以表面仿生优化的超微孔ePTFE为瓣膜材料的新型经导管人工心脏瓣膜的实验研究

Since 2000, transcatheter heart valve implantation(THVI) has rapidly advanced. However, the available transcatheter prosthetic valves are restricted to bioprosthesis which have defects like poor durability. Polymeric prosthetic heart valve is a so-called ‘‘biomechanical valve’’ which is thought as a combination of the advantages of mechanical and bioprosthetic valves: long-term durability and no necessity for permanent anticoagulation, and as a promising alternative to bioprosthetic valves for THVI. Ultramicroporous expanded polytetrafluoroethylene（ePTFE）is a representative of polymer material. In our previous studies, we designed and manufactured a novel trileaflet transcatheter pulmonary valve with a balloon-expandable stent, and the valve leaflets were made of ultramicroporous ePTFE. We had successfully implanted the novel ePTFE valves in situ in sheep, and the 12 weeks' follow-up results were good. However, pannus overgrowth was found at the bottom of the ePTFE valves, which led to valve stenosis. Phosphorylcholine(PC) is an importantnt part in cell membrane lipid bilayers. In order to avoid pannus overgrowth, in our previous studies, we chose biomimetic surface modification of ultramicroporous ePTFE by PC-coating, assessed its biocompatibility in vitro, and demonstrated that PC-coating could improve anti-thrombus function, suppress protein adsorption,and enhance biocompatibility of ePTFE. Based on the results in our previous studies, in this study, we aim to design a novel trileaflet transcatheter pulmonary valve, the valve leaflets of which are made of PC-coating ultramicroporous ePTFE, and to evaluate its feasibility, safety, and medium and long-term effect by implanting it in situ in sheep, attempting to provide the basis for the next step of clinical application.

2000年以来，经导管心脏瓣膜植入术得到迅速发展，然而目前经导管用心脏瓣膜只能选择生物瓣，而生物瓣易衰败的问题大大限制了其临床应用。研究发现，高分子材料心脏瓣膜集合了机械瓣耐久性好和生物瓣无需抗凝的优点，可能成为新一代经导管用心脏瓣膜，而超微孔膨体聚四氟乙烯（ePTFE）则是高分子材料的代表。我们在前期研究中研制出超微孔ePTFE介入肺动脉瓣膜并取得了绵羊体内原位植入的成功，随访12周效果良好，但瓣膜根部会出现血管翳增生导致瓣膜狭窄。磷酰胆碱是细胞膜外层结构的重要成分，为解决血管翳增生的问题，我们在前期研究中对超微孔ePTFE进行了磷酰胆碱表面仿生优化，体外实验证实可显著增强其生物相容性。本课题拟在此基础上，以磷酰胆碱表面改性的超微孔ePTFE为瓣膜材料，制作成三叶球囊扩张型介入肺动脉瓣，并通过绵羊体内原位植入对其可行性、安全性、耐久性以及中长期疗效进行全面评价，为下一步临床应用提供基础。

本世纪以来，介入肺动脉瓣膜置换术得到迅速发展，然而目前介入瓣膜只能选择生物瓣，生物瓣衰败的问题大大限制了其临床应用。高分子材料心脏瓣膜是新型人造瓣膜的研究热点，它集合了机械瓣耐久性好和生物瓣无需抗凝的优点，可能成为新一代介入瓣膜，而超微孔膨体聚四氟乙烯（ePTFE）则是高分子材料的代表。我们在前期研究中研制出超微孔ePTFE介入肺动脉瓣并取得了绵羊体内原位植入的成功，但瓣膜根部会出现明显血管翳增生导致瓣膜狭窄。磷酰胆碱是细胞膜外层结构的重要成分，为解决血管翳增生的问题，我们对超微孔ePTFE进行了磷酰胆碱表面仿生优化，体外实验证实可显著增强其生物相容性。我们将以磷酰胆碱表面接枝的超微孔ePTFE为瓣膜材料，制作成三叶球囊扩张型介入肺动脉瓣，并通过绵羊体内原位植入，观察了中长期（20 周）的体内实验结果，证实该表面仿生优化的超微孔ePTFE瓣膜中长期疗效良好，随访20周人工瓣膜工作基本正常，绵羊右心室大小、心功能正常，虽然仍有不同程度的血管翳增生并导致了轻度人工瓣膜狭窄，但较没有表面改性前有了明显改善，这些实验结果为不断改进这种新型高分子材料介入瓣膜以期将来应用于临床提供了良好的基础。