NANOTEXTURED POLYURETHANES FOR REDUCED PLATELET ADHESION

描述（由申请人提供）： 聚氨酯生物材料在血管移植物和循环支持装置等血液接触医疗器械的开发中发挥着重要作用。据信，这一类重要生物材料的许多关键特性源于它们所表现出的独特的微相分离结构，而这种结构源于嵌段共聚物中两个链段的热力学不混溶性。在没有化学变化的情况下，改变这种聚合物薄膜的表面形貌可能足以改变与这种材料接触的片晶的粘附系数，同时保留该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，从而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在一系列生理相关剪切应力下对纤维蛋白原吸附和血小板粘附的影响，2) 通过测量血小板活化标记物的表达、粘附血小板形态的变化以及通过测量凝血级联复合物的激活来确定纳米纹理和非纹理聚氨酯膜上粘附血小板的血栓形成性，3) 通过评估确定纳米纹理聚氨酯对散装血小板悬浮液的影响使用双标记流式细胞术随时间的推移血小板激活。 粘附的血小板在生物材料诱导的血栓形成中发挥着核心作用，提供有助于血栓生长的血小板栓塞，并提供凝血级联复合物组装所需的磷脂膜。这些具体目标的完成将导致限制血小板粘附的新材料的开发，并将适用于许多用于血液接触应用的医疗设备。此外，使用直径 150 毫米的硅晶片将生产适合制造成隔膜的纳米纹理聚合物薄膜，用作循环支持装置中的血液接触表面。

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.