NANOTEXTURED POLYURETHANES FOR REDUCED PLATELET ADHESION

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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.