IMMOBILIZATION OF HEPARIN ON POLYLACTIDE FOR APPLICATION TO DEGRADABLE BIOMATERIALS IN CONTACT WITH BLOOD

The poly-(D, L-lactide) RESOMER(R) R208 (Boehringer-Ingelheim, Germany ) was modified with heparin to improve the blood contacting properties of the material. The immobilization of herapin was carried out by cov alent binding with glutaraldehyde as the coupling agent. The reaction conditions, such as temperature and time, were varied to optimize the binding of herapin. The efficiency of the immobilization was monitored with respect to the total amount of coupled herapin with a toluidine blue assay and the anticoagulant activity of immobolized heparin with a factor Xa assay. The hemocompatibility of the modified polylactide w as estimated after blood-material contact by the activation of platele ts measured with an enzyme immune assay for GMP140. Immobilization at ambient temperature and a reaction time of 2 h resulted in maximal hep arin binding, high anticoaylant activity, and low thrombogenicity. Sin ce the remaining unsaturated aldehyde groups of the coupling agent may cause a low hemocompatibiIity of the material, washing of the heparin ized polylactide was carried out with ethanol. However, it was shown t hat washing diminished the anticoagulant activity of heparin and incre ased the thrombogenicity. The prolonged storage of heparinized polylac tide in phosphate buffered saline for 8 days demonstrated that small q uantities of herapin were released but the hemocompatibility was furth er improved, indicated by an increasing anticoagulant potential and a decrease in platelet activiation with incubation time. A comparison of polylactide, heparinized polylactide, polypropylene, and Pellethane(R ) with respect to platelet activation by GMP140 assay and scanning ele ctron microscopy, revealed that the heparinization of polylactide subs tantially improved the hemocompatibility of RESOMER(R) R208, making th e material comparable to Pellethane(R).