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

Enhanced diabetic wound healing by electrospun core-sheath fibers loaded with dimethyloxalylglycine
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通过负载二甲基乙二酰甘氨酸的电纺芯鞘纤维增强糖尿病伤口愈合

DOI:
10.1039/c7tb02342a
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发表时间:
2018-01-14
影响因子:
7
通讯作者:
Chen, X.
Chen, X.
中科院分区:
工程技术2区
文献类型:
--
作者:
Gao, W.;Sun, L.;Chen, X.

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The destabilization and dysfunction of hypoxia-inducible factor 1 alpha (HIF-1 alpha) caused by hyperglycemia are important reasons for delayed healing of diabetic chronic wounds. Hence, it is worth designing HIF-1 alpha-stabilizing wound dressings to counteract the effects of a hyperglycemic microenvironment. Dimethyloxalylglycine (DMOG), a competitive inhibitor of prolyl hydroxylases (PHDs), can stabilize HIF-1 alpha 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-1 alpha 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.