Residence-time dependent changes in fibrinogen adsorbed to polymeric biomaterials

It has generally been accepted that biomaterials adsorbing the least amount of the plasma protein fibrinogen following exposure to blood will support less platelet adhesion and therefore exhibit less thrombogenicity. Several studies suggest, however, that the conformation or orientation of immobiliz ed fibrinogen rather than the total amount adsorbed plays an important role in determining the blood compatibility of biomaterials. The purpose of thi s study was to investigate time-dependent functional changes in fibrinogen adsorbed to polytetrafluoroethylene (PTFE), polyethylene (PE), and silicone rubber (SR). Fibrinogen was adsorbed to these materials for 1 min and then allowed to "reside" on the surfaces for up to 2 h prior to assessing its b iological activity. Changes in fibrinogen reactivity were determined by mea suring the adhesion of Cr-51-labeled platelets, the binding of a monoclonal antibody (mAb) directed against an important functional region of the fibr inogen molecule (the gamma-chain dodecapeptide sequence 400-411), and the a bility of blood plasma to displace previously adsorbed fibrinogen. Platelet adhesion differed among the polymeric materials studied, and PTFE and PE s amples exhibited a small decrease in adhesion with increasing fibrinogen re sidence time. Platelet adhesion to SR was the least among all materials stu died and showed no variation with residence time. When using PTFE and SR as substrates, mAb recognition of adsorbed fibrinogen did not change with res idence time whereas that on PE decreased slightly. The mAb binding was leas t to fibrinogen adsorbed to SR, which is in agreement with the platelet adh esion results. Finally, the ability of plasma to displace previously adsorb ed fibrinogen decreased dramatically with increasing residence time on all materials. These in vitro studies support the hypothesis that fibrinogen un dergoes biologically significant conformational changes upon adsorption to polymeric biomaterials, a phenomenon that may contribute to the hemocompati bility of the materials following implantation in the body. (C) 1999 John W iley & Sons, Inc.