NIR-Enhanced Catalytic High Entropy Alloy Nanozyme Hydrogel for Synergistic Biofilm Elimination and Wound Regeneration

Drug-resistant bacterial biofilm infections severely impede wound healing. Here, we report a nanozyme-integrated hydrogel (HEA@OAH) that combines high-entropy alloy nanozymes with an injectable self-healing hydrogel cross-linked by dynamic Schiff base bonds for treating methicillin-resistant Staphylococcus aureus (MRSA) biofilm-infected wounds. Under NIR irradiation, HEA@OAH exerts photothermal therapy to disrupt biofilms and photothermally enhances dual enzyme-mimicking activities: peroxidase-like activity generates bactericidal ·OH from H2O2, while glutathione peroxidase-like activity scavenges excess H2O2, to protect tissue. Theoretical calculations reveal the synergistic effects of multimetallic sites. In vitro, the reduction rate of the MRSA biofilm reached 84.5%. In vivo, it effectively eliminates biofilms, alleviates inflammation, and promotes near-scarless wound healing. This study provides a synergistic therapeutic strategy for next-generation intelligent wound dressings.