Adhesive and Antioxidant Hydrogel with Glucose/ROS Dual-Responsive Drug Release for Diabetic Oral Mucosal Wound Healing

Diabetes mellitus is a global health threat, with chronic wounds, including oral mucosal wounds, being a severe complication. These wounds are characterized by delayed healing and increased inflammation due to hyperglycemia, affecting patients' quality of life. Current treatments for oral mucosal wounds cannot offer sustained management of these injuries in diabetic patients. Here, a glucose/ROS dual-responsive hydrogel incorporating sitagliptin was developed for the treatment of diabetic oral mucosal wounds. After chemical modification of tetra-armed poly(ethylene glycol) succinimidyl glutarate (tetra-PEG-SG) by dopamine (DA) and tetra-armed poly(ethylene glycol) amine (tetra-PEG-NH₂) by phenylboronic acid (PBA), the resulting hydrogel was capable of rapid gelation, robust tissue adhesion, self-healing, antioxidant capacity, and dual response to glucose and reactive oxygen species (ROS), enabling the feasible injection and stable adherence in the moist oral environment while ensuring sustained therapeutic sitagliptin release. <i>In vivo</i> experiments on oral mucosal defects in diabetic mice revealed that the sitagliptin-loaded hydrogel could effectively reduce inflammation and promote wound healing. Collectively, this finding identifies a potential wound dressing as a therapeutic strategy for diabetic oral mucosal wounds.