Paeonol-Loaded Black Phosphorus Hydrogel with Photothermal and Macrophage-Polarizing Activities for Drug-Resistant Wound Infection Therapy

Drug-resistant bacterial infections in wounds represent a major clinical challenge associated with bacterial persistence, oxidative stress, and immune dysregulation. To effectively manage these issues, we developed a multifunctional composite hydrogel (Pae-BP@Gel) by incorporating paeonol-loaded black phosphorus nanosheets (BP) into a glycidyl methacrylate-modified gelatin matrix for the treatment of infected wounds. Upon near-infrared region (NIR) irradiation, Pae-BP@Gel produces photothermal heat that disrupts bacteria, while paeonol and BP further contribute to bacterial membrane damage and antibacterial activity. Notably, Pae-BP@Gel demonstrates antioxidant activity through paeonol and BP, which cooperatively scavenge reactive oxygen species (ROS) and reactive nitrogen species (RNS). This restoration of redox homeostasis, combined with efficient drug-resistant bacterial clearance, improves the wound microenvironment and promotes macrophage polarization toward the prohealing M2 phenotype, facilitating inflammation resolution and angiogenesis. In vivo studies in methicillin-resistant Staphylococcus aureus -infected wound models demonstrate that Pae-BP@Gel significantly accelerates re-epithelialization, enhances collagen deposition, and promotes comprehensive tissue repair. This composite hydrogel thus provides a safe, multifunctional, and efficient strategy for clinical applications in drug-resistant bacterial-infected wound repair.