Multifunctional and Self-Healing Oxidized Bacterial Nanocellulose-Based Composite Hydrogels with pH-Switchable Cascade Enzyme Catalytic Activity for Accelerating Diabetic Wound Healing.

Abstract

Effective healing of diabetic wounds remains a major clinical challenge due to persistent hyperglycemia, bacterial infections, and hypoxia. In this study, a multifunctional self-healing hydrogel by embedding Fe₃O₄ nanoparticles (NPs) immobilized with glucose oxidase (Fe₃O₄/GOD) into a dynamic Schiff base-crosslinked hydrogel matrix of composed of oxidized bacterial nanocellulose (OBNC-D), carboxymethyl chitosan (CMC), and ε-poly-L-lysine (ε-PL) is developed. The resulting Fe₃O₄/GOD@H hydrogel exhibited excellent injectability, mechanical robustness, and self-healing capability, attributed to dynamic imine bond formation. Functionally, the embedded Fe₃O₄/GOD nanozyme enabled glucose-responsive cascade reactions, generating hydroxyl radicals (·OH) under mildly acidic conditions for potent antibacterial activity, and producing oxygen under neutral conditions to alleviate local hypoxia. In vitro experiments confirmed efficient ·OH generation, sustained oxygen release, and significant antibacterial efficacy against Staphylococcus aureus and Escherichia coli. The hydrogel also exhibited good hemocompatibility and cytocompatibility, particularly at optimized nanozyme concentrations. In a diabetic rat model, Fe₃O₄/GOD@H markedly accelerated wound closure and achieved complete re-epithelialization within 14 days, with minimal tissue toxicity. This intelligently responsive hydrogel provides a promising strategy for diabetic wound treatment by integrating glucose regulation, antibacterial action, and oxygen delivery to overcome multiple healing barriers.