Dual-network gallic acid-functionalized chitosan methacryloyl/FGelMA hydrogel for diabetic wound healing via enhanced...

Excessive oxidative stress, persistent chronic inflammation, impaired angiogenesis, and delayed extracellular matrix (ECM) remodeling contribute to the chronic non-healing of diabetic wounds, which is a major clinical challenge worldwide that decreases patients' quality of life. Herein, a novel photocrosslinked hydrogel based on gallic acid functionalized chitosan methacryloyl (GA-CSMA) and fish gelatin methacryloyl (FGelMA) was developed for diabetic chronic wound treatment without exogenous therapeutic agents to provide structural stability and intrinsic bioactivity. Quantitative pore-size analysis and bulk mechanical testing confirmed that incorporation of GA-CSMA generated a denser porous architecture and improved the compressive and tensile mechanical performance of the FGelMA-based hydrogel. In addition, the optimized hydrogel formulation showed cytoprotective effects against oxidative stress by reducing intracellular reactive oxygen species (ROS) and exhibited macrophage-associated immunomodulatory activity, as evidenced by reduced pro-inflammatory mediators and enhanced pro-healing marker expression. Furthermore, GM/G-CMIII significantly promotes the proliferation, migration and in vitro angiogenesis. In vivo experiments further reveal that the hydrogel significantly accelerated wound closure via improved re-epithelialization, collagen production, and neovascularization and modulated macrophage polarization toward M2 phenotype in full-thickness wound model in streptozotocin (STZ)-induced diabetic mice. Therefore, this photocrosslinked hydrogel system can serve as a promising wound dressing for hard-to-heal chronic wounds.