Efficient Antimicrobial Nanoenzymatic Functionalized Hydrogels for Diabetic Infected Wound Treatment

The high glycemic environment of diabetic wounds predisposes to bacterial infections that seriously threaten the wound healing process. Therefore, inhibition of bacterial infection and remodeling of the wound microenvironment are crucial for the healing of diabetic infected wounds. In this study, gold nanoparticles (Au NPs) and glucose oxidase (GOx) were loaded in situ onto the surface of zeolitic imidazolate framework-8 nanoparticles (ZIF-8 NPs) to prepare ZIF-8@Au@GOx (ZAG) nanoenzymes. It catalyzed the production of glucuronic acid and H2O2 from glucose, lowered the wound pH, promoted the release of Zn2+, and catalyzed the production of hydroxyl radicals (·OH) from H2O2, thus serving to regulate the wound microenvironment, reducing glucose levels, and providing efficient antimicrobial activity. Subsequently, the nanoenzymes were loaded into β-cyclodextrin-based host-guest interaction and perylene-bonded tandem highly dynamic adaptive (DSA) hydrogels to obtain nanoenzyme-functionalized hydrogels (ZAG@Gel). The hydrogel could adapt to the shape of the wound, effectively fit the damaged skin, and play a role in reducing the toxicity and slowing down the release. In vitro studies showed that ZAG@Gel could release ZAG nanoenzymes in situ, causing the bacterial surface to crumple, the cell membrane structure to be disrupted, and the internal substances to be leaked. In vivo animal experiments showed that the wound healing rate after ZAG@Gel treatment reached nearly 98.06%. Thus, this highly effective antibacterial nanoenzyme-functionalized hydrogel has a strong bactericidal ability and shows good pro-diabetic infected wound healing properties.