Fabrication Of Cell Outer Membrane Mimetic Structure On Polysulfone Surface

Polysulfone (PSF) has been used in hemodialysis membranes, because of its excellent mechanical strength, chemical resistance and thermal stability. Because polysulfone itself has poor blood compatibility, surface modification of the polysulfone membranes is required for use as hemodialysis membranes. As it is well know that non-specific protein adsorption and cell adhesion are the main cause of membrane fouling in biomedical applications, zwitterion containing polymers such as poly[2-(methacryloyloxy)ethyl phosphorylcholine](PMPC) have been shown to be particularly effective in fabricating antifouling coatings. PMPC contains pendant phosphorylcholine (PC) side-groups that are a major component of the outer surface of the erythrocyte membrane. It is well known that phosphorylcholine-based polymers can be used to produce surfaces which are remarkably resistant to protein adsorption and cellular adhesion. Due to the significant interest of MPC polymer coatings, this dissertation employs different techniques such as Reversible Addition Fragmentation Chain Transfer (RAFT) radical polymerization, Surface-Initiaed Atom Transfer Radical polymerization (ATRP) and Michael addition for grafting MPC polymer or PC groups onto PSF surfaces.(1) Fabrication of cell outer membrane mimetic coating on polysulfone surface via RAFT technique. Cell membrane mimetic antifouling brush was grown on polysulfone (PSF) membrane by surface-induced reversible addition-fragmentation chain-transfer (RAFT) polymerization of MPC. The RAFT agent-immobilized PSF substrate was prepared by chloromethylation, amination with ethylenediamine (EDA) and by the amide reaction of amine groups of EDA with the carboxylic groups of4-cyanopentanoic acid dithiobenzoate (CPAD). The surface RAFT polymerization of MPC was initiated in aqueous solution by4,4’-azobis-4-cyanopentanoic acid (ACPA). The formation of PMPC brush coating is evidenced by X-ray photoelectron spectroscopy and water contact angle measurements. The average number of chloromethyl groups in one PSF unit of the CMPSF polymer was calculated to be1.5with the1H-NMR result. The results of dynamic contact angle (DCA) indicated that both of the θadv and θrec of PSF-PMPC surface reduced significantly to8±2°and5±2°. These low contact angles and low hysterisis indicate that the PSF-PMPC surface is extremely hydrophilic and does not change its hydrophilic structure during dry. The XPS result showed that the density of amine groups was also1.5per unit of PSF. The density of the coupled CPAD was calculated to be0.6per unit. The degree of polymerization (DP) of MPC was calculated to be19. Thus the average molecular weight of the grafted PMPC was4491g/mol and the average length of the grafted PMPC brush was around5nm. The adsorption ammounts of Fg (0.15μg/cm2) and BSA (0.04μg/cm2) on the PSF-PMPC surfaces were much lower than that on other PMPC polymer modified surfaces. This excellent result could be attributed to the formation of dense brush of PMPC chains on the PSF-PMPC membrane surface. The platelet adhesion and protein adsorption results showed that the PMPC-grafted PSF surface has excellent antifouling ability to resist platelet adhesion completely andsuppress protein adsorption significantly.(2) Fabrication of cell outer membrane mimetic coating on polysulfone surface via ATRP process. First, chloromethyl polysulfone was perpared. And then PMPC was grafted on the chloromethylated PSF surface by SI-ATRP. The formation of PMPC brush coating is evidenced by X-ray photoelectron spectroscopy and water contact angle measurements. The modified surface was characterized by water contact angle and X-ray photoelectron spectroscopy. The results of DCA indicated that the receding angle of PSF-PMPC membrane was less than10°. The average molecular weight of the grafted PMPC is1892g/mol and the average length of the grafted PMPC brush is around2nm that was calculated by the XPS results. The platelet-resistant property of the PMPC-grafted surface was evidenced by a90%reduction in platelet adhesion. The protein adsorption ammounts of Fg (0.07μg/cm2) and BSA (0.02μg/cm2) on the PSF-PMPC surfaces were much lower than that of the unmodified PSF surfaces. The platelet adhesion and protein adsorption results show that the MPC-grafted PSF surface has excellent antifouling ability to resist platelet adhesion completely and suppress protein adsorption significantly. These excellent results can be attributed to the formation of dense brush of PMPC chains on the PSF-MPC surface.(3) Fabrication of cell outer membrane mimetic coating on polysulfone surface via Michael addition. The PSF-EDA substrate was prepared by chloromethylation and then amination with EDA. The surface grafting of MPC was initiated in methanol by Michael addition. The formation of MPC coating on PSF membrane was evidenced by X-ray photoelectron spectroscopy and water contact angle measurements. The results of DCA indicated that the receding angle of PSF-PMPC membrane was reduced by40°. The content of P on the PSF-MPC surface was1.5%and the content of N was5.5%. The platelet-resistant property of the MPC-grafted surface was evaluated by platelet adsorption experiments with platelet-rich plasma. The result showed that the hemocompatibility of the PSF surface was improved with the formation of cell outer membrane mimetic structure. The adsorption ammounts of Fg (0.10μg/cm) and BSA (0.01μg/cm2) on the PSF-MPC surfaces were much lower than the unmodified PSF surfaces. The platelet adhesion and protein adsorption results showed that the MPC-grafted PSF surface has excellent antifouling ability to resist platelet adhesion completely and suppress protein adsorption significantly.