A WR3-NH2-loaded polysaccharide hydrogel with antibacterial, anti-inflammatory, and pro-healing properties for enhanced wound healing.

Wound healing is a complex process often compromised by infection, excessive inflammation, and impaired tissue regeneration. In this study, the antimicrobial peptide WR3-NH2 loaded multifunctional polysaccharide hydrogel (SGHC-WR) was developed. This hydrogel demonstrated favorable physicochemical properties, including porosity, injectability, degradability, and sustained release capability, while maintaining stability under storage conditions. In vitro studies indicated that WR3-NH2 significantly enhanced the proliferation and migration of HUVECs, HFF, and HaCaT cells, while also regulating cytokine secretion and modulating the MAPK signaling pathway to mitigate inflammation. SGHC-WR exhibited strong antimicrobial activity against both Gram-positive and Gram-negative bacteria, including resistant strains, with low hemolysis rates and excellent cytocompatibility. In vivo evaluations using a full-thickness skin wound model in mice revealed that SGHC-WR accelerated wound closure, enhanced angiogenesis, promoted collagen deposition, and facilitated tissue remodeling. Histological analysis confirmed the regeneration of well-structured epidermis and hair follicles, while biosafety assessments showed no pathological damage in major organs and no dermal irritation following repeated application. Collectively, these findings demonstrate that SGHC-WR creates an optimized wound healing microenvironment by integrating antibacterial, anti-inflammatory, and regenerative functions. This work highlights SGHC-WR as a promising therapeutic biomaterial for advanced wound management and offers new insights into the synergistic application of antimicrobial peptides and polysaccharide hydrogels in regenerative medicine.