A dual-network supramolecular hydrogel dressing encapsulating Cu/EGCG nanoenzyme and glucose oxidase for closed cascade catalytic therapy of diabetic wounds

Abstract

Poor diabetic wound healing represents a significant threat to public health. Key obstacles include heightened oxidative stress resulting from the hyperglycemic microenvironment and increased susceptibility to bacterial infections. These factors synergistically exacerbate one another, creating a self-perpetuating cycle that hampers healing. Despite advancements in wound care, developing effective strategies to simultaneously mitigate these interconnected issues and disrupt the detrimental loop remains a critical challenge. Herein, we developed a multifunctional hydrogel dressing (PACN@CG) with glucose-depleting, reactive oxygen species (ROS)-scavenging and antibacterial properties, consisting of a double-network hydrogel, copper-based nanoenzyme and glucose oxidase (GOx), forming a combination therapy system for diabetic wound treatment. The integration of covalent and non-covalent bonds within the hydrogel endows it with a range of exceptional properties, including injectability, mechanical robustness, self-healing capability, strong biological adhesion, and biodegradability. The synergistic cascade enzyme system formed by the nanoenzyme and GOx enables self-regulated glucose depletion and ROS scavenging, thereby modulating the diabetic microenvironment while enhancing antibacterial efficacy. The efficacy of the PACN@CG hydrogel in enhancing diabetic wound healing was demonstrated using full-thickness skin wound models in diabetic mice. Consequently, this hydrogel dressing successfully reestablishes tissue redox homeostasis and promotes wound healing, presenting a highly promising approach for the treatment of diabetic wounds.