Preparation and characterization of hemodialysis membranes with improved biocompatibility through anticoagulant, antioxidant and enzyme immobilization

Abstract

The objective of this thesis is to improve blood compatibility of polysulfone (PSF) based hemodialysis membranes through generating thromboresistant and/or antioxidative surfaces with biomolecule immobilization. To create a nonthrombogenic surface, support membrane was modified with layer by layer (LBL) deposition of polyethyleneimine (PEI) and alginate (ALG) and heparin (HEP) was immobilized on the outermost surface of the assembly by blending with ALG. α-lipoic acid (ALA) and superoxide dismutase (SOD)/catalase (CAT) enzyme couple were choosen to provide antioxidative properties. ALA was immobilized site-specifically to PEI deposited support membrane while SOD/CAT enzyme couple were attached both covalently and ionically on the plasma treated and PEI deposited membranes, respectively. Blending a small amount of HEP with alginate remarkably prolonged the coagulation time (APTT) of HEP free membranes. The stability of ALA under typical hemodialysis conditions was improved by immobilization, and the greatest enhancement was achieved when it was sandwiched between two PEI layers. In vitro studies showed that all ALA or SOD/CAT coated PSF membranes are capable of reducing reactive oxygen species levels in blood, furthermore, they can significantly prolong APTT. The hemocompatibility results also demonstrated that the adsorption of human plasma proteins, platelet and cell activation on all modified membranes decreased significantly compared with the unmodified PSF membranes due to the change in surface properties such as hydrophilicity, surface charge and roughness upon immobilization of the biomolecules. The modification methods proposed in this study did not change high permeability, mechanical strength and nontoxic property of the PSF membranes.