Nanozyme-Mediated Supramolecular Hydrogel for Diabetic Wound Repair via a Near-Infrared-Driven Photo-Chemical-Thermal Triple-Mode Synergistic Effect.

Diabetic wounds pose a threat to global human health, with their microenvironment presenting challenges such as high glucose levels, infection, and inflammation, which lead to prolonged nonhealing of wounds. Here, a nanozyme supramolecular hydrogel (UCFH) doped with upconversion nanoparticles (UCs) and ferrocene (Fc) was constructed via self-assembly, and glucose oxidase (GOX) was loaded to form the UCFH@GOX therapeutic system. Driven by a single near-infrared (NIR) light, this system showed deep UV emission performance, which not only addressed the issues of insufficient penetration depth and tissue damage of traditional UV light but also achieved efficient chemodynamic therapy (CDT) by utilizing cyclic generation of reactive oxygen species. Meanwhile, combined with the photothermal effect of UCs, it enhances the antibacterial performance and blood circulation, significantly inhibiting recurrent wound infections. In vitro and in vivo experiments demonstrated that the UCFH@GOX system had good biosafety and hemostatic properties. Importantly, it accelerated the repair of diabetic wounds through the synergistic effects of hypoglycemic regulation, antibacterial activity, anti-inflammation, and wound healing promotion. In conclusion, the therapeutic platform with proposed "photo-chemo-thermo" multimodal synergy provides a potentially safe and effective strategy for the treatment of chronic wounds.