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Research Article | Open Access

Protein-based functional hydrogel improves cutaneous nerve repair and diabetic wound healing

Hanzhi Lu1,§, Mingrui Cui2,§, Yi Wang1,§, Xinran Du1, Xinyi Zhou1, Yuhan Fang1, Xiaoyan Gao1, Ying Peng3, Jianyong Zhu3, Guang Yang2 ( ), Fulun Li1 ( )
Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, China
Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative Medicine, College of Biological Science and Medical Engineering, Donghua University, Shanghai 201620, China
Clinical Laboratory Medicine Center, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, China

§ Hanzhi Lu, Mingrui Cui, and Yi Wang contributed equally to this work.

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Graphical Abstract

This work addresses the challenge of impaired nerve regeneration in diabetic ulcers through the development of a novel dynamic cross-linked hydrogel based on natural proteins. The hydrogel displays injectability, skin adhesion, and antimicrobial capacity, and demonstrates accelerated cutaneous nerve regeneration and angiogenic processes in full-thickness diabetic ulcers.

Abstract

Cutaneous nerve regeneration in diabetic wounds remains a challenge for current clinical treatment. Herein, a natural protein-based functional hydrogel is developed using keratin as the sole matrix, and protocatechuic aldehyde (PA) and zinc ions as the building blocks through dual-dynamic crosslinking reactions of thiol-aldehyde addition and catechol-zinc ions coordination. The unique structural design endows the hydrogel with excellent injectability, skin adhesion, self-healing and antibacterial ability, and biocompatibility. In addition, this hydrogel acts as a drug carrier for the loading and sustained release of phellopterin (PP), a natural compound extracted from traditional Chinese medicine Angelica dahurica. Our findings demonstrate that the PP-loaded hydrogel promotes cutaneous nerve regeneration, angiogenesis and tissue remodeling in the full-thickness wounds in both db/db and streptozotocin-induced C57BL/6 diabetic mice, notably by the synergistic effect of zinc ions and PP, showing a great potential in diabetic wound therapy.

Keywords

functional hydrogelcutaneous nerve regenerationdynamic crosslinkingdiabetic wounds

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Nano Research
Volume 18 Issue 1,
January 2025
Article number: 94907012
DOI: 10.26599/NR.2025.94907012
Cite this article:
Lu H, Cui M, Wang Y, et al. Protein-based functional hydrogel improves cutaneous nerve repair and diabetic wound healing. Nano Research, 2025, 18(1): 94907012. https://doi.org/10.26599/NR.2025.94907012
Topics:
Nano biology

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Received: 05 July 2024
Revised: 22 August 2024
Accepted: 28 August 2024
Published: 25 December 2024
© The Author(s) 2025. Published by Tsinghua University Press.

This is an open access article under the terms of the Creative Commons Attribution 4.0 International License (CC BY 4.0, https://creativecommons.org/licenses/by/4.0/).
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