NANOTEXTURED POLYURETHANES FOR REDUCED PLATELET ADHESION

描述（由申请人提供）： 聚氨酯生物材料在血液接触医疗器械（包括血管移植物和循环支持器械）的开发中发挥着重要作用。这类重要的生物材料的许多关键性质被认为是由它们所表现出的独特的微相分离结构引起的，所述微相分离结构由嵌段共聚物中的两个链段的热力学不相容性引起。在没有化学变化的情况下，这种聚合物的膜的表面形貌的变化可能足以改变与这种材料接触的血小板的粘附系数，同时保持材料的独特化学性质。推动这些研究的中心假设是： 聚氨酯生物材料上血小板可及接触面积的减少将导致血小板粘附减少，随后减少表面诱导的血栓形成。 为了检验这一假设，提出了以下具体目标：1）具有尺寸和间距范围为0.4至1.6 gm的柱阵列的图案聚氨酯。比较纳米纹理聚氨酯表面与平面聚氨酯表面的表面化学，并确定这些纳米形貌参数对纤维蛋白原吸附和在生理相关剪切应力范围内对血小板粘附的影响，2）通过测量血小板活化标志物的表达来确定粘附在纳米纹理和非纹理聚氨酯膜上的血小板的血栓形成性，粘附血小板形态的变化，并通过测量凝血级联的复合物的活化，3）通过使用双标记流式细胞术评估血小板活化随时间的变化来确定纳米纹理化聚氨酯对大量血小板悬浮液的影响。 粘附血小板在生物材料诱导的血栓形成中发挥核心作用，提供有助于血栓生长的血小板栓，并提供凝血级联复合物组装所需的磷脂膜。这些特定目标的完成将导致限制血小板粘附的新材料的开发，并将适用于预期用于血液接触应用的许多医疗器械。此外，使用150 mm直径的硅晶片将产生适于制造成隔膜的纳米织构聚合物膜，所述隔膜用作血液接触表面，用于循环支持装置。

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.