Scalable synthesis of asymmetric hemodialysis membranes to enhance performance and biocompatibility in flat sheet and hollow fiber configurations

Abstract

Hemodialysis is indispensable for patients with end-stage renal disease (ESRD). Yet, the performance of conventional polymeric membranes is restricted by protein adsorption, poor hemocompatibility, and thrombo-inflammatory responses. We hypothesized that functional modification of a cellulose acetate (CA) matrix with selected additives could overcome these limitations. By enhancing hydrophilicity, permeability, and anticoagulant behavior, such membranes could provide improved therapeutic potential. To evaluate this, CA-based flat sheet membranes (FSMs) were fabricated through non-solvent-induced phase separation and scaled into hollow fiber membranes (HFMs) by dry-wet jet spinning. Polyethyleneimine (PEI) and polyethylene glycol (PEG) were incorporated to adjust the pore structure, surface chemistry, and transport properties. Citric acid and gelatin were introduced as anticoagulant agents to assess their impact on blood compatibility. A comprehensive characterization was carried out, including SEM, FESEM, AFM, FTIR, tensile testing, porosity measurements, and contact angle analysis. Membrane performance was evaluated through pure water flux and dialysis simulations with urea, creatinine, lysozyme, and bovine serum albumin (BSA). Among the FSMs, CA-4 achieved a water flux of 54.40 L m⁻² h⁻¹ at 2 bar, with 78% urea clearance, 31% creatinine clearance, and 94% BSA retention. Transition to a hollow fiber geometry enhanced scalability and clinical relevance. HF-2 displayed a flux of 83.34 L m⁻² h⁻¹ at 2 bar, ∼66.5% urea clearance, and 90.3% protein retention. These values indicate a clinically significant balance between permeability and selectivity. Biocompatibility testing showed that citric acid-modified membranes reduced platelet adhesion and thrombus formation, while maintaining hemolysis ratios below the ASTM F-756-08 threshold of 5.5%. Gelatin-modified membranes lowered hemolysis up to 2.4% but promoted protein adsorption and platelet adhesion. This makes them more suited for regenerative applications than for dialysis. Overall, the results validate the hypothesis that the integration of PEI, PEG, citric acid, and gelatin into CA membranes enhances both physicochemical and biological performance. The scalable fabrication approach presented here provides a framework for next-generation hemodialysis membranes. These membranes improve solute clearance, minimize blood incompatibility, and support safer renal replacement therapy.