两性离子原位聚合交联构筑介入生物瓣膜及其抗凝血抗钙化性能研究

当前临床使用的介入生物瓣膜植入后瓣叶血栓发生率高达15-40%，会增加瓣叶活动障碍和瓣叶钙化风险。针对这些问题，本项目基于前期开发的自由基聚合交联体系，设计合成两性离子聚合物修饰交联的生物瓣膜。首先利用脱细胞和自由基共聚制备交联生物瓣膜，研究制备工艺、单体种类和浓度对交联度、嫁接度和结构形貌的影响，建立和优化瓣膜功能化交联的调控方法，并评估其力学性能和稳定性，确保可以满足生物瓣膜的一般使用要求。通过蛋白吸附、血细胞相互作用、血栓生成、内皮细胞生长和体内血管植入实验，进一步评估两性离子聚合物嫁接种类和密度对瓣叶抗凝血性能的影响，并揭示其抗凝血机制。通过体内体外实验，研究两性离子聚合物抗凝血表面修饰以及血栓生成对瓣叶钙化性能的影响，补充完善生物瓣膜钙化的调控机制。本研究可同时实现瓣膜的功能化和交联，对设计抗凝血抗钙化瓣叶材料和延长介入生物瓣膜的使用寿命具有重要的实用价值。

Currently, the incidence of leaflet thrombosis after interventional bioprosthetic heart valve(BHV) implantation is as high as 15-40%, which will increase the risk of impaired leaflet motion and calcification. Aiming at reducing valve thrombosis and valve calcification, a BHV modified by zwitterionic polymer based on the radical polymerization cross-linking system of BHV developed earlier would be designed and synthesized. The BHV will be prepared by decellularization in combination with radical crosslinking copolymerization, where the effect of polymerization parameters, variety, and concentration of monomer on the crosslinking degree, grafting degree and morphology of BHV will be investigated to establish and optimize this functionalized crosslinking of BHV. The mechanical performance and componential stability will be evaluated to ensure that could meet the basic requirements of the BHV. Through experiments of protein adsorption, blood cell interaction, thrombogenesis, endothelial cell growth and in vivo vascular implantation, the effects of the variety and density of zwitterionic polymer grafts on the anticoagulant performance of the valvular leaflets will be evaluated, and the anticoagulant mechanism will be revealed. In vitro and in vivo experiments will be conducted to study the effects of anticoagulant surface modification on the calcification performance of valvular leaflets, so as to complement and improve the mechanism for mediating BHV calcification. This study can achieve the goal of functionalization and cross-linking of BHV at the same time, which is of important practical value for the design of anticoagulant and anti-calcification valve materials and the prolonging of the service life of interventional BHV.