Previous research from our group has demonstrated that bromoalkylation of polyurethane elastomers via base mediated activation of the urethane-hard segment nitrogen groups can be used to either attach bisphosphonate groups to confer calcification resistance or append cholesterol to promote endothelial cell adhesion. In the present studies we further explore the potential of this chemical approach by investigating bulk carboxylation of polyurethanes via bromoalkylation to enable surface heparinization for thromboresistance. Thus, polyurethane (PU) was modified with pendant 7-carboxy-5-thiaheptyl groups using a polymer-analogous reaction of bromobutylated PU with tetrabutylammonium 3-mercaptopropionate in mild conditions. The grafting of polyallylamine (PAA) onto the surface of carboxylated. PU via direct coupling of amino and carboxy groups resulted in high levels of PAA (up to 8,mu g/cm2). The surface-aminated PU was further covalently modified with unfractionated heparin as confirmed by FTIR. Fluorescence labeling of PAA hydrochloride and heparin with BODIPY-FL was used to quantify the extent of surface modifications. Heparin was covalently bound at a high level (1.11 +/- 0.06 mu g/cm(2)) and was shown to be active, with demonstrable Factor Xa inhibition and platelet factor IV binding. It is concluded that surface amination of bulk-carboxylated PU represents a novel approach for heparinizing PU; carboxylation followed by surface amination represents another important dimension of bromo-alkyl activation of polyurethane hard segments, thereby enabling heparinization.