Immobilization of Novel Synthesized Phosphobetaine Zwitterions on Polyethersulphone (PES) Hemodialysis Membranes to Induce Hemocompatibility: Experimental, Molecular Docking, and Ex-Vivo Inflammatory Biomarker Investigations

Abstract

Hemodialysis therapy is a crucial life-saving treatment for severe kidney conditions, particularly in cases where organ transplantation is limited. However, the use of polymeric membranes in clinical dialyzers can trigger undesirable reactions in the blood, such as complement, leukocyte, and coagulation activations. These reactions can lead to hypertension, cardiovascular diseases, and even death, due to compatibility issues. This paper presents a study on the development and application of a novel phosphobetaine zwitterion, immobilized on polyethersulphone (PES) clinical hemodialysis membranes, to improve hemocompatibility. The study also introduces a new method for immobilizing a zwitterionic PVP-phosphobetaine polymer on a PES membrane, using a polydopamine (PDA) crosslinker. The synthesized membranes were characterized, and their performance in terms of blood-protein adsorption and subsequent interaction, specifically with fibrinogen, was investigated to evaluate hemocompatibility. The selection of the phosphobetaine polymer was driven by its capacity to form an electrically neutral zwitterionic hydration layer, which serves as a protective barrier, preventing fibrinogen adsorption. Without this zwitterionic polymer, blood proteins interact with the bare membrane, initiating biological processes that lead to inflammation when exposed to uremic blood. Molecular docking studies were conducted to understand the interactions between various ligands and specific serum protein components. The phosphate and carbonyl chemical groups on the pyrrolidinone zwitterionic moiety were found to form polar interactions with specific amino acids. Exvivo investigations involving incubated coated membranes and uremic blood samples from end-stage renal disease (ESRD) patients revealed that they caused weaker complement and coagulation activation compared to bare PES membranes. In addition, the inflammatory biomarkers have been studied to shed light on their potential impact on patients' quality of life. This study contributes to our understanding of the implications of blood-protein fouling and the hemocompatibility challenges faced by blood-contacting devices used in hemodialysis for ESRD patients, who are prone to membrane-related health complications.