肝素纳米修饰促进小管径异种血管通畅率的研究

There are millions of patients under surgical repairs with small diameter alternative vessel (diameter<6mm) every year. Autologous vessels and vascular allografts are ideal alternative vessels, but an insufficient supply of donor vessels limits their widespread clinical application. There is a plentiful supply in synthetic vascular grafts, but low graft patency greatly limits surgical utilization of small-caliber synthetic grafts because of thrombosis. So creating small diameter alternative vessels with high patency will bring good economic and social benefits. Establishing a thromboresistant surface is crucial to prevent formation of blood clots in the initial phase of small-caliber grafts implantation. Much effort has been devoted to improving the antithrombogenicity of xenografts by surface modification using heparin, but the amount of linked heparin is small, and long-term results are not ideal. The applicant had been developed the technique to link heparin into collagen fibers surface of vascular scaffold via layer-by-layer self-assembly and formate nanoscale anticoagulation coatings(obtained a patent).The evaluation showed heparin was firmly fixed on vascular surface, and the modified scaffolds effectively prevented thrombosis with sustained release of heparin, significantly reduced platelet adhesion and stimulated proliferation of endothelial cells in vitro. Bovine saphenous artery is an ideal small-caliber vessel which has long length, less branch, uniform caliber and other feathers. This study include the preparation of heparin nanomodified acellular bovine saphenous artery, replantation canine femoral artery with the modified vascular scaffolds and evalucation its features in canine model in vivo. This project is expected to develop a high graft patency rate and surgical utilization of small-caliber vascular xenograft.

每年有数百万的患者需要小管径(直径<6mm)替代血管进行外科修复治疗。目前理想小管径替代血管是自体血管，但供体有限，不能满足临床需要；异种和合成材料小管径血管来源广泛，但其通畅率低。故研发一种高通畅率的小管径替代血管将带来良好的经济效益和社会效益。构建抗凝内膜表面是预防小血管移植物形成血栓的关键，目前国内外使用多种方法将肝素固定在血管内膜表面，由于结合的肝素量小，均不能有效的增加通畅率。申请者利用自组装技术将肝素固定在血管基质胶原纤维的表面并形成具有纳米厚度的抗凝涂层(已获专利)；体外实验证实大量肝素与血管基质牢固结合并能长时间缓释肝素，具有优良的抗凝、抗血小板粘附、促内皮细胞增殖等性能；牛隐动脉具有长度长、侧支少、管径均匀等特点，是理想的小管径异种血管材料。本研究包括制备肝素纳米修饰去细胞牛隐动脉，通过替换犬股动脉评价其性能。本项目有望研发出一种高通畅、临床实用的异种小管径替代血管。

[研究背景] 每年有数百万的患者需要小管径(直径<6mm)替代血管进行外科修复治疗。目前理想小管径替代血管是自体血管，但供体有限，不能满足临床需要；异种和合成材料小管径血管来源广泛，但其通畅率低。故研发一种高通畅率的小管径替代血管将带来良好的经济效益和社会效益。构建抗凝内膜表面是预防小血管移植物形成血栓的关键，目前国内外使用多种方法将肝素固定在血管内膜表面，由于结合的肝素量小，均不能有效的增加通畅率。.[研究内容] 申请者将牛隐动脉经过去细胞和戊二醛处理后，利用自组装技术将肝素固定在去细胞后的牛隐动脉表面并形成具有纳米厚度的抗凝涂层，取长度为5cm的牛隐动脉替换比格犬的股动脉，通过血管造影和多普勒彩超分别在1周、1月、3月、6月、12月检查，了解置换血管的血流动力学和通畅率，并取回移植血管，检测管腔内皮细胞生长情况、吻合口内膜增生和平滑肌增生和钙化情况。.[研究结果] 移植血管在1周、1月、3月、6月、12月的通畅率分别为100%、100%、99%、95%、90%，吻合口成纤维细胞和平滑肌细胞未见明显增生，血管内皮细胞完全覆盖，血管壁未见明显钙化。.[研究结论] 经过去细胞肝素纳米修饰的牛隐动脉是一种高通畅的异种小管径替代血管。