CELL AND PROTEIN REACTIONS WITH FOREIGN MATERIALS

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The need for biomaterials with enhanced blood compatibility is illustrated by the failure of synthetic small diameter vascular grafts and the embolic complications associated with the artificial heart. Improvement of biomaterials which contact blood or soft tissue awaits better understanding of the molecular and cellular processes involved. Since the cellular interactions with biomaterials are strongly influenced by the amount and reactivity of specific proteins in the adsorbed layer formed on contact with biological fluids, a series of studies on the relationship between the organization of the adsorbed protein layer and cellular interactions is proposed. Several classes of polymers will be used in this work, including: (1) polyurethanes; (2) RF-plasma deposited films; (3) poly(ethylene oxide) surfaces; and (4) methacrylic polymers. Platelet adhesion, spreading, and release will be compared with fibrinogen (FGN), fibronectin (FN), IgG, and VWF adsorption from plasma. Platelet/adsorbed protein interactions will be studied with peptides which block FN and FGN binding to platelets, with antibody blocking of specific adsorbate proteins, and with a cell blotting technique capable of revealing the importance of other proteins in platelet interactions. Platelet response to how a protein is adsorbed, rather than only how much of it is adsorbed, will be examined using a series of co-adsorbed proteins (including albumin/FGN and albumin/FN). The effect of aging on pre-adsorbed proteins on their interactions with cells will be examined because this appears to alter the conformation of the protein on the surface as evidenced by increases in the tightness with which the proteins are held. Macrophage adhesion, spreading and growth factor release will be compared to IgG and C3 adsorption on several polymer series. Cell blotting, antibody blocking, co-adsorbate, and protein aging studies will be done in this system as well. Endothelial cells (both bovine aortic and human saphenous) will be grown in culture on RF-plasma modified surfaces that specifically enhance FN adsorption from serum to find a treatment which could improve the endothelialization of vascular grafts. FN and growth factor adsorption will be measured on these surfaces. The use of preadsorbed growth factor and/or heparin to promote extremely rapid endothelial cell growth and firm adhesion of the cell layer to the substrate will be studied.