Fabrication and characterization of heparin functionalized membrane-mimetic assemblies

A membrane-mimetic assembly incorporating surface bound heparin was fabricated as a system to improve the hemocompatibility of blood-contacting devices. As a model system, heparin was chemically modified by end-point conjugation to biotin and immobilized onto membrane-mimetic thin films via biotin–streptavidin interactions. Heparin surface density, determined by radiochemical titration, confirmed that surface density was directly related to the molar concentration of biotinylated lipid within the assembled membrane-mimetic film. The capacity of surface bound heparin to promote ATIII-mediated thrombin inactivation was investigated in a parallel plate flow chamber under simulated venous and arterial wall shear rates of 50 and 500 s−1, respectively. Significantly, we observed that the rate of thrombin inactivation approached a maximum at a heparin surface concentration greater than 4.4 pmol/cm2 (61 ng/cm2). In the process, mass transport limited regimes were identified for heparin potentiated thrombin inactivation under both simulated venous and arterial conditions.