Fabrication And Applications Of Substrate-independent Cell Membrane And Mussel Adhesive Inspired Biomimetic Antifouling Coatings

The attachment of biofoulants,such as proteins,platelets and bacteria,on biomedical materials restricts their clinical applications seriously and maybe bring considerate threaten to the life of patients.At present,one of the most widely used methods to realize the excellent fouling resistance performance is surface modification.Hydrophilic polymers are used as surface modifiers and fixed on the substrates to fabricate an anti-biofouling coating.However,the high solubility of polymers makes them difficult to be attached onto a surface.Therefore,specific interactions between the polymers and the substrates are required to immobilize such hydrophilic polymers,which restrict the application of the hydrophilic polymer to only a few given materials.Hence the development of a simple and versatile method for surface modification is crucially important for the construction of functional interfaces.Bio-inspired by mussel adhesive function,catechol group emerges as a surface-independent anchor molecule in the field of surface modification.Functional molecules bearing catechol group can be fixed on various substrates by the self-anchoring catechols,providing a versatile method to modify hydrophilic,hydrophobic,even fluorine-containing materials.Focused on the mussel mimetic adhesion,several cell membrane and mussel adhesive double mimetic polymers were synthesized.Simple,convenient,and substrate-independent surface coating strategy was developed.The anti-biofouling performances of several modified substrates were evaluated systematically The research mainly includes the following four parts:(1)The self-polymerization and coating formation of dopamine was monitored in real-time by surface plasmon resonance(SPR)under different conditions.By studying the effects of initial concentrations of dopamine,pH of the dopamine solutions and the deposition time of polydopamine(PDA)coating,we could provide a theoretical guidance for the fabrication of thickness-controllable PDA coatings.The adsorption/adhesion of biofoulants,including proteins,platelets,cells and bacteria,was examined on PDA coatings with gradient thicknesses.The adsorbed/adhered amount of biofoulants increased with the increase of the deposited PDA thickness.The PDA coating-thickness-dependent biofoulant attachment was correlated with the accumulation of the reactive functional groups.Then,the PDA coating was treated by FeC13 coordination,NaIO4 oxidation and heating in air.The results of attenuated total reflection Fourier transform infrared(ATR-FTIR)spectroscopy and X-ray photoelectron spectra(XPS)measurements revealed that the amount of reactive functional groups on the treated PDA coating obviously declined,resulting in the significant reduction of adsorption/adhesion of proteins,platelets,cells and bacteria.However,the benzene rings and possible ?-? stacking structure of PDA coating couldn't be completely eliminated.Consequently,the antifouling performance of PDA coating could only be improved in a limited range by changing the functional groups' composition of PDA surface.(2)A random copolymer poly(MPC-co-NPECMA),simplified as PMEN,was synthesized by free radical polymerization of p-nitrophenoxycarbonyloxyethyl methacrylate(NPCEMA)and 2-methacryloxoethyl phosphorylcholine(MPC).Substrates including glass,silicon,steel,polycarbonate,polypropylene,gold and polytetrafluoroethylene were firstly precoated with PDA coating.Then the dip-coated or spin-coated PMEN was fixed on the PDA sublayer via the amidation coupling between the active ester groups in PMEN and amino groups of the PDA sublayer,forming a cell membrane mimetic surface.Protein adsorption,platelet attachment,L929 fibroblast cells adhesion and three common pathogenic bacteria(E.coli,P.aeruginosa and S.aureus)attachment on the PDA/PMEN coating were significantly suppressed.(3)Different content of phosphorylcholine(PC)and catechol(c)groups was introduced into the arm-ends of a multi-armed PEG,resulting in three kinds of PC and/or c end-capped 8-arm PEGs,simplified as PEG-2c-23PC,PEG-6c-23PC and PEG-8c,respectively.The doubly biomimetic multi-armed PEGs were anchored onto hydrophilic glass and hydrophobic polycarbonate via the self-anchoring of catechol groups.Dynamic contact angles,XPS,ATR-FTIR and atomic force microscope(AFM)offered the hydrophilicity,chemical groups,elemental composition and morphology information,which confirming the successful settlement of PC and/or c end-capped multi-armed PEG onto the substrates.Protein adsorption measured by BCA method,platelet attachment and cell viability measured by MTT assay revealed that the self-anchoring of the doubly biomimetic multi-armed PEG coatings could improve the biocompatibility of biomaterials in some extent.However,the limited catechol content and high water solubility of the polymers led to a very thin film,leaving extra improvement margin for the coating fabrication and antifouling performance.(4)The coating fabrication of PC and/or c end-capped multi-armed PEG was optimized by PDA mediated method on glass,steel,polycarbonate,gold and polytetrafluoroethylene.Static contact angles,XPS,AFM morphological and thickness information confirmed that the PDA-mediated coating formation was successful.SPR sensorgrams of protein adsorption,SEM images of attached platelets,fluorescence microscopic images of adhered cells and bacteria on each surface indicated excellent biofouling resistance of the PDA mediated doubly biomimetic multi-armed PEG coatings.Comparison of quantitative adsorption/adhesion results demonstrated that the anti-protein,platelet,cell and bacteria performance of PC-containing coatings(PDA/PEG-2c-23PC and PDA/PEG-6c-23PC)was obviously superior to the pure multi-arm PEG coating(PDA/PEG-8c).Furthermore,when the PC content was the same,the PDA/PEG-2c-23PC coating with the minimal catechol groups suppressed more biofoulants for the biofouling-promotion effect of catechol groups.