Photocrosslinked polylysine/oxidized hyaluronic acid double-network hydrogel with anti-inflammatory and antibacterial functions for skin wound healing.

Conventional wound dressings often struggle to simultaneously address infection control, inflammatory regulation, and tissue regeneration during skin wound healing. To overcome these limitations, we developed a multifunctional dual-network hydrogel dressing (GE-OHA2@Rut), which integrates antibacterial, anti-inflammatory, and pro-regenerative functions. This system was constructed via UV-initiated crosslinking of methacrylated poly-l-lysine (GE) and Schiff base crosslinking of oxidized hyaluronic acid (OHA), followed by incorporation of the natural anti-inflammatory flavonoid rutin. The GE-OHA2@Rut exhibited outstanding physicochemical properties, including improved mechanical properties, suitable swelling capacity, structural integrity, sustained drug release and antioxidant capacity. CCK-8 assay revealed that GE-OHA2@Rut significantly promoted L929 cell proliferation with >90% cell viability. It also accelerated cell migration, effectively reducing TNF-α levels and increasing IL-10 expression. Moreover, the composite hydrogel exhibited broad spectrum antimicrobial activity against Staphylococcus aureus and Escherichia coli. The full-thickness wound model by Kunming mice demonstrated that GE-OHA2@Rut group achieved the best wound closure within 14 days. Histological evaluation revealed enhanced collagen deposition by Masson staining and reduced inflammatory infiltration by H&E staining, which confirmed effective tissue remodeling and inflammation resolution. This dual-network hydrogel GE-OHA2@Rut provides an innovative solution for skin wound repair through synergistic anti-inflammatory, antibacterial, and tissue regeneration mechanisms, which offers a promising advanced strategy for comprehensive wound management.