Gelatin-based injectable hydrogel with dual ROS generation and biofilm disruption for infected wound healing

Chronic wounds present a major clinical challenge due to methicillin-resistant Staphylococcus aureus (MRSA) biofilm formation. Here, we developed an injectable gelatin-based hydrogel (Pgel-EGCG-DMY) with dynamic spatiotemporal antibacterial activity. By integrating epigallocatechin gallate (EGCG) and dihydromyricetin (DMY), the hydrogel enabled pH-responsive release, synergistically induces reactive oxygen species (ROS) generation and MRSA biofilm disruption. The hydrogel exhibited robust mechanical property, self-healing ability, and achieved>90% antibacterial efficacy against MRSA via combined ROS induction and gene expression (lrgA/B, mprF, narK/nasA, and saeR/S). In vivo, it accelerated tissue repair by downregulating pro-inflammatory cytokines (TNF-α, IL-1β), upregulating anti-inflammatory factors (IL-10, TGF-β), and promoting angiogenesis. This intelligent hydrogel platform offers a promising strategy for treating drug-resistant wound infections.