基于聚合物串晶结构的抗血栓性小口径人工血管材料的构建研究

Currently, there are still urgent demands to the small-diameter vascular grafts which can be used clinically. Thrombosis is one of the dominant reasons that result in the transplant failure. For one thing, the design and fabrication of vascular grafts requires favorable mechanical and biocompatible performance of the material, for another, it is also indispensable to concern the anti-thrombogenic and endothelialization-facilitating properties, in order to decrease the thrombogenic possibility after the surgery. According to the previous research of the applicant, the shish-kebab-structured polymeric fibers could mimic the nanotopography of the extracellular matrix and influence the cell behavior. It is expected to control and manipulate cell behavior of the endothelial cells by means of the adjustment of the shish-kebab structure, so that the endothelial regeneration can be accelerated.Hense, this study aims to combine the controllable preparation of polymeric shish-kebab structure with surface chemical modification, in order to design and fabricate an anti-thrombogenic nanomaterial for small-diameter vascular regeneration which could also induce endothelialization in vivo. In addition, the influence of fibrous pattern and dimension of shish-kebab structure upon the cell behavior of endothelial cells and smooth muscle cells will be investigated. The theoretic mechanism of using the microstructural of the shish-kebab-structured nanofibers to manipulate the specific cell behavior will be studied and established. Moreover, a three-dimensional small-sized vascular graft with be fabricated via a custom-made collector of the electrospinning device. The application prospects of the shish-kebab-structured nanofibers in artificial vascular grafts will be evaluated. This study will potentially provide new perspectives in the area of anti-thrombotic functionalization and endothelialization of small-diameter vascular tissue engineering.

目前临床上仍然缺乏能够满足移植要求的小口径人工血管材料，血栓的形成是移植失效的主要原因之一。在满足良好的力学、细胞相容性的同时，针对小口径人工血管材料的设计构建还需协同考虑材料的抗凝血性和促内皮化的能力，以降低移植后血栓的形成几率。申请人前期研究发现，聚合物串晶结构纤维可在一定程度上模仿细胞外基质的微形貌、影响细胞的行为，有望通过对其微形貌的设计构建来调控内皮细胞的行为，促进内皮再生。因此，本项目拟将串晶纤维材料微形貌的可控制备与表面抗凝修饰相结合，构建一种具有促内皮化和抗凝性的小口径人工血管材料，降低移植后的血栓形成几率。研究串晶纤维的微结构对血管特定细胞的行为影响，建立通过改变串晶纤维微结构来调控细胞行为的理论机制；以之为基础自制静电纺丝收集装置，制备具有抗血栓性能的三维小口径人工血管，评价串晶纤维材料作为小口径人工血管支架的应用前景，为人工血管材料的内皮化策略和抗凝性研究提供新思路。

临床上仍然缺乏能够满足移植要求的小口径人工血管材料，血栓的形成是移植失效的要原因之一。在满足良好的力学、细胞相容性的同时，针对小口径人工血管材料的设计构建需考虑材料促内皮化的能力，以降低移植后血栓的形成几率。前期研究发现聚合物串晶结构纤维可在一定程度上模仿细胞外基质的微形貌、影响细胞的行为，有望通过对其微形貌的设计构建来调控内皮细胞的行为，促进内皮再生。因此，项目从材料的制备构建到材料的体外细胞培养研究再到管状支架体内移植为研究主线。自项目自开展以来，主要在以下几个方面取得了一定的研究成果：设计和制备了聚合物串晶纤维结构材料，研究了串晶微形貌结构对内皮细胞行为的调控和影响，探索了其对内皮细胞增殖和功能表达的促进作用，自主设计构建了三维管状材料的实验装置，制备了结构稳定、性能优良的管状结构材料，开展了动物体内中长期移植研究，评价了串晶纤维材料作为促内皮化小口径人工血管的应用前景，为人工血管材料的内皮化策略研究提供了新思路。