Glucose‐Responsive Antioxidant Hydrogel Accelerates Diabetic Wound Healing

Diabetic complications can be ameliorated by inhibiting excessive oxidative stress with antioxidants. To enhance therapeutic intervention, it is crucial to develop intelligent scaffolds for efficient delivery of antioxidants to diabetic wounds. This study introduces reversible boronic bonds to create an intelligent antioxidant hydrogel scaffold. This study modifies gelatin methacryloyl (GelMA) with 4-carboxyphenyboronic acid (CPBA) to synthesize a derivative of GelMA (GelMA-CPBA), and then photo cross-links GelMA-CPBA with (-)-epigallocatechin-3-gallate (EGCG) to form GelMA-CPBA/EGCG (GMPE) hydrogel. The GMPE hydrogel responds to changes in glucose levels, and more EGCG is released as glucose level increases due to the dissociation of boronic ester bonds. The GMPE hydrogel shows good biocompatibility and biodegradability, and its mechanical property is similar to that of the skin tissue. Both in vitro and in vivo results demonstrate that the GMPE hydrogel scaffolds effectively eliminate reactive oxygen species (ROS), reduce the inflammation, and promote angiogenesis, thereby improve collagen deposition and tissue remodeling during diabetic wound healing. This strategy offers new insight into glucose-responsive scaffolds, and this responsive antioxidan hydrogel scaffold holds great potential for the treatment of chronic diabetic wounds.