Hyaluronic Acid-Based Hydrogel with a Glucose-Responsive ROS Scavenging Ability for Diabetic Wound Healing

Chronic diabetic wounds are associated with the excessive production of reactive oxygen species (ROS) under hyperglycemic conditions, which contribute to impaired tissue regeneration. In this study, we developed a dual-crosslinked hyaluronic acid (HA)-based hydrogel dressing with a glucose-responsive ROS-scavenging behavior. The hydrogel was composed of methacrylated HA-phenylboronic acid (HAMA-PBA) and HA-dopamine (HA-DA), forming a stable primary network through photocrosslinking and a dynamic secondary network via reversible boronate-catechol interactions. Under hyperglycemic conditions, the competitive binding of glucose to PBA modulates these dynamic interactions, enabling the glucose-responsive regulation of antioxidant activity. The resulting hydrogel exhibited mechanical properties suitable for wound dressing applications and showed good biocompatibility. Glucose-dependent ROS scavenging and enhanced keratinocyte migration were observed in vitro. In a mouse model of chronic diabetic wounds, hydrogel treatment was associated with accelerated wound closure accompanied by improved re-epithelialization and collagen organization compared with those in control groups. Overall, these findings indicated that glucose-responsive antioxidant modulation using HA-based hydrogels can be a useful approach for managing oxidative stress in chronic diabetic wounds.