Immobilization of novel synthesized phosphobetaine zwitterions on polyethersulphone (PES) hemodialysis membranes to induce hemocompatibility: Experimental, molecular docking, and ex-vivo inflammatory biomarker investigations
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Bibliographic record
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.
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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it