunbingACS Applied Materials & Interfaces (2020), 12 (37), 40990-40999CODEN: AAMICK; ISSN:1944-8244. (American Chemical Society)Flexible bioelectronics for biomedical applications requires a stretchable, conductive, self-healable, and biocompatible material that can be obtained by cost-effective chems. and strategies. Herein, we synthesized polypyrrole or Zn-functionalized chitosan mols., which are cross-linked with poly(vinyl alc.) to form a hydrogel through dynamic di-diol complexations, hydrogen bonding, and zinc-based coordination bonds. These multiple dynamic interactions endow the material with excellent stretchability and autonomous self-healing ability. The choice of Food and Drug Administration (FDA)-approved materials (poly(vinyl alc.) and chitosan) as the matrix materials ensures the good biocompatibility of the hydrogel. The cond. contributed by the polypyrrole allowed the hydrogel to sense strain and temp., and the coordinated Zn significantly enhanced the antibacterial activity of the hydrogel. Moreover, using a diabetic rat model, we have proved that this hydrogel is capable of promoting the healing of the infected chronic wounds with elec. stimulation.
- 15Lu, Y.; Wang, Y.; Zhang, J.; Hu, X.; Yang, Z.; Guo, Y.; Wang, Y. In-situ doping of a conductive hydrogel with low protein absorption and bacterial adhesion for electrical stimulation of chronic wounds. Acta Biomater. 2019, 89, 217– 226, DOI: 10.1016/j.actbio.2019.03.01815https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXltFCqtrg%253D&md5=879fc1f1771d1a6ddd1971ea999f04adIn-situ doping of a conductive hydrogel with low protein absorption and bacterial adhesion for electrical stimulation of chronic woundsLu, Yuhui; Wang, Yanan; Zhang, Jieyu; Hu, Xuefeng; Yang, Zeyu; Guo, Yi; Wang, YunbingActa Biomaterialia (2019), 89 (), 217-226CODEN: ABCICB; ISSN:1742-7061. (Elsevier Ltd.)Elec. stimulation (ES) via electrodes is promising for treating chronic wounds, but this electrode-based strategy is unable to stimulate the whole wound area and the therapeutic outcome may be compromised. In this study, a conductive poly(2-hydroxyethyl methacrylate) (polyHEMA)/polypyrrole (PPY) hydrogel was developed, and 3-sulfopropyl methacrylate was covalently incorporated in the hydrogel's network to in-situ dope the PPY and maintain the hydrogel's cond. in the weak alk. physiol. environment. The obtained hydrogel was superior to the com. Hydrosorb dressing for preventing bacterial adhesion and protein absorption, and this is helpful to reduce the possibilities of infection and secondary damage during dressing replacement. The in vitro scratch assay demonstrates that ES through the hydrogel enhanced fibroblast migration, and this enhancement effect remained even after the ES was ended. The in vivo assay using diabetic rats shows that when ES was conducted with this polyHEMA/PPY hydrogel, the healing rate was faster than that achieved by the electrode-based ES strategy. Therefore, this polyHEMA/PPY hydrogel shows a great potential for developing the next generation of ES treatment for chronic wounds. Elec. stimulation (ES) via sepd. electrodes is promising for treating chronic wounds, but this electrode-based strategy is unable to stimulate the whole wound area, compromising the therapeutic outcome. Herein, a hydrogel was developed with stable elec. cond. in the physiol. environment and strong resistance to protein absorption and bacterial adhesion. The in vitro and in vivo tests proved that ES applied through the flexible and conductive hydrogel that covered the wound was superior to ES through electrodes for promoting the healing of the chronic wound. This hydrogel-based ES strategy combines the advantages of ES and hydrogel dressing and will pave the way for the next generation of ES treatment for chronic wounds.
- 16Yu, C.; Hu, Z. Q.; Peng, R. Y. Effects and mechanisms of a microcurrent dressing on skin wound healing: a review. Mil. Med. Res. 2014, 1, 1– 8, DOI: 10.1186/2054-9369-1-24There is no corresponding record for this reference.
- 17(a) Isseroff, R. R.; Dahle, S. E. Electrical Stimulation Therapy and Wound Healing: Where Are We Now?. Adv. Wound Care 2012, 1, 238– 243, DOI: 10.1089/wound.2011.035117ahttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC2sbps12isQ%253D%253D&md5=8a1a37d35b6d66405c9132be4f3d243cElectrical Stimulation Therapy and Wound Healing: Where Are We Now?Isseroff R Rivkah; Dahle Sara EAdvances in wound care (2012), 1 (6), 238-243 ISSN:2162-1918.BACKGROUND: Healing chronic wounds is an ongoing challenge for clinicians and poses a serious public health burden. Electrical stimulation (ES), broadly defined as the application of electrical current via electrodes placed on the skin adjacent to or directly within the wound, has been proposed as a therapeutic modality over a century ago, and recent advances in understanding the biology of electrical phenomena in the skin have rekindled an interest in this modality. THE PROBLEM: Despite evidence that has shown ES to be effective for wound healing, it has been slow to gain acceptance in the United States. Also, there has been no consensus in terms of standardization of parameters to devise a systematic protocol for implementation of this technology. BASIC/CLINICAL SCIENCE ADVANCES: The epidermis maintains a "skin battery" that generates an endogenous electric field and current flow when wounded. Experimental models have demonstrated that most of the cell types within the wound can sense an electric field in the range of that endogenously generated in the wound, and respond with a variety of biological and functional responses that can contribute to healing. Multiple animal wound models have demonstrated enhancement of a number of parameters of healing when ES is exogenously supplied. CLINICAL CARE RELEVANCE: Clinical trials have investigated the efficacy of multiple forms of ES for improving healing in a wide variety of human chronic wounds. In 2002 the Centers for Medicare and Medicaid Services approved reimbursement for use of ES in a clinical setting for certain chronic wounds. CONCLUSION: THERE REMAIN MANY VOIDS IN OUR KNOWLEDGE BASE: clinical evidence is limited by deficiencies in the design of many of the trials, a multiplicity of ES application modes and waveforms used in trials prevent selection of an optimal modality, and lack of uniformity in reporting ES dosages leave us not much advanced from our clinical knowledge base a decade ago.(b) Whitcomb, E.; Monroe, N.; Hope-Higman, J.; Campbell, P. Demonstration of a microcurrent-generating wound care device for wound healing within a rehabilitation center patient population. J. Am. Coll. Clin. Wound Spec. 2012, 4, 32– 39, DOI: 10.1016/j.jccw.2013.07.00117bhttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC2cvltFaruw%253D%253D&md5=c2c094612e9bbd6bf65213506a024d0cDemonstration of a microcurrent-generating wound care device for wound healing within a rehabilitation center patient populationWhitcomb Emily; Monroe Nina; Hope-Higman Jennifer; Campbell PennyThe journal of the American College of Clinical Wound Specialists (2012), 4 (2), 32-9 ISSN:2213-5103.PURPOSE: Wound care in a rehabilitation environment is a costly and difficult problem. The goal of this retrospective study is to evaluate differences in wound closure outcomes in acute and chronic wounds when treated with a microcurrent-generating wound care device as compared to standard wound care methods. METHODS: Data files of 38 patients who received either standard wound treatment (SOC; n = 20), or were treated with a microcurrent-generating wound device (MCD, n = 18), were retrospectively reviewed. Wounds were assessed until deemed clinically to have closed or healed with up to 100% epithelialization. All patients (18-99 years) with single wounds were included. The number of days to wound closure and the rate of wound volume reduction were compared across groups. Persistent reduction of wound size improvement was also examined. RESULTS: The wounds in the SOC group closed on average at 36.25 days (SD = 28.89), while the MCD group closed significantly faster in 19.78 days (SD = 14.45), p = 0.036. The rate of volume reduction per day was -3.83% for SOC vs. -9.82% volume reduction per day (p = 0.013) for the MCD group. The SOC group had 50% of its wounds close monotonically vs. 83.3% in the MCD group (p = 0.018). CONCLUSION: This two-center retrospective study demonstrated a 45.4% faster, and more robust healing of wounds with the use of the MCD, when compared to SOC in a rehabilitation center environment. This translates into improved patient care, and potentially significant cost savings. Economic benefits for the use of MCD compared to other wound care methods are planned for future research.
- 18Ud-Din, S.; Bayat, A. Electrical Stimulation and Cutaneous Wound Healing: A Review of Clinical Evidence. Healthcare 2014, 2, 445– 467, DOI: 10.3390/healthcare204044518https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC2s3hvVCnug%253D%253D&md5=c15b8dc4f8ecc043db58370925c5ab00Electrical Stimulation and Cutaneous Wound Healing: A Review of Clinical EvidenceUd-Din Sara; Bayat Ardeshir; Ud-Din Sara; Bayat ArdeshirHealthcare (Basel, Switzerland) (2014), 2 (4), 445-67 ISSN:2227-9032.Electrical stimulation (ES) has been shown to have beneficial effects in wound healing. It is important to assess the effects of ES on cutaneous wound healing in order to ensure optimization for clinical practice. Several different applications as well as modalities of ES have been described, including direct current (DC), alternating current (AC), high-voltage pulsed current (HVPC), low-intensity direct current (LIDC) and electrobiofeedback ES. However, no one method has been advocated as the most optimal for the treatment of cutaneous wound healing. Therefore, this review aims to examine the level of evidence (LOE) for the application of different types of ES to enhance cutaneous wound healing in the skin. An extensive search was conducted to identify relevant clinical studies utilising ES for cutaneous wound healing since 1980 using PubMed, Medline and EMBASE. A total of 48 studies were evaluated and assigned LOE. All types of ES demonstrated positive effects on cutaneous wound healing in the majority of studies. However, the reported studies demonstrate contrasting differences in the parameters and types of ES application, leading to an inability to generate sufficient evidence to support any one standard therapeutic approach. Despite variations in the type of current, duration, and dosing of ES, the majority of studies showed a significant improvement in wound area reduction or accelerated wound healing compared to the standard of care or sham therapy as well as improved local perfusion. The limited number of LOE-1 trials for investigating the effects of ES in wound healing make critical evaluation and assessment somewhat difficult. Further, better-designed clinical trials are needed to improve our understanding of the optimal dosing, timing and type of ES to be used.
- 19Banerjee, J.; Das Ghatak, P.; Roy, S.; Khanna, S.; Sequin, E. K.; Bellman, K.; Dickinson, B. C.; Suri, P.; Subramaniam, V. V.; Chang, C. J.; Sen, C. K. Improvement of Human Keratinocyte Migration by a Redox Active Bioelectric Dressing. PLoS One 2014, 9, e89239 DOI: 10.1371/journal.pone.008923919https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhsVWgu7fK&md5=74aeabf0da3b8d78b5bd558029a0d8d1Improvement of human keratinocyte migration by a redox active bioelectric dressingBanerjee, Jaideep; Ghatak, Piya Das; Roy, Sashwati; Khanna, Savita; Sequin, Emily K.; Bellman, Karen; Dickinson, Bryan C.; Suri, Prerna; Subramaniam, Vish V.; Chang, Christopher J.; Sen, Chandan K.PLoS One (2014), 9 (3), e89239/1-e89239/14, 14 pp.CODEN: POLNCL; ISSN:1932-6203. (Public Library of Science)Exogenous application of an elec. field can direct cell migration and improve wound healing; however clin. application of the therapy remains elusive due to lack of a suitable device and hence, limitations in understanding the mol. mechanisms. Here we report on a novel FDA approved redox-active Ag/Zn bioelec. dressing (BED) which generates elec. fields. To develop a mechanistic understanding of how the BED may potentially influence wound re-epithelialization, we direct emphasis on understanding the influence of BED on human keratinocyte cell migration. Mapping of the elec. field generated by BED led to the observation that BED increases keratinocyte migration by three mechanisms: (i) generating hydrogen peroxide, known to be a potent driver of redox signaling, (ii) phosphorylation of redox-sensitive IGF1R directly implicated in cell migration, and (iii) redn. of protein thiols and increase in integrin αv expression, both of which are known to be drivers of cell migration. BED also increased keratinocyte mitochondrial membrane potential consistent with its ability to fuel an energy demanding migration process. Elec. fields generated by a Ag/Zn BED can cross-talk with keratinocytes via redox-dependent processes improving keratinocyte migration, a crit. event in wound re-epithelialization.
- 20Blount, A. L.; Foster, S.; Rapp, D. A.; Wilcox, R. The use of bioelectric dressings in skin graft harvest sites: a prospective case series. J. Burn Care Res. 2012, 33, 354– 357, DOI: 10.1097/BCR.0b013e31823356e420https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC38zmtlWjsg%253D%253D&md5=9f6af7a4bfabf827e87a6dc4ec82a41eThe use of bioelectric dressings in skin graft harvest sites: a prospective case seriesBlount Andrew L; Foster Sarah; Rapp Derek A; Wilcox RichardJournal of burn care & research : official publication of the American Burn Association (2012), 33 (3), 354-7 ISSN:.Despite advances in wound care treatments for the management of acute and chronic wounds, there remains an unmet need for interventions that accelerate epithelialization. Many authors in the past have advocated the use of electric currents to accelerate wound healing. Novel wound dressings with inherent electric activity are emerging, and studies of these specific modalities are lacking. The principal aim of this study is to evaluate the impact of a bioelectric dressing on acute wound healing. Thirteen patients who underwent skin grafting were enrolled. One half of all skin graft donor sites were treated with the bioelectric dressing and semi-occlusive dressing (SOD) and the other half using solely a SOD. Epithelialization was rated by a blinded burn surgeon attending. Participants also provided a self-assessment of their scar appearance. At week 1 postprocedure, average epithelialization of 71.8% was noted on the bioelectric dressing-treated side, compared with 46.9% on the SOD side, representing an average 34.62% faster wound healing (P = .015). At 1 month, patients rated the bioelectric dressing-treated half as superior in terms of scar color (P = .198), stiffness (P = .088), thickness (P = .038), and overall quality (P = .028). These early data show promise in terms of faster healing, improved scarring, and improved patient subjective outcome with the use of the bioelectric dressing on acute wounds. With fulfillment of an extended study population, the authors hope to provide a solid foundation for extrapolating their data beyond skin graft donor sites to all areas of wound care.
- 21Tandon, B.; Blaker, J. J.; Cartmell, S. H. Piezoelectric materials as stimulatory biomedical materials and scaffolds for bone repair. Acta Biomater. 2018, 73, 1– 20, DOI: 10.1016/j.actbio.2018.04.02621https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXoslyrs7c%253D&md5=216ce623e06c494a56ae47b1cb7c2bcbPiezoelectric materials as stimulatory biomedical materials and scaffolds for bone repairTandon, Biranche; Blaker, Jonny J.; Cartmell, Sarah H.Acta Biomaterialia (2018), 73 (), 1-20CODEN: ABCICB; ISSN:1742-7061. (Elsevier Ltd.)The process of bone repair and regeneration requires multiple physiol. cues including biochem., elec. and mech. - that act together to ensure functional recovery. Myriad materials have been explored as bioactive scaffolds to deliver these cues locally to the damage site, amongst these piezoelec. materials have demonstrated significant potential for tissue engineering and regeneration, esp. for bone repair. Piezoelec. materials have been widely explored for power generation and harvesting, structural health monitoring, and use in biomedical devices. They have the ability to deform with physiol. movements and consequently deliver elec. stimulation to cells or damaged tissue without the need of an external power source. Bone itself is piezoelec. and the charges/potentials it generates in response to mech. activity are capable of enhancing bone growth. Piezoelec. materials are capable of stimulating the physiol. elec. microenvironment, and can play a vital role to stimulate regeneration and repair. This review gives an overview of the assocn. of piezoelec. effect with bone repair, and focuses on state-of-the-art piezoelec. materials (polymers, ceramics and their composites), the fabrication routes to produce piezoelec. scaffolds, and their application in bone repair. Important characteristics of these materials from the perspective of bone tissue engineering are highlighted. Promising upcoming strategies and new piezoelec. materials for this application are presented. Elec. stimulation/elec. microenvironment are known effect the process of bone regeneration by altering the cellular response and are crucial in maintaining tissue functionality. Piezoelec. materials, owing to their capability of generating charges/potentials in response to mech. deformations, have displayed great potential for fabricating smart stimulatory scaffolds for bone tissue engineering. The growing interest of the scientific community and compelling results of the published research articles has been the motivation of this review article. This article summarizes the significant progress in the field with a focus on the fabrication aspects of piezoelec. materials. The review of both material and cellular aspects on this topic ensures that this paper appeals to both material scientists and tissue engineers.
- 22Long, Y.; Wei, H.; Li, J.; Yao, G.; Yu, B.; Ni, D.; Gibson, A. L.; Lan, X.; Jiang, Y.; Cai, W. Effective Wound Healing Enabled by Discrete Alternative Electric Fields from Wearable Nanogenerators. ACS Nano 2018, 12, 12533– 12540, DOI: 10.1021/acsnano.8b0703822https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXitlaktbbE&md5=80104e6fdb34474303a42fafa30c3c63Effective Wound Healing Enabled by Discrete Alternative Electric Fields from Wearable NanogeneratorsLong, Yin; Wei, Hao; Li, Jun; Yao, Guang; Yu, Bo; Ni, Dalong; Gibson, Angela LF; Lan, Xiaoli; Jiang, Yadong; Cai, Weibo; Wang, XudongACS Nano (2018), 12 (12), 12533-12540CODEN: ANCAC3; ISSN:1936-0851. (American Chemical Society)Skin wound healing is a major health care issue. While elec. stimulations have been known for decades to be effective for facilitating skin wound recovery, practical applications are still largely limited by the clumsy elec. systems. Here, we report an efficient elec. bandage for accelerated skin wound healing. On the bandage, an alternating discrete elec. field is generated by a wearable nanogenerator by converting mech. displacement from skin movements into electricity. Rat studies demonstrated rapid closure of a full-thickness rectangular skin wound within 3 days as compared to 12 days of usual contraction-based healing processes in rodents. From in vitro studies, the accelerated skin wound healing was attributed to elec. field-facilitated fibroblast migration, proliferation, and transdifferentiation. This self-powered elec.-dressing modality could lead to a facile therapeutic strategy for nonhealing skin wound treatment.
- 23Yang, B.; Yao, F.; Hao, T.; Fang, W.; Ye, L.; Zhang, Y.; Wang, Y.; Li, J.; Wang, C. Development of Electrically Conductive Double-Network Hydrogels via One-Step Facile Strategy for Cardiac Tissue Engineering. Adv. Healthcare Mater. 2016, 5, 474– 488, DOI: 10.1002/adhm.20150052023https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhvFaltbjK&md5=59ca6c2c957e039a7c6295117311dd76Development of Electrically Conductive Double-Network Hydrogels via One-Step Facile Strategy for Cardiac Tissue EngineeringYang, Boguang; Yao, Fanglian; Hao, Tong; Fang, Wancai; Ye, Lei; Zhang, Yabin; Wang, Yan; Li, Junjie; Wang, ChangyongAdvanced Healthcare Materials (2016), 5 (4), 474-488CODEN: AHMDBJ; ISSN:2192-2640. (Wiley-VCH Verlag GmbH & Co. KGaA)Cardiac tissue engineering is an effective method to treat the myocardial infarction. However, the lack of elec. cond. of biomaterials limits their applications. In this work, a homogeneous electronically conductive double network (HEDN) hydrogel via one-step facile strategy is developed, consisting of a rigid/hydrophobic/conductive network of chem. crosslinked poly(thiophene-3-acetic acid) (PTAA) and a flexible/hydrophilic/biocompatible network of photo-crosslinking methacrylated aminated gelatin (MAAG). Results suggest that the swelling, mech., and conductive properties of HEDN hydrogel can be modulated via adjusting the ratio of PTAA network to MAAG network. HEDN hydrogel has Young's moduli ranging from 22.7 to 493.1 kPa, and its cond. (≈10-4 S cm-1) falls in the range of reported conductivities for native myocardium tissue. To assess their biol. activity, the brown adipose-derived stem cells (BADSCs) are seeded on the surface of HEDN hydrogel with or without elec. stimulation. Our data show that the HEDN hydrogel can support the survival and proliferation of BADSCs, and that it can improve the cardiac differentiation efficiency of BADSCs and upregulate the expression of connexin 43. Moreover, elec. stimulation can further improve this effect. Overall, it is concluded that the HEDN hydrogel may represent an ideal scaffold for cardiac tissue engineering.
- 24Han, L.; Yan, L.; Wang, M.; Wang, K.; Fang, L.; Zhou, J.; Fang, J.; Ren, F.; Lu, X. Transparent, Adhesive, and Conductive Hydrogel for Soft Bioelectronics Based on Light-Transmitting Polydopamine-Doped Polypyrrole Nanofibrils. Chem. Mater. 2018, 30, 5561– 5572, DOI: 10.1021/acs.chemmater.8b0144624https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXhtlKqur%252FE&md5=3540dc40df8fe8ab558943e057e98938Transparent, Adhesive, and Conductive Hydrogel for Soft Bioelectronics Based on Light-Transmitting Polydopamine-Doped Polypyrrole NanofibrilsHan, Lu; Yan, Liwei; Wang, Menghao; Wang, Kefeng; Fang, Liming; Zhou, Jie; Fang, Ju; Ren, Fuzeng; Lu, XiongChemistry of Materials (2018), 30 (16), 5561-5572CODEN: CMATEX; ISSN:0897-4756. (American Chemical Society)Conductive hydrogels are promising materials for soft electronic devices. To satisfy the diverse requirement of bioelectronic devices, esp. those for human-machine interfaces, hydrogels are required to be transparent, conductive, highly stretchable, and skin-adhesive. However, fabrication of a conductive-polymer-incorporated hydrogel with high performance is a challenge because of the hydrophobic nature of conductive polymers making processing difficult. Here, we report a transparent, conductive, stretchable, and self-adhesive hydrogel by in situ formation of polydopamine (PDA)-doped polypyrrole (PPy) nanofibrils in the polymer network. The in situ formed nanofibrils with good hydrophilicity were well-integrated with the hydrophilic polymer phase and interwoven into a nanomesh, which created a complete conductive path and allowed visible light to pass through for transparency. Catechol groups from the PDA-PPy nanofibrils imparted the hydrogel with self-adhesiveness. Reinforcement by the nanofibrils made the hydrogel tough and stretchable. The proposed simple and smart strategy of in situ formation of conductive nanofillers opens a new route to incorporate hydrophobic and undissolvable conductive polymers into hydrogels. The fabricated multifunctional hydrogel shows promise in a range of applications, such as transparent electronic skins, wound dressings, and bioelectrodes for see-through body-adhered signal detection.
- 25Han, L.; Yan, L.; Wang, K.; Fang, L.; Zhang, H.; Tang, Y.; Ding, Y.; Weng, L.-T.; Xu, J.; Weng, J. Tough, self-healable and tissue-adhesive hydrogel with tunable multifunctionality. NPG Asia Mater. 2017, 9, e372– e372, DOI: 10.1038/am.2017.3325https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXlslegsbY%253D&md5=af4c4c6366d5be4e9fdb7097b18fcbdeTough, self-healable and tissue-adhesive hydrogel with tunable multifunctionalityHan, Lu; Yan, Liwei; Wang, Kefeng; Fang, Liming; Zhang, Hongping; Tang, Youhong; Ding, Yonghui; Weng, Lu-Tao; Xu, Jielong; Weng, Jie; Liu, Yujie; Ren, Fuzeng; Lu, XiongNPG Asia Materials (2017), 9 (4), e372CODEN: NAMPCE; ISSN:1884-4057. (Nature Publishing Group)An ideal hydrogel for biomedical engineering should mimic the intrinsic properties of natural tissue, esp. high toughness and self-healing ability, in order to withstand cyclic loading and repair skin and muscle damage. In addn., excellent cell affinity and tissue adhesiveness enable integration with the surrounding tissue after implantation. Inspired by the natural mussel adhesive mechanism, we designed a polydopamine-polyacrylamide (PDA-PAM) single network hydrogel by preventing the overoxidn. of dopamine to maintain enough free catechol groups in the hydrogel. Therefore, the hydrogel possesses super stretchability, high toughness, stimuli-free self-healing ability, cell affinity and tissue adhesiveness. More remarkably, the current hydrogel can repeatedly be adhered on/stripped from a variety of surfaces for many cycles without loss of adhesion strength. Furthermore, the hydrogel can serve as an excellent platform to host various nano-building blocks, in which multiple functionalities are integrated to achieve versatile potential applications, such as magnetic and elec. therapies.
- 26Ju, J.; Shi, Z.; Deng, N.; Liang, Y.; Kang, W.; Cheng, B. Designing waterproof breathable material with moisture unidirectional transport characteristics based on a TPU/TBAC tree-like and TPU nanofiber double-layer membrane fabricated by electrospinning. RSC Adv. 2017, 7, 32155– 32163, DOI: 10.1039/c7ra04843b26https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXhtVGnsbzM&md5=a17dcf986e4277da9ae1183a576ee32dDesigning waterproof breathable material with moisture unidirectional transport characteristics based on a TPU/TBAC tree-like and TPU nanofiber double-layer membrane fabricated by electrospinningJu, Jingge; Shi, Zhijie; Deng, Nanping; Liang, Yueyao; Kang, Weimin; Cheng, BowenRSC Advances (2017), 7 (51), 32155-32163CODEN: RSCACL; ISSN:2046-2069. (Royal Society of Chemistry)In this study, a thermoplastic polyurethane (TPU) tree-like nanofiber membrane was fabricated via one-step electrospinning by adding a small amt. of tetrabutylammonium chloride (TBAC). On the basis of the "push and pull" effect, double-layer membranes composed of pure TPU nanofiber membranes (hydrophobic) and TPU/TBAC tree-like nanofiber membranes (hydrophilic) were prepd. by the direct electrospinning compounding method. The double-layer membranes were used as waterproof breathable materials with moisture unidirectional transport properties and good shielding properties. The water resistance, mech., waterproof, moisture permeability, air permeability, air filtration and moisture unidirectional transport performances of the double-layer membranes were tested. The results showed that the double-layer TPU membranes displayed good performances compared with the existing products on the market; they provide a new approach for the development of waterproof breathable materials.
- 27(a) Sedó, J.; Saiz-Poseu, J.; Busqué, F.; Ruiz-Molina, D. Catechol-based biomimetic functional materials. Adv. Mater. 2013, 25, 653– 701, DOI: 10.1002/adma.20120234327ahttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XhslejtL7F&md5=9f8a316acb87614fd7da40d87b750f4bCatechol-Based Biomimetic Functional MaterialsSedo, Josep; Saiz-Poseu, Javier; Busque, Felix; Ruiz-Molina, DanielAdvanced Materials (Weinheim, Germany) (2013), 25 (5), 653-701CODEN: ADVMEW; ISSN:0935-9648. (Wiley-VCH Verlag GmbH & Co. KGaA)A review. Catechols are found in nature taking part in a remarkably broad scope of biochem. processes and functions. Though not exclusively, such versatility may be traced back to several properties uniquely found together in the o-dihydroxyaryl chem. function; namely, its ability to establish reversible equil. at moderate redox potentials and pHs and to irreversibly cross-link through complex oxidn. mechanisms; its excellent chelating properties, greatly exemplified by, but by no means exclusive, to the binding of Fe3+; and the diverse modes of interaction of the vicinal hydroxyl groups with all kinds of surfaces of remarkably different chem. and phys. nature. Thanks to this diversity, catechols can be found either as simple mol. systems, forming part of supramol. structures, coordinated to different metal ions or as macromols. mostly arising from polymn. mechanisms through covalent bonds. Such versatility has allowed catechols to participate in several natural processes and functions that range from the adhesive properties of marine organisms to the storage of some transition metal ions. As a result of such an astonishing range of functionalities, catechol-based systems have in recent years been subject to intense research, aimed at mimicking these natural systems in order to develop new functional materials and coatings. A comprehensive review of these studies is discussed in this paper.(b) Ryu, J. H.; Hong, S.; Lee, H. Bio-inspired adhesive catechol-conjugated chitosan for biomedical applications: A mini review. Acta Biomater. 2015, 27, 101– 115, DOI: 10.1016/j.actbio.2015.08.04327bhttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhsFWmtLzJ&md5=b1f4e3d23d20e08ca08398b1388de0f1Bio-inspired adhesive catechol-conjugated chitosan for biomedical applications: A mini reviewRyu, Ji Hyun; Hong, Seonki; Lee, HaeshinActa Biomaterialia (2015), 27 (), 101-115CODEN: ABCICB; ISSN:1742-7061. (Elsevier Ltd.)The development of adhesive materials, such as cyanoacrylate derivs., fibrin glues, and gelatin-based adhesives, has been an emerging topic in biomaterial science because of the many uses of these materials, including in wound healing patches, tissue sealants, and hemostatic materials. However, most bio-adhesives exhibit poor adhesion to tissue and related surfaces due to the presence of body fluid. For a decade, studies have aimed at addressing this issue by developing wet-resistant adhesives. Mussels demonstrate robust wet-resistant adhesion despite the ceaseless waves at seashores, and mussel adhesive proteins play a key role in this adhesion. Adhesive proteins located at the distal end (i.e., those that directly contact surfaces) are composed of nearly 60% of amino acids called 3,4-dihydroxy-L-phenylalanine (DOPA), lysine, and histidine, which contain side chains of catechol, primary amines, and secondary amines, resp. Inspired by the abundant catecholamine in mussel adhesive proteins, researchers have developed various types of polymeric mimics, such as polyethylenimine-catechol, chitosan-catechol, and other related catecholic polymers. Among them, chitosan-catechol is a promising adhesive polymer for biomedical applications. The conjugation of catechol onto chitosan dramatically increases its soly. from zero to nearly 60 mg/mL (i.e., 6% w/v) in pH 7 aq. solns. The enhanced soly. maximizes the ability of catecholamine to behave similar to mussel adhesive proteins. Chitosan-catechol is biocompatible and exhibits excellent hemostatic ability and tissue adhesion, and thus, chitosan-catechol will be widely used in a variety of medical settings in the future. This review focuses on the various aspects of chitosan-catechol, including its (1) prepn. methods, (2) physicochem. properties, and (3) current applications.
- 28Li, Z.; Xu, Y.; Fan, L.; Kang, W.; Cheng, B. Fabrication of polyvinylidene fluoride tree-like nanofiber via one-step electrospinning. Mater. Des. 2016, 92, 95– 101, DOI: 10.1016/j.matdes.2015.12.03728https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XksVSrsbs%253D&md5=dc259ad5b0a876ca1d2c03e93769e136Fabrication of polyvinylidene fluoride tree-like nanofiber via one-step electrospinningLi, Zongjie; Xu, Yongzheng; Fan, Lanlan; Kang, Weimin; Cheng, BowenMaterials & Design (2016), 92 (), 95-101CODEN: MADSD2; ISSN:0264-1275. (Elsevier Ltd.)A novel polyvinylidene fluoride (PVDF) tree-like nanofiber was controllably fabricated via one-step electrospinning by adding certain amt. of salt into PVDF soln. A possible mechanism for the formation of the tree-like nanofibers was proposed by analyzing high speed camera photos of the spin jet and the result showed that the formation of tree-like nanofibers was due to the splitting of jets. The effects of salt type, salt content and processing parameter on the content of tree-like branches were investigated. The electrospun nanofibers were characterized by field emission SEM(FE-SEM), energy disperse spectroscopy (EDS), X-ray diffraction (XRD), pore size meter and mech. properties measurement. It was found that the PVDF/TBAC tree-like nanofibers with improved crystallinity and mech. strength. The decreased av. pore size caused by the tree-like structure and the resistance to org. solvent, can make it as a potential candidate for membrane sepn.
- 29Hu, C.; Zhang, F.; Long, L.; Kong, Q.; Luo, R.; Wang, Y. Dual-responsive injectable hydrogels encapsulating drug-loaded micelles for on-demand antimicrobial activity and accelerated wound healing. J. Controlled Release 2020, 324, 204– 217, DOI: 10.1016/j.jconrel.2020.05.01029https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXpvVKjtLY%253D&md5=d284004a6bca463f0ff87006c3e396eeDual-responsive injectable hydrogels encapsulating drug-loaded micelles for on-demand antimicrobial activity and accelerated wound healingHu, Cheng; Zhang, Fanjun; Long, Linyu; Kong, Qunshou; Luo, Rifang; Wang, YunbingJournal of Controlled Release (2020), 324 (), 204-217CODEN: JCREEC; ISSN:0168-3659. (Elsevier B.V.)Disease microenvironment stimuli-responsive hydrogels are of special interests in enhancing the drug delivery specificity for biomedical applications. In order to achieve specific drug release characteristic at the inflammation region, a smart pH- and reactive oxygen species (ROS)-responsive injectable hydrogel with self-healing and remodeling capability was designed in our present work. Such hydrogel formulation not only preserved the structural integrity and excellent rheol. properties of the hydrogel but also allowed for a controllable drug release rate at inflammation sites. The antibacterial expt. results in vitro demonstrated that the hydrogel could effectively kill bacteria by amikacin release, with the inhibitive rate reached to 90% for S. aureus and 98% for P.aeruginosa. In addn., it efficiently reduced the levels of TNF-a (the pro-inflammatory cytokine) by 2.80 times, and increased IL-10 (anti-inflammatory cytokine) by 2.41 times than the hydrogel control without antibiotic and anti-inflammatory drug. Within the dual-responsiveness of pH and ROS, the hydrogel reduced the inflammation response of the surrounding tissues significantly and accelerated the healing process of the infected area. Collectively, this smart hydrogel formula contg. antibiotic and drug-loaded micelles is very promising to be applied topically against various microbial infections. We believe that this strategy can also be applied to various disease treatments.
- 30Yu, G.; Dan, N.; Dan, W.; Chen, Y. Wearable Tissue Adhesive Ternary Hydrogel of N-(2-Hydroxyl) Propyl-3-trimethyl Ammonium Chitosan, Tannic Acid, and Polyacrylamide. Ind. Eng. Chem. Res. 2022, 61, 5502– 5513, DOI: 10.1021/acs.iecr.2c0005530https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB38XpvVGhsbk%253D&md5=ac7d53ab3175d530715fbbc2a704e34bWearable Tissue Adhesive Ternary Hydrogel of N-(2-Hydroxyl) Propyl-3-trimethyl Ammonium Chitosan, Tannic Acid, and PolyacrylamideYu, Guofei; Dan, Nianhua; Dan, Weihua; Chen, YiningIndustrial & Engineering Chemistry Research (2022), 61 (16), 5502-5513CODEN: IECRED; ISSN:0888-5885. (American Chemical Society)Bionic electronic skin has aroused widespread attention in intelligent robots, health detection, and other aspects. To improve the inherent fragility and adhesion of the hydrogel, a multifunctional electronic skin mediated by tannic acid and chitosan quaternary ammonium salt was manufd. In this work, by simply mixing chitosan quaternary ammonium salt, tannic acid, and acrylamide without further treatment, a flexible, conductive, and antibacterial adhesive hydrogel was directly prepd. The chitosan quaternary ammonium salt plays a leading role in the electromech. properties and antibacterial properties of the hydrogel. Tannic acid gives the hydrogel good and reproducible adhesion and oxidn. resistance. More importantly, the obtained hydrogel has good sensing properties and can detect mech. conduction signals of human body motion. This work provides a feasible method to prep. hydrogel sensors with high antibacterial efficiency, excellent mech. properties, and good adhesion for broad-range application in human motion detection and intelligence skins.
- 31Habibur, R. M.; Yaqoob, U.; Muhammad, S.; Uddin, A. S. M. I.; Kim, H. C. The effect of RGO on dielectric and energy harvesting properties of P(VDF-TrFE) matrix by optimizing electroactive β phase without traditional polling process. Mater. Chem. Phys. 2018, 215, 46– 55, DOI: 10.1016/j.matchemphys.2018.05.01031https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXps1Oiu7k%253D&md5=aca44bf9bf94c39e43007527a49af6fcThe effect of RGO on dielectric and energy harvesting properties of P(VDF-TrFE) matrix by optimizing electroactive β phase without traditional polling processHabibur, Rahaman Md.; Yaqoob, Usman; Muhammad, Sheeraz; Uddin, A. S. M. Iftekhar; Kim, Hyeon CheolMaterials Chemistry and Physics (2018), 215 (), 46-55CODEN: MCHPDR; ISSN:0254-0584. (Elsevier B.V.)This study explores the role of RGO in improving the energy harvesting potentiality of P(VDF-TrFE) matrix without applying the conventional polling process. Five different piezoelec. sheets were prepd. by varying the RGO contents in P(VDF-TrFE) matrix to realize its optimum concn. in the matrix. The effect of RGO on the electroactive polar beta (β) phase of P(VDF-TrFE) was investigated through the X-ray diffraction (XRD) pattern and the Fourier transform IR spectroscopy (FT-IR). To elaborate the RGO role, dielec. properties of the as-prepd. piezoelec. sheets were also checked over the frequency range of kHz-100 kHz at room temp. Finally, these piezoelec. sheets were used to fabricate the piezoelec. nanogenerators (PENGs) devices. Among the fabricated PENGs, the PENG with 0.1% RGO contents reveals the max. open circuit voltage of 2.4 V and highest peak of short-circuit current around 0.8 μA at an applied force of 2 N. Moreover, it exhibits the highest output power of 3.2 μW at 1.8 MΩ load resistance, all the outputs were recorded without applying polling process. It was estd. that our fabricated self-poled, flexible piezoelec. nanogenerator can be a useful candidate to powering futuristic nanodevices.
- 32Sharma, P.; Reece, T.; Wu, D.; Fridkin, V. M.; Ducharme, S.; Gruverman, A. Nanoscale domain patterns in ultrathin polymer ferroelectric films. J. Phys. Condens. Matter 2009, 21, 485902 DOI: 10.1088/0953-8984/21/48/48590232https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXnvV2itQ%253D%253D&md5=b463fa0aec4014469b615445926a10ffNanoscale domain patterns in ultrathin polymer ferroelectric filmsSharma, P.; Reece, T.; Wu, D.; Fridkin, V. M.; Ducharme, S.; Gruverman, A.Journal of Physics: Condensed Matter (2009), 21 (48), 485902/1-485902/6CODEN: JCOMEL; ISSN:0953-8984. (Institute of Physics Publishing)High-resoln. studies of domain configurations in Langmuir-Blodgett films of ferroelec. polymer poly(vinylidene fluoride-trifluoroethylene), P(VDF-TrFE), have been carried out by means of piezoresponse force microscopy (PFM). Changes in film thickness and morphol. cause significant variations in polarization patterns. In continuous films and nanomesas with relatively low thickness/grain aspect ratio (<1/10), the relationship between the av. domain size and thickness follows the Kittel law. Nanomesas with high aspect ratio (>1/5) exhibit significant deviations from this law, suggesting addnl. surface-energy-related mechanisms affecting the domain patterns. Polarization reversal within a single crystallite has been demonstrated and local switching parameters (coercive voltage and remnant piezoresponse) have been measured by monitoring the local hysteresis loops. Reliable control of polarization at the sub-grain level demonstrates a possibility of studying the mechanism of the intrinsic switching behavior down to the mol. scale.
- 33Baji, A.; Mai, Y. W.; Li, Q.; Liu, Y. Electrospinning induced ferroelectricity in poly(vinylidene fluoride) fibers. Nanoscale 2011, 3, 3068– 3071, DOI: 10.1039/c1nr10467e33https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXhtValtLzI&md5=c62b96967953b1df00e7ddbee84759a0Electrospinning induced ferroelectricity in poly(vinylidene fluoride) fibersBaji, Avinash; Mai, Yiu-Wing; Li, Qian; Liu, YunNanoscale (2011), 3 (8), 3068-3071CODEN: NANOHL; ISSN:2040-3372. (Royal Society of Chemistry)Poly(vinylidene fluoride) (PVDF) fibers with diams. ranging from 70-400 nm are produced by electrospinning and the effect of fiber size on the ferroelec. β-cryst. phase is detd. Domain switching and assocd. ferro-/piezoelec. properties of the electrospun PVDF fibers were also detd. The fibers showed well-defined ferroelec. and piezoelec. properties.
- 34Ji, S.; Yun, J. Fabrication and Characterization of Aligned Flexible Lead-Free Piezoelectric Nanofibers for Wearable Device Applications. Nanomater 2018, 8, 206, DOI: 10.3390/nano804020634https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXpsFSqs78%253D&md5=d217029710b3455ead854e64256bacefFabrication and characterization of aligned flexible lead-free piezoelectric nanofibers for wearable device applicationsJi, Sang Hyun; Yun, Ji SunNanomaterials (2018), 8 (4), 206/1-206/9CODEN: NANOKO; ISSN:2079-4991. (MDPI AG)Flexible lead-free piezoelec. nanofibers, based on BNT-ST (0.78Bi0.5Na0.5TiO3-0.22SrTiO3) ceramic and poly(vinylidene fluoride-trifluoroethylene) (PVDF-TrFE) copolymers, were fabricated by an electrospinning method and the effects of the degree of alignment in the nanofibers on the piezoelec. characteristics were investigated. The microstructure of the lead-free piezoelec. nanofibers was obsd. by field emission scanning electron microscope (FE-SEM) and the orientation was analyzed by fast Fourier transform (FFT) images. X-ray diffraction (XRD) anal. confirmed that the phase was not changed by the electrospinning process and maintained a perovskite phase. Polarization-elec. field (P-E) loops and piezoresponse force microscopy (PFM) were used to investigate the piezoelec. properties of the piezoelec. nanofibers, according to the degree of alignment-the well aligned piezoelec. nanofibers had higher piezoelec. properties. Furthermore, the output voltage of the aligned lead-free piezoelec. nanofibers was measured according to the vibration frequency and the bending motion and the aligned piezoelec. nanofibers with a collector rotation speed of 1500 rpm performed the best.
- 35Zhang, B.; He, J.; Shi, M.; Liang, Y.; Guo, B. Injectable self-healing supramolecular hydrogels with conductivity and photo-thermal antibacterial activity to enhance complete skin regeneration. Chem. Eng. J. 2020, 400, 125994 DOI: 10.1016/j.cej.2020.12599435https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhtlCqtLrM&md5=91f2c8963cbc21ebb022fbd9e2745339Injectable self-healing supramolecular hydrogels with conductivity and photo-thermal antibacterial activity to enhance complete skin regenerationZhang, Beilin; He, Jiahui; Shi, Mengting; Liang, Yuqing; Guo, BaolinChemical Engineering Journal (Amsterdam, Netherlands) (2020), 400 (), 125994CODEN: CMEJAJ; ISSN:1385-8947. (Elsevier B.V.)Hydrogel dressings with good biocompatibility and the ability to maintain a moist environment at the wound site have great potential for clin. application. Multifunctional injectable self-healing supramol. hydrogel with cond. and photo-thermal property as wound dressing to promote wound healing has been not reported. Herein, a series of antibacterial, injectable self-healing and conductive supramol. hydrogels were fabricated through host-guest interaction based on quaternized chitosan-graft-cyclodextrin (QCS-CD), quaternized chitosan-graft-adamantane (QCS-AD) and graphene oxide-graft-cyclodextrin (GO-CD) polymer solns. which combined the good antibacterial activity of QCS and photo-thermal property of reduced graphene oxide (rGO). These supramol. hydrogels wound dressings have a cond. value similar to that of the skin and a rapid self-healing behavior, and have great antibacterial property against E. coli (gram-neg.), S. aureus (gram-pos.), and multi-drug resistant bacteria (such as Methicillin-resistant Staphylococcus aureus, MRSA). Furthermore, QCS-CD-AD/GO4 (0.4 wt% of rGO in the sample) shows a good balance between antibacterial activity, cell proliferation and hemocompatibility. Compared with com. dressings (Tegaderm film) and QCS-CD-AD/GO0, the hydrogel QCS-CD-AD/GO4 significantly accelerated the in vivo healing process of full-thickness wounds with promoted epidermis and granulation tissue thickness, increased area coverage of collagen, and up-regulated VEGF expression. In short, these antibacterial, conductive self-healing supramol. hydrogels are promising biomaterials as wound dressings for full-thickness skin repair.
- 36(a) Correia, C.; Sousa, R. O.; Vale, A. C.; Peixoto, D.; Silva, T. H.; Reis, R. L.; Pashkuleva, I.; Alves, N. M. Adhesive and biodegradable membranes made of sustainable catechol-functionalized marine collagen and chitosan. Colloids Surf., B 2022, 213, 112409 DOI: 10.1016/j.colsurfb.2022.11240936ahttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB38XjvFWqu7s%253D&md5=1f66bbb3cbea51fe91bcf044ca2517c3Adhesive and biodegradable membranes made of sustainable catechol-functionalized marine collagen and chitosanCorreia, Catia; Sousa, Rita O.; Vale, A. Catarina; Peixoto, Daniela; Silva, Tiago H.; Reis, Rui L.; Pashkuleva, Iva; Alves, Natalia M.Colloids and Surfaces, B: Biointerfaces (2022), 213 (), 112409CODEN: CSBBEQ; ISSN:0927-7765. (Elsevier B.V.)We describe bioadhesive membranes developed from marine renewable biomaterials, namely chitosan and collagen extd. from fish skins. Collagen was functionalized with catechol groups (Coll-Cat) to provide the membranes with superior adhesive properties in a wet environment and blended with chitosan to improve the mech. properties. The blended membranes were compared to chitosan and chitosan blended with unmodified collagen in terms of surface morphol., wettability, wt. loss, water uptake, mech. and adhesive properties. The metabolic activity, the viability and the morphol. of L929 fibroblastic cells seeded on these membranes were also assessed. Our results show that the functionalization with catechol groups improves the adhesive and mech. properties of the membranes and enhances cell attachment and proliferation. These data suggest that the developed marine origin-raw membranes present a potential towards the restoration of the structural and functional properties of damaged soft tissues.(b) Chi, J.; Li, A.; Zou, M.; Wang, S.; Liu, C.; Hu, R.; Jiang, Z.; Liu, W.; Sun, R.; Han, B. Novel dopamine-modified oxidized sodium alginate hydrogels promote angiogenesis and accelerate healing of chronic diabetic wounds. Int. J. Biol. Macromol. 2022, 203, 492– 504, DOI: 10.1016/j.ijbiomac.2022.01.15336bhttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB38Xislyrsr0%253D&md5=bf634b781c6b64d4a113bd0b2c1dff2bNovel dopamine-modified oxidized sodium alginate hydrogels promote angiogenesis and accelerate healing of chronic diabetic woundsChi, Jinhua; Li, Ai; Zou, Mingyu; Wang, Shuo; Liu, Chenqi; Hu, Rui; Jiang, Zhiwen; Liu, Wanshun; Sun, Rongju; Han, BaoqinInternational Journal of Biological Macromolecules (2022), 203 (), 492-504CODEN: IJBMDR; ISSN:0141-8130. (Elsevier B.V.)Herein, the dopamine (DA) was grafted with oxidized sodium alginate (OSA) via Schiff base redn. reaction, aiming to fabricate novel DA-grafted OSA (OSA-DA) hydrogels with enhanced biocompatibility and suitable adhesion for clin. applications. The chem. structures of OSA-DA were characterized via UV-Vis, FTIR and 1H NMR spectroscopy anal. The hydrogel characteristics, biocompatibility, as well as the chronic diabetic wound healing efficacy were investigated. Our results demonstrated that DA was grafted with OSA successfully with highest grafting rate of 7.50%. Besides, OSA-DA hydrogels possessed suitable swelling ratio and appropriate adhesion characteristics. Addnl., OSA-DA exhibited satisfactory cytocompatibility and cell affinity in L-929 cells, and superior biocompatibility in SD rats. Moreover, OSA-DA exerted remarkable promoting effects on migration and tube formation of human umbilical vein endothelial cells (HUVECs). Studies on full-thickness excision chronic diabetic wounds further revealed that OSA-DA hydrogels could accelerate healing via promoting angiogenesis, reducing inflammation response, and stimulating collagen deposition. Overall, our studies would provide basis for SA-based hydrogels as clin. wound dressings.
- 37(a) Lee, J. Y.; Bashur, C. A.; Goldstein, A. S.; Schmidt, C. E. Polypyrrole-coated electrospun PLGA nanofibers for neural tissue applications. Biomaterials 2009, 30, 4325– 4335, DOI: 10.1016/j.biomaterials.2009.04.04237ahttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXos1OrtLg%253D&md5=28226b514cd5a834e842c9c0ba8c2f66Polypyrrole-coated electrospun PLGA nanofibers for neural tissue applicationsLee, Jae Y.; Bashur, Chris A.; Goldstein, Aaron S.; Schmidt, Christine E.Biomaterials (2009), 30 (26), 4325-4335CODEN: BIMADU; ISSN:0142-9612. (Elsevier Ltd.)Electrospinning is a promising approach to create nanofiber structures that are capable of supporting adhesion and guiding extension of neurons for nerve regeneration. Concurrently, elec. stimulation of neurons in the absence of topog. features also has been shown to guide axonal extension. Therefore, the goal of this study was to form elec. conductive nanofiber structures and to examine the combined effect of nanofiber structures and elec. stimulation. Conductive meshes were produced by growing polypyrrole (PPy) on random and aligned electrospun poly(lactic-co-glycolic acid) (PLGA) nanofibers, as confirmed by scanning electron micrographs and X-ray photon spectroscopy. PPy-PLGA electrospun meshes supported the growth and differentiation of rat pheochromocytoma 12 (PC12) cells and hippocampal neurons comparable to non-coated PLGA control meshes, suggesting that PPy-PLGA may be suitable as conductive nanofibers for neuronal tissue scaffolds. Elec. stimulation studies showed that PC12 cells, stimulated with a potential of 10 mV/cm on PPy-PLGA scaffolds, exhibited 40-50% longer neurites and 40-90% more neurite formation compared to unstimulated cells on the same scaffolds. In addn., stimulation of the cells on aligned PPy-PLGA fibers resulted in longer neurites and more neurite-bearing cells than stimulation on random PPy-PLGA fibers, suggesting a combined effect of elec. stimulation and topog. guidance and the potential use of these scaffolds for neural tissue applications.(b) Ghasemi-Mobarakeh, L.; Prabhakaran, M. P.; Morshed, M.; Nasr-Esfahani, M. H.; Ramakrishna, S. Electrical Stimulation of Nerve Cells Using Conductive Nanofibrous Scaffolds for Nerve Tissue Engineering. Tissue Eng., Part A 2009, 15, 3605– 3619, DOI: 10.1089/ten.tea.2008.068937bhttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXhsF2hsr%252FE&md5=fb25ba696faa9d2fbcda0a3f55029a6fElectrical stimulation of nerve cells using conductive nanofibrous scaffolds for nerve tissue engineeringGhasemi-Mobarakeh, Laleh; Prabhakaran, Molamma P.; Morshed, Mohammad; Nasr-Esfahani, Mohammad Hossein; Ramakrishna, SeeramTissue Engineering, Part A (2009), 15 (11), 3605-3619CODEN: TEPAB9; ISSN:1937-3341. (Mary Ann Liebert, Inc.)Fabrication of scaffolds with suitable chem., mech., and elec. properties is crit. for the success of nerve tissue engineering. Elec. stimulation was directly applied to electrospun conductive nanofibrous scaffolds to enhance the nerve regeneration process. In the present study, electrospun conductive nanofibers were prepd. by mixing 10 and 15 wt% doped polyaniline (PANI) with poly (ε-caprolactone)/gelatin (PG) (70:30) soln. (PANI/PG) by electrospinning. The fiber diam., pore size, hydrophilicity, tensile properties, cond., Fourier transform IR (FTIR), and XPS spectra of nanofibers were detd., and the in vitro biodegradability of the different nanofibrous scaffolds was also evaluated. Nanofibrous scaffolds contg. 15% PANI was found to exhibit the most balanced properties to meet all the required specifications for elec. stimulation for its enhanced cond. and is used for in vitro culture and elec. stimulation of nerve stem cells. 3-(4,5-Dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay and SEM results showed that conductive nanofibrous scaffolds are suitable substrates for the attachment and proliferation of nerve stem cells. Elec. stimulation through conductive nanofibrous PANI/PG scaffolds showed enhanced cell proliferation and neurite outgrowth compared to the PANI/PG scaffolds that were not subjected to elec. stimulation.
- 38Zhao, M.; Song, B.; Pu, J.; Wada, T.; Reid, B.; Tai, G.; Wang, F.; Guo, A.; Walczysko, P.; Gu, Y. Electrical signals control wound healing through phosphatidylinositol-3-OH kinase-gamma and PTEN. Nature 2006, 442, 457– 460, DOI: 10.1038/nature0492538https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD28XnsVajurs%253D&md5=b606066a5d16ed8efecabc75f18c8ef9Electrical signals control wound healing through phosphatidylinositol-3-OH kinase-γ and PTENZhao, Min; Song, Bing; Pu, Jin; Wada, Teiji; Reid, Brian; Tai, Guangping; Wang, Fei; Guo, Aihua; Walczysko, Petr; Gu, Yu; Sasaki, Takehiko; Suzuki, Akira; Forrester, John V.; Bourne, Henry R.; Devreotes, Peter N.; McCaig, Colin D.; Penninger, Josef M.Nature (London, United Kingdom) (2006), 442 (7101), 457-460CODEN: NATUAS; ISSN:0028-0836. (Nature Publishing Group)Wound healing is essential for maintaining the integrity of multi-cellular organisms. In every species studied, disruption of an epithelial layer instantaneously generates endogenous elec. fields, which have been proposed to be important in wound healing. The identity of signaling pathways that guide both cell migration to elec. cues and elec.-field-induced wound healing have not been elucidated at a genetic level. Here we show that elec. fields, of a strength equal to those detected endogenously, direct cell migration during wound healing as a prime directional cue. Manipulation of endogenous wound elec. fields affects wound healing in vivo. Elec. stimulation triggers activation of Src and inositol-phospholipid signaling, which polarizes in the direction of cell migration. Notably, genetic disruption of phosphatidylinositol-3-OH kinase-γ (PI(3)Kγ) decreases elec.-field-induced signaling and abolishes directed movements of healing epithelium in response to elec. signals. Deletion of the tumor suppressor phosphatase and tensin homolog (PTEN) enhances signaling and electrotactic responses. These data identify genes essential for elec.-signal-induced wound healing and show that PI(3)Kγ and PTEN control electrotaxis.
- 39(a) Damaraju, S. M.; Shen, Y.; Elele, E.; Khusid, B.; Eshghinejad, A.; Li, J.; Jaffe, M.; Arinzeh, T. L. Three-dimensional piezoelectric fibrous scaffolds selectively promote mesenchymal stem cell differentiation. Biomaterials 2017, 149, 51– 62, DOI: 10.1016/j.biomaterials.2017.09.02439ahttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXhs1WqtrrI&md5=863330da32a573fe18f542f112e38189Three-dimensional piezoelectric fibrous scaffolds selectively promote mesenchymal stem cell differentiationDamaraju, Sita M.; Shen, Yueyang; Elele, Ezinwa; Khusid, Boris; Eshghinejad, Ahmad; Li, Jiangyu; Jaffe, Michael; Arinzeh, Treena LivingstonBiomaterials (2017), 149 (), 51-62CODEN: BIMADU; ISSN:0142-9612. (Elsevier Ltd.)The discovery of elec. fields in biol. tissues has led to efforts in developing technologies utilizing elec. stimulation for therapeutic applications. Native tissues, such as cartilage and bone, exhibit piezoelec. behavior, wherein elec. activity can be generated due to mech. deformation. Yet, the use of piezoelec. materials have largely been unexplored as a potential strategy in tissue engineering, wherein a piezoelec. biomaterial acts as a scaffold to promote cell behavior and the formation of large tissues. Here we show, for the first time, that piezoelec. materials can be fabricated into flexible, three-dimensional fibrous scaffolds and can be used to stimulate human mesenchymal stem cell differentiation and corresponding extracellular matrix/tissue formation in physiol. loading conditions. Piezoelec. scaffolds that exhibit low voltage output, or streaming potential, promoted chondrogenic differentiation and piezoelec. scaffolds with a high voltage output promoted osteogenic differentiation. Electromech. stimulus promoted greater differentiation than mech. loading alone. Results demonstrate the additive effect of electromech. stimulus on stem cell differentiation, which is an important design consideration for tissue engineering scaffolds. Piezoelec., smart materials are attractive as scaffolds for regenerative medicine strategies due to their inherent elec. properties without the need for external power sources for elec. stimulation.(b) Jeong, S. I.; Jun, I. D.; Choi, M. J.; Nho, Y. C.; Lee, Y. M.; Shin, H. Development of electroactive and elastic nanofibers that contain polyaniline and poly(L-lactide-co-epsilon-caprolactone) for the control of cell adhesion. Macromol. Biosci. 2008, 8, 627– 637, DOI: 10.1002/mabi.20080000539bhttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1cXovFWgs7g%253D&md5=c74c199a7502323f4340a54acb6368e2Development of electroactive and elastic nanofibers that contain polyaniline and poly(L-lactide-co-ε-caprolactone) for the control of cell adhesionJeong, Sung In; Jun, In Dong; Choi, Moon Jae; Nho, Young Chang; Lee, Young Moo; Shin, HeungsooMacromolecular Bioscience (2008), 8 (7), 627-637CODEN: MBAIBU; ISSN:1616-5187. (Wiley-VCH Verlag GmbH & Co. KGaA)Elec. conductive polyaniline (PAni) doped with camphorsulfonic acid (CPSA) is blended with poly(L-lactide-co-ε-caprolactone) (PLCL), and then electrospun to prep. uniform nanofibers. The CPSA-PAni/PLCL nanofibers show a smooth fiber structure without coarse lumps or beads and consistent fiber diams. (which range from 100 to 700 nm) even with an increase in the amt. of CPSA-PAni (from 0 to 30 wt.-%). However, the elongation at break decreases from 391.54% to 207.85% when 30% of CPSA-PAni is incorporated. Anal. of the surface of the nanofibers demonstrates the presence of homogeneously blended CPSA-PAni. Most importantly, a four-point probe anal. reveals that elec. properties are maintained in the nanofibers where the cond. is significantly increased from 0.0015 to 0.0138 S/cm when the nanofibers are prepd. with 30% CPSA-PAni. The cell adhesion tests using human dermal fibroblasts, NIH-3T3 fibroblasts, and C2C12 myoblasts demonstrate significantly higher adhesion on the CPSA-PAni/PLCL nanofibers than pure PLCL nanofibers. In addn., the growth of NIH-3T3 fibroblasts is enhanced under the stimulation of various d.c. flows. The CPSA-PAni/PLCL nanofibers with elec. conductive properties may potentially be used as a platform substrate to study the effect of elec. signals on cell activities and to direct desirable cell function for tissue engineering applications.
- 40Tandon, N.; Cimetta, E.; Villasante, A.; Kupferstein, N.; Southall, M. D.; Fassih, A.; Xie, J.; Sun, Y.; Vunjak-Novakovic, G. Galvanic microparticles increase migration of human dermal fibroblasts in a wound-healing model via reactive oxygen species pathway. Exp. Cell Res. 2014, 320, 79– 91, DOI: 10.1016/j.yexcr.2013.09.01640https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhs1Clt7vO&md5=458bc6fe0d6a99f0ab71e46ca31e0823Galvanic microparticles increase migration of human dermal fibroblasts in a wound-healing model via reactive oxygen species pathwayTandon, Nina; Cimetta, Elisa; Villasante, Aranzazu; Kupferstein, Nicolette; Southall, Michael D.; Fassih, Ali; Xie, Junxia; Sun, Ying; Vunjak-Novakovic, GordanaExperimental Cell Research (2014), 320 (1), 79-91CODEN: ECREAL; ISSN:0014-4827. (Elsevier B.V.)Elec. signals have been implied in many biol. mechanisms, including wound healing, which has been assocd. with transient elec. currents not present in intact skin. One method to generate elec. signals similar to those naturally occurring in wounds is by supplementation of galvanic particles dispersed in a cream or gel. We constructed a three-layered model of skin consisting of human dermal fibroblasts in hydrogel (mimic of dermis), a hydrogel barrier layer (mimic of epidermis) and galvanic microparticles in hydrogel (mimic of a cream contg. galvanic particles applied to skin). Using this model, we investigated the effects of the properties and amts. of Cu/Zn galvanic particles on adult human dermal fibroblasts in terms of the speed of wound closing and gene expression. The collected data suggest that the effects on wound closing are due to the ROS-mediated enhancement of fibroblast migration, which is in turn mediated by the BMP/SMAD signaling pathway. These results imply that topical low-grade elec. currents via microparticles could enhance wound healing.
- 41Bai, H.; Forrester, J. V.; Zhao, M. DC electric stimulation upregulates angiogenic factors in endothelial cells through activation of VEGF receptors. Cytokine+ 2011, 55, 110– 115, DOI: 10.1016/j.cyto.2011.03.00341https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXmvFWmu7Y%253D&md5=0e33000e6838dec1fe199d1b58f94a3bDC electric stimulation upregulates angiogenic factors in endothelial cells through activation of VEGF receptorsBai, Huai; Forrester, John V.; Zhao, MinCytokine+ (2011), 55 (1), 110-115CODEN: CYTIE9; ISSN:1043-4666. (Elsevier Ltd.)Small d.c. (DC) elec. fields direct some important angiogenic responses of vascular endothelial cells. Those responses indicate promising use of elec. fields to modulate angiogenesis. We sought to det. the regulation of elec. fields on transcription and expression of a serial of import angiogenic factors by endothelial cells themselves. Using semi-quant. PCR and ELISA we found that elec. stimulation upregulates the levels of mRNAs and proteins of a no. of angiogenic proteins, most importantly VEGF165, VEGF121 and IL-8 in human endothelial cells. The up-regulation of mRNA levels might be specific, as the mRNA encoding bFGF, TGF-beta and eNOS are not affected by d.c. elec. stimulation at 24 h time-point. Inhibition of VEGF receptor (VEGFR1 or VEGFR2) signaling significantly decreased VEGF prodn. and completely abolished IL-8 prodn. D.c. elec. stimulation selectively regulates prodn. of some growth factors and cytokines important for angiogenesis through a feed-back loop mediated by VEGF receptors.
- 42Kaur, S.; Lyte, P.; Garay, M.; Liebel, F.; Sun, Y.; Liu, J.-C.; Southall, M. D. Galvanic zinc–copper microparticles produce electrical stimulation that reduces the inflammatory and immune responses in skin. Arch. Dermatol. Res. 2011, 303, 551– 562, DOI: 10.1007/s00403-011-1145-942https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXht1Siur%252FK&md5=c84d8ab24b66c54979dba862d1708eaaGalvanic zinc-copper microparticles produce electrical stimulation that reduces the inflammatory and immune responses in skinKaur, Simarna; Lyte, Peter; Garay, Michelle; Liebel, Frank; Sun, Ying; Liu, Jue-Chen; Southall, Michael D.Archives of Dermatological Research (2011), 303 (8), 551-562CODEN: ADREDL; ISSN:0340-3696. (Springer)The human body has its own innate elec. system that regulates the body's functions via communications among organs through the well-known neural system. While the effect of low-level elec. stimulation on wound repair has been reported, few studies have examd. the effect of elec. potential on non-wounded, intact skin. A galvanic couple comprised of elemental zinc and copper was used to det. the effects of low-level elec. stimulation on intact skin physiol. using a Dermacorder device. Zn-Cu induced the elec. potential recorded on intact skin, enhanced H2O2 prodn. and activated p38 MAPK and Hsp27 in primary keratinocytes. Treatment with Zn-Cu was also found to reduce pro-inflammatory cytokines, such as IL-1α, IL-2, NO and TNF-α in multiple cell types after stimulation with PHA or Propionibacterium acnes bacteria. The Zn-Cu complex led to a dose-dependent inhibition of TNF-α-induced NF-κB levels in keratinocytes as measured by a dual-luciferase promoter assay, and prevented p65 translocation to the nucleus obsd. via immunofluorescence. Suppression of NF-κB activity via crosstalk with p38 MAPK might be one of the potential pathways by which Zn-Cu exerted its inflammatory effects. Topical application of Zn-Cu successfully mitigated TPA-induced dermatitis and oxazolone-induced hypersensitivity in mice models of ear edema. Anti-inflammatory activity induced by the Zn-Cu galvanic couple appears to be mediated, at least in part, by prodn. of low level of hydrogen peroxide since this activity is reversed by the addn. of Catalase enzyme. Collectively, these results show that a galvanic couple contg. Zn-Cu strongly reduces the inflammatory and immune responses in intact skin, providing evidence for the role of elec. stimulation in non-wounded skin.
- 43Mycielska, M. E.; Djamgoz, M. B. Cellular mechanisms of direct-current electric field effects: galvanotaxis and metastatic disease. J. Cell Sci. 2004, 117, 1631– 1639, DOI: 10.1242/jcs.0112543https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2cXjvFCitLs%253D&md5=619afb5bc29369723b3641037d9af85eCellular mechanisms of direct-current electric field effects: Galvanotaxis and metastatic diseaseMycielska, Maria E.; Djamgoz, Mustafa B. A.Journal of Cell Science (2004), 117 (9), 1631-1639CODEN: JNCSAI; ISSN:0021-9533. (Company of Biologists Ltd.)A review. Endogenous direct-current elec. fields (dcEFs) occur in vivo in the form of epithelial transcellular potentials or neuronal field potentials, and a variety of cells respond to dcEFs in vitro by directional movement. This is termed galvanotaxis. The passive influx of Ca2+ on the anodal side should increase the local intracellular Ca2+ concn., whereas passive efflux and/or intracellular redistribution decrease the local intracellular Ca2+ concn. on the cathodal side. These changes could give rise to "push-pull" effects, causing net movement of cells towards the cathode. However, such effects would be complicated in cells that possess voltage-gated Ca2+ channels and/or intracellular Ca2+ stores. Moreover, voltage-gated Na+ channels, protein kinases, growth factors, surface charge and electrophoresis of proteins have been found to be involved in galvanotaxis. Galvanotactic mechanisms might operate in both the short term (seconds to minutes) and the long term (minutes to hours), and recent work has shown that they might be involved in metastatic disease. The galvanotactic responses of strongly metastatic prostate and breast cancer cells are much more prominent, and the cells move in the opposite direction compared with corresponding weakly metastatic cells. This could have important implications for the metastatic process and has clin. implications. Galvanotaxis could thus play a significant role in both cellular physiol. and pathophysiol.
- 44Kotwal, A. Electrical stimulation alters protein adsorption and nerve cell interactions with electrically conducting biomaterials. Biomaterials 2001, 22, 1055– 1064, DOI: 10.1016/S0142-9612(00)00344-644https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3MXisVWjurY%253D&md5=5a346be5925b5e8c2097c8cdc081f7dcElectrical stimulation alters protein adsorption and nerve cell interactions with electrically conducting biomaterialsKotwal, A.; Schmidt, C. E.Biomaterials (2001), 22 (10), 1055-1064CODEN: BIMADU; ISSN:0142-9612. (Elsevier Science Ltd.)Elec. charges have been shown to enhance nerve regeneration; however, the mechanisms for this effect are unclear. One hypothesis is that an elec. stimulus alters the local elec. fields of extracellular matrix mols., changing protein adsorption. We have investigated this hypothesis - that elec. stimulation increases the adsorption of serum proteins, specifically fibronectin (FN), to the elec. conducting polymer polypyrrole (PP), thereby, increasing neurite extension. PP was used because elec. stimulation of PP has been shown to significantly enhance neurite outgrowth, and more importantly, PP can be formed into conduits to guide nerve regeneration in vivo. Here, we looked at the effects of elec. stimulation on protein adsorption when an elec. current was applied to PP (1) during protein adsorption (immediate stimulation) and (2) several hours after protein adsorption (delayed stimulation). We found that immediate stimulation of PP increases FN adsorption from purified FN and serum-contg. solns. Correspondingly, PC-12 cells grown on PP films that had been previously adsorbed with FN during immediate stimulation expressed longer neurites. However, for delayed stimulation, no significant differences in adsorption or neurite outgrowth were obsd. These studies suggest that increased FN adsorption with immediate elec. stimulation may explain enhanced neurite extension on elec. stimulated PP.
- 45Balakatounis, K. Electrical stimulation for wound healing. In Advanced Wound Repair Therapies; Woodhead Publishing Limited, 2011; pp. 571– 586.There is no corresponding record for this reference.
- 46Torkaman, G. Electrical Stimulation of Wound Healing: A Review of Animal Experimental Evidence. Adv. Wound Care 2014, 3, 202– 218, DOI: 10.1089/wound.2012.040946https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC2sbpvVWltQ%253D%253D&md5=16d6acf7e898551707219dfc9427b1cfElectrical Stimulation of Wound Healing: A Review of Animal Experimental EvidenceTorkaman GitiAdvances in wound care (2014), 3 (2), 202-218 ISSN:2162-1918.Significance: Electrical stimulation (ES) is a therapeutic intervention that may help specialists facilitate wound healing rates. The purpose of this section is to compile the available animal research regarding the effectiveness of ES on the injury potential, healing rate, cellular and molecular proliferation, mechanical properties, and survival rate of skin flaps. Recent Advances: Regardless of the type of ES current and polarity used, most of the animal experimental evidence suggests that application of ES can facilitate wound healing. However, treatment time should be sufficiently long to attain good mechanical strength of regenerated tissue, because tensile strength is not consistent with augmented collagen deposition. ES improves the survival rate and skin blood flow of animal flaps, but clinical studies are needed to substantiate the findings from these animal experiments. Critical Issues: Impaired or delayed healing is a major clinical problem that can lead to wound chronicity. ES with various strategies has been used to facilitate the healing process, but many aspects remain controversial. Despite much research, no consensus exists regarding the detailed effects of ES on wound healing. Nevertheless, ES has been approved by the Center for Medicare and Medicine Services for reimbursement of the treatment of some chronic ulcers. Future Directions: Exogenous ES may promote the directional migration of cells and signaling molecules via electrotaxis; however, its underlying mechanism is still poorly understood. Future studies that further elucidate the mechanisms regulating electrotaxis will be necessary to optimize the use of ES in different wound states.
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Supporting Information
The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acs.biomac.2c01520.
SEM images, diameter distribution, typical stretch curves, tensile strength, elongation at break, contact angle, open circuit voltage output curves, FTIR spectra, XRD patterns of P(VDF-TrFE) NFs with different additives; conductivity of P(VDF-TrFE) electrospinning solution; SEM images, pore size distribution, mean pore size, and porosity, rheological properties, water content, swelling rate, conductivity, and adhesion strength of hydrogels; the H&E staining, bFGF immunohistochemical analysis, PDGF immunohistochemical analysis, and VEGF immunohistochemical analysis of wound areas treated by the CF-Gel-PAM hydrogel and gauze control group (PDF)
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