COVALENT IMMOBILIZATION OF HIRUDIN IMPROVES THE HEMOCOMPATIBILITY OF POLYLACTIDE-POLYGLYCOLIDE IN-VITRO

A biodegradable polymer, poly(D,L-lactide-co-glycolide) RESOMER(R) RG7 56, was modified by surface immobilization of recombinant hirudin (r-H ir) with glutaraldehyde as coupling reagent to improve the blood conta cting properties of the polymer. The activity of immobilized hirudin o n the polymer was estimated by a chromogenic assay to about 2.5 ATU r- Hir cm(-2). The improvement of the haemocompatibility of the modified RG756 was evaluated in terms of platelet adhesion/activation, whole bl ood clotting times and clot formation rate. Fluorescence microscopy re vealed that surface modification with r-Hir resulted in decreased plat elet adhesion and activation. An ELISA for P-selectin, a marker of pla telet activation, was used to confirm this result. Clotting time exper iments demonstrated significantly prolonged non-activated partial thro mboplastin times, and a decreased clot formation rate of whole blood i n contact with r-Hir modified RG756 compared with the plain polymer. C omparison of immobilized r-Hir with bound heparin yielded equivalent i mprovement of blood-contacting properties of the investigated polymers . These in vitro investigations indicate that the immobilization of r- Hir on RG756 is a useful method to improve the blood contacting proper ties of polylactides/polyglycolides and other polymers as well. (C) 19 97 Elsevier Science Limited. All rights reserved.