Accelerated dermal wound healing in diabetic mice by a H₂O₂-generating catechol-functionalized gelatin microgel

Physically crosslinked gelatin microgels were functionalized with a bioadhesive molecule, catechol, to study the effect of in situ generated H₂O₂ on full-thickness wound repair in diabetic mice. Due to the physically crosslinked nature of the microgels, they transition into a hydrogel film upon hydration. The formation of a hydrogel film was confirmed by the changes in their morphology and viscoelastic properties. Additionally, these microgels released up to 86 μM of H₂O₂ as a result of catechol autoxidation. The generated H₂O₂ completely eradicated Staphylococcus epidermidis with an initial concentration of 10³ CFU mL^-1. These microgels were not cytotoxic and promoted VEGF upregulation in immortalized human keratinocytes (HaCaT) in vitro. When the microgels were applied to a full-thickness dermal wound in diabetic mice, dermal wound closure was accelerated over 14 days, achieving a wound closure of 90% based on the wound area. Microgel-treated wounds also resulted in complete re-epithelialization and regeneration of new dermal tissues with morphology and structure resembling those of native tissues. These results indicate that the release of micromolar concentrations of H₂O₂ can accelerate wound healing in a healing-impaired animal.