Abstract

Diabetic foot ulcers (DFUs) present a persistent clinical challenge, posing a significant and ongoing threat to patient health. Current treatment strategies are failing to concurrently address the excessive oxidative stress and impaired angiogenesis during whole-course management of diabetic wounds. To overcome these limitations, this study developed an innovative microneedle (MN)-based drug delivery system incorporating cerium-based metal‒organic frameworks (MOFs) loaded with dihydrocapsaicin (DHC). Fabricated from a Gelatin Methacryloyl (GelMA) hydrogel, the resulting MN-MOF@DHC system exhibited a sustained release profile of DHC that nearly covered the whole-course management of diabetic wounds. Our results revealed that the MN-MOF@DHC system effectively reduced the levels of reactive oxygen species (ROS), promoted the transformation of macrophage phenotypes from the pro-inflammatory M1 subtype to the anti-inflammatory M2 subtype, and significantly enhanced endothelial cell angiogenesis. These combined actions markedly accelerated wound closure. Collectively, the advanced MN platform offers a highly promising strategy for the treatment of DFUs.