Photocrosslinked polylysine/oxidized hyaluronic acid double-network hydrogel with anti-inflammatory and antibacterial...

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.