Heparin Immobilization by Surface Amplification

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Abstract
A method to increase the amount and improve the bioactivity of heparin (HEP) immobilized on a polymer surface was developed. The surface of polyurethane-urea (PU) coated glass beads was first modified with diisocyanates, followed by surface grafting of polyfunctional polymers (PFP), including: poly(vinyl alcohol), poly(ethyleneimine), and poly(allylamine). The functional groups of the surface grafted PFP (-OH, -NH, or -NH2) were modified with diisocyanates (TDI) to amplify the surface concentration of isocyanate groups, alpha, omega-diamino-terminated polyethylene oxide (PEO; molecular weight, 4,000 daltons) was then coupled to the surface grafted PFP, and the free amino groups were derivatized with TDI. Finally, HEP was coupled to the amplified surface through free -NCO groups of PU-PFP-PEO. The surfaces were quantified during each step of the procedures for -NCO groups and HEP. All grafted surfaces showed a four to eightfold increase in -NCO content and a twofold increase in immobilized HEP content compared with HEP immobilized directly onto the PU surface. The HEP bioactivity tests (including activated partial thromboplastin time, thrombin times, and factor Xa) demonstrated an increased bioactivity of HEP when immobilized through PFP-PEO compared with PFP and PU alone.

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