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Enhanced diabetic wound healing by electrospun core–sheath fibers loaded with dimethyloxalylglycine†
Journal of Materials Chemistry B ( IF 6.1 ) Pub Date : 2017-12-01 00:00:00 , DOI: 10.1039/c7tb02342a W. Gao 1, 2, 3, 4, 5 , L. Sun 1, 2, 3, 4, 5 , X. Fu 1, 2, 3, 4, 5 , Z. Lin 6, 7, 8, 9, 10 , W. Xie 1, 2, 3, 4, 5 , W. Zhang 1, 2, 3, 4, 5 , F. Zhao 1, 2, 3, 4, 5 , X. Chen 1, 2, 3, 4, 5
Journal of Materials Chemistry B ( IF 6.1 ) Pub Date : 2017-12-01 00:00:00 , DOI: 10.1039/c7tb02342a W. Gao 1, 2, 3, 4, 5 , L. Sun 1, 2, 3, 4, 5 , X. Fu 1, 2, 3, 4, 5 , Z. Lin 6, 7, 8, 9, 10 , W. Xie 1, 2, 3, 4, 5 , W. Zhang 1, 2, 3, 4, 5 , F. Zhao 1, 2, 3, 4, 5 , X. Chen 1, 2, 3, 4, 5
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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.
中文翻译：
负载二甲基草酰甘氨酸的电纺芯鞘纤维可增强糖尿病伤口的愈合作用†
高血糖引起的缺氧诱导因子1α（HIF-1α）的失稳和功能障碍是糖尿病慢性伤口延迟愈合的重要原因。因此，值得设计稳定HIF-1α的伤口敷料以抵消高血糖微环境的影响。二甲基草酰甘氨酸（DMOG）是脯氨酰羟化酶（PHD）的竞争性抑制剂，可以通过抑制HIF-1α的降解来使其稳定。因此，在这项研究中，我们开发了可释放DMOG的纳米纤维伤口敷料，用于糖尿病伤口的愈合。我们系统地评估了DMOG释放纳米纤维对人包皮成纤维细胞（HFFs）的体外调控生物学评估。结果表明，纳米纤维的同轴结构可以有效地控制DMOG从纳米纤维中的释放。DMOG在同轴纳米纤维中的持续释放增强了HFFs中伤口愈合相关基因的迁移和表达。此外，我们在大鼠中使用糖尿病伤口模型进行了一项体内研究，以检查DMOG负载的纳米纤维伤口敷料对伤口愈合过程的影响。的体内研究证实，在纳米纤维掺入的DMOG伤口稳定本地HIF-1α的水平，并随后改善通过加速再上皮，血管发生和伤口闭合，这是与相一致的糖尿病伤口再生体外评估。结果表明，释放DMOG的纳米纤维可能是有希望的用于糖尿病伤口的功能性伤口敷料。
更新日期：2017-12-01
中文翻译：
负载二甲基草酰甘氨酸的电纺芯鞘纤维可增强糖尿病伤口的愈合作用†
高血糖引起的缺氧诱导因子1α（HIF-1α）的失稳和功能障碍是糖尿病慢性伤口延迟愈合的重要原因。因此，值得设计稳定HIF-1α的伤口敷料以抵消高血糖微环境的影响。二甲基草酰甘氨酸（DMOG）是脯氨酰羟化酶（PHD）的竞争性抑制剂，可以通过抑制HIF-1α的降解来使其稳定。因此，在这项研究中，我们开发了可释放DMOG的纳米纤维伤口敷料，用于糖尿病伤口的愈合。我们系统地评估了DMOG释放纳米纤维对人包皮成纤维细胞（HFFs）的体外调控生物学评估。结果表明，纳米纤维的同轴结构可以有效地控制DMOG从纳米纤维中的释放。DMOG在同轴纳米纤维中的持续释放增强了HFFs中伤口愈合相关基因的迁移和表达。此外，我们在大鼠中使用糖尿病伤口模型进行了一项体内研究，以检查DMOG负载的纳米纤维伤口敷料对伤口愈合过程的影响。的体内研究证实，在纳米纤维掺入的DMOG伤口稳定本地HIF-1α的水平，并随后改善通过加速再上皮，血管发生和伤口闭合，这是与相一致的糖尿病伤口再生体外评估。结果表明，释放DMOG的纳米纤维可能是有希望的用于糖尿病伤口的功能性伤口敷料。
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