Surface Modification Of Artificial Lung With Cell Membrane Mimetic Polymers

Inspired by the excellent hemocompatibility of the red blood cell outer membrane,this dissertation designed and synthesized four kinds of cell membrane mimetic phosphorylcholine polymers containing crosslinkable trimethoxysilane group,mussel adhesive protein catechol group,PEG antifouling group or UV excitation graft-crosslinkable aromatic azido group respectively.The polymers were used to modify polypropylene hollow fiber membrane and the circulation loop of the membrane artificial lung.The main research work and innovations were summarized as follows.Firstly,trimethoxysilane group containing crosslinkable cell membrane mimetic polymer(PMBT)was synthesized and coated on the polypropylene hollow fiber membrane of the artificial lung by dip coating method to improve hemocompatibility.The X-ray photoelectron spectroscopy,attenuated total reflection fouriertransform infrared spectroscopy,dynamic contact angle results proved that the coating could tolerate ethanol disinfectant treatment and SDS solution ultrasonic washing.This crosslinkable cell membrane mimetic polymer coating strategy overcame the dissolution problem of ordinary amphiphilic polymer coating in a complicated environment.In vitro fibrinogen(Fg)and bovine serum albumin(BSA)adsorption were decreased by 73%and 72%respectively on the coating surfaces.Meanwhile,in vitro platelet adhesion and whole blood composition adhesion were decreased significantly.Furthermore,a simple solution perfusion method was developed for modifying the whole circulation loop of the artificial lung with the crosslinkable cell membrane mimetic polymer.Animal extracorporal blood circulation experiment showed that the red blood cell,white blood cell,platelet adhesion and fibrinogen adsorption were reduced significantly.The?-TG and complement C5a activation were decreased by 79%and 80%in the modified artificial lung.More importantly,the cell membrane mimetic polymer coating did not hinder gas exchange ability of the coated polypropylene hollow fiber membrane.Secondly,catechol group containing mussel adhesive protein mimetic and cell membrane mimetic polymer(PMNC)was synthesized and coated on the polypropylene hollow fiber membrane of the artificial lung from an aqueous solution by a simple dip coating method.Dynamic contact angle results proved that the cell membrane biomimetic polymer can be fixed on the polypropylene hollow fiber membrane by the catechol group.In vitro Fg and BSA adsorptions were decreased by more than 87%and 57%.Platelet adhesion was almost completely prevented.Then the doubly biomimetic polymer water solution was further used to modify the artificial lung circulation system by simple perfusion method.Animal extracorporal blood circulation experiment showed that the red blood cell and platelet adhesion as well as the fibrinogen adsortion were reduced significantly.The ?-TG and complement C5a activation were decreased by 79%and 68%in the modified artificial lung.Thirdly,croslinkable polymer containing both phosphorycholine and PEG antifouling groups(PMLT-PEG)was synthesized and coated on the polypropylene hollow membrane of the artificial lung by a simple dip coating method.Dynamic contact angle results proved that the coating can tolerate ethanol disinfectant treatment and SDS solution ultrasonic washing.Though the hydrophilicity of the coating was not as strong as the(PMBT)coating,the hemocompatibility was excellent due to the dual antifouling functions of the PC and PEG groups.In vitro Fg and BSA adsorptions were decreased by more than 72%and 62%.The platelet adhesion was almost completely inhibited.Animal extracorporal blood circulation experiment showed that the white blood cell and platelet adhesion,as well as the fibrinogen adsorption were reduced significantly.The ?-TG and complement C5a activation were decreased by 81%and 82%in the modified artificial lungFourthly,aromatic azido group containing UV excitation graft-crosslinkable and cell membrane mimetic polymer(PMBZ)was synthesized and used to modify the flexible and deformable material in the artificial lung circulation.As illustrated by the results on PVC blood(drug)storage bags,the UV graft-crosslinkable cell membrane mimetic polymer coating showed excellent stability in ethanol disinfectant and ultrasonic SDS solution.Compared with the bare PVC,UV graft-crosslinkable cell mimetic polymer coating inhibited diazepam,puerarin,insulin,cyclosporine A and chlorpromazine adsorptions significantly.Furthermore,it inhibited the plasticizer leaking from the PVC bag by 85%.In conclusion,four kinds of cell membrane mimetic phosphorylcholine polymers were synthesized to improve the binding stability of the cell membrane mimetic polymer coating.The excellent biocompatibility of the cell membrane mimetic polymer coating can be used to improve the biocompatibility of medical materials and devices.This dissertation provides a simple and effective method and new materials to promote the renovation of the related biomedical industry.