A lack of angiogenesis is the key problem in the healing of diabetic foot ulcers. Stem cells have already been proven to have a high potential for angiogenesis. The most important aspects of stem cell therapy are improving the microenvironment, cell homing and continuous factor stimulation. We investigated the effect of Klotho protein to heal wounds by promoting the proliferation and migration of bone mesenchymal stem cells and endothelial cells in vitro. Based on the above study, we produced a compound material by using poly(lactic-co-glycolic acid) (PLGA), chitosan microspheres and gelatin through electro spining technology. The structure of the compound material, just like a sandwich, is that two pieces of PLGA nanofiber films clamped gelatin film which contained chitosan microspheres. In the in vitro release experiment, we could detect the release of Klotho after seven days in the compound material, but the release time was approximately 40 hours for the chitosan microspheres. After seeded bone mesenchymal stem cells (BMSCs) on the surface of the compound material, we observed morphologies of the chitosan microsphere, the PLGA nanofiber and BMSCs by scanning electron microscopy. The nanofiber mesh biological tissue materials could supply an appropriate microenvironment and cell factors for the survival of BMSCs. Compared with the control group, the biological tissue material seeded with BMSCs significantly promoted angiogenesis in the lower limb of diabetic C57BL/6J mice and accelerated diabetic foot wound healing. The compound biomaterial which could continuously stimulate BMSCs through releasing Klotho protein could accelerate wound healing in the diabetic foot and other ischemic ulcers.

中文翻译：

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Klotho蛋白复合纳米材料对骨髓间充质干细胞治疗糖尿病缺血性溃疡性能的影响。

缺乏血管生成是糖尿病足溃疡愈合的关键问题。干细胞已被证明具有很高的血管生成潜力。干细胞疗法最重要的方面是改善微环境、细胞归巢和持续因子刺激。我们研究了 Klotho 蛋白通过促进体外骨髓间充质干细胞和内皮细胞的增殖和迁移来治愈伤口的作用。基于上述研究，我们采用聚乳酸-乙醇酸共聚物（PLGA）、壳聚糖微球和明胶通过静电纺丝技术制备了一种复合材料。这种复合材料的结构就像一个三明治，是由两片PLGA纳米纤维薄膜夹住含有壳聚糖微球的明胶薄膜。在体外释放实验中，我们可以在复合材料中 7 天后检测到 Klotho 的释放，但壳聚糖微球的释放时间约为 40 小时。在复合材料表面接种骨髓间充质干细胞（BMSCs）后，我们通过扫描电子显微镜观察了壳聚糖微球、PLGA纳米纤维和BMSCs的形态。纳米纤维网状生物组织材料可为骨髓间充质干细胞的生存提供适宜的微环境和细胞因子。与对照组相比，接种BMSCs的生物组织材料可显着促进糖尿病C57BL/6J小鼠下肢血管新生，加速糖尿病足创面愈合。