β‑Ecdysone-Loaded Gelatin Methacryloyl Hydrogel Accelerates Diabetic Wound Healing by Improving Angiogenesis

Delayed diabetic wound healing is partly attributed to vascular endothelial cell dysfunction induced by persistent hyperglycemia. β-Ecdysone (β-E), a naturally occurring steroidal compound, has been reported to protect endothelial function and alleviate hyperglycemia. This study aimed to develop a β-E-loaded gelatin methacryloyl (GelMA) hydrogel and evaluate its potential as a dressing to promote diabetic wound healing. The effects of β-E on human umbilical vein endothelial cells (HUVECs) under high-glucose conditions were evaluated by assessing proliferation, migration, and angiogenic capacity in vitro, along with the physicochemical properties, biocompatibility, and bioactivity of the resulting β-E/GelMA hydrogel. The therapeutic efficacy of the β-E/GelMA hydrogel in promoting diabetic wound healing was systematically assessed in rodent models. The results showed that β-E at concentrations ranging from 5 to 640 μmol/L was noncytotoxic to HUVEC viability. Among the tested concentrations, 20 μmol/L β-E conferred the optimal enhancement of HUVEC proliferation, migration, and angiogenic capacity. The β-E/GelMA hydrogels achieved sustained β-E release in vitro and exhibited physicochemical properties, biocompatibility, and bioactivity comparable to those of unmodified GelMA hydrogels. In vivo, β-E/GelMA hydrogels could efficiently promote the closure of diabetic wounds in diabetic rats. Immunohistochemical staining for CD31 and α-SMA demonstrated that β-E/GelMA hydrogels significantly promoted neovascularization and vascular maturation in vivo. We conclude that the β-E/GelMA hydrogels could be developed as a novel wound dressing for diabetic wound treatment. Altogether, the findings of this study show that the β-E/GelMA hydrogels could be developed as a novel wound dressing for diabetic wound treatment.