Adsorption of plasma proteins on to poly(ethylene oxide)/poly(propylene oxide) triblock copolymer films: a focus on fibrinogen.

Abstract

Triblock copolymers of the form PEO(alpha)PPO(beta)PEO(alpha) [where PEO is poly(ethylene oxide) and PPO is poly(propylene oxide)] have many biomedical applications, many of which depend on the surface properties of the copolymers and the influence that those properties have on the adsorption of proteins. As a tool to help us better understand, predict and exploit the influence of these triblock copolymers on protein adsorption, we developed a model system in which well-defined monolayers of the copolymers are supported by solid, hydrophobic, microscopic beads. At the bead/water interface, the copolymers all form stable films in which the nominal molecular areas correspond to those of the molecules when they are packed rather tightly at the air/water interface. Beads coated with condensed films of copolymers that contain short PEO segments and elicit appreciable inflammation absorb appreciable quantities of plasma proteins, including fibrinogen, from aqueous solution. Beads coated with fibrinogen aggregate when they are stirred in the presence of thrombin, a consequence of interbead fibrin formation. Beads coated with condensed films of copolymers that contain long PEO segments and elicit little inflammation absorb little plasma protein, and they do not aggregate in the presence of thrombin. Our data and observations are consistent with the prevailing notion that the utility of triblock copolymers as agents for modifying the surface properties of blood-contacting surfaces derives from the influence of the copolymers on the adsorption of plasma proteins. In this regard, the ability of the copolymers to influence fibrinogen-mediated adhesive events may be particularly important. As to the mechanism of protein resistance, our data support the proposal that sibling PEO segments of copolymers in condensed films fold back across their parental PPO cores, limiting access of proteins to the hydrophobic cores themselves.