Pro-angiogenic functionalized hyaluronic acid-based hydrogel encapsulating metformin coordinates in situ...

Diabetic wounds present significant challenges due to persistent inflammation and impaired angiogenesis, often resulting in delayed healing or, in severe cases, amputation. Hence, there is an urgent need for innovative wound dressings tailored to the specific needs of diabetic wounds. Deferoxamine (DFO) and metformin (Met) offer promising properties for promoting angiogenesis and modulating the immune-inflammatory response, respectively, but their burst release limits their further application in wound management. Based on this, we developed a novel multifunctional diabetic wound dressing composed of DFO-grafted hyaluronic acid methacrylate (HAMA) hydrogel loaded with Met (Met/DMA hydrogel). In vitro studies demonstrated that the Met/DMA hydrogel enhances fibroblast proliferation and migration, reduces intracellular reactive oxygen species, and accelerates endothelial cell angiogenesis and macrophage polarization to an anti-inflammatory phenotype. Animal experiments further revealed that the hydrogel significantly accelerated wound healing in diabetic rats (41.6±8.7 % improvement vs. control group) by promoting neovascularization, collagen maturation, and regulation of the inflammatory microenvironment at the wound site. In conclusion, this study successfully developed a Met/DMA hydrogel platform that effectively treats diabetic wounds through synergistic promotion of angiogenesis and modulation of the immune-inflammatory response.