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Electrical stimulation-based conductive hydrogel for immunoregulation, neuroregeneration and rapid angiogenesis in diabetic wound repair

基于电刺激的导电水凝胶用于糖尿病伤口修复中的免疫调节、 神经再生和快速血管生成

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Abstract

Diabetic wounds are hard-healing chronic wounds, mainly caused by wound infection, excessive inflammation, diabetic neuropathy, and peripheral vascular disease. Hence, comprehensive improvement of diabetic wound healing is of great significance in clinical practice. However, the current research on diabetic wounds mainly focuses on wound infection and angiogenesis, lacking the exploration of neuroregeneration and immunomodulation. In this study, we develop a multifunctional conductive hydrogel (PACPH) based on polydopamine-modified silver nanoparticles (AgNPs@PDA), cellulose nanocrystals (CNC)/polypyrrole (PPy) composites, and polyvinyl alcohol as an efficient wound dressing. The PACPH scaffold features multiple functions, including desirable mechanical properties, tissue adhesion, conductivity, and broad-spectrum antibacterial activity. Inspired by the endogenous electric field, the strategy of combining hydrogel with electrical stimulation (ES) is also proposed to accelerate the healing of diabetic wounds. Notably, the participation of ES can effectively promote nerve repair, realize the polarization of macrophages toward the M2 phenotype, and rapid angiogenesis, comprehensively improving the healing of diabetic wounds. This advanced collaborative strategy opens a new avenue in treating diabetic wounds.

摘要

糖尿病创面是难以愈合的慢性创面, 主要由创面感染、 过度炎症、 糖尿病神经病变、 外周血管病变等引起. 因此, 全面改善糖尿病创面愈合在临床上具有重要意义. 然而, 目前对糖尿病创面的研究主要集中在创面感染和血管生成方面, 缺乏对神经再生和免疫调节的探索. 在这项研究中, 我们开发了多功能导电水凝胶作为一种有效的伤口敷料. 该水凝胶具有多种功能, 包括优异的机械性能、 组织粘附性、 导电性和广谱抗菌活性. 受内源性电场的启发, 我们提出了将水凝胶与电刺激相结合的策略来加速糖尿病伤口的愈合. 值得注意的是, 电刺激结合导电水凝胶的治疗手段可有效促进神经修复, 实现巨噬细胞向M2表型的极化以及快速血管生成, 从而全面改善糖尿病创面的愈合. 这种先进的协作策略为治疗糖尿病伤口开辟了一种新途径.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (81901365 and 82003284), the Department of Finance of Jilin Province (2019SRCJ005 and 2020SCZT051), Jilin Science and Technology Agency Funds in China (20210402001GH), the Key Research and Development Project of Jilin Provincial Science and Technology Department (20210204142YY), and the Norman Bethune Program of Jilin University (2022B44).

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Authors and Affiliations

  1. State Key Laboratory of Supramolecular Structure and Materials, College of Chemistry, Jilin University, Changchun, 130000, China

    Lin Guan  (关琳), Ze Wang  (王泽), Xingchen Li  (李星辰), Yubin Feng  (冯钰斌), Xinting Yang  (杨欣婷), Bai Yang  (杨柏) & Quan Lin  (林权)

  2. Department of Hand Surgery, The Second Hospital of Jilin University, Changchun, 130041, China

    Xiaolan Ou  (欧小兰) & Wenrui Qu  (瞿文瑞)

Authors
  1. Lin Guan  (关琳)
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  2. Xiaolan Ou  (欧小兰)
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  3. Ze Wang  (王泽)
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  4. Xingchen Li  (李星辰)
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  9. Quan Lin  (林权)
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Contributions

Author contributions Guan L designed the research ideas and wrote the article. Ou X performed the animal experiment. Wang Z, Li X, Feng Y, and Yang X participated in the data analysis. Qu W, Yang B, and Lin Q conceived and guided the program. All authors contributed to the general discussion.

Corresponding authors

Correspondence to Wenrui Qu  (瞿文瑞) or Quan Lin  (林权).

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Conflict of interest The authors declare that they have no conflict of interest.

Additional information

Supplementary information Experimental details and supporting data are available in the online version of the paper.

Lin Guan is currently a PhD candidate at the State Key Laboratory of Supramolecules, Jilin University. Her current research focuses on the design of adhesive hydrogel materials as well as their applications for diabetic wound dressing.

Wenrui Qu is a deputy chief physician at the Department of Hand Surgery, the Second Hospital of Jilin University, a doctor of medicine, and a postgraduate tutor. He received his PhD degree from Jilin University and worked as a visiting scholar at the School of Medicine, Indiana University-Purdue University Indianapolis, from 2013 to 2016. His research focuses on mechanisms of neuroprotection, nerve regeneration and diabetic neuropathy and unique repair strategies to promote healing of diabetic wound.

Quan Lin is a professor at the State Key Laboratory of Supramolecules, Jilin University. His current research focuses on the application of polymer hydrogels in medical dressings, flexible electronics, and energy storage.

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Electrical stimulation-based conductive hydrogel for immunoregulation, neuroregeneration and rapid angiogenesis in diabetic wound repair

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Guan, L., Ou, X., Wang, Z. et al. Electrical stimulation-based conductive hydrogel for immunoregulation, neuroregeneration and rapid angiogenesis in diabetic wound repair. Sci. China Mater. 66, 1237–1248 (2023). https://doi.org/10.1007/s40843-022-2242-y

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