Tissue plasminogen activator-containing polyurethane surfaces for fibrinolytic activity

With the aim of minimizing thrombus formation in blood-contacting devices, tissue plasminogen activator (t-PA)-containing polyurethane (PU) materials have been developed Cationic PU surfaces were prepared by grafting poly(dimethylaminoethyl methacrylate) and quaternizing the tertiary amino groups with iodomethane or 1,6-diiodohexane or alpha,alpha'-dichloro-p-xylene. The surfaces were characterized by water contact angles and X-ray photoelectron spectroscopy. The materials (PU-CH(3)I, PU-I(CH(2))(6)I, PU-CI) were treated with t-PA in Tris-buffered saline (pH 9.0) to give t-PA-loaded PU surfaces. The t-PA content of the surfaces was determined using radiolabeled t-PA. The quantities of t-PA taken up by the cationic surfaces were significantly greater than on the unmodified PU: approximately 14-fold greater for PU-CI, 10-fold for PU-CH(3)I and 13-fold for PU-I(CH(2))(6)I The activity of the bound t-PA, as measured by a plasma clotting-dissolution assay and a chromogenic substrate assay, was similar to that of normal, unbound t-PA. Release of t-PA from these materials in contact with plasma was measured using the labeled protein and was found to be the most rapid on the PU-CH(3)I material. This approach may have potential for the development of surfaces which can lyse clots that begin to form on them. (C) 2011 Acta Materialia Inc. Published by Elsevier Ltd All rights reserved.