Heparin releasing and immobilized polymers have demonstrated a significant reduction in thrombus formation on the blood/polymer interface. In vitro studies revealed that prevention of fibrin formation using the designed systems were mainly due to heparin activity, in terms of APTT, TT, and anti- Factor Xa tests. In vivo studies of heparin immobilized surfaces displayed minimum fibrin formation, although platelet adhesion was not significantly reduced. In this application, both commercial and fractionated heparin will be immobilized onto a model surface (Sepharose 6B) and a practical surface (polyurethane) using both hydrophilic and polar spacer arm groups. Based on our previous studies it is expected that the hydrophilic environment of the block spacer interface will reduce protein adsorption and subsequent platelet adhesion. Heparin-PGE1 conjugate will also be immobilized on the surface by similar chemistry to achieve the dual pharmacological actions of reducing fibrin formation and inhibiting platelet adhesion. The experimental parameters, hydrophilic environment via hydrophilic spacer groups, heparin activity, and a heparin-PGE1 conjugate, will be investigated by utilizing a design variable of differing spacer group lengths between the surface and immobilized heparin or heparin-PGE1 conjugate. The animal experiments include rabbit ex vivo shunt (short term) catheter implant (short term) and vascular implant in dogs (long term). The results of the experimental data will verify possible mechanisms involved in thrombus formation (role of adsorbed protein, clotting factors, and platelet interaction) and provide a more effective model for the design of a blood compatible polymer surface. This will eliminate the need or systemic administration of anticoagulants in patients using blood contacting medical devices.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL020251-12
Application #
3336087
Study Section
Surgery, Anesthesiology and Trauma Study Section (SAT)
Project Start
1976-12-01
Project End
1991-11-30
Budget Start
1988-12-01
Budget End
1989-11-30
Support Year
12
Fiscal Year
1989
Total Cost
Indirect Cost
Name
University of Utah
Department
Type
Schools of Pharmacy
DUNS #
City
Salt Lake City
State
UT
Country
United States
Zip Code
84112
Byun, Y; Jacobs, H A; Feijen, J et al. (1996) Effect of fibronectin on the binding of antithrombin III to immobilized heparin. J Biomed Mater Res 30:95-100
Byun, Y; Jacobs, H A; Kim, S W (1996) Binding of antithrombin III and thrombin to immobilized heparin under flow conditions. Biotechnol Prog 12:217-25
Kim, S W; Jacobs, H (1996) Design of nonthrombogenic polymer surfaces for blood-contacting medical devices. Blood Purif 14:357-72
Byun, Y; Jacobs, H A; Kim, S W (1994) Heparin surface immobilization through hydrophilic spacers: thrombin and antithrombin III binding kinetics. J Biomater Sci Polym Ed 6:1-13
Byun, Y; Jacobs, H A; Kim, S W (1992) Binding kinetics of thrombin and antithrombin III with immobilized heparin using a spacer. ASAIO J 38:M649-53
Piao, A Z; Jacobs, H A; Park, K D et al. (1992) Heparin immobilization by surface amplification. ASAIO J 38:M638-43
Nojiri, C; Okano, T; Koyanagi, H et al. (1992) In vivo protein adsorption on polymers: visualization of adsorbed proteins on vascular implants in dogs. J Biomater Sci Polym Ed 4:75-88
Park, K D; Kim, W G; Jacobs, H et al. (1992) Blood compatibility of SPUU-PEO-heparin graft copolymers. J Biomed Mater Res 26:739-56
Kim, W G; Park, K D; Mohammad, S F et al. (1991) SPUU-PEO-heparin graft copolymer surfaces. Patency and platelet deposition in canine small diameter arterial grafts. ASAIO Trans 37:M148-9
Lin, S C; Jacobs, H A; Kim, S W (1991) Heparin immobilization increased through chemical amplification. J Biomed Mater Res 25:791-5

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