Dendrite-Structured and Multienzyme-Like AuCu@Pd Metallic Hydrogels for Methicillin-Resistant Staphylococcus aureus-Infected Wound Healing

Antimicrobial resistance has become a pivotal global public health concern, significantly moderating the effectiveness of antibiotic therapies. Metallic hydrogels, as a highly representative nanozyme, have shown promise in combating drug-resistant bacterial infections. Herein, we develop an innovative AuCu@Pd hydrogel nanozyme utilizing a facile water/ethanol-phase method, achieving gelation within 40 min. The building blocks of AuCu@Pd hydrogels exhibit dendritic and core–shell structures, facilitated by the regulation of nanowire-like morphologies through galvanic replacement and ascorbic acid induction effects. The AuCu@Pd hydrogels demonstrate peroxidase-like (POD-like) and oxidase-like (OD-like) activities, facilitating the conversion of H2O2 and O2 into highly cytotoxic reactive oxygen species (ROS) to disrupt bacterial cell structures. Moreover, the AuCu@Pd hydrogels modulate the infectious microenvironment by depleting glutathione (GSH), thereby promoting the production of reactive oxygen species (ROS) and enhancing their bactericidal effects against methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli (E. coli). Notably, AuCu@Pd hydrogels demonstrate a high photothermal conversion efficiency (η) of 61.1% and superior photothermal stability, significantly boosting the multienzyme-like activity for efficient antibacterial therapy. In addition, these hydrogels exhibit excellent biocompatibility in vivo and significantly accelerate MRSA-infected skin wound healing. This work offers novel insights into the design of highly efficient metallic hydrogels and proposes an effective strategy for the synergistic treatment of MRSA infections for biomedical applications.