Abstract

BACKGROUND:Thrombus formation and neointimal hyperplasia still limit the use of small-caliber expanded poly(tetrafluoroethylene) (ePTFE) vascular prosthesis with a diameter less than 6 mm for revascularization in the coronary or peripheral circulation. Bioactive surface heparin coating is one conceivable path for above-mentioned problems.
OBJECTIVE: To elevate the anticoagulant property of ePTFE, this study promoted the patency of a novel small-caliber ePTFE vascular graft by modifying its luminal surface with covalently crosslinked poly(vinyl alcohol)/ p-diazonium diphenyl amine polymer/heparin gel (PVA/PA/Hep gel) and examined the hemocompatibility of the graft.
DESIGN, TIME AND SETTING: Observational experiments were performed at the Nanomedicine and Biosensor Lab, Biomedical Engineering Center, Harbin Institute of Technology from May 2006 to June 2007.
MATERIALS: The ePTFE vascular grafts (diameter of 4 mm), Nafion (Naf) and Poly(vinyl alcohol) (Aldrich, USA), heparin (MW 12 000-14 000) (Calbiochem, USA), p-diazonium diphenyl amine polymer (PA) (this lab, China) were used in this study.
METHODS: ①The vascular graft surface was firstly modified with Nafion. ②Following the impregnation of the mixture of PVA/PA/Hep, covalent crosslinking between polyvinyl alcohol and heparin was performed using crosslinker PA under ultraviolet radiation.
MAIN OUTCOME MEASURES: ①Contact angles, ②Attenuated total reflection-fourier transform infrared spectroscopy (ATR-FTIR), ③Activated partial thromboplastin time (APTT) and prothrombin time (PT), ④hemolysis test, ⑤platelet adhesion test and ⑥thrombosin inactivation test.
RESULTS: ①The water contact angle of the vascular graft surface was greatly decreased after modifying. ATR-FTIR revealed the disappearance of diazonium groups at 2 172 cm-1 and 2 224 cm-1. Vascular prosthesis after modifying had prolonged APTT and PT, low percent hemolysis and low amount of platelet adhesion. Modified vascular prosthesis had inhibitory effect on thrombosin activity and good coating stability.
CONCLUSION: Converage of PVA/PA/Hep has good antithrombotic function and low percent hemolysis, resulting in improving hemocompatibility of vascular prosthesis.

1Nanomedicine and Biosensor Lab, Biomedical Engineeering Center, Harbin Institute of Technology, Harbin 150080, Heilongjiang Province, China; 2College of Urban Water Resources and Environment, Harbin Institute of Technology, Harbin 150001, Heilongjiang Province, China

Ma Yan☆, Studying for doctorate, Nanomedicine and Biosensor Lab, Biomedical Engineeering Center, Harbin Institute of Technology, Harbin 150080, Heilongjiang Province, China
littlebird_05@163.com

Correspondence to: Dai Zhi-fei, Professor, Tutor of doctor, Nanomedicine and Biosensor Lab, Biomedical Engineeering Center, Harbin Institute of Technology, Harbin 150080, Heilongjiang Province, China

Supported by: the National Natural Science Foundation of China, No. NSFC- 50573015*; the Plan Program for Supporting Excellent Talent in the New Century

Received: 2007-12-25 Accepted: 2008-02-22 (07-50-12-7204/N)

Ma Y, Yue XL, Liu M, Liu SQ, Dai ZF.Small- caliber expanded poly(tetrafluoroethylene) vascular prosthesis impregnated with heparin and polyvinyl alcohol gel.Zhongguo Zuzhi Gongcheng Yanjiu yu Linchuang Kangfu 2008;12(14): 2773-2776(China)
[www.zglckf.com/zglckf/ejournal/upfiles/ 12-14/14k-2773
(ps).pdf]

肝素/聚乙烯醇凝胶灌注修饰的小口径膨体聚四氟乙烯人工血管**☆

摘要
背景：小口径（直径小于6 mm）膨体聚四氟乙烯人工血管由于血栓形成和内膜增生等原因，在冠状和外周血液循环中的应用受到了限制，而生物活性表面肝素涂层是解决上述问题的一条有效途径。
目的：为了提高膨体聚四氟乙烯人工血管的抗凝血性能，采用新型肝素涂层——共价交联的聚乙烯醇/重氮树脂/肝素凝胶修饰小口径膨体聚四氟乙烯人工血管以提高其通畅性，并观察其血液相容性。
设计、时间及地点：观察性实验，于2006-05/2007-06在哈尔滨工业大学生物医学工程中心的纳米医药与生物传感器实验室完成。
材料：膨体聚四氟乙烯人工血管（直径4 mm），全氟磺酸和聚乙烯醇购于美国Aldrich公司，肝素购于Calbiochem公司（MW12 000~ 14 000），重氮树脂由实验室自己合成。
方法：①用全氟磺酸修饰膨体聚四氟乙烯表面。②用聚乙烯醇/重氮树脂/肝素凝胶进行灌注修饰，在紫外光照射的条件下，重氮树脂作为交联剂，将肝素和聚乙烯醇分子进行共价交联。
主要观察指标：①接触角。②衰减全反射-傅里叶变换红外光谱表征材料表面的化学结构。③活化部分凝血激酶时间、凝血酶原时间。④溶血试验。⑤血小板黏附试验。⑥凝血酶失活试验。
结果：①修饰后的人工血管的接触角降低，衰减全反射-傅立叶变换红外光谱显示在2 172 cm-1和2 224 cm-1处出现了重氮基团的特征峰位。②与未修饰的人工血管相比，修饰后的人工血管具有较长的活化部分凝血激酶时间和凝血酶原时间、较低的溶血度、很少数量的血小板黏附。③与未修饰的人工血管相比，修饰后的人工血管对凝血酶的活性有较强的抑制作用，且涂层稳定。
结论：聚乙烯醇/重氮树脂/肝素凝胶形成的肝素涂层不仅具有很好的抗血栓形成的性能，而且具有较低的溶血度，因此显著提高了人工血管的血液相容性。
关键词：膨体聚四氟乙烯人工血管；共价交联；抗凝血表面修饰；血液相容性

马 艳1，岳秀丽2，刘 萌1，刘绍琴1，戴志飞1
1哈尔滨工业大学生物医学工程中心纳米医药与生物传感器实验室，黑龙江省哈尔滨市 150080；2哈尔滨工业大学市政与环境工程学院，黑龙江省哈尔滨市 150001
马 艳☆，女，1983年生，河北省唐山市人，汉族，哈尔滨工业大学在读博士，主要从事生物医用材料的研究。
通讯作者：戴志飞，教授，博士生导师，哈尔滨工业大学生物医学工程中心纳米医药与生物传感器实验室，黑龙江省哈尔滨市 150080
国家自然科学基金资助项目（NSFC-50573015）*；新世纪优秀人才支持计划资助项目

中图分类号: R318.08 文献标识码: A 文章编号: 1673-8225(2008)14-02773-04
马艳，岳秀丽，刘萌，刘绍琴，戴志飞.肝素/聚乙烯醇凝胶灌注修饰的小口径膨体聚四氟乙烯人工血管[J].中国组织工程研究与临床康复，2008，12(14):2773-2776
[www.zglckf.com/zglckf/ejournal/upfiles/12-14/14k-2773(ps).pdf]
(Edited by Mo XM/Qiu Y/Wang L)