SURFACE MODIFIED MATERIALS--BLOOD INTERACTION

表面改性材料--血液相互作用

• 批准号: 2519265
• 负责人: MICHAEL V SEFTON
• 金额: $ 12.16万
• 依托单位: UNIVERSITY OF TORONTO
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-09-30 至 1999-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2519265
• 关键词: antithrombogenic surface; arteriovenous shunt surgery; blood coagulation; blood flow measurement; cell cell interaction; complement pathway; dogs; flow cytometry; human tissue; leukocyte activation /transformation; platelet activation; thrombin; thrombosis

DESCRIPTION: (Adapted from the applicant's abstract) The objective of the investigators is to understand better the role of the biomaterial in thromboembolic complications of vascular prostheses, catheters, and stents. Platelet activation is hypothesized to be due to direct material contact or indirect effects of complement, platelet release or activation of the coagulation cascade. A unique canine AV shunt will be used to assess the effect of material surface chemistry on ex vivo platelet consumption. Flow cytometry (FAFC) will be used to study the activation of platelets and leukocytes in vitro and in the chronic shunt. In vitro and ex vivo shunt studies will be employed to show 1) which surfaces are platelet and leukocyte reactive, 2) what alterations they induce in platelets and leukocytes, and 3) what the extent of platelet destruction/removal is via microparticle formation and activated platelet associations with leukocytes. They are especially interested in the reactive roles of thrombin and activated complement in these processes and how pharmacologic agents (thrombin or complement inhibitors) may define these contributions. Hydrogel coated surfaces and hydrophobic surfaces appear to act differently in this context, with hydrogels resulting in low platelet adhesion but high consumption, including microparticle generation. Understanding the mechanism(s) behind this phenomenon is important to the design of biomaterials with truly low thrombogenicity.

描述：（改编自申请人的摘要）该项目的目标 研究人员的目的是更好地了解生物材料在 血管假体、导管和支架的血栓栓塞并发症。 假设血小板活化是由于直接材料接触或 补体、血小板释放或激活的间接影响 凝血级联。 将使用独特的犬 AV 分流器来评估 材料表面化学对离体血小板消耗的影响。 流动 细胞计数术（FAFC）将用于研究血小板的活化和 体外和慢性分流中的白细胞。 体外和离体分流 将采用研究来表明 1) 哪些表面是片状的， 白细胞反应性，2) 它们引起血小板和 白细胞，以及 3) 血小板破坏/去除的程度是通过 微粒形成和激活的血小板与白细胞的结合。 他们对凝血酶和凝血酶的反应作用特别感兴趣 这些过程中激活的补体以及药物制剂如何 （凝血酶或补体抑制剂）可以定义这些贡献。 水凝胶涂层表面和疏水表面似乎表现不同 在这种情况下，水凝胶导致血小板粘附力低，但血小板粘附力高 消耗，包括微粒的产生。 了解 这种现象背后的机制对于设计很重要 真正具有低血栓形成性的生物材料。