Enhanced diabetic wound healing by electrospun core–sheath fibers loaded with dimethyloxalylglycine

Abstract

The destabilization and dysfunction of hypoxia-inducible factor 1 α (HIF-1α) caused by hyperglycemia are important reasons for delayed healing of diabetic chronic wounds. Hence, it is worth designing HIF-1α-stabilizing wound dressings to counteract the effects of a hyperglycemic microenvironment. Dimethyloxalylglycine (DMOG), a competitive inhibitor of prolyl hydroxylases (PHDs), can stabilize HIF-1α by inhibiting its degradation. Therefore, in this study, we developed DMOG releasing nanofibrous wound dressings for diabetic wound healing. We systematically evaluated the regulation of DMOG-releasing nanofibers on human foreskin fibroblasts (HFFs) with in vitro biological assessments. The results showed that the release of DMOG from nanofibers can be effectively controlled by the co-axial structure of nanofibers. The sustained release of DMOG in co-axial nanofibers enhanced the migration and expression of wound healing-related genes in HFFs. In addition, we conducted an in vivo study using a diabetic wound model in rat to examine the effects of DMOG-loaded nanofibrous wound dressings on the wound healing process. The in vivo study confirmed that the DMOG incorporated in nanofibers stabilized local HIF-1α levels in wounds and subsequently improved the diabetic wound regeneration by accelerating re-epithelialization, angiogenesis and wound closure, which was consistent with the in vitro evaluation. The results suggest that DMOG-releasing nanofibers may be promising functional wound dressings for diabetic wounds.