Heparin immobilized graphene oxide in polyetherimide membranes for hemodialysis with enhanced hemocompatibility and removal of uremic toxins

Intermittent hemodialysis is a life-saving renal replacement therapy that removes excess water and uremic salts from patients who suffer from loss of kidney function. Hemocompatible polyetherimide membranes were fabricated by the incorporation of functionalized graphene oxide (f-GO). The f-GO was prepared by immobilizing heparin via the polydopamine anchor onto the nanosheets. The role of the f- GO in altering membrane morphology, surface roughness, wettability, porosity, and surface chemistry were evaluated in detail. The addition of f-GO suppressed the protein adsorption from platelet-poor plasma (>90%) lowered the adhesion (10(3) times)/activation of platelets, improved the blood clotting time (aPTT/TCT - similar to 235 s/58.5 s), decreased the thrombin generation and did not activate either complement pathways. Low aggregation of erythrocytes and <2% hemolysis ratio was another indication of improved membrane hemocompatibility. The cell proliferation of Chang liver cells on the f-GO incorporated membranes is an indication of low cytotoxicity of the prepared membranes. The modified hollow fiber membranes displayed exceptional capabilities compared to its pristine counterpart, evidenced by - four times higher ultrafiltration coefficient, outstanding removal of uremic toxins after 4 h (Urea- 77 +/- 2.5%, creatinine- 68 +/- 2% and Lysozyme 44 +/- 2%) and similar to 95% retention of essential protein (albumin). No leaching of the f-GO could be observed from the membrane, and the prepared membranes were robust as they exhibited a sufficiently high solute removal (urea, creatinine, and phosphate) in the ex-vivo run using spiked goat blood. These preliminary investigations point to the fact that f-GO is a suitable modifier, and these membranes can be further explored for hemodialysis application.