基于两性离子抗血栓血管组织工程支架的设计研究

In situ vascular tissue engineering has been proposed as a promising approach to fulfill the need for small-diameter blood vessel substitutes. The approach comprises the use of a cell-free instructive scaffold to guide and control cell recruitment, differentiation, and tissue formation at the locus of implantation. Poor haemocompatibility by thrombopoiesis is a main issue for vascular tissue engineering scaffold. Rapid endothelialization combined with an in situ nitric oxide release strategy is recognized as an effective approach.The purpose of this project is to fabricate blood compatible and cell growth scaffolds. The biodegardable polymers such as PCL and PHBV are coelectrospun with zwitterionic polymers including keratin biopolymer, sufobetaine polymer, and carboxybetaine polymer.The zwitterions of sulfobetaine and carboxybetaine are well-known for blood compatibility and can be impoved their cytocompatibility by coupling of bioactive molecules such as anti CD34 antibody and RGD.The human hair keratins(HHKs) possess cytocompatibility, biodegadability, good cell attachment and growth,low immunogenicity.Especially, HHKs have the potential to catalytically release nitro oxide in human blood, which is a well-known inhibitor of platelet adhesion and activation. The asspun scaffold should be safisfactory with cytocompatiblity, blood compatibility, endothelial progenitor cell capture, cell recruitment promotion, tissue formation stimulation and is potencial for tissue engineering and blood-contacting materials.

运用原位血管组织工程方法修复重建血管，可以同时解决小口径血管的血栓形成及其来源不足的难题。快速内皮细胞化策略联合原位释放一氧化氮信号分子策略可长效解决血管组织工程所需支架的血栓形成问题。本项目拟选择细胞亲和性好且能在外周血中原位催化内源性一氧化氮（NO）供体释放 NO分子的人发角蛋白，和自身血液相容性好的两性离子生物复合材料为研究对象，利用静电纺丝技术、结合生命科学和医学交叉学科方法，探讨复合材料的制备和性质，功能和机理的关系，以及与血液和细胞的相互作用，获得可催化一氧化氮分子控释、可捕获内皮祖细胞、抗血栓形成、生物可降解、组织和细胞相容性好、无免疫原性、具有一定的强度和生长性的支架，为小口径血管组织工程支架的制备提供理论与实验依据。

支架植入式原位再生组织工程化血管是理想的临床血管修复重建方法。两性离子聚合物联合角蛋白原位释放一氧化氮信号分子策略可长效解决支架的血栓形成问题及其平滑肌细胞过度增生问题。本项目设计并合成了活性端基两性离子单体并偶联到材料表面，通过多巴胺涂层构建了氨基酸型两性离子，通过多种途径表面引发可控接枝两性离子聚合物刷，静电纺丝制备了两性离子聚合物人工血管。结果表明，两性离子表面具有良好的血液相容性和抗生物污染性能，弱阳离子/两性离子协同表面具有抗污抗菌双重功能。另外，本项目确认了角蛋白能够催化血液中内源性一氧化氮供体释放一氧化氮，并验证了对内皮细胞和平滑肌细胞生长的影响。电纺了角蛋白复合血管组织工程支架和抗菌伤口敷料，并尝试制备了酸/还原性双重敏感角蛋白药物载体。通过项目实施，为血管组织工程支架的制备和角蛋白的生物医学应用拓展提供了理论与实验依据。