The occurrence of thrombosis at polymer-blood interfaces presents major difficulties in the development of blood compatible materials. It has been shown that the spreading of contact adhered platelets is the first step toward the formation of thrombi. It is hypothesized that the adhesivity between spread platelets and a surface determines whether the spread platelets are able to support thrombus growth in the shear field of the flowing blood or they are eliminated from the surface. Thus, the ability of biomaterial to induce platelet spreading and the platelet -surface adhesivity can serve as useful parameters for predicting surface thrombogenicity. These parameters, however, have not been fully examined yet. The major goal of this study is to achieve the complete characterization of platelet behavior at biomaterial-blood interfaces. The kinetics and extent of platelet morphological changes on various biomaterials will be examined using a video- enhanced differential interference contrast light microscope. Biochemical signals that are triggered by platelet contact with surfaces will be examined on the same platelets used for the morphology study. As representative biochemical signals, the movement of Ca++ ions and the change in membrane potential will be measured using fluorescence probes. The adhesive strength between platelets and a surface will be determined using the parallel-plate flow cell. The interaction of platelets with a protein layer which is formed on biomaterials upon blood exposure will be studied employing antibody exclusion methods, immunogold staining techniques, and interchromophore energy transfer measurements. A new in vitro technique which simulated in vivo thrombus formation will be developed using the parallel-plate flow cell. The in vitro formation of thrombus-like mural platelet aggregates can serve as a model for the in vivo thrombus formation. This new method will be able to screen large number of polymers for their potential thrombogenicity in the same condition and generate the same information as that from animal experiments, at least for the acute surface-induced thrombosis. Completion of this study will produce valuable information for the design of truly blood compatible materials.
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