Constructing hierarchical surface structure of hemodialysis membranes to intervene in oxidative stress through Michael addition reaction between tannic acid and PEtOx brushes

Abstract

Chronic kidney disease (CKD) patients undergoing hemodialysis is often accompanied by high levels of oxidative stress, profoundly affecting the survival rate and long-term outcome of patients. Functionalized hemodialysis membranes with relieving oxidative stress and outstanding biocompatibility have aroused more attention among researchers. In this work, we incorporated a tannic acid (TA) coating onto the poly (ether sulfone) (PES) hemodialysis membrane in order to alleviate the increased oxidative stress status during hemodialysis. Further modification of poly(2-ethyl-2-oxazoline) (PEtOx) brushes devoted to improving the biocompatibility of hemodialysis membrane. The TA/PEtOx brushes functionalized membranes effectively eliminated reactive oxygen species (ROS), increased serum antioxidant level, and inhibited lipid peroxides and glycation products generation. The functionalized membranes attenuated the H2O2-induced oxidative damage to cardiomyocytes (H9C2) and vascular endothelial cells (HUVEC) by modulating the antioxidant enzymes expression (SOD, CAT and GSH). The immobilization of PEtOx brushes significantly improved the biocompatibility, and the TA/PEtOx brushes functionalized membranes have been constructed through the Michael addition reaction between TA and PEtOx brushes. Simultaneously, the cyclic PEtOx (C-PEtOx) brushes simulating the structure of endothelial glycocalyx formed a stronger steric hindrance and a denser hydration layer that significantly suppressed the platelets and erythrocytes adhesion on membrane surface. The optimal functionalized membrane exhibited a 76.5% of urea clearance, 53.4% of lysozyme clearance and 95.9% of bovine serum albumin (BSA) retention. This present work fabricated a biomimetic surface structure for the development and preparation of novel hemodialysis membrane, which would greatly improve the therapeutic effect in patients.