Double-sided Functionalized PVDF Multifunctional Composite Membrane To Remove Bilirubin

Although haemoperfusion is the main treatment for hyperbilirubinemia,the biocompatibility of haemoperfusion materials is still insufficient.Traditional methods used to strengthen biocompatibility usually lead to decrease bilirubin removal.Thus,the development of new biomaterials with high bilirubin removal and biocompatibility remains a huge challenge.Herein,double-sided functional modification of polyvinylidene fluoride(PVDF)plasma separation membrane is proposed for the first time instead of developing new adsorbents.The outstanding hemocompatible inner surface and efficient bilirubin removal outer surface have been successfully constructed on PVDF plasma separation membrane.When the blood flows in the hollow fiber membrane,the anticoagulant properties of inner surface can prolong clotting time.Meanwhile,plasma is filtrated through the membrane,and bilirubin in plasma is adsorbed on the outer surface.It makes self-anticoagulation one-step "filtration-adsorption" to remove bilirubin by the same membrane become a reality.Firstly,the macromolecular interaction of additives was adopted to form compound additives.Utilizing the large-pore-formation and residue characteristics of compound additives,the large pore PVDF plasma separation membrane with asymmetric structure was prepared successfully by non solvent phase transformation(NIPS)for the first time.This would be a breakthrough in preparing large-pore PVDF hollow fiber membrane by NIPS.The PVDF plasma separation membrane shows the similar plasma sieving properties and biocompatibility with the import plasma separation membrane.And the biocompatibility has passed the test entrusted by the state designated unit.However,the membrane is similar to the normal plasma separation membrane in clinical application,which has not the properities of selfanticoagulant and bilirubin removal.Then,PVDF plasma separation membrane was double-sided modified by polyethyleneimine and heparin.The results showed that the outer surface of the doublesided functional membrane had high adsorption specificity for bilirubin,and the inner surface had self-anticoagulation with activated partial thromboplastin time prolonging3 times.The membrane can effectively remove bilirubin by "filtration-adsorption".However,the total protein adsorption rate of the outer surface of the membrane reached(11.6±4.1)%.To reduce protein adsorption and construct a new self-anticoagulant functional layer,sodium alginate and albumin were used to modify the double-side of PVDF plasma separation membrane.The results showed that alginate/HSA double-sided functional PVDF membrane had higher adsorption specificity for bilirubin.The "macrospore structure" on the inner surface is conducive to grafting more alginate.The self-anticoagulation property of membrane was strengthened.Activated partial thromboplastin time was prolonged by 2.5 times.The membrane had excellent "filtration-adsorption" properties with a higher plasma protein sieving coefficient.Meanwhile,the plasma total bilirubin adsorption ratio in hyperbilirubinemia plasma was as high as 55.8 %.The PVDF multifunctional composite membrane developed in this paper can effectively solve the "trade-off" effect between biocompatibility and bilirubin removal of traditional haemoperfusion adsorption materials.It provided a new treatment scheme for hyperbilirubinemia and has great potential in clinical application.