Tissue-Adhesive and Antibacterial Hydrogel Promotes MDR Bacteria-Infected Diabetic Wound Healing via Disrupting Bacterial Biofilm, Scavenging ROS and Promoting Angiogenesis

Abstract

Effective treatment of diabetic wounds remains challenging because of multidrug-resistant (MDR) bacterial infections, excessive oxidative stress, and impaired angiogenesis. In this study, a tissue-adhesive and antibacterial hydrogel incorporating MXene and deferoxamine (DFO)-loaded microspheres is developed for the treatment of MDR bacteria-infected diabetic wounds. The hydrogel is built based on covalent crosslinking between ε-poly(L-lysine) and o-phthalaldehyde-terminated four-arm poly(ethylene glycol). The hydrogel exhibited excellent mechanical properties, tissue adhesion strength, biocompatibility, and biodegradability. Under near-infrared (NIR) irradiation, the MXene converted light into heat and elevated the local temperature rapidly, enabling the rapid disintegration of MDR bacterial biofilms. Simultaneously, the hydrogel exerted inherent antibacterial activity, persistently killing planktonic bacteria, and effectively controlling wound infections. The encapsulated DFO is then released from the hydrogel in a sustained and controlled manner, and promoted angiogenesis during diabetic wound healing. Additionally, MXenes can scavenge excessive reactive oxygen species and alleviate wound inflammation. In the methicillin-resistant Staphylococcus aureus-infected diabetic wound model in mice, the composite hydrogel along with NIR irradiation efficiently reduced the infectious bacteria, and accelerated the wound healing by promoting angiogenesis and alleviating inflammation. This composite hydrogel has great clinical potential for the treatment of diabetic wounds, particularly in challenging healing environments involving motion and infection.