Preparation And Properties Of Polyvinylidene Fluoride Membrane For Hemodialysis

As the main renal replacement therapy,hemodialysis has become one of the research focuses in biomedical field.The development of hemodialysis moves forward following the evolution process of dialysis membranes.At present,the most widely used synthetic polymer dialysis membranes still have some problems such as unsatisfactory clearance rate of middle molecular toxins especially for?2-microglobulin,high ultrafiltration speed attenuation during dialysis,and the blood compatibility of membrane materials still needs to be improved.Therefore,the researches and development of hemodialysis membrane materials with high-flux,high middle molecular toxin clearance rate and excellent blood compatibility are still the important research directions for hemodialysis membranes.Poly(vinylidene fluoride)(PVDF)has shown outstanding application potential in biomedical field because of its excellent chemical stability,thermal stability,mechanical property,UV resistance,aging resistance and non-toxicity.As a superior ultrafiltration membrane,PVDF membrane has a higher flux and a smaller ultrafiltration speed attenuation compared with current high-flux polyethersulfone hemodialysis membrane,which makes PVDF be expected to become a new hemodialysis membranes material.However,the strong hydrophobicity of PVDF may result in protein adsorption,platelet adhesion,hemolysis and activation of blood coagulation,thus restricts the application of PVDF membrane in hemodialysis field seriously.Therefore,this work attempts to improve the blood compatibility and middle molecular solute separation efficiency of membranes from molecule design and membrane-forming regulation of PVDF membrane materials.Firstly,PVDF-g-PACMO copolymer was synthesized by free radical polymerization of PVDF and acryloylmorpholine(ACMO).Then the copolymer was used as an additive to blend with PVDF,and the modified PVDF blend hollow fiber membrane was prepared by NIPS method.In the process of membrane-forming,the hydrophilic segments from PACMO were enriched onto membrane surface and membrane pore surface,with a pore-forming ability to some extent.With the increase of blend ratio,the average pore size and porosity of the membrane increased gradually,the membrane surface hydrophilicity was significantly enhanced,which made an increased pure water flux and anti-protein fouling property.In the meantime,the increasing of blend ratio also decreased the amount of bovine serum albumin(BSA)adsorption amount on the membrane surface,prolonged the clotting time and decreased the hemolysis rate,thus improved the hemocompatibility of the modified PVDF membrane significantly.In addition,modified membranes showed a high retention rate of macromolecule BSA(>90%)and high clearance rates of middle molecular lysozyme and small molecular urea up to 65%and 83%,respectively.Then,PVDF hollow fiber membranes were prepared by NIPS method,and then the membranes were coated by DOPA to obtain a polydopamine(PDA)active coating layer.After that,zwitterionic L-cysteine was grafted onto the active coating layer surface via Michael addition reaction in order to prepare a modified PVDF membrane with zwitterionic membrane surface.Membrane pore size and porosity were controlled by DOPA coating time to make the average pore size more suitable for middle molecular solute removal.The zwitterionic L-cysteine on membrane surface could also construct a hydrophilic layer during dialysis.The result confirmed that the optimal DOPA coating time was 10h,and DOPA coating layer increased the hydrophilicity of the membrane surface.With the increase of L-cysteine graft concentration,the hydrophilicity of the membrane surface increased,BSA adsorption amounts were gradually decreased,the hemolysis rates were significantly lower than that of pure PVDF membrane and all met the national standards,the clotting time prolonged,thus improved the blood compatibility of the modified membrane.In addition,the results also showed that increase of L-cysteine grafting concentration nearly had no changes in the membrane pore structure,and the membrane still had a high BSA retention,and the clearance rates of small molecular urea and middle molecular lysozyme.Afterwards,the membrane surface construction with both good anti-hemolytic property and anti-coagulantion property was a new approach for the research of hemocompatibility modification of dialysis membranes without heparin post-treatment.PVDF-g-(PACMO-PAA)copolymer was synthesized by free-radical polymerization from PVDF and ACMO and acrylic acid(AA),and this copolymer was used as an additive to blend with PVDF to prepare copolymer modified PVDF hollow fiber membranes.Then L-arginine was grafted to the inner surface of the blend membrane by surface amidation reaction,thus dual-modified PVDF hollow fiber membrane through ACMO and L-arginine were obtained.ACMO and L-arginine improved the anti-hemolytic and anticoagulation properties on the membrane surface,respectively.The surface hydrophilicity,anti-protein adsorption property and hemolysis resistance of the copolymer modified PVDF membranes were significantly improved.With the increase of L-arginine graft concentration,the clotting time of the dual-modified PVDF membranes was significantly prolonged,thus improved the blood compatibility of the modified membranes greatly.At the same time,the dual-modified PVDF membranes also maintained a high BSA retention and a good solute removal capacity of both urea and lysozyme.Finally,taking the mass transfer resistance into account,and aiming to improve the membrane surface blood compatibility and solute clearance rate simultaneously during dialysis,the PVDF electrospinning membrane was prepared by electrospinning method.Then the membrane was coated by DOPA,and heparin and BSA were covalently cross-linked onto the PDA layer subsequently in order to prepare a dual modified PVDF electrospinning membrane.Membrane pore size and porosity were controlled by DOPA coating time to make the average pore size more suitable for middle molecular solute removal and to reduce the mass transfer resistance for the molecular solute passes through the membrane matrix.The result showed that the optimal coating time for DOPA was 18h.And BSA grafting layer gradually increased the hydrophilicity of membrane surface,and the anti-protein adsorption and anti-fouling property were also increased,thus the anti-hemolysis property increased and could meet the national standards.Heparin grafting layer provided the anti-coagulation property on membrane surface,and the clotting time was significantly prolonged(>250s).The blood compatibility of dual modified PVDF electrospinning membranes were significantly improved,and the modified membranes showed good cell growth behavior.More importantly,the solute passed through the membrane matrix with low mass transfer resistance for dual modified PVDF electrospinning membrane.The dual modified membrane maintained a high retention of BSA(97.5%)and a high clearance rate of lysozyme and urea(80%and 87%).At the same time,compared with the membranes prepared by phase inversion and the commercialized FX60 serial hemodialysis membrane,the dual modified membrane had a significantly lower mass transfer resistance.In a word,dual modified electrospinning PVDF membrane achieved synchronization increase with the blood compatibility and solute clearance rate,and was expected to be applied in the hemodialysis field.In summary,taking blood compatibility modification,membrane-forming with pore-forming process regulation,mass transfer resistance during dialysis,and the characteristics of PVDF membrane into common considerations,we have prepared modified hollow-fiber membranes and modified electrospinning PVDF membranes with good blood compatibility,high efficient removal of small and medium molecular toxins,and high retention of macromolecular proteins.The modified PVDF-based membranes show a potential application in the field of hemodialysis.