Genetically Encodablein situGelation Redox-Responsive Collagen-Like Protein Hydrogel for Accelerating Diabetic Wound Healing

Abstract Genetically encoded collagen-like protein-based hydrogels have demonstrated remarkable efficacy in promoting the healing process in diabetic patients. However, the current methods for preparing these hydrogels pose significant challenges due to harsh reaction conditions and the reliance on chemical crosslinkers. In this study, we present a genetically encoded approach that allows for the creation of protein hydrogels without the need for chemical additives. Our design involves the genetic encoding of paired-cysteine residues at the C- and N-terminals of a meticulously engineered collagen-like recombination protein. The protein-based hydrogel undergoes a gel-sol transition in response to redox stimulation, achieving a sol-gel transition. We provide evidence that the co-incubation of the protein hydrogel with 3T3 cells not only enhances cell viability but also promotes cell migration. Moreover, the application of the protein hydrogel significantly accelerates the healing of diabetic wounds by upregulating the expression of COL-1α and CK-14, while simultaneously reducing oxidant stress in the wound microenvironment. Our study highlights a straightforward and chemical-free strategy for the preparation of redox-responsive protein hydrogels. Importantly, our findings underscore the potential of this hydrogel system for effectively treating diabetic wounds, offering a promising avenue for future therapeutic applications.