SURFACE MODIFIED MATERIALS - BLOOD INTERACTION

表面改性材料 - 血液相互作用

• 批准号: 3337473
• 负责人: MICHAEL V SEFTON
• 金额: $ 9.71万
• 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 1994-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3337473
• 关键词: anticoagulants; antithrombogenic surface; arteriovenous shunt surgery; auxiliary heart prosthesis; biomaterial evaluation; blood flow measurement; cardiovascular prosthesis; cell adhesion; cell sorting; dogs; fibrin; fibrinolytic agents; fluorescence microscopy; gel; heart catheterization; heparin; human tissue; isocyanates; platelet activation; platelet aggregation; platelets; polyethylenes; polyvinyls; surface property; thromboembolism

The ultimate objective of this research is to understand further role of the material in the pathogenesis of the thromboembolic complications of cardiovascular implants such as vascular catheters or prostheses. Our immediate objectives are: (A) to understand the basis for the differences among materials (e.g., PE and PVA) in the platelet consumption as observed in our unique chronic canine arterio-venous shunt and (B) to study the mechanism underlying the transient contact of platelets with hydrogel (high water content) surfaces - contact that does not result in adhesion yet appears to yield to their premature consumption. It is hypothesized that hydrogel surfaces (e.g., PVA), being "slippery", are less able to retain platelets on their surface yet the transient contact of platelets is sufficient to damage them and cause them to be removed from the circulation prematurely. Hence consumption is high but adhesion is low; the opposite is found with PE. We will (1) study the thrombogenicity (111In canine platelet lifespan, etc) of well characterized materials of different surface chemistries and thereby define the particular characteristics that distinguish PE from PVA. Special emphasis will be given to short chain alkylated surfaces, one of which (butylated PVA) has eliminated the platelet reactivity of the PVA in preliminary studies. We also propose to (2) prepare a partially alkylated surface with low platelet reactivity that can be subsequently heparinized to yield a surface which would also have high anticoagulant activity. This material may be uniquely suitable for the minimization of the thromboembolic complications of cardiovascular devices since the immobilized heparin can prevent fibrin formation while the low reactivity will not result in high platelet consumption. Additional control materials that differ from PVA in a single functional group will also be evaluated. Furthermore, we propose to better understand the mechanism of biomaterial associated platelet activation. We will (3) exploit the sensitivity of flow cytometry (FAFC) and immunologic platelet membrane markers to characterize human platelet activation after exposure to PVA, PE, etc and (4) assess the relationship among surface chemistry, protein adsorption and transient platelet contact through fluorescent videomicroscopy measurement of human platelet residence time distribution and platelet attachment/detachment dynamics. We expect to identify strategies suitable for the preparation and ultimately the clinical evaluation (i.e. by FAFC) of low thrombogenicity, platelet compatible materials for cardiovascular devices. By minimizing the thromboembolic consequences of surgical intervention, existing therapies can be made safer and new ones developed as a consequence of material development.

本研究的最终目的是进一步了解 血栓栓塞并发症发病机制的材料 心血管植入物，例如血管导管或假体。 我们的 近期目标是： (A) 了解差异的基础 所观察到的材料（例如 PE 和 PVA）之间的血小板消耗 在我们独特的慢性犬动静脉分流术中以及（B）研究 血小板与水凝胶短暂接触的机制（高 水含量）表面 - 尚未产生粘附力的接触 似乎屈服于他们的过早消费。 假设 水凝胶表面（例如 PVA）“很滑”，不太能够保留 血小板在其表面，但血小板的短暂接触是 足以损坏它们并导致它们从循环中去除 过早地。 因此消耗量高但附着力低；相反 是用PE发现的。 我们将 (1) 研究血栓形成性 (111In canine 不同材料的良好表征材料的血小板寿命等） 表面化学，从而定义了特定的特性 区分PE和PVA。 将特别强调短链 烷基化表面，其中之一（丁基化 PVA）消除了 初步研究中PVA 的血小板反应性。 我们还建议 (2) 制备具有低血小板反应性的部分烷基化表面， 随后可以肝素化以产生也具有 高抗凝活性。 这种材料可能特别适合 最大限度地减少心血管血栓栓塞并发症 装置，因为固定化肝素可以防止纤维蛋白形成，同时 低反应性不会导致高血小板消耗。 与PVA在单一功能上不同的附加控制材料 组也将被评估。 此外，我们建议更好地了解生物材料的机制 相关的血小板活化。 我们将（3）利用敏感性 流式细胞术 (FAFC) 和免疫血小板膜标记物 暴露于 PVA、PE 等后人类血小板活化的特征 (4)评估表面化学、蛋白质吸附和 通过荧光视频显微镜测量进行瞬时血小板接触 人血小板停留时间分布与血小板的关系 依恋/脱离动态。 我们期望找到合适的策略 用于准备和最终的临床评估（即由福特金融） 用于心血管的低血栓形成性、血小板相容性材料 设备。 通过最大限度地减少手术的血栓栓塞后果 干预，可以使现有疗法更安全并开发新疗法 作为物质发展的结果。