Functional Coatings Made Of Self-assembled Colloidal Particles On Medical Mg Surfaces

Magnesium(Mg)and its alloys have recently been considered as promising biodegradable bone fixation and repair implants.Compared to traditional artificial implant materials(stainless steels,titanium.etc),Mg-based implants are able to degrade on demand in vivo environment with the completion of their intended functions.Moreover,they can lower long-term complications risk associated with permanent implants,such as foreign-body caused inflammatory response,and painful secondary removal surgery.However,the most challenge of biodegradable Mg-based implants is their fast degradation rate in human ambient.Although many methods are possible ways to control the corrosion behavior of Mg alloys,surface polymer coatings have become more promising because they can not only act as a corrosion barrier but can be prepared with a wide range of properties and functions.However,though reasonable good results were obtained,there are still some issues should be considered,including the effect of polymer composition and coating process on coating performance,and the influence of coating chemical structure and composition on the degradation rate of Mg implants.Amphiphilic copolymer self-assembled nanoparticles of various morphologies,such as spheres,rods,bowls,and vesicles,have attracted much attention during the past decade.These polymeric nanoparticles can be useful in many potential applications,such as drug delivery,nanocontainers,catalysts,sensors.Since polymer self-assembly can fabricate functional and smart materials under mild condition,thus using self-assembly technique to make new materials and devices is promising.In our previous work,we always pay an attention to the research of functional coating materials and polymer self-assembly,thus we try to use self-assembly units to fabricate Mg-based surface coatings.The main contribution of our work lies in the creation of a novel strategy to fabricate Mg-based biomedical coatings in view of the versatility of self-assembled colloidal particles and the controllability of the electrodeposition process.It is believed that our work provides new ideas and reliable data to design novel functional biomedical coatings.Considering the above aspects,novel biomedical coatings were prepared from self-assembled colloidal particles through direct electrodeposition.The route of this thesis is: firstly,negatively charged colloidal particles were prepared by self-assembly of natural macromolecules,then the particles were deposited on the magnesium alloy to form a nanostructured coating through direct electrodeposition,the self-assembly process and coating formation mechanism were investigated in detail;secondly,we proposed a protective coating based on the electrodeposition of self-assembled colloidal particles that stably load and release bioactive agents in a controlled manner on Mg surfaces;thirdly,the inorganic HA were encapsulated into self-assembled nanoparticles,the nanostructured composite coating was fabricated to improve the long-term corrosion protection of the surface coating;finally,functional copolymers were prepared through chemical synthesis,they were self-assembled into nanoparticles in ethanol,then the particles were deposited on Mg substrate to endow Mg surfaces with coating materials.The work in this dissertation includes the following parts: 1.Self-assembly of photo-sensitive ?-PGA-AMC and functional coatings on Mg surfaces7-amino-4-methylcoumarin(AMC)was used to modify ?-PGA to obtain novel photo-sensitive 7-amino-4-methylcoumarin modified poly(?-glutamic acid)(?-PGA-AMC)copolymers with 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride(EDC·HCl),1-hydroxy benzotriazole(HOBt)as catalyst.The particle size,morphology and surface charge of the resulting colloidal particles and their dependence on the pH,slat concentrations and UV irradiation were successfully characterized by dynamic light scattering(DLS),transmission electron microscopy(TEM)and zeta potential measurements.Nanostructured coatings were formed in situ on the surface of magnesium alloys by electrodeposition of colloidal particles.The composition,morphology,and phase of the coating were monitored using Fourier transform infrared spectroscopy,energy-dispersive X-ray spectros-copy,scanning electron microscopy,and X-ray diffraction.The results show that nearly 20% of AMC was grafted to ?-PGA main chains,the copolymers can self-assemble into particles in DMSO/CH3CH2 OH mixed solvent because of interpolymer hydrogen bonding and mutual electrostatic repulsion.And the resulting self-assembled colloidal particles are also responsive to initial copolymer concentration,pH,and UV irradiation.Electrodeposition was carried out at 150 V for 30 min,pH~7.5,the magnesium alloys were covered with the nanostructured coating.The proposed mechanism of coating formation is the classical Derjaguin-Landau-Verwey-Overbeek(DLVO)theory of colloidal stability.The corrosion test showed that the formation of the nanostructured coating on magnesium alloys effectively improved their initial anticorrosion properties.More importantly,the corrosion resistance was further enhanced by chemical photo-cross-linking.In addition,the low cytotoxicity of the coated samples was confirmed by MTT assay against NIH-3T3 normal cells.2.Controlled release and corrosion protection by self-assembled colloidal particles electrodeposited onto magnesium alloysWe report a potential example of using surface functionalization to provide magnesium alloys(Mg-Ca)with controlled release and corrosion resistance properties in this part.A key feature of this approach is to treat the Mg-Ca surfaces with nanoparticles via electrodeposition that can stably load and controllably release bioactive agents or drugs.These photo-cross-linkable and nano-scale particles were prepared by the self-assembly of an amphiphilic poly(?-glutamic acid)-7-amino-4-methylcoumarin(?-PGA-AMC)with encapsulation of a vitamin,which is vital to cell differentiation and proliferation.Moreover,the size and morphology of the resulting particles were studied.Fluorescence microscopy analysis indicated that Vm was effectively incorporated into the ?-PGA-AMC particles.Scanning electron microscopy(SEM)images showed that the colloidal particles could be uniformly electrodeposited on the Mg-Ca alloys.Fourier transform infrared spectroscopy(FTIR)and X-ray diffraction(XRD)analyses confirmed the successful anchoring of the particles.After the surface electrodeposition of self-assembled colloidal particles,the in vitro degradation results show that deposition of the particles was found to reduce the degradation rate of the magnesium alloys;moreover,the vitamin was controllably released for up to 20 days.Furthermore,the Mg-Ca substrate functionalized with colloidal particles containing a vitamin significantly promoted the attachment,proliferation and spread of NIH-3T3 normal cells.The entire strategy may be used in various medical devices to create functional coatings for improved biomedical performance.3.Corrosion resistance of biodegradable Mg with a composite polymer coatingIn order to improve the biocompatibility and anticorrosion property of pure Mg,a biodegradable nanocomposite coating to control the performance of Mg alloy was reported in this part.The key feature of this treatment was to equip the Mg alloy surfaces with hybrid nanoparticles via electrodeposition in ethanol.The particles were prepared by self-assembly of photo-cross-linking ?-PGA-AMC copolymers with encapsulation of hydroxyapatite(HA).The size and morphology of the particles were investigated by dynamic light scattering(DLS)and transmission electron microscope(TEM).The microstructures of the resulting nanocomposite coating were characterized by Fourier transform infrared spectroscopy(FTIR),X-ray diffraction(XRD),scanning electron microscopy(SEM),and optical microscope.The corrosion resistance and degradation performance of different Mg samples were evaluated in simulated body fluid(SBF).The results of standard electrochemical measurements along with long-term immersion tests indicated that the nanocomposite coating had preferable in vitro degradation and corrosion resistance behavior than bare Mg.Cytocompatibility was conducted using NIH3T3 cells and the coated sample showed better cell viability and cell adhesion than pure Mg substrate over the whole incubation period.Sample rods of bare Mg and coated Mg are implanted intramedullary into the femora of New Zealand white rabbits,periodic radiography and post-autopsy histopathology of each sample are analysed.The obtained in vivo results clearly confirm that the coating material decreases degradation rate of the underlying Mg sample and appears good histocompatibility and osteoinductivity.The favorable anticorrosion behavior and in vivo results of the nanocomposite coating suggested that the developed ?-PGA-AMC/HA biodegradable nanocomposite coating may have a great potential to improve the biological performance of Mg-based biomedical implants.4.Electrodeposition of colloidal particles on Mg with cytocompatibility,antibacterial performance,and corrosion resistanceTo improve the corrosion resistance meanwhile not compromise other excellent performance of Mg,self-assembled colloidal particles made of synthetic P(ISA-co-DMA)copolymers were deposited onto magnesium surfaces in ethanol by a simple and effective electrodeposition method.The copolymers were synthesized from isobornyl acrylate(ISA)and dimethylaminoethyl methacrylate(DMA)by through the free radical copolymerization.By using tannic acid(TA),a naturally occurring water-soluble polyphenol dendroid,as the functional assembly unit,colloidal particles were fabricated by self-assembly process between P(ISA-co-DMA)and TA in ethanol.Then,these particles were deposited on Mg substrate through electrodeposition to endow Mg surfaces with coating materials.The fabricated functional nanostructured coatings were investigated using Fourier transform infrared spectroscopy(FTIR),X-ray diffraction(XRD)analyses,and scanning electron microscopy(SEM).The electrochemical test,pH value,and Mg ion concentration data show that the corrosion resistance of Mg samples is enhanced appreciably after surface treatment.In vitro cellular response and antibacterial capability of the modified Mg metal samples are performed.Significantly increased cell adhesion and viability are observed from the coated Mg samples,and the amounts of adherent bacteria on the treated Mg surfaces diminish remarkably compared to the bare Mg.Furthermore,the bare and coated Mg samples were implanted in New Zealand white rabbits for 12 weeks to examine the in vivo long-term corrosion performance and in situ inflammation behavior.The experiment results confirmed that compared with bare Mg substrate the corrosion and foreign-body reactions of the coated Mg samples were suppressed.The above results suggested that our coatings,which effectively enhance the biocompatibility,antimicrobial properties,and corrosion resistance of Mg substrate,provide a simple and practical strategy to expedite clinical acceptance of biodegradable Mg and its alloys.In summary,we used functional copolymers and functional elements as the multi-component units of assembly to prepare nanoparticles via weak interactions.The resultant nanoparticles were then electrodeposited on the surface of Mg or its alloys under constant voltage method to obtain nanostructured coating materials.The result implies that non-biodegradable oxides are barely formed in our organic systems,since the magnesium sample can maintain its original surface composition without a chemical reaction with an electrolyte during the electrodeposition procedure;all coating materials contributed to the corrosion resistance and biocompatibility of Mg samples,and functional Mg surfaces can be fabricated by loading drugs;the coatings and their degradation products are all biocompatible.Thus,the application of self-assembled nanoparticles was expanded to Mg-based biomedical functional coatings.