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与血液接触的医疗设备的发展中起着重要的作用。这类重要的生物材料的许多关键性质被认为源于它们所表现出的独特的微相分离结构，这种结构源于嵌段共聚物中两个链段的热力学不混溶。在没有化学变化的情况下，这种聚合物薄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合系数，同时保持这种材料的独特化学成分。推动这些研究的中心假设是： 聚氨酯生物材料上血小板可接触面积的减少将导致血小板粘附性的减少，从而减少表面诱导的血栓形成。为了验证这一假设，提出了以下具体目标：1)具有尺寸和间距范围为0.4到1.6克的柱子阵列的图案聚亚安酯。比较纳米结构和平面聚氨酯表面的表面化学，确定这些纳米形貌参数对纤维蛋白原吸附和在一系列生理相关剪应力范围内对血小板黏附的影响；2)通过测量血小板激活标志物的表达、黏附的血小板形态的变化以及通过测量凝固级联复合体的激活来确定黏附在纳米结构和非织构的聚氨酯薄膜上的血栓形成能力；3)通过使用双标记流式细胞仪评估随时间推移的血小板激活来确定纳米结构聚氨酯对块状血小板悬浮的影响。 黏附的血小板在生物材料诱导的血栓形成中起着核心作用，它提供了促进血栓生长的血小板堵塞，并提供了凝血级联复合体组装所需的磷脂膜。这些特定目标的完成将导致限制血小板黏附的新材料的开发，并将在许多用于血液接触应用的医疗设备中具有适用性。此外，使用直径150 mm的硅晶片将制造出适合制作成横隔膜的纳米结构聚合物薄膜，用作循环支持设备中的血液接触表面。

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.