Glucose-responsive multifunctional hydrogel incorporating GOx@ZIF-8 for NO/Zn²⁺-mediated antibacterial and pro-angiogenic diabetic wound healing

The hyperglycemic microenvironment of diabetic chronic wounds is a major driver of severe bacterial infections, excessive inflammatory responses, and impaired angiogenesis, all of which delay wound healing. To address these challenges, we prepared a glucose oxidase (GOx)-loaded zeolitic imidazolate framework-8 (GOx@ZIF-8). Furthermore, a multifunctional hydrogel (AACZ) was fabricated by incorporating 5-methylfurfural- and L-arginine-grafted alginate and maleimide-grafted chondroitin sulfate with GOx@ZIF-8 through the Diels-Alder reaction. Results showed that immobilized GOx remained active for a longer time than of free GOx. At the wound site, GOx catalyzed the conversion of excess glucose to gluconic acid and hydrogen peroxide (H₂O₂). The reduced pH in the local region induced Zn²⁺ release from zeolitic imidazolate framework-8, simultaneously, H₂O₂ mediated the generation of nitric oxide (NO) from L-arginine. The synergy between Zn²⁺ and NO endowed AACZ with excellent antibacterial properties. The biocompatible hydrogel promoted cell proliferation and migration, regulated local blood glucose levels, inhibited bacterial activity, alleviated inflammation and promoted angiogenesis and collagen deposition at the diabetic wound site. These findings suggest that AACZ holds promise as a responsive dressing material in healing for complex wounds.