Injectable glucose-responsive hydrogels with hemorrhage control and microenvironmental regulation for diabetic wound repair.

The healing of diabetic wounds is collectively impeded by the complex pathological environment, acute oxidative stress, and chronic inflammation, where uncontrolled bleeding and elevated glucose levels seriously impaired healing process. Although considerable efforts have been devoted to addressing these issues, treatment of diabetic wounds remains a major clinical obstacle. Herein, an injectable glucose-responsive hydrogel is developed to promote diabetic wound repair. The gelatin is functionalized with cystamine and phenylboronic acid (PBA) to enhance loading capacity of Prussian blue (PB) and enable stimuli-responsive behavior to glucose fluctuations in the wound environment, while the incorporation of oxidized dextran (OD) further improves the robust adhesion onto diabetic wounds. The resulting hydrogel (ODpCG-PB) exhibits shape adaptability, robust adhesion, self-healing ability and glucose responsiveness. It also presents excellent radical scavenging efficiency and macrophage polarization toward anti-inflammatory M2 phenotype to mitigate oxidative stress, attenuate inflammatory response and enhance angiogenesis. A significant improved hemostatic efficacy of ODpCG-PB surpasses clinically used fibrin glue in liver, femoral artery, and cardiac injury models. Remarkably, this all-in-one ODpCG-PB can accelerate wound closure via promoting re-epithelialization and collagen deposition in a diabetic skin defect model. Overall, this work provides a new design of dressing toward an effective healing of diabetic wound.