Biomimetic Hydrogel Scaffolds with Copper Peptide‐Functionalized RADA16 Nanofiber Improve Wound Healing in Diabetes

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 advantages to provide a biomimetic extracellular matrix nanofiber structure. However, it still lacks biological cues to promote angiogenesis that is of vital significance for diabetic wound healing. With a customized copper peptide glycyl‐histidyl‐lysine (GHK) functionalized RADA16, an integrated approach using functionalized RADA16 nanofiber to chelate copper ion, is innovatively proposed in this present study. The acquired composite hydrogel holds the biomimetic nanofiber architecture, and exhibits promoting angiogenesis by both enhancing adhesion and proliferation of endothelial cells (EC) in vitro and neovascularization in vivo. It shows that the functionalized nanofiber scaffolds significantly accelerated wound closure, collagen deposition, and tissue remodeling both in healthy and diabetic mice. Furthermore, immunohistochemical analysis give 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.

Self-Assembling Peptide SCIBIOIII Hydrogel for Three-Dimensional Cell Culture That Promotes Wound Healing in Diabetic Mice

“…Recently, hydrogel-based dressings have shown powerful effects in accelerating trauma-repairing in animal experiments and clinical trials [ 15 , 18 , 19 ]. Promising results have been shown by SAP hydrogels when promoting the regenerative repair of nerve injuries [ 20 ], cartilage regeneration [ 21 ], and skin wound healing [ 22 ], owing to the unique advantage of mimicking natural ECM. However, the ability of SAP hydrogel therapy alone to treat diabetic wounds still needs to be explored.…”

Peptide Hydrogels and Nanostructures Controlling Biological Machinery

“…For example, RADA16 peptide nanofiber has advantages in providing an ECM-like environment for promoting cell attachment and proliferation. Utilization of this scaffold in combination with a copper peptide glycyl-histidyl-lysine (GHK) functionalized the system to also promote angiogenesis and accelerate diabetic wound closure . The design and integration of bioactive peptides into scaffold materials should take into consideration the application of the material, tissue type, and presentation of epitopes presented in the peptide network.…”

Recent advances in the medical applications of hemostatic materials

“…They demonstrated that the peptide significantly reduced bleeding time and reduced bleeding volume 119 . Yang et al prepared a copper peptide-functionalized RADA16 system that was used to study a diabetic mouse model to effectively accelerate the processes of wound closure and tissue repair 26 . Self-assembled peptide sequences can be potentially used to realize hemostasis, although some persistent disadvantages hinder their clinical applications.…”