PROTEIN AND THROMBUS DEPOSITION ON VASCULAR GRAFTS

血管移植物上的蛋白质和血栓沉积

• 批准号: 3336329
• 负责人: STUART L COOPER
• 金额: $ 14.5万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 1978
• 资助国家: 美国
• 起止时间: 1978-07-01 至 1991-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3336329
• 关键词: X ray spectrometry; adsorption; antithrombogenic surface; biomaterial evaluation; biomaterial interface interaction; blood proteins; blood vessel prosthesis; conformation; dogs; fibrinogen; fibronectins; fluorescence; fluorocarbon polymers; gel electrophoresis; human tissue; implant; infrared spectrometry; laboratory rabbit; monoclonal antibody; platelet activation; polyethylenes; polymers; polyurethanes; proteolysis; radiotracer; scanning electron microscopy; serum albumin; thromboembolism; video recording system

The occurrence of thrombosis at a blood-polymer interface presents major design difficulties in the development of small-diameter artificial vascular grafts. The interaction between blood and an artificial surface results in an adsorbed protein layer which affects the extent of platelet deposition and thrombus formation. The factors that determine the nature of this protein layer are not well-defined. We have determined that both the chemical nature of the surface and the conditions of protein adsorption influence the amount of thrombus formation and rate of embolization. We propose to study surface-protein interactions at the molecular level. Commercially-available and laboratory-synthesized biomaterials which have markedly different chemical surface properties will be used in in vitro and canine ex vivo experiments to study the effect of modifications in chemical properties on protein deposition. In vitro deposition of human or canine fibrinogen, fibronectin, vitronectin, and serum albumin onto these materials will be assessed. These proteins will be adsorbed singly, competitively, and sequentially to examine protein-protein interactions on the surfaces. Conformation of the adsorbed protein will be determined by Fourier Transform Infrared spectroscopy and by enzymatic methods. Orientation and distribution of adsorbed proteins will be assessed by immunological methods. In addition, the canine proteins will be preadsorbed onto the materials and tested in the canine ex vivo shunt to determine the whole-blood response in the absence of anticoagulants. The influence of protein conformation, orientation, and distribution on platelet activation will be examined. Scanning and high voltage electron microscopy will be used to assess morphological and cytoskeletal changes in platelets. Video-enhanced microscopy will be used to measure the granule secretion induced by the protein-surface interaction. These studies will extend the current research on the mechanisms involved in artificial surface-induced thrombogenesis and provide information that will aid in the design of biomaterials.

血液聚合物界面处的血栓形成出现主要 小直径人造的设计困难 血管移植物。 血液与人造表面之间的相互作用 导致吸附的蛋白质层影响血小板的程度 沉积和血栓形成。 决定性质的因素 该蛋白质层的定义不明确。 我们已经确定两个 表面的化学性质和蛋白质吸附的条件 影响血栓形成的量和栓塞速率。 我们建议在分子水平研究表面蛋白质相互作用。 具有商业上可用的实验室合成的生物材料 明显不同的化学表面特性将用于体外和 犬类离体实验，以研究化学修饰的影响 蛋白质沉积的特性。 人类或犬的体外沉积 在这些上 材料将被评估。 这些蛋白质将被单独吸附， 竞争性和顺序检查蛋白质 - 蛋白质相互作用 表面。 吸附蛋白的构象将由 傅立叶转化红外光谱和酶促方法。 吸附蛋白的方向和分布将通过 免疫学方法。 另外，犬蛋白将是 预先吸引材料并在犬类外分流中进行测试 在没有抗凝剂的情况下确定全血反应。 蛋白质构象，方向和分布对 血小板激活将进行检查。 扫描和高压电子 显微镜将用于评估形态学和细胞骨架变化 血小板。 视频增强显微镜将用于测量颗粒 蛋白质表面相互作用引起的分泌。 这些研究将扩展有关涉及机制的当前研究 在人工表面引起的血栓形成中，并提供了信息 将有助于设计生物材料。