Vorapaxar-modified polysulfone membrane with high hemocompatibility inhibits thrombosis

摘要

Hemodialysis therapy is intended for patients suffering from renal insufficiency, pancreatitis, and other serious diseases. Platelets are an important active ingredient in the thrombosis induced by hemodialysis membranes. So far, there are few studies of hemodialysis membranes focusing on the effects of protease-activated receptor 1 (PAR1) activation on the platelet membrane. Among various antithrombotic agents, vorapaxar is a novel PAR1 inhibitor with high efficacy. In this study, we constructed a vorapaxar-modified polysulfone (VMPSf) membrane using immersion-precipitation phase transformation methods and characterized the microstructure in terms of hydrophilicity and mechanical properties. The water contact angle of the VMPSf membrane was 22.45% lower than that of the PSf membrane. A focused determination of platelet morphology was obtained using scanning electron microscopy. Meanwhile, we evaluated the effects of a VMPSf membrane on platelet adhesion. We observed that the VMPSf membrane could reduce the number of adhered platelets without altering their spherical or elliptical shape. The PAR1 levels in VMPSf membranes were 7.4 MFI lower than those in PSf membranes, suggesting that this modified membrane can effectively inhibit platelet activation. Activated partial thromboplastin time (APTT, 5.3 s extension) and thrombin time (TT, 2.1 s extension) reflect good anticoagulant properties. Recalcification time (80.6 s extension) and fibrinogen adsorption (9.9 mu g/cm(2) reduction) were related to antithrombotic properties. To determine the biosafety of VMPSf membranes, we investigated anti-anaphylactic and anti-inflammatory properties in vitro and acute toxicity in vivo, it was obvious that C3a and C5a had decreased to 9.6 and 0.8 ng/mL, respectively. The results indicated that the VMPSf membrane has potential for clinical application.