Dendrite-Structured and Multienzyme-Like AuCu@Pd Metallic Hydrogels for Methicillin-Resistant <i>Staphylococcus aureus</i> -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 <i>Staphylococcus aureus</i> (<i>MRSA</i>) and <i>Escherichia coli</i> (<i>E. coli</i>). 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 <i>in vivo</i> and significantly accelerate <i>MRSA</i>-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 <i>MRSA</i> infections for biomedical applications.