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.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL024046-08
Application #
3337478
Study Section
Surgery and Bioengineering Study Section (SB)
Project Start
1979-05-01
Project End
1988-06-30
Budget Start
1987-07-01
Budget End
1988-06-30
Support Year
8
Fiscal Year
1987
Total Cost
Indirect Cost
Name
University of Wisconsin Madison
Department
Type
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
Silver, J H; Lin, J C; Lim, F et al. (1999) Surface properties and hemocompatibility of alkyl-siloxane monolayers supported on silicone rubber: effect of alkyl chain length and ionic functionality. Biomaterials 20:1533-43
Lim, F; Cooper, S L (1995) Effect of sulphonate incorporation on in vitro leucocyte adhesion to polyurethanes. Biomaterials 16:457-66
Silver, J H; Hergenrother, R W; Lin, J C et al. (1995) Surface and blood-contacting properties of alkylsiloxane monolayers supported on silicone rubber. J Biomed Mater Res 29:535-48
Silver, J H; Myers, C W; Lim, F et al. (1994) Effect of polyol molecular weight on the physical properties and haemocompatibility of polyurethanes containing polyethylene oxide macroglycols. Biomaterials 15:695-704
Hergenrother, R W; Yu, X H; Cooper, S L (1994) Blood-contacting properties of polydimethylsiloxane polyurea-urethanes. Biomaterials 15:635-40
Lim, F; Yang, C Z; Cooper, S L (1994) Synthesis, characterization and ex vivo evaluation of polydimethylsiloxane polyurea-urethanes. Biomaterials 15:408-16
Lin, H B; Sun, W; Mosher, D F et al. (1994) Synthesis, surface, and cell-adhesion properties of polyurethanes containing covalently grafted RGD-peptides. J Biomed Mater Res 28:329-42
Hergenrother, R W; Wabers, H D; Cooper, S L (1993) Effect of hand segment chemistry and strain on the stability of polyurethanes: in vivo biostability. Biomaterials 14:449-58
Pitt, W G; Weaver, D R; Cooper, S L (1993) Fibronectin adsorpton kinetics on phase segregated polyurethaneureas. J Biomater Sci Polym Ed 4:337-46
Lin, H B; Lewis, K B; Leach-Scampavia, D et al. (1993) Surface properties of RGD-peptide grafted polyurethane block copolymers: variable take-off angle and cold-stage ESCA studies. J Biomater Sci Polym Ed 4:183-98

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