NANOTEXTURED POLYURETHANES FOR REDUCED PLATELET ADHESION

用于降低血小板粘附的纳米纹理聚氨酯

• 批准号: 6988498
• 负责人: CHRISTOPHER A SIEDLECKI
• 金额: $ 18.27万
• 依托单位: PENNSYLVANIA STATE UNIV HERSHEY MED CTR
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-12-01 至 2007-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6988498
• 关键词: adsorption; antibody; antithrombogenic surface; biomaterial development /preparation; biomaterial evaluation; cell adhesion; cell morphology; cow; fibrinogen; flow cytometry; nanotechnology; platelet activation; platelets; polyurethanes; shear stress; adsorption; antibody; antithrombogenic surface; biomaterial development /preparation; biomaterial evaluation; cell adhesion; cell morphology; cow; fibrinogen; flow cytometry; nanotechnology; platelet activation; platelets; polyurethanes; shear stress

DESCRIPTION (provided by applicant): Polyurethane biomaterials play an important role in the development of blood-contacting medical devices including vascular grafts and circulatory support devices. Many of the key properties of this important class of biomaterials are believed to arise from the unique microphase separated structure they exhibit, arising from the thermodynamic immiscibility of the two segments in the block copolymer. Changes to the surface topography of films of this polymer in the absence of chemical change may be sufficient to change the adhesive coefficient of platelets coming into contact with this material while retaining the unique chemistry of the material. The central hypothesis driving these studies is that: A reduction in the platelet accessible contact area on polyurethane biomaterials will lead to a reduction in platelet adhesion, and subsequently a reduction in surface-induced thrombogenesis. To test this hypothesis, the following specific aims are proposed: 1) Pattern polyurethane with arrays of pillars having dimensions and spacings ranging from 0.4 to 1.6 gm. Compare the surface chemistry of nanotextured polyurethane surfaces with planar polyurethane surfaces and determine the effect of these nanotopography parameters on fibrinogen adsorption and on platelet adhesion across a range of physiologically relevant shear stresses, 2) Determine the thrombogenicity of adherent platelets on both nanotextured and non-textured polyurethane films by measuring expression of platelet activation markers, changes in adherent platelet morphology and by measuring activation of the complexes of the coagulation cascade, 3) Determine the effect of nanotexturing polyurethane on bulk platelet suspension by assessing platelet activation Over time using dual-labeled flow cytometry. Adherent platelets play a central role in biomaterial-induced thrombogenesis, providing a platelet plug that contributes to the growing thrombus and supplying the phospholipid membrane necessary for assembly of the complexes of the coagulation cascade. Completion of these specific aims will lead to the development of new materials that limit platelet adhesion and will have applicability in a number of medical devices intended for use in blood contacting applications. Furthermore, the use of 150 mm diameter silicon wafers as will produce nanotextured polymer films suitable for fabrication into diaphragms for use as the blood-contacting surface for use in circulatory support devices.

描述（由申请人提供）： 聚氨酯生物材料在包括血管移植物和循环支撑装置在内的血液接触医疗设备的开发中起着重要作用。据信，这种重要类型生物材料的许多关键特性是由它们所表现出的独特的微相分离结构产生的，这是由于块共聚物中两个片段的热力学不混溶而产生的。在没有化学变化的情况下，该聚合物膜的表面形貌的变化可能足以改变与该材料接触的血小板的粘合剂系数，同时保留材料的独特化学性质。推动这些研究的中心假设是： 聚氨酯生物材料的血小板接触区域的降低将导致血小板粘附的降低，然后降低表面诱导的血栓形成。 为了检验这一假设，提出了以下特定目的：1）模式聚氨酯，具有尺寸为0.4至1.6 gm的柱子和间距的阵列阵列。 Compare the surface chemistry of nanotextured polyurethane surfaces with planar polyurethane surfaces and determine the effect of these nanotopography parameters on fibrinogen adsorption and on platelet adhesion across a range of physiologically relevant shear stresses, 2) Determine the thrombogenicity of adherent platelets on both nanotextured and non-textured polyurethane films by measuring expression of platelet activation标记，粘附血小板形态的变化以及通过测量凝血级联反应的复合物的激活，3）通过使用双标记的流式细胞仪评估纳米卵形聚氨酯对散装血小板悬浮液的影响。 粘附的血小板在生物材料诱导的血栓形成中起着核心作用，提供了一个血小板塞，有助于增长的血栓并提供磷脂膜的磷脂膜，以组装凝结级联的络合物。这些特定目标的完成将导致开发限制血小板粘附的新材料，并将适用于许多用于血液接触应用的医疗设备。此外，使用150毫米直径的硅晶片，将产生适合制造成隔膜的纳米刺激的聚合物膜，以用作血液接触表面，用于循环支撑装置。