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Implant-related infections often involve stubborn biofilm formation, antibiotic resistance, and immune evasion, and because traditional treatments are limited, they pose a serious clinical burden in orthopedics. Tackling this challenge requires innovative strategies that can both break down the biofilm and overcome bacterial defenses. To this end, we developed patterned copper phosphate (CuP) nanozymes with dual enzyme activities (peroxidase and glutathione peroxidase-like). These work by mimicking copper phosphate–induced cell death and using a two-component system (TCS) inhibition to synergistically remove biofilms associated with implants. In vitro antibacterial tests showed that the CuP nanozymes significantly inhibited and disrupted bacterial biofilms. These CuP nanozymes generate reactive oxygen species (ROS) while consuming glutathione (GSH), damaging bacterial membranes and interfering with metabolic processes like the TCA cycle and glycolysis. Transcriptome analysis showed that genes for oxidative phosphorylation and quorum sensing regulators were suppressed, confirming a dual-target effect on bacterial survival and spread. In vivo, the CuP nanozymes effectively eliminated biofilm infections on implants, reduced inflammation, and displayed excellent biocompatibility. By combining enzyme-driven ROS amplification, metabolic interference, and TCS inhibition, this strategy offers a transformative approach to fighting implant infections, outperforming traditional therapies in both efficacy and safety.
