DMOG复合手性超分子水凝胶联合BMSCs移植促进糖尿病创面愈合的作用和机制研究

Diabetic wound, as a kind of refractory wound, is still a difficult problem in clinic. BMSCs could improve diabetic wound healing to some extent. But because of shortage and dysfunction of reparative cells and shortage of many growth factors in diabetic wound tissues, only BMSCs transplantation cannot get a very satisfactory result for some patients. To address this problem, we found that hypoxia inducible factor (HIF)-1α could improve the level of cytokins and improve the function of BMSCs. While HIF-1α would be resolve fleetly under normoxic condition. Dimethyloxalylglycine (DMOG) is a cell permeable prolyl-4-hydroxylase inhibitor, can activate the expression of HIF-1α in cells at normal oxygen tension. Supramolecular chiral hydrogels as a new material can promote cell adhesion and induce three-dimensional cell growth. The purpose of our research is to find out if DMOG could improve the function of BMSCs, and analysis the possible mechanism. This study will provide a novel way to treat diabetic wound more efficiently and improve the therapeutic effect of the BMSCs transplantation.

糖尿病(DM)创面是慢性难愈性创面，是目前临床上的治疗难题。骨髓间充质干细胞(BMSCs)移植可促进其愈合，但DM创面内修复性细胞缺乏及功能异常，多种生长因子不足，使得单独应用BMSCs移植效果有限。低氧诱导因子-1α（HIF-1α）可以促进成血管因子的分泌，提高BMSCs的成血管效应。但在常氧状态下，HIF-1α易被脯氨酸羟化酶分解，难以保持一定浓度。而二甲氧乙二酰甘氨酸（DMOG）作为一种脯氨酸羟化酶抑制剂，可以抑制HIF-1α的分解，上调HIF-1α基因在正常细胞中的表达。超分子手性水凝胶作为一种新型材料具有促进细胞粘附，诱导细胞三维生长的作用。同时也是DMOG的良好载体。本研究的目的是为了探索负载DMOG的超分子手性水凝胶促进BMSCs成血管的有效性，同时探讨其可能的机制，为临床上DM创面的治疗提供新方法。

慢性难治性创面是糖尿病最严重的并发症之一，常规治疗效果有限。手性水凝胶联合二甲基甘氨酸(DMOG)作为敷料是一种很有前景的治疗慢性创面的方法。在本研究中，我们开发了一种负载DMOG的超分子手性氨基酸衍生物水凝胶，用于慢性伤口的全层皮肤再生。本研究体外测试了材料的性质、缓释药物的能力和促进血管生成的能力，体内测试全层皮肤的再生率和修复能力。研究结果表明手性水凝胶具有缓慢释放药物的能力。在体外能有效促进细胞迁移和血管生成，在体内能促进皮肤全层再生和血管新生。本研究为负载DMOG的超分子手性水凝胶修复慢性创面提供了理论基础。