Anticoagulant dialyzer with enhanced Ca2+ chelation and hydrophilicity for heparin free hemodialysis

Abstract

Inhibiting thrombosis in extracorporeal dialyzer is predominantly determined by the compatible interface design. It is challenging to develop anticoagulant dialyzers for clinical heparin free dialysis. Herein, we develop an environmentally friendly approach to construct a hydrogel skin composed of poly (sodium alginate-acrylic acid) P (SA-AA) network on polysulfone (PSf) membranes via pre-seeding initiator into membrane matrix and subsequently crosslinking SA and AA in aqueous solution. Physicochemical properties of modified membranes with different SA/AA ratio were characterized by attenuated total reflectance fourier transform infrared spectra (ATR-FTIR) spectrum, proton nuclear magnetic resonance (13 C NMR), scanning electron microscopy (SEM) and atomic force microscope (AFM) and contact angle. Antifouling property was demonstrated by proteins adsorption and E. coli adhesion. Hemocompatibility was comprehensively evaluated by hemolysis ratio, anticoagulation activity (APTT and TT), complement activation, platelets activation and contact activation. Anticoagulant dialyzer was fabricated via skin implantation strategy to implement a chronic renal swine dialysis with heparin free administration. Clotting was significantly inhibited during the whole dialysis session, moreover, the dialyzer showed improved toxins clearance, including urea (~185 mL/min), creatine (~153 mL/min), inorganic phosphorous (~120 mL/min) and β2-microglobulin (~110 mL/min). The modified membrane bearing abundant carboxylate groups contributes to excellent hydrophilicity and Ca2+ chelation capability, which is considered to be the predominant anti-clotting mechanism via both intrinsic and extrinsic cascades. The anticoagulant PSf dialyzer demonstrates promising clinical application for heparin free dialysis.