ZnO‐CuS/F127 Hydrogels with Multienzyme Properties for Implant‐Related Infection Therapy by Inhibiting Bacterial Arginine Biosynthesis and Promoting Tissue Repair

Abstract Implant‐related infections are characterized by the formation of bacterial biofilms. Current treatments have various drawbacks. Nanozymes with enzyme‐like activity can produce highly toxic substances to kill bacteria and remove biofilms without inducing drug resistance. However, it is difficult for current monometallic nanozymes to function well in complex biofilm environments. Therefore, the development of multimetallic nanozymes with efficient multienzyme activities is crucial. In the present study, bimetallic nanozyme, ZnO‐CuS nanoflowers with peroxidase (POD), glutathione oxidase (GSH‐Px), and catalase (CAT) activity are successfully synthesized via calcination and loaded into F127 hydrogels for the treatment of implant‐related infections. The ability of ZnO‐CuS nanoflowers to bind bacteria is key for efficient antimicrobial activity. In addition, ZnO‐CuS nanoflowers with H 2 O 2 disrupt the metabolism of MRSA , including arginine synthesis, nucleotide excision repair, energy metabolism, and protein synthesis. ZnO‐CuS/F127 hydrogel in combination with H 2 O 2 has been demonstrated to be effective in clearing biofilm infection and facilitating the switch of M1 macrophages to M2‐repairative phenotype macrophages for the treatment of implant infections in mice. Furthermore, ZnO‐CuS/F127 hydrogels have favorable biosafety, and their toxicity is negligible. ZnO‐CuS/F127 hydrogel has provided a promising biomedical strategy for the healing of implant‐related infections, highlighting the potential of bimetallic nanozymes for clinical applications.