Wound healing in diabetes is retarded by the dysfunctional local microenvironment. Although there are many studies using hydrogels as substitutes for natural extracellular matrices (ECMs), hydrogels that can mimic both… Click to show full abstract
Wound healing in diabetes is retarded by the dysfunctional local microenvironment. Although there are many studies using hydrogels as substitutes for natural extracellular matrices (ECMs), hydrogels that can mimic both the structure and functions of natural ECM remain a challenge. Self-assembling peptide RADA16 nanofiber has distinct advantageous to provide a biomimetic extracellular matrix nanofiber structure. However, it is still lack of biological cues to promote angiogenesis that is of vital significance for diabetic wounds healing. With a customized copper peptide GHK functionalized RADA16, an integrated approach using functionalized RADA16 nanofiber to chelate copper ion, has been innovatively proposed in this present study. The acquired composite hydrogel held the biomimetic nanofiber architecture, and exhibited promoting angiogenesis by both enhancing adhesion and proliferation of endothelial cells (EC) in vitro and neovascularization in vivo. It showed that the functionalized nanofiber scaffolds significantly accelerated wound closure, collagen deposition, and tissue remodeling both in healthy and diabetic mice. Furthermore, immunohistochemical analysis gave evidence that an upregulated expression of eNOS and CD31 in the copper peptide-functionalized RADA16 treated group. It can be envisioned that this scaffold can serve as a promising dressing for diabetic wound healing. This article is protected by copyright. All rights reserved.
               
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