The main goal of this proposal is to test the hypothesis that the surface modification of biomaterials should be based on the steric repulsion theory to be consistently effective for the prevention of protein adsorption and platelet adhesion. Poly(ethylene oxide) (PEO) has been chosen for the study because of its well known protein- and platelet- resistant properties.
The specific aims of this project are: (1) to graft PEO chains on glass and polyethylene in a controlled manner using self- assembled monolayers; (2) to identify the minimum length and density of the grafted PEO chains necessary for effective steric repulsion; (3) to obtain molecular level understanding of the steric repulsion phenomenon using scaling analysis and computer simulation; and (4) to test steric repulsion theory in the prevention of protein adsorption and platelet adhesion in a canine ex vivo model. The main methodology includes synthesis of silanized PEO using either triethoxychlorosilane or 3-isocyanatopropyltriethoxysilane. The silanized PEO will react with glass to form covalently grafted PEO monolayers. PEO will also be covalently grafted to hydrophobically modified glass and polyethylene using PEO/PPO/PEO triblock copolymers. Special emphasis will be given to control the length and surface density of the grafted PEO chains. The grafted PEO layers will be characterized by measuring their resistance to protein adsorption and platelet adhesion as well a- the surface PEO concentration. Molecular modeling study is designed to understand the steric repulsion properties of the grafted PEO layers at the molecular level. The steric repulsion theory will be examined in an acute canine ex vivo model using the best surfaces obtained from the above study as well as the knitted polyester and silicone rubber vascular prostheses after surface modification. This study is novel in that it represents a systematic analysis of the protein- and platelet-resistant properties of the grafted PEO chains based on the steric repulsion theory, scaling analysis and computer simulation. The importance of this research is that it provides molecular level guidelines for the surface modification of biomaterials. it lays the foundation for the rational development of surfaces resistant to blood proteins and platelets, thereby eliminating the problems associated with surface-induced thrombosis.
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|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|
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