Surface-induced platelet activation and subsequent thrombus formation has been a major obstacle to the perfection of blood-contacting artificial organs. The ideal biomaterial would be the one which does not allow platelet adhesion at all. The main goal of this proposal is to test the hypothesis that protein adsorption and platelet adhesion to biomaterials can be prevented by long-range steric repulsion originating from water-soluble polymers grafted to the surface.
The specific aims of this study are: (1) to prepare surfaces grafted with various water-soluble polymers (i.e., diffuse surfaces); (2) to analyze protein adsorption and platelet activation on the diffuse surfaces based on the steric repulsion mechanism; (3) to enhance our understanding on the mechanisms of protein adsorption using computer simulations; and (4) to present a unified theory on the prevention of platelet adhesion onto biomaterial surfaces. Highly water-soluble polymers, such as polyethylene oxide (PEO), polyvinylpyrrolidone, dextran, albumin, and gelatin, will be grafted to the model surfaces by radio frequency plasma polymerization and graft coupling methods. The surface coverage by grafted polymers and the thickness of diffuse layers will be varied. Specific emphasis will be given to the grafting of PEO. An efficient means to couple PEO to the surfaces will be developed by synthesizing PEO-containing amphipathic block copolymers with photo-reactive coupling groups. The prepared diffuse surfaces will be characterized by contact angle, ATR-FTIR, ESCA, ellipsometry, and protein adsorption. Platelet behavior on the prepared surfaces will be analyzed by examining morphological changes, cytoskeletal restructuring, and clustering of fibrinogen receptors. The minimum thickness of the diffuse layer necessary for preventing protein adsorption will be examined by calculating the protein-surface interaction energy as a function of distance from the surface. The importance of this research is that it establishes a general theory on the prevention of protein adsorption and platelet adhesion to the biomaterials, and provides guidelines for the preparation of surfaces which are not recognizable by platelets.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL039081-07
Application #
3355643
Study Section
Surgery and Bioengineering Study Section (SB)
Project Start
1987-09-01
Project End
1994-08-31
Budget Start
1993-09-01
Budget End
1994-08-31
Support Year
7
Fiscal Year
1993
Total Cost
Indirect Cost
Name
Purdue University
Department
Type
Schools of Pharmacy
DUNS #
072051394
City
West Lafayette
State
IN
Country
United States
Zip Code
47907
Jo, S; Park, K (2000) Surface modification using silanated poly(ethylene glycol)s. Biomaterials 21:605-16
Kidane, A; Park, K (1999) Complement activation by PEO-grafted glass surfaces. J Biomed Mater Res 48:640-7
Kidane, A; Lantz, G C; Jo, S et al. (1999) Surface modification with PEO-containing triblock copolymer for improved biocompatibility: in vitro and ex vivo studies. J Biomater Sci Polym Ed 10:1089-105
Park, K; Gemeinhart, R A; Park, H (1998) Movement of fibrinogen receptors on the ventral membrane of spreading platelets. Biomaterials 19:387-95
Kidane, A; Szabocsik, J M; Park, K (1998) Accelerated study on lysozyme deposition on poly(HEMA) contact lenses. Biomaterials 19:2051-5
Jo, I; Nielsen, S; Harris, H W (1997) The 17 kDa band identified by multiple anti-aquaporin 2 antisera in rat kidney medulla is a histone. Biochim Biophys Acta 1324:91-101
McPherson, T B; Shim, H S; Park, K (1997) Grafting of PEO to glass, nitinol, and pyrolytic carbon surfaces by gamma irradiation. J Biomed Mater Res 38:289-302
Szleifer, I (1997) Protein adsorption on surfaces with grafted polymers: a theoretical approach. Biophys J 72:595-612
Park, H; Park, K (1996) Biocompatibility issues of implantable drug delivery systems. Pharm Res 13:1770-6
Tseng, Y C; McPherson, T; Yuan, C S et al. (1995) Grafting of ethylene glycol-butadiene block copolymers onto dimethyl-dichlorosilane-coated glass by gamma-irradiation. Biomaterials 16:963-72

Showing the most recent 10 out of 23 publications