Bioresorbable, heparinized polymers for stent coating: In vitro studies on heparinization efficiency, maintenance of anticoagulant properties and improvement of stent haemocompatibility

Biodegradable poly-(D,L-lactide) RESOMER(R) R208 and poly(D,L-lactide-co-glycolide) RESOMER(R) RG756 were heparinized to improve the blood contacting properties of the materials. The immobilization of heparin was performed with glutaraldehyde as coupling agent. The efficacy of the surface modification was monitored with respect to the total amount of bound heparin measured by a toluidine blue assay, the anticoagulant potential estimated by a factor Xa assay, and the activation of platelets estimated by a GMP140 assay. It was found that a reaction at ambient temperature for 2 h resulted in optimal heparin binding, with high anticoagulant activity and low thrombogenicity. The storage of heparinized polylactide in saline solutions up to 8 days demonstrated the release of small quantities of heparin into the fluid. A further finding was that with prolonged storage the anticoagulant potential was improved, whereas the thrombogenicity decreased. Comparison of platelet activation on RESOMER(R) R208 as unmodified and heparinized material with polypropylene and Pellethane(R) revealed that heparinization of R208 substantially improved the haemocompatibility. Coating and subsequent heparinization of intravascular stents were carried out with RESOMER(R) RG756 because of its more appropriate mechanical properties. in vitro studies with blood under flow conditions demonstrated that platelet activation on Palmaz(TM) stents was considerably diminished after polymer coating and heparinization.