谷氨酰胺合成酶结合EPC源性外泌体构建小口径人造血管用于病理状态下血管再生的研究

动脉粥样硬化（Atherosclerosis，AS）是导致冠心病、心肌梗塞等高致残率、高致死率心血管疾病的主要病因之一。由于AS患者的生理环境与正常人显著不同，因此研制针对AS患者病理状态下的新型小口径人造血管，对临床上AS患者的血管修复重建具有重要意义。在申请人前期研究工作的基础上，本项目拟利用脂质体包载谷氨酰胺合成酶，采用同轴共纺技术将包载谷氨酰胺合成酶的脂质体复合在磺酸化丝素蛋白/PLCL/壳聚糖管状纳米纤维支架中，并使用内皮祖细胞源性外泌体（EPC-Exo）功能化修饰其表面制备小口径人造血管。希望该小口径人造血管能够增强病理状态下血管内皮细胞的增殖和迁移能力，加快人造血管移植后的自发性内皮化；同时促进巨噬细胞的表型向M2型转化，降低炎症反应，并抑制AS后血管钙化的发生，旨在提高小口径人造血管在病理状态下的移植成功率和远期通畅率。

Atherosclerosis (AS) is one of the main causes of cardiovascular diseases which have high disability and mortality such as coronary heart disease and myocardial infarction. Since the physiological environment of AS patients is significantly different from that of normal people, it is of great significance to develop a new small-diameter vascular graft under the pathological state of AS patients for the vascular repair and reconstruction of clinical AS patients. To solve this problem, based on our previous studies, we propose to fabricate sulfated silk fibroin/PLCL/chitosan core-shell nanofibrous scaffolds with embedded glutamine synthetase (GS) liposomes by coaxial electrospinning. Moreover, we use endothelial progenitor cell-derived exosome (EPC-Exo) to functionalize the scaffold surface for developing small-diameter vascular grafts. We hypothesize that the small-diameter vascular graft can promote the proliferation and migration of endothelial cells under pathological conditions and accelerate the spontaneous endothelialization after transplantation. In the meantime, it can promote the transformation of macrophage phenotype to M2 type, reduce the inflammatory response, and inhibit the occurrence of vascular calcification after AS. Therefore, the aim of this study is to improve the transplantation success rate and long-term patency rate of small-diameter vascular graft under pathological conditions and provide reliable experimental data for its future clinic application.