Calcium-copper bimetallic peroxide with intrinsic H2O2 supply and catalysis for biofilm elimination and wound repair

Infections involving antimicrobial resistant (AMR) bacteria have become a major global health threat. Pathogenic bacteria employ diverse resistance mechanisms, including drug target bypass, target modification, and biofilm formation, to evade therapeutic intervention. However, current strategies that simultaneously eradicate biofilms, resolve excessive inflammation, and promote tissue regeneration remain limited. To address this unmet need, herein we report a self-catalytic antimicrobial platform based on calcium copper bimetallic peroxide nanoparticles (CuCaOx), constructed by incorporating Cu species into the CaO 2 lattice. This design enables sustained self-supply of H 2 O 2 followed by its in situ Cu-mediated Fenton-like conversion into multiple highly cytotoxic reactive oxygen species ( OH, 1 O 2 , and O 2 − ), establishing a self-supplied, self-catalyzed cascade that circumvents the inherently sluggish ROS generation kinetics of pristine CaO 2 . CuCaOx exhibited potent antibiofilm activity against methicillin-resistant Staphylococcus aureus (MRSA) via membrane depolarization, structural disintegration, and ATP depletion, along with favorable biocompatibility. In a MRSA-infected murine full-thickness skin defect model, CuCaOx accelerated wound closure, attenuated inflammatory infiltration, promoted organized collagen deposition, extracellular matrix remodeling and re-epithelialization, thereby improving infected wound repair. Transcriptomic analysis revealed treatment-associated changes in immune response-, bacterial infection-, and lipid metabolism-related pathways, which may partly reflect the reduced bacterial burden and improved wound microenvironment following CuCaOx treatment. This work presents an integrated metal peroxide nanoplatform that combines biofilm eradication and wound reparative functions for the management of infected wounds.