外层空间结构调控小口径人工血管内皮细胞覆盖率及其机制研究

小口径人工血管内皮覆盖率低是导致小口径人工血管远期通畅率差的关键因素，研究表明人工血管表面的孔隙、纤维直径能影响人工血管内皮化及相应血管层的形成，但复杂空间结构对人工血管的影响研究仍是空白。我们提出人工血管的外层空间结构可以影响人工血管内皮细胞的覆盖的科学假说。申请人的前期研究已经制备了可用于人工血管的纳米纤维管，在预实验中利用3D打印技术在纳米纤维管上制作了外层微纤维格栅支架，并初步进行了模拟与表征。在此基础上，本项目将首先检测双层小口径人工血管结构特性及对细胞的影响；再通过新西兰兔颈动脉人工血管置换模型，采用对照研究，评价不同外层空间结构对人工血管内皮覆盖率的影响，筛选出适用于小口径人工血管设计及制备的空间结构方案；最后通过分子生物学及基因芯片等技术探索空间构筑对人工血管功能影响的调控机制。本项目有望成为人工血管研究的新的突破方向，为制备小口径人工血管提供新的理论依据。

Low endothelial coverage in small diameter artificial vascular grafts is a key factor leading to poor long-term patency of small-diameter artificial blood vessels. Previous studies reveal that pores on the surface and the fiber diameter of small diameter artificial vascular grafts can affect endothelialization of artificial vascular grafts and the formation of the corresponding vascular layers. However, the research around the influence of complex spatial structures on artificial vascular grafts is still being absent. We propose the assumption that different outer spatial structural designs of the artificial vascular grafts can affect the endothelial coverage of artificial vascular grafts. The applicant’s previous research has prepared nanofiber tubes which is suitable for artificial vascular grafts. In the pre-experiment, the applicant has produced the micro-fiber grid stent of the outside layer via 3D printing, and have simulated and testified. Based on the result of this pre-experiment, this project will first inspect the structural characteristics of the double-layer small diameter artificial vascular grafts and its effects on cells; then use the New Zealand rabbit carotid artery artificial vascular replacement model as a control group, to evaluate the influence of different outer spatial structures on the endothelial coverage of artificial vascular grafts, filtering out the proper spatial structure scheme to design and produce small diameter artificial vascular grafts; finally, use existing techniques such as molecular biology and gene chip technologies etc. to explore the control mechanism of spatial structures have on artificial vascular grafts’ functionalities. This project is expected to become a new research direction of artificial vascular grafts studies, in the meantime, provide a new theoretical basis for the preparation of small diameter artificial vascular grafts.