Effect of Immobilized Antithrombin III on the Thromboresistance of Polycarbonate Urethane

Karin Lukas,Karin Stadtherr,Hans Wendel,Daniel Wehner,Christof Schmid,Andre Gessner,Thomas Schmid,Karla Lehle

doi:10.3390/ma10040335

Abstract

The surface of foils and vascular grafts made from a thermoplastic polycarbonate urethanes (PCU) (Chronoflex AR) were chemically modified using gas plasma treatment, binding of hydrogels—(1) polyethylene glycol bisdiamine and carboxymethyl dextran (PEG-DEX) and (2) polyethyleneimine (PEI)—and immobilization of human antithrombin III (AT). Their biological impact was tested in vitro under static and dynamic conditions. Static test methods showed a significantly reduced adhesion of endothelial cells, platelets, and bacteria, compared to untreated PCU. Modified PCU grafts were circulated in a Chandler-Loop model for 90 min at 37 °C with human blood. Before and after circulation, parameters of the hemostatic system (coagulation, platelets, complement, and leukocyte activation) were analyzed. PEI-AT significantly inhibited the activation of both coagulation and platelets and prevented the activation of leukocytes and complement. In conclusion, both modifications significantly reduce coagulation activation, but only PEI-AT creates anti-bacterial and anti-thrombogenic functionality.

Highlights

Polycarbonate urethanes (PCUs) have been used in implantable medical devices because of their superior biocompatibility, attractive mechanical properties, and improved oxidative biostability [1,2,3,4,5].thrombus formation may still occur when artificial organs and biomedical devices made of polycarbonate urethanes (PCU) are in contact with blood for extended periods of time [6,7,8]
In a previous study we showed that covalent binding of antithrombin III (AT) improved anti-thrombotic properties of untreated PCU, independent of the type of connecting hydrogel [20]
This difference in glass transition temperatures was attributed to a greater flexibility of the modified PCU samples than that of the untreated PCU samples

Summary

Introduction

Thrombus formation may still occur when artificial organs and biomedical devices made of PCU are in contact with blood for extended periods of time [6,7,8]. This is managed by anti-platelet therapy, this presents a risk of bleeding [8]. Approved surface coatings include the immobilization of drugs that block fibrin formation and prevent platelet adhesion/activation. Promising coating strategies for blood contacting medical devices are the immobilization of heparin [9,10,11], thrombomodulin [12], phosphatidylcholine [13], and argatroban [14,15]

Methods

Results

Conclusion