钛合金表面聚乙烯亚胺/肝素聚电解质多层膜的体外和体内血液相容性研究  

In vitro and in vivo Blood Compatibility of Titanium Alloy Surface Modification with Polyethyleneimine/Heparin Polyelectrolyte Multilayers

作　　者：李源[1] 程龙[1] 王永生[1] 刘成珪[1] 郭兴蓬[2] 张凯伦[1] 

机构地区：[1]华中科技大学同济医学院附属协和医院心血管外科,武汉430022 [2]华中科技大学化学与化工学院,武汉430074

出　　处：《华中科技大学学报（医学版）》2012年第4期415-422,共8页Acta Medicinae Universitatis Scientiae et Technologiae Huazhong

基　　金：国家高技术研究发展计划(863计划)资助项目(No.2007AA027Z439)

摘　　要：目的利用静电自组装技术在钛合金表面涂层聚电解质多层膜,评价其体外和体内血液相容性,探讨该技术在医用金属表面改性领域内的应用前景。方法利用静电自组装技术制备以肝素为最外层的聚乙烯亚胺/肝素聚电解质多层膜。并对该聚电解质多层膜进行物理表征分析,再进行体外溶血实验、凝血时间测定、蛋白吸附实验、血小板粘附实验和兔颈动脉腔内植入实验,对其进行血液相容性评价,与裸钛合金和(或)膨体聚四氟乙烯作平行对照。结果钛合金表面聚乙烯亚胺/肝素聚电解质多层膜的体外溶血率为0.690%,该涂层可以延长活化部分凝血酶原时间到(51.33±2.87)s,减少白蛋白的吸附量,尤其减少纤维蛋白原的吸附量,并且减少血小板的粘附与激活;体内动物实验中进一步证实聚乙烯亚胺/肝素聚电解质多层膜可以有效地减少材料表面血栓的形成。结论聚乙烯亚胺/肝素聚电解质多层膜为一种新型的生物化膜,可以使钛合金的血液相容性得到显著改善,显示了静电自组装技术在医用金属表面改性领域的广泛应用前景。Objective To investigate in vitro and in vivo blood compatibility of titanium alloy（TA4）by coating polyelectrolyte multilayers（PEM）via electrostatic self-assembly（ESA）technique and explore its application in the area of medical metal surface modification.Methods Polyethyleneimine/heparin polyelectrolyte multilayerswith an outermost layer of heparin（Hep）were produced by using ESA technique.The surface character of polyelectrolyte multilayers was analyzed firstly.Then,in vitro and in vivo blood compatibility of the multilayers was investigated in terms of hemolysis,prothrombin time（PT）,activated partial thromboplastin time（APTT）,protein adsorption and platelet adhesion.In the latter six analyses bare TA4 and expanded polytetrafluoroethylene（ePTFE）were both or either used as references.Results The ratio of hemolysis of polyethyleneimine/heparin polyelectrolyte multilayers was 0.690%,and polyethyleneimine/heparin polyelectrolyte multilayers could prolong APTT to（51.33±2.87）s,reduce the amount of adsorption of albumin,in particular,reduce the amount of fibrinogen adsorption,and reduce platelet adhesion and activation.It was further confirmed that polyethylenimine/heparin polyelectrolyte multilayers could effectively reduce the surface thrombus formation in the in vivo animal experiments.Conclusion Polyethyleneimine/heparin multilayer is new biologic surface,and it makes a great improvement to the blood compatibility of titanium alloy,suggesting ESA technique shows favorable prospects in the area of medical metal surface modification.

关 键 词：钛合金 肝素 血液相容性 静电自组装 表面改性 

分 类 号：R654.2[医药卫生—外科学]