Collagen‐polyurethane‐dextran hydrogels enhance wound healing by inhibiting inflammation and promoting collagen fibrillogenesis

Abstract Diabetic foot ulcers are a serious complication of uncontrolled diabetes, emphasizing the need to develop wound healing strategies that are not only effective but also biocompatible, biodegradable, and safe. We aimed to create biomatrices composed of semi‐interpenetrated polymer networks of collagen, polyurethane, and dextran, to enhance the wound healing process. The hydrogels were extensively characterized by various analytical techniques, including analysis of their structure, crystallinity, thermal properties, gelation process, reticulation, degradation, cell proliferation, and healing properties, among others. Semi‐interpenetrated hydrogels containing dextran at levels of 10%, 20%, and 30% exhibited porous interconnections between collagen fibers and entrapped dextran granules, with a remarkable crosslinking index of up to 94% promoted by hydrogen bonds. These hydrogels showed significant improvements in mechanical properties, swelling, and resistance to proteolytic and hydrolytic degradation. After 24 h, there was a significant increase in the viability of several cell types, including RAW 264.7 cells, human peripheral blood mononuclear cells, and dermal fibroblasts. In addition, these hydrogels demonstrated an increased release of interleukin‐10 and transforming growth factor‐beta1 while inhibiting the release of monocyte chemotactic protein‐1 and tumor necrosis factor‐alpha after 72 h. Furthermore, these hydrogels accelerated the wound healing process in diabetic rats after topical application. Notably, the biomaterial with 20% dextran (D20) facilitated wound closure in only 21 days. These results highlight the potential of the D20 hydrogel, which exhibits physicochemical and biological properties that enhance wound healing by inhibiting inflammation and fibrillogenesis while remaining safe for application to the skin.