<p>Chronic infected wounds present formidable clinical challenges due to microbial persistence, excessive oxidative stress, and impaired vascularization. To overcome these limitations, we engineered an injectable polydopamine-modified cerium oxide nanozyme (PDA@CeO₂NPs) composite hydrogel via covalent integration into polyethylene glycol/chitosan (PEG/CS) networks through NHS–amine coupling under mild aqueous conditions (near-neutral pH, room temperature). This design leverages PDA’s adhesive properties to enhance tissue integration while enabling sustained nanozyme release kinetics. In vitro studies demonstrated triple functionality: potent antibac terial activity against Gram-positive Staphylococcus aureus, significant reactive oxygen species (ROS) scavenging capacity, and significant pro-angiogenic effects on endothelial cells. These functionalities arise from synergistic mechanisms where Ce³⁺/Ce⁴⁺ redox cycling mimics natural antioxidant enzymes, while PDA contributes radical-neutralizing quinone groups. In vivo evaluation in infected full-thickness wounds revealed accelerated healing with enhanced epithelial regeneration, collagen deposition, and neovascularization. Histopathological analysis confirmed reduced bacterial burden and no obvious histological abnormalities in major organs. Collectively, this platform achieves spatiotemporal coordination of nanocatalytic therapy, providing a promising strategy for refractory wound management.</p>