Sustained Oxygen-Releasing Hydrogel Implants Enhance Flap Regeneration by Promoting Mitochondrial Biogenesis under Mild Hypoxia

This study developed catalase-coated oxygen-generating microparticle-loaded GelMA (cOMP-GelMA) hydrogels to promote healing in ischemic surgical skin flaps. By releasing oxygen in a controlled manner, cOMP-GelMA created a mildly hypoxic microenvironment that activated HIF-1α and PGC-1α signaling, enhancing angiogenesis, arteriogenesis, and mitochondrial biogenesis while reducing oxidative stress and inflammation. In a 3×9 cm² rat random-pattern flap model, the optimized 0.2 % cOMP-GelMA formulation increased flap survival to > 54 %, upregulated VEGF and SOD, and decreased apoptotic and pro-inflammatory markers. The implant’s mechanical properties matched dermal elasticity, supporting stable integration and long-term biocompatibility.