Cu/Mn bimetallic nanozyme enhanced carboxymethyl chitosan/oxidized sodium alginate-based hydrogel promotes diabetic...

Diabetic wound healing disorders are a major challenge currently facing clinical treatment. To address this issue, we developed a multifunctional composite hydrogel system (CuTMn/CMCS-OSA) based on carbohydrate polymers. This system incorporates bimetallic nanozymes (Cu-TCPP-Mn) with synergistic antioxidant and antibacterial properties into a polysaccharide-based hydrogel network composed of carboxymethyl chitosan and oxidized sodium alginate (CMCS-OSA). This engineered wound dressing exhibits both robust mechanical strength and therapeutic functionality, enabling comprehensive modulation of the diabetic wound microenvironment. Experimental results demonstrate that the CuTMn/CMCS-OSA hydrogel not only exhibits outstanding mechanical properties, self-healing capability, and hemostatic efficacy, but also mimics the cascade catalytic effects characteristic of superoxide dismutase (SOD) and catalase (CAT), effectively scavenging reactive oxygen species (ROS) while suppressing bacterial infections. Furthermore, in vitro studies reveal that CuTMn/CMCS-OSA regulates macrophage polarization by targeting the NF-κB and JAK-STAT signaling pathways, substantially ameliorating the inflammatory microenvironment. In vivo experiments confirm that this hydrogel significantly enhances infected wound healing by accelerating epithelial regeneration, promoting collagen deposition, mitigating inflammation, and stimulating neovascularization. Our results demonstrate the significant clinical potential of this hydrogel dressing in the treatment of chronically infected diabetic wounds.