Protein binding mediation of biomaterial-dependent monocyte activation on a degradable polar hydrophobic ionic polyurethane.

Protein adsorption is an important phenomenon influencing the cellular response to biomaterials. Previous studies comparing monocyte activation on a degradable polar hydrophobic ionic polyurethane (D-PHI) indicated a reduced pro-inflammatory monocyte response relative to tissue culture polystyrene (TCPS) and poly(lactide-co-glycolide) (PLGA) substrates. The present study investigated the influence of protein binding in order to gain further insight into the observed differential monocyte activation. Several proteins, identified in different relative amounts within the bound protein layers on D-PHI vs. PLGA and TCPS, were evaluated for their effect on monocyte activation. It was found that, in general, both non-coated and protein pre-adsorbed D-PHI supported a reduced pro-inflammatory response relative to PLGA, as indicated by lower levels of tumor necrosis factor-α (TNF-α) release. An initial increase in TNF-α release occurred when α(2)-macroglobulin (A2M) was pre-adsorbed to D-PHI, which was shown to involve the α(2)-macroglobulin receptor and was active on D-PHI but not on the two other biomaterials. This response was not observed during competitive protein binding in the presence of fetal bovine serum (FBS), suggesting that a more complex arrangement of the bound proteins and their interactions with one another, as well as with the surface chemistry of the individual biomaterials, resulted in the low-activating character of D-PHI when interacting with human monocytes.