One of the significant biomaterials problems impeding further development of cardiovascular prosthetics is that of thromboemboli formation with resulting potential damage to organs downstream of the implanted device. The blood compatibility of a material should include a measure if its thromboembolic character and not just its ability to remain patent, since blood compatibility evaluation based upon long-term thrombus buildup has been shown to be ineffective in determining the number density of emboli generated by a biomaterial. A technique we have developed for real time analysis of size and number density of microemboli in-vitro and in-vivo is an important contribution to the evaluation of biomaterials. The objective of this project is to further develop a fundamental understanding of the mechanisms relating initial events occurring when blood first contacts a biomaterial to acute thromboembolization so as to develop an in-vitro test system to predict the tendency of a biomaterial to produce thromboemboli in-vivo. To accomplish this goal we will measure the size, number, and rate of thromboemboli produced by a series of tubular biomaterials in contact with blood under controlled conditions of hemodynamic flow ex-vivo on the arteriovenous baboon shunt and in-vitro on a newly developed closed-loop blood flow system, utilizing a laser scattering technique. Acute thromboembolization measurements will be performed in-vitro using blood in which variations in anticoagulants, pH, and temperature will be controlled to produce a modification of the rates of embolization in-vitro so as to obtain a set of highly correlated data comparing the acute in-vitro embolic response to that in-vivo. These results will be extended in a similar fashion to include the embolic response of blood to the same series of biomaterials preadsorbed with specific plasma proteins to provide another set of highly correlated in-vivo and in-vitro data directly relevant to the development of a satisfactory in-vitro test for in-vivo thromboembolization. These measurements will be performed on a set of polyurethanes chosen for having a wide range in embolic response to blood so that clinically relevant data can be produced. It is expected that these experiments will produce data for the development of an in-vitro test for in-vivo thromboembolization, thus potentially reducing the need for costly and sometimes controversial animal experiments.
