基于微流控多管凝胶纺丝技术的血管平滑肌组织构建及诱导内皮化研究

慢性肾脏病及其所引起的尿毒症严重威胁人类健康，人造血管内瘘移植物具有巨大的市场需求和临床意义，然而移植后易形成血栓且长期通畅率不高,这些问题均制约着其进一步的临床应用。已有研究发现：血管平滑肌组织不仅能维持血管的力学强度和顺应性而且为内皮祖细胞的增殖和分化提供微环境。我们推测：可以通过血管平滑肌组织的仿生构建，实现对内皮祖细胞的募集和分化，有助于构建长期通畅的人工血管组织。本项目拟采用微流控多管纺丝技术与纤维间的组装，构建出能模拟体内细胞取向生长和收缩功能的血管平滑肌组织，揭示支架材料的理化性能与拓扑结构等材料学因素对血管平滑肌组织再生的影响机制，进一步探讨构建的血管平滑肌组织与体内诱导快速内皮化的关系，建立“支架材料-血管平滑肌重建-内皮层再生”的相互作用模型。该研究针对目前人造血管临床应用中面临的诸多问题，实现真正意义上的结构仿生进而功能仿生，为构建长期通畅率血管提供新的思路。

The uremia caused by chronic renal disease is a serious threat to human health. Artificial vessel arteriovenous fistula for the hemodialysis application has a huge market demand and clinical significance. However, the artificial vascular grafts have been proven unsatisfactory due to thrombosis and occlusion after transplantation. Improving the long-term patency rate of the artificial vascular graft is a world-wide problem. Previous studies have demonstrated that the vascular smooth muscle tissue (VSMT) can not only maintain the mechanical strength and compliance of the blood vessel, but also provide a microenvironment for the proliferation and differentiation of endothelial progenitor cells. We hypothesis that the VSMT could be constructed by simulating cellular alignment and contractile phenotype. The engineered VSMT would be helpful for the endothelial progenitor cell recruitment and differentiation and finally improve the long-term patency of the engineered blood vessel graft. In this study, we intend to adopt the multibarrel microfluidic spinning system to build the engineered VSMT by simulating the cellular circumferential alignment. The relationship between the physicochemical properties of scaffolds and the VSMT regeneration will be revealed. Moreover, we will explore the rapid endothelialization induced by the engineered VSMT and establish the interaction model between the engineered vascular smooth muscle tissue and endothelialization. This study aim at the problems faced by the clinical application of artificial blood vessels, achieve the functional bionics from the structural bionics, will provide a new route for the construction of the artificial vascular graft with long-term patency rate.