Reactive Oxygen Species-Scavenging Nanozyme Hydrogel for Microenvironment Modulation in Diabetic Chronic Wound Healing.

Diabetic chronic wounds are difficult to heal because persistent hyperglycemia is associated with excessive reactive oxygen species (ROS), impaired angiogenesis, and prolonged inflammation. Here, we developed an Fe3O4@PDA-containing PVA/gelatin/borate hydrogel (FP-PVG) with catalase-like activity. FP-PVG scavenged ROS and promoted H2O2-responsive oxygen generation, while the FP nanocomposite and hydrogel matrix contributed to antibacterial activity. In vitro, FP-PVG showed strong ABTS radical-scavenging activity (98.97% at 2 mg mL-1), favorable cytocompatibility, and improved cell migration under oxidative stress. It also reduced CD86 expression and increased CD163 expression in macrophages, consistent with a shift toward a reparative phenotype. In a diabetic mouse wound model, FP-PVG accelerated wound closure and was associated with reduced oxidative stress and inflammation, increased angiogenesis, and improved tissue regeneration. These findings support FP-PVG as a multifunctional hydrogel dressing for regulating the diabetic wound microenvironment.