Wound microenvironment self-adaptive all-in-one hydrogel for rapid healing of the diabetic wound

Abstract

The natural healing of diabetic wounds is collectively impeded by multiple factors, including hyperglycemia, angiogenesis disorders, acute oxidative stress, and prolonged inflammation. Although considerable effort has been devoted to solving these problems, the treatment of diabetic wounds remains a major clinical obstacle. In light of this, we developed an innovative wound microenvironment self-adaptive hydrogel to promote the healing of diabetic wounds. The hydrogel was constructed by the crosslinking of 3-aminobenzeneboronic acid (PBA)-modified gelatin (Gel) and polyvinyl alcohol (PVA) by borate ester bonds, which showed high responsiveness to glucose. Meanwhile, the liposomes that encapsulated metformin, L-arginine, and L(+)-ascorbic acid were incorporated into the hydrogel framework. The hydrogel@lipo composite demonstrated shape adaptability, glucose responsiveness, and all-in-one capability, thereby effectively improving the intricate microenvironment of diabetic wounds. In vitro and in vivo experiments demonstrated the ability of hydrogel@lipo to mitigate oxidative stress, enhance angiogenesis, and attenuate inflammatory responses. Consequently, the hydrogel@lipo could accelerate diabetic wound healing (within two weeks). The cumulative findings strongly suggest the potential of hydrogel@lipo as a highly promising therapeutic dressing for advancing diabetic wound recovery.