Nanoenzyme-Reinforced Injectable Hydrogel for Healing Diabetic Wounds Infected with Multidrug Resistant Bacteria

Abstract

Diabetic wound healing remains a critical challenge due to its vulnerability to multidrug-resistant (MDR) bacterial infection, as well as the hyperglycemic and oxidative wound microenvironment. Herein, an injectable multifunctional hydrogel (FEMI) was developed to simultaneously overcome these hurdles. The FEMI hydrogel was fabricated through a Schiff-based reaction between ε-polylysine (EPL)-coated MnO₂ nanosheets (EM) and insulin-loaded self-assembled aldehyde Pluronic F127 (FCHO) micelles. Through a synergistic combination of EPL and "nanoknife-like" MnO₂ nanosheets, the FEMI hydrogel exhibited extraordinary antimicrobial capacities against MDR bacteria. The MnO₂ nanoenzyme reshaped the hostile oxidative wound microenvironment by decomposing the endogenous H₂O₂ into O₂. Meanwhile, the pH/redox dual-responsive FEMI hydrogel achieved a sustained and spatiotemporal controlled release of insulin to regulate the blood glucose. Our FEMI hydrogel demonstrated an accelerated MDR bacteria-infected diabetic wound healing <i>in vivo</i> and represents a versatile strategy for healing a broad range of tissue damages caused by diabetes.