Nanozyme doped chitosan hydrogel driven by glucose oxidase for dual regulation of ROS homeostasis and macrophage...

Diabetic wounds are characterized by persistent oxidative stress, dysregulated inflammation, hypoxia due to impaired microcirculation, and heightened susceptibility to infection, posing significant challenges for effective treatment. In this work, a multifunctional hydrogel delivery system based on tannic acid-Cu²⁺ (TA/Cu) chelated CeO₂ nanocomposites was developed for synergistic diabetic wound repair. The system utilizes a succinyl chitosan-PVA hydrogel matrix incorporating glucose oxidase (GOx), which specifically catalyzes excess glucose at the wound site to generate H₂O₂. The CeO₂ nanoparticles then decompose H₂O₂ into O₂ through their catalase-like activity, effectively alleviating tissue hypoxia. Additionally, CeO₂ scavenges reactive oxygen species (ROS), significantly reducing oxidative stress while promote the polarization of macrophages toward the M2 phenotype to regulate wound inflammation. The TA/Cu complex exhibits pH-responsive release of Cu²⁺ in the acidic infection microenvironment, enabling targeted antibacterial action. In vitro studies demonstrated the excellent ROS-scavenging capacity of the system, O₂ generating performance, and pH-dependent Cu²⁺ release properties. In a diabetic mouse model with full-thickness skin defects, the hydrogel significantly accelerated wound re-epithelialization, promoted angiogenesis, reduced bacterial infection, and improved tissue oxygenation. This integrated therapeutic strategy combining "oxidative stress/inflammation regulation and pH-responsive antibacterial activity" offers a novel approach for the treatment of chronic diabetic wounds.