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Dialysis membranes are not hemocompatible with human blood, as the patients are suffering from the blood–membrane interactions' side effects. Zwitterionic structures have shown improved hemocompatibility; however, their complicated synthesis hinders their commercialization. The goal of the study is to achieve fast functionalization for carboxybetaine and sulfobetaine zwitterionic immobilization on PES membranes while comparing the stability and the targeted hemocompatibility. The chemical modification approach is based on an aminolysis reaction. Characterization, computational simulations, and clinical analysis were conducted to study the modified membranes. Atomic force microscopy (AFM) patterns showed a lower mean roughness for carboxybetaine-modified (6.3 nm) and sulfobetaine-modified (7.7 nm) membranes compared to the neat membrane (52.61 nm). The pore size of the membranes was reduced from values above 50 nm for the neat PES to values between 2 and 50 nm for zwitterionized membranes, using Brunauer–Emmett–Teller (BET) analysis. More hydrophilic surfaces led to a growth equilibrium water content (EWC) of nearly 6% for carboxybetaine and 10% for sulfobetaine-modified membranes. Differential scanning calorimetry (DSC) measurements were 12% and 16% stable water for carboxybetaine- and sulfobetaine-modified membranes, respectively. Sulfobetaine membranes showed better compatibility with blood with respect to C5a, IL-1a, and IL-6 biomarkers. Aminolysis-based zwitterionization was found to be suitable for the improvement of hemodialysis membranes. The approach introduced in this paper could be used to modify the current dialysis membranes with minimal change in the production facilities. [ABSTRACT FROM AUTHOR]

ESRD patients suffer from side effects of the dialysis process. Comprehension of different operational parameters' effect on the hemocompatibility profiles of the separative membranes, i.e. dialyzers, could result in designing more compatible materials. This study includes a computational approach to assess the effect of pH by assessing different uremic metabolites' behavior. The pH effect was assessed by comparing the water interaction ability of different uremic metabolites (which appear at different bloodstream pH levels) using molecular dynamics (MD) simulations. Based on the findings of the studies, a new class of zwitterionic materials is introduced. The proposed modification, containing guanidine (GNDM) was experimentally implemented on poly ether sulfone (PES) membranes. Aminolysis and sultone-ring opening reactions were used to immobilize the zwitterionic structure. Attuned total reflectance-Furrier transmission infrared spectroscopy (ATR-FTIR) was used to characterize the functional groups of the modified membrane. Gravimetry was used to measure the amount of modification layer added to the membrane as well as the equilibrium water content (EWC). Atomic force microscopy (AFM) was used to measure the roughness patterns of the neat and modified membranes. Zeta potential analyzer was used to check the trend of surface charge variations. Differential scanning calorimetry (DSC) was used to assess the stable water content of the membranes. A filtration test was performed to check the stability of the immobilized materials on the membranes. The newly modified PES membranes were nearly 50 % smoother and negatively charged. DSC reflects a 16 % higher content of stable water for the modified membranes. Computational assessments also reflected that the modified structure created more hydrogen bonds and could keep the water molecules more stable on the surface of the membrane. As the new membrane owned a higher capability to keep the water more stable on its surface, it could be a perfect candidate for a hemocompatible dialysis membrane. [Display omitted] • A uremic metabolite-attached zwitterionic dialysis membrane was fabricated. • The stability of the hydration layer on the modified membranes was measured. • Standard membrane characterizations were performed to confirm the structure. • The behavior of the water molecules on the modified membrane was assessed computationally. • The durability of the modification layer was assessed using filtration and ATR-FTIR-assisted functional group tracking. [ABSTRACT FROM AUTHOR]

Fibrinogen (FB) can trigger several biological reactions and is one of the critical proteins targeted during hemodialysis (HD). A better understanding of the thermal behavior of FB and its interactions with polymeric membranes during the HD process is needed in both normal and fever temperature conditions. This study calculated the thermal behavior of FB along with its interaction energy with polyarylethersulfone (PAES) clinical HD membranes using molecular dynamics (MD) approaches. The Dreiding force field was used for the MD simulations. The influence of temperature on the thermal conductivity (TC) and the interaction energy of the FB structure was assessed to understand the activation trends in fever conditions. Based on the MD simulation, the TC of FB at normal body temperature was 0.044 and 0.084 W/m·K according to equilibrium and non-equilibrium approaches, respectively. The elevation of temperature from normal to fever conditions increased the thermal conduction of FB to 0.577 and 0.114 W/m·K for equilibrium and non-equilibrium approaches, respectively. In addition, the elevation of patient blood temperature resulted in nearly 32 kcal/mol higher total interaction energy between FB and the PAES model. When end-stage renal disease (ESRD) patients have a HD session and experience fever and elevated temperature as a side effect, the interaction between FB and the membrane increases. More importantly, FB is exposed to more heat passage and accordingly more temperature-induced confirmation and activation compared to other human serum proteins such as albumin. [ABSTRACT FROM AUTHOR]

End stage renal disease (ESRD) affects ≈10% of the world's population. Hemodialysis (HD) is a life‐sustaining extracorporeal blood purifying treatment for ESRD patients. Despite the advances in technology, the hemoincompatibility of the dialyzers leads to a high morbidity and mortality rate. Decreasing interactions between polymers and blood constituents will result in controlled binding of human serum proteins to the surface and consequently enhanced biocompatibility. This study aims to assess the interaction energy between common hemodialysis polymer structures and human serum proteins using molecular dynamics simulation to offer a framework for understanding the dominant interactions as a reference for material development. Molecular dynamics and molecular docking simulations are conducted for calculating polymerprotein binding energies. Common serum proteins are selected for protein models. Poly aryl ether sulfone (PAES) with and without polyvinyl pyrrolidone (PVP), polyvinylidene fluoride (PVDF), cellulose triacetate (CTA), polyacrylonitrile (PAN), and polymethyl methacrylate (PMMA) membrane structures are chosen as the different classes of dialyzers. The van der Waals interactions between polymers and proteins dominate the binding energies sequence. Molecular docking results of the affinity between protein receptors‐ligands are aligned with the MD binding interaction. [ABSTRACT FROM AUTHOR]

Despite advances in the field, hemoincompatibility remains a critical issue for hemodialysis (HD) as interactions between various human blood constituents and the polymeric structure of HD membranes results in complications such as activation of immune system cascades. Adding hydrophilic polymer structures to the membranes is one modification approach that can decrease the extent of protein adsorption. This study conducted molecular dynamics (MD) simulations to understand the interactions between three human serum proteins (fibrinogen [FB], human serum albumin, and transferrin) and common HD membranes in untreated and modified forms. Poly(aryl ether sulfone) (PAES) and cellulose triacetate were used as the common dialyzer polymers, and membrane modifications were performed with 2‐hydroxymethyl methacrylate (HEMA) and poly (2‐methoxyethyl acrylate) (PMEA), using polydopamine‐assisted co‐deposition. The MD simulations were used as the framework for binding energy simulations, and molecular docking simulations were also performed to conduct molecular‐level investigations between the two modifying polymers (HEMA and PMEA) and FB. Each of the three proteins acted differently with the membranes due to their unique nature and surface chemistry. The simulations show PMEA binds less intensively to FB with a higher number of hydrogen bonds, which reflects PMEA's superior performance compared to HEMA. The simulations suggest PAES membranes could be used in modified forms for blood‐contact applications as they reflect the lowest binding energy to blood proteins. [ABSTRACT FROM AUTHOR]

Computational frameworks have been under specific attention within the last two decades. Molecular Dynamics (MD) simulations, identical to the other computational approaches, try to address the unknown question, lighten the dark areas of unanswered questions, to achieve probable explanations and solutions. Owing to their complex microporous structure on one side and the intricate biochemical nature of various materials used in the structure, separative membrane materials possess peculiar degrees of complications. More notably, as nanocomposite materials are often integrated into separative membranes, thin-film nanocomposites and porous separative nanocomposite materials could possess an additional level of complexity with regard to the nanoscale interactions brought to the structure. This critical review intends to cover the recent methods used to assess membranes and membrane materials. Incorporation of MD in membrane technology-related fields such as desalination, fuel cell-based energy production, blood purification through hemodialysis, etc., were briefly covered. Accordingly, this review could be used to understand the current extent of MD applications for separative membranes. The review could also be used as a guideline to use the proper MD implementation within the related fields. [Display omitted] • Overview of molecular dynamics simulation for membrane separation and porous materials. • MD-driven Initial Parameters. • Contribution of Computational Tools to Different Membrane Technology Subsections. • Instances of MD Applications for Characterization Membrane Materials. [ABSTRACT FROM AUTHOR]

Hemodialysis is a life-sustaining procedure for patients with end-stage renal disease (ESRD). The efficiency of hemodialysis is limited by the dialysis membrane biocompatibility and the poor clearance of middle-molecule uremic toxins. As a result, hemodialysis is associated with acute chronic side-effects that threaten patients' lives. During hemodialysis, interfacial interactions of blood-polymeric membranes result in several consequences. These interactions lead to the body's various system activations, including the coagulation of blood components, leukocytes (i.e., immune system activation) and complement activations, thrombogenesis, cytokine production, and appearance of radicals with free oxygen. Despite advances in research, the most vital issue in dialysis therapies is the biocompatibility and hemoincompatibility of the membranes. The process of enhancing membrane hemocompatibility is currently posing a global challenge. Reactions to incompatibility can cause severe injuries to the patients and result in morbidity and mortality. This critical review offers a focused analysis of the latest efforts to enhance the hemodialysis membrane's hemocompatibility as well as emphasize current research gaps. Recent innovations (since 2014) in hemodialysis membranes are analyzed in correlation to categories of modified polymer structure chemistry tuning, and surface modifications and their influences on membrane hemocompatibility. Particular attention is paid to: (1) chemical immobilization of functional groups (surface grafting); (2) layer-by-layer chemical attachment of species (LBL); (3) covalent attachment of super hydrophilic-hydrogel; (4) mixed matrix membranes (MMM); and (5) base polymer membrane modification (blending method). This critical review provides an overview of the effects the modification methods can have on biocompatibility and how they can pave the way for optimum enhancement of hemodialysis membrane biocompatibility. Unmodified membrane with blood clots and cascade reaction products (Image 2 representing cytokines, Image 3 representing leucocytes, Image 4 representing complement activation enzymes, Image 5 representing blood clots), modification techniques for polymeric hemodialysis membranes: chemical immobilization of functional groups (surface grafting), layer by layer chemical attachment of species (LBL), covalent attachment of super-hydrophilic hydrogel, mixed matrix membrane (MMM) and base polymer modification (blending). Image 1 • Body systems' response to hemodialysis membranes were reviewed. • Biocompatibility issues regarding complement activation and thrombogenesis were discussed. • Conventional hemodialysis modified membrane assessments were introduced. • Advances in hemodialysis modification researches targeting biocompatibility issues were reviewed. [ABSTRACT FROM AUTHOR]