THROMBOSIS ON BIOMATERIALS:ROLE OF VASCULAR COMPONENTS

生物材料上的血栓形成：血管成分的作用

• 批准号: 3355420
• 负责人: VINCENT T. TURITTO
• 金额: $ 19.1万
• 依托单位: UNIVERSITY OF MEMPHIS
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-09-30 至 1992-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3355420
• 关键词: antithrombogenic surface; biomaterial interface interaction; blood vessel prosthesis; cell adhesion; coagulation factor VIII; collagen; fibrin; glycoproteins; human tissue; platelet aggregation; radiotracer; swine; thrombosis; vascular endothelium; von Willebrand factor

The problem of limited availability of biological replacements for diseased vessels and organs is exacerbated by the failure of most prosthetic implants and organ substitutes due to repeated thrombo-embolic events. The mechanism which underlie the deposition of thrombotic masses on biomaterial surfaces is poorly understood. The objective of the present proposal is to investigate the influence of vascular surfaces on the deposition of platelets and fibrin on selected prosthetic surfaces. A tubular perfusion chamber has been developed for mounting the materials immediately downstream of injured vascular surfaces exposing the composite substrates to blood in an ex vivo perfusion system. Blood from both swine and human subjects will be utilized to investigate the specific mechanisms which are important in determining the deposition of thrombotic material on the biomaterial surface. Evaluation of the surface deposits will be performed by several techniques. In swine, III-In labelled platelets will be injected and the quantity of deposited radioactivity determined. In swine and humans, morphometric analysis of epoxy embedded semi-thin sections will be utilized to quantify platelet and fibrin deposits. The thrombotic deposits will be evaluated for several exposure times, axial positions from the proximal surface and wall shear rates, such that the full physiological range of flow conditions is investigated (wall shear rates from 50-5000 sec-1). Variation of proximal (vascular) and distal (biomaterial) surfaces and the condition of the blood will utilized to explore the mechanisms of platelet and fibrin deposition on the prosthetic surface. Various components of the vessel wall, including, subendothelium and its modifications, collagen, and tissue factor will be utilized as the activating proximal surface. Blood from patients and animal models with various bleeding disorders will be utilized to investigate the importance of von Willebrand factor, platelet glycoproteins Ib and IIb-IIIa, platelet released products and the relative importance of the Factor XI, coagulation and the tissue factor, Factor VII, IX pathways. Antibodies of VWF, and glycoproteins Ib and IIb-IIIa will also be employed and compared to results obtained with the corresponding naturally occurring deficiency. The mechanisms of growth of thrombotic deposits will also be investigated in nonstreamline (recirculation) flow by appropriately modifying the perfusion chambers and a theory for particle deposition will be developed.

生物替代品的有限可获得性问题 疾病的血管和器官因MOST的失败而恶化 因反复植入假体和器官代用品 血栓栓塞症。这一机制构成了 血栓性肿块在生物材料表面沉积较差 明白了。本提案的目的是 研究血管表面对血管沉积的影响。 选定假体表面的血小板和纤维蛋白。一根管子 已经开发了灌注室来安装材料。 紧靠受伤血管表面的下游，暴露出 体外灌流系统中血液的复合基质。 来自猪和人类的血液将被用来 研究在以下方面非常重要的特定机制 测定血栓形成物质在血管上的沉积 生物材料表面。对地表矿藏的评价将是 通过几种技术完成的。在猪身上，III-in标记 将注射的血小板和沉淀量 放射性测定。在猪和人身上，形态测量 将利用环氧嵌套半薄切片的分析来 量化血小板和纤维蛋白沉积。血栓沉淀物将 要评估几个曝光时间，轴向位置从 近端表面和壁面的剪切率，以便完全 研究流动条件的生理范围(壁面剪切 速率从50-5000秒-1)。 近端(血管)和远端(生物材料)表面的变化 血液的状况将被用来探索 假体上血小板和纤维蛋白沉积的机制 浮出水面。管壁的各种组件，包括， 内皮下层及其修饰、胶原蛋白和组织因子 将被用作激活近端表面。血液来自于 患有各种出血性疾病的患者和动物模型将被 用来研究von Willebrand因子的重要性， 血小板释放产物--血小板膜糖蛋白Ib和IIb-IIIa 以及凝血因子XI、凝血酶原激活剂和 组织因子、因子VII、因子IX途径。VWF抗体，以及 糖蛋白Ib和IIb-IIIa也将被使用和比较 得到的结果与相应的自然发生的 缺乏症。 血栓沉积的生长机制也将是 对非流线型(再循环)流动进行了适当的研究 灌注室的改进和颗粒理论 将开发沉积技术。