The occurrence of thrombosis at the blood-polymer interface presents major difficulties in the design of artificial organs and extracorporeal devices. Advances in the development of improved biomaterials could be realized through the use of improved testing methods and through a more complete understanding of the mechanism of surface-induced thrombogenesis. We have developed a sensitive in-vivo technique to measure transient thrombus deposition onto synthetic surfaces. Each polymer surface which we have studied to date has a unique protein and platelet deposition response during the 120 min. period of blood exposure evaluated. We propose to extend this in-vivo technique to include evaluation of blood-materials interactions in a newly developed series shunt model (10 materials - 120 min.), and a chronic model (1 material - 2+ wks.). Non-anticoagulated canine subjects will be utilized for all studies. Both of these applications employ radiolabeled platelets and proteins and extensive electron microscopic evaluation of deposited thrombi. The series shunt model allows short-term comparison and evaluation of up to 10 different surfaces simultaneously in the same animal. This more efficient technique will be utilized to correlate physical and chemical surface properties (i.e., polyurethane hard and soft segment type and composition, solvent composition, surface roughness effects, etc.) of polymeric biomaterials with their short-term in-vivo thrombogenic response. Chronic studies involving implantation of iliac A-V shunts in canine subjects, continuous blood-flow monitoring and laser-light scattering detection of shed emboli will provide a means for studying the long-term thrombogenic response of these polymeric biomaterials. The chronic and acute single-shunt models will be utilized to evaluate the role of proteins in artificial-surface induced thrombogenesis. Studies are planned to measure the in-vivo desorption and exchange of radiolabeled plasma proteins (fibronectin, albumin, IgG, fibrinogen, and Alpha-2 macroglobulin) from polymer surfaces over long-term periods, and to elucidate the role of various glycoproteins (transferrin, haptoglobin, ceruloplasmin, C3 complement, plasminogen) and """"""""sugar-modified"""""""" (i.e., desialyated) proteins in initiating or diminishing thrombosis.
Showing the most recent 10 out of 51 publications
