Pathology guided catalytic photothermal nanozyme technology integrates infection control with macrophage regulation for vascularized repair of infected wounds

Background Infected wounds persist because bacteria and biofilms remain in the wound bed. Sustained macrophage inflammation, impaired angiogenesis, and inadequate matrix reconstruction further delay healing. Most catalytic photothermal therapies are designed and evaluated mainly for bacterial killing. Their effects on the later repair phase remain uncertain. Technology We developed a near infrared driven photothermal catalytic amplification technology based on an Ag/Pt decorated Ti 3 C 2 MXene nanozyme. Ti 3 C 2 nanosheets were prepared by etching and delamination, followed by chemical reduction to anchor Ag and Pt nanodomains onto the nanosheet surface. Ti 3 C 2 served as the NIR responsive photothermal framework, Pt provided POD like catalytic activity toward H 2 O 2 for •OH generation, and Ag was incorporated to provide direct antibacterial activity. Under NIR irradiation, photothermal heating from Ti 3 C 2 further enhanced Pt associated •OH generation, thereby coupling photothermal conversion with catalytic oxidation within a single nanozyme platform. This architecture couples NIR responsive heating with catalytic oxidation and direct antibacterial activity to strengthen bacterial and biofilm control while supporting subsequent wound repair. Results Under near infrared irradiation, Ti 3 C 2 /Ag/Pt enhanced hydroxyl radical generation and showed antibacterial and antibiofilm activity against methicillin resistant Staphylococcus aureus (MRSA) and Escherichia coli ( E. coli ). Bacterial viability fell to 1.15% and 1.04%, respectively. In lipopolysaccharide stimulated macrophages, RNA sequencing, RT-qPCR, and Western blotting showed attenuation of TNF/NF-κB signaling, and pharmacological inhibition with BAY11-7082 further supported the involvement of NF-κB signaling. Conditioned medium from treated macrophages increased VEGF expression and improved endothelial migration and tube formation. The treatment also showed favorable cytocompatibility, with no evident systemic or local tissue toxicity under the tested conditions. In MRSA infected rat wounds, the treatment reduced bacterial burden and inflammation, improved collagen deposition and vascular repair, and lowered the residual wound area on day 9 to 8.8 ± 1.6%, compared with 52.1 ± 5.1% in untreated wounds.