Hierarchical Surface Architecture of Hemodialysis Membranes for Eliminating Homocysteine Based on the Multifunctional Role of Pyridoxal 5'-phosphate.

Abstract

Patients with end-stage renal disease are prone to developing a complication of hyperhomocysteinemia, manifesting as an elevation of the homocysteine (Hcy) concentration in human plasma. However, Hcy as a protein-bound toxin is barely removed by conventional hemodialysis membranes. Here, we report a novel hemodialysis membrane by preparing a bioactive coating of pyridoxal 5'-phosphate (PLP) and adding biocompatible hyperbranched polyglycerol (HPG) brushes to achieve Hcy removal. The dip-applied PLP coating, a coenzyme with a role in Hcy metabolism, dramatically promoted a decrease in the Hcy concentration in human plasma. Moreover, the aldehyde group of PLP had an intrinsic chemical reactivity toward the terminal amino group to immobilize the HPG brushes on the hemodialysis membrane surface. The hierarchical PLP-HPG layer-functionalized membranes had a high efficacy for eliminating Hcy, with a concentration from the initial stage of 150 μmol/L reduced to a nearly normal level of 20 μmol/L in simulated dialysis. By analyzing the impact of HPG brushes with various chain lengths, we found that HPG brushes with a medium length enabled the PLP coating with the bioactive function of Hcy conversion to additionally protect Hcy-attacked target cells by providing excellent hydrophilicity and a dense enough chain volume overlap of the hyperbranched architecture. Simultaneously, the densely packed HPG brushes generated a maximal steric and hydration barrier that significantly improved biofouling resistance against blood proteins. The optimally functionalized membranes showed a clearance of 83.1% urea and 49.6% lysozyme and a rejection of 96.0% bovine serum albumin. The diversely functionalized PLP-HPG layers demonstrate a potential route for a more integrated hemodialysis membrane that can cope with the urgent issue of hyperhomocysteinemia in clinical hemodialysis therapy.