The applications of polyurethanes in medicine continue to increase. Advantages cited for polyurethanes include excellent mechanical properties, blood compatibility, and biostability. While these advantages are extolled by some researchers, serious shortcomings in both blood compatibility and biostability have been identified for conventional segmented block copolyurethanes (PEUs). This credibility gap can, we believe, be largely attributed to non-standardized or poorly designed test methods. We have recently found a high platelet reactivity for conventional PEUs and found that many surface chemical functionalities of conventional PEUs are susceptible to degradation by agents similar to those found in the inflammatory sequence. We have recently synthesized PEUs with surface structures dominated by hydrocarbon moieties that show extremely low platelet reactivity, and may be resistant to biodegradation and calcification. This proposal is directed towards the development and evaluation of PEUs with improved blood compatibility under arterial, flow conditions, and enhanced resistance to biodegradation and calcification compared with conventional PEUs. Therefore, five research components are necessary. Synthesis: New PEUs with high, stable surface concentrations of hydrocarbon and fluorocarbon groups will be synthesized. We hypothesize that these surface layers protect the polymer from degradation, reduce calcification sites, and impart low platelet reactivity. Characterization: PEUs will be extensively characterized using the resources of the National ESCA and Surface Analysis Center for Biomedical Problems. Biodegradation: The susceptibility of the PEUs to oxidative and enzymatic attack will be assessed in vitro and in rat implant studies. Blood Compatibility: The good performance of hydrocarbon surface-enriched PEUs is believed to be associated with high albumin affinity. Protein adsorption studies will evaluate the ability of the PEUs to selectively adsorb albumin from plasma and measure the surface albumin retention strength. The adsorption, retention, and immunologic recognizability of fibrinogen to these polyurethanes will also be explored since these factors have been associated with platelet reactivity. A new circulating loop blood compatibility model that can measure four classes of interactions between platelets and surfaces will be used to assess blood compatibility. Results will be compared to chronic in vivo canine studies (AV shunt). Calcification: The susceptibility of the PEUs to calcification in an unstrained and strained state will be assessed in vitro. Given the high blood reactivity and biostability problems often observed for the conventional, commercial PEUs (Biomer, Biolon, Pellethane) that have dominated blood contact device development, the demise of commercial sources for these polymers may be beneficial to progress. This research points the way to a new generation of PEUs that might exhibit excellent blood compatibility in the arterial tree.
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