A cascade-responsive fibrous platform combining nanozyme and NO donor therapy for infected diabetic wound healing

Chronic diabetic wounds present a formidable clinical challenge due to persistent hyperglycemia, impaired angiogenesis, and recurrent bacterial infection, often resulting in delayed healing. Here, we report a multi-responsive electrospun fibrous platform (ACE/ZAZ/Arg) that integrates pH- and NIR-responsive ZnO₂@Au@ZIF-67 nanozymes (ZAZ NPs) within the fiber shell and L-arginine (L-Arg) in the core. The coaxial electrospinning design enables hierarchical structural evolution and allows for sustained, sequential release of therapeutic agents. Mechanistically, ZAZ NPs catalyze glucose oxidation and trigger Fenton-like reactions to generate hydroxyl radicals (·OH), while L-Arg produces nitric oxide (NO) in the presence of hydrogen peroxide (H₂O₂). These reactive species act synergistically to enhance antibacterial efficacy and support wound repair, with NIR irradiation further amplifying the therapeutic outcome through photothermal conversion. In vitro studies confirmed excellent cytocompatibility, hemocompatibility, and enhanced endothelial tube formation, indicating strong pro-angiogenic potential. In an infected diabetic rat model, the ACE/ZAZ/Arg platform achieved rapid photothermal heating, significantly reduced bacterial burden, and accelerated wound closure to 98.0% within 14 days. Histological analysis demonstrated complete re-epithelialization, increased collagen deposition, and well-organized dermal tissue without detectable systemic toxicity. Together, this study presents a multifunctional fibrous platform that combines cascade antibacterial mechanisms, NO-mediated pro-healing activity, and structural guidance, offering a promising strategy for the treatment of chronic diabetic wounds.