Poly(DTE-co-PEG Carbonate) as a Model System for Investigating the Effects of Physicochemical Polymer Characteristics on Protein Adsorption and Cell Attachment

Protein adsorption is one of the first events to occur upon implantation of a biomaterial, and can modulate both the initial and long-term cellular response. Poly(ethylene glycol) (PEG) is often copolymerized with other biomedical polymers to control and reduce protein adsorption. The thermodynamic incompatibility stemming from copolymerization of a highly hydrophilic polymer such as PEG with a copolymer often results in phase separation. The spatial distribution of phase-separated structures may allow for protein adsorption to occur even in PEG-containing polymers. Physical properties that affect phase separation, such as polymer molecular weight and polydispersity, may also play a role in modifying protein adsorption behavior.;To study the physicochemical factors that modulate phase separation and subsequent protein adsorption and cell attachment, a model random multiblock hydrophobic-hydrophilic copolymer system consisting of desaminotyrosyl-tyrosine ethyl ester (DTE) as the hydrophobic component and PEG as the hydrophilic component was investigated. The effect of systematic changes in PEG molecular weight and PEG composition on phase separation was explored. The spatial effects of phase separation on protein adsorption were examined using proteins with different dimensions. Additional changes in physicochemical properties were achieved by isolating specific molecular weight chains from certain polymer compositions. Finally, the effects of phase separation on cell attachment and spreading were examined.;Variations in PEG content and molecular weight produced clear, systematic changes in the spatial distribution of hydrophobic and hydrophilic regions within each polymer composition. The effects of phase separation were initially inconclusively linked to protein adsorption behavior. However, variations in polymer molecular weight and chain distribution within certain polymer compositions appear to modulate protein adsorption capabilities. Phase separation also appears to play a significant role in cell attachment and spreading. While intermediate amounts of PEG repelled cells and proteins, high amounts of PEG caused cells to increase spreading on the polymeric substrates. The increased spreading was linked to dynamic overexpression of integrin a5 over time. The results of this study elucidate additional design parameters in the rational design of biomaterials, and also suggest that intermediate amounts of PEG may be optimal for developing cell-repellent surfaces.