The lack of knowledge of the biochemical mechanisms underlying the reactions of blood with polymeric biomaterials continues to be an obstacle to the design of better materials for use in contact with blood. Yet there is a large existing and continually expanding need for materials that would be more compatible with blood. The proposed research will allow more rational design of biomaterials to occur in place of the current empirical search for better materials. In addition, since new materials will be developed to test the proposed mechanisms, improved materials may result directly from the work.
The specific aims are as follows: 1. The further development and application of a new, in situ, high accuracy, high resolution method for studying platelet interactions with materials will be done. By measuring calcium mobilization inside platelets as they contact the surface of the polymer using a newly acquired cooled CCD megapixel camera and epi-fluorescent microscope, a powerful new tool will be available allowing us to assess the role of surface properties in platelet activation. Coagulation factor assays will be done using the same imaging equipment using fluorescent markers. 2. The hypothesis that adsorbed fibrinogen is the major mediator of platelet adhesion to polymeric biomaterials will be tested. By measuring platelet adhesion and activation to surfaces pre- adsorbed with plasma selectivity depleted or genetically deficit in the adhesion proteins fibrinogen, fibronectin, vitronectin, and von Willebrand factor, we will assess the importance of these proteins. Dose-response studies of the effect of restoration of the deficient factors will also be done. 3. To test the hypothesis that the platelet adhesion and activation by biomaterials are determined by the amount as well as the state of fibrinogen binding to the material, the behavior of platelets and fibrinogen on four series of polymers will be studied. The polymer series to be used are: a) plasma deposited fluorocarbon surfaces made with TFE, including a new type made by deposition of TFE in the presence of varying amounts of H2 or CH4; b) PVA and PEO containing polymers that exhibit weak binding of fibrinogen. Alkylated PVAs and PEO/PPO copolymers that should exhibit variable degrees of tighter binding will also be studied: c) HEMA-EMA copolymers; and d) commercial and novel polyurethanes. Surface characterization data will be correlated with protein adsorption characteristics and platelet interactions using multivariate statistical methods.
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