Fabrication and characterization of heparin functionalized membrane-mimetic assemblies.

Abstract

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/cm(2) (61 ng/cm(2)). In the process, mass transport limited regimes were identified for heparin potentiated thrombin inactivation under both simulated venous and arterial conditions.