Porphyrinic MOF-Confined Nanozyme Hydrogel with CuS-Mediated Photoregulation for Infected Wound Healing

Bacterial-infected wounds pose substantial therapeutic challenges due to persistent infection, sustained inflammation, and a hypoxic microenvironment. Photothermal therapy and photodynamic therapy are promising nonantibiotic approaches for bacterial eradication; however, their effectiveness is often limited by restricted oxygen availability in the tissue microenvironment and uncontrolled production of reactive oxygen species (ROS). In this study, a nanozyme hydrogel was developed using a metal-organic framework (PCN-224) that combines CuS-mediated photothermal effects with Fe-doped graphitic carbon nitride (g-C₃N₄-Fe) redox activity for near-infrared (NIR)-activated targeted therapy. The metal-organic framework integrates photothermal, photodynamic, and nanozyme redox mechanisms to modulate ROS in hypoxic environments. This injectable, self-healing hydrogel conforms to wound surfaces, adheres to tissue, and remains localized at the injury site, enabling precise therapy upon NIR irradiation. In vitro and in vivo experiments demonstrate that the integrated photothermal, photodynamic, and nanozyme redox activities reduce bacterial load, attenuate inflammation, and restore oxidative balance in wounds. As a result, hydrogel promotes granulation tissue formation, collagen deposition, and skin regeneration in infected wound models.