No description available.

Biocompatibility is an important issue for the development of chromatographic stationary phases for the analysis of biomolecules (including proteins and peptides). A biocompatible stationary phase material is a material that resists nonspecific adsorption of biomolecules and does not interact with them in a way that would alter or destroy their structures or biochemical functions. The monolithic column format is a good alternative to typical spherical particle packed columns for capillary liquid chromatography of biomacromolecules. Several novel anion-exchange polymer monoliths for the analysis of proteins were synthesized for improved biocompatibility. Two novel polymeric monoliths were prepared in a single step by a simple photoinitiated copolymerization of 2-(diethylamino)ethyl methacrylate and polyethylene glycol diacrylate (PEGDA), or copolymerization of 2-(acryloyloxy)ethyl trimethylammonium chloride (AETAC) and PEGDA, in the presence of selected porogens. The resulting monoliths contained functionalities of diethylaminoethyl (DEAE) as a weak anion exchanger and quaternary amine as a strong anion exchanger, respectively. An alternative weak anion exchange monolith with DEAE functionalities was also synthesized by chemical modification after photoinitiated copolymerization of glycidyl methacrylate (GMA) and PEGDA. The dynamic binding capacities of the three monoliths were comparable or superior to values that have been reported for various other monoliths. Chromatographic performances were also similar to those provided by a modified poly(GMA-co-ethylene glycol dimethacrylate) monolith. Separations of standard proteins were achieved under gradient elution conditions using these monolithic columns. This work represents a successful attempt to prepare functionalized monoliths via direct copolymerization of monomers with desired functionalities. Compared to earlier publications, laborious surface modifications were avoided and the PEGDA crosslinker improved the biocompatibility of the monolithic backbone. Protein separations by capillary size exclusion chromatography (SEC) require a monolith that is biocompatible, has sufficient pore volume, has the appropriate pore size distribution, and is rigid. Most polymer monoliths have not possessed a biomodal pore-size distribution, i.e., especially with one distribution in the macropore region and the other in the mesopore region. Furthermore, non-specific adsorption of proteins in these stationary phases has persisted as a major unresolved problem. To overcome these difficulties, a porous poly[polyethylene glycol methyl ether acrylate (PEGMEA)-co-PEGDA] monolith which can resist adsorption of both acidic and basic proteins when using an aqueous buffer without any organic solvent additives was developed. Based on this biocompatible monolith, surfactants were introduced as porogens with the hope of significantly increasing the mesopore volume within the polymer. Two types of surfactants were studied, including poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO) or PPO-PEO-PPO and Brij. Pore size distributions were examined using a well-defined molecular weight range series of proteins and peptides by inverse size exclusion chromatography, which indicated relatively large volume percentages of mesopores and micropores. The two new monoliths demonstrated different SEC behaviors, low nonspecific adsorption of proteins, and high mechanical rigidity. High density lipoprotein (HDL) is a heterogeneous class of lipoprotein particles with subspecies that differ in apolipoprotein and lipid composition, size, density, and charge. In this work, I developed a new capillary SEC method for size separation of native HDL particles from plasma using a capillary packed with BioSep-SEC-4000 particles, Three major sizes of HDL particles were separated. Additionally, capillary SEC and capillary strong anion-exchange chromatography of non-delipidated HDL were accomplished using poly(PEGMEA-co-PEGDA) and poly(AETAC-co-PEGDA) monoliths. These new LC methods using packed and monolithic stationary phases provided rapid separation of HDLs and excellent reproducibility.

In recent years, nanostructured materials incorporated with inorganic particles and polymers have attracted attention for simultaneous multifunctional biomedical applications. This thesis summarized three works, which are preparation of mesoporous silica coated superparamagnetic iron oxide (Fe3O4@mSiO2) nanoparticles (NPs) as magnetic resonance imaging T2 contrast agents, polymer grafted Fe3O4@mSiO2 NPs response to temperature change, synthesis and biocompatibility evaluation of high aspect ratio (AR) gold nanorods. Monodisperse Fe3O4@mSiO2 NPs have been prepared through a sol-gel process. The coating thickness and particle sizes can be precisely controlled by varying the synthesis parameters. Impact of surface coatings on magnetometric and relaxometric properties of Fe3O4 NPs is studied. The efficiency of these contrast agents, evaluated by MR relaxivities ratio (r2/r1), is much higher than that of the commercial ones. This coating-thickness dependent relaxation behavior is explained due to the effects of mSiO2 coatings on water exclusion. Multifunctional core-shell composite NPs have been developed by growing thermo-sensitive poly(N-isopropylacrylamide-co-acrylamide) (P(NIPAAm-co-AAm)) on Fe3O4@mSiO2 NPs through free radical polymerization. Their phase transition behavior is studied, and their lower critical solution temperature (LCST) can be subtly tuned from ca. 34 to ca. 42 °C, suitable for further in vivo applications. A seedless surfactant-mediated protocol has been applied for synthesis of high AR gold nanorods with the additive of HNO3. A growth mechanism based on the effect of nitrate ions on surfactant micelle elongation and Ostwald ripening process is proposed. The biocompatibility of high AR nanorods was evaluated on primary human monocyte derived dendritic cells (MDDCs). Their minor effects on viability and immune regulatory markers support further development for medical applications. / QC 20110701

Some of the major obstacles the microfluidics industry has yet to overcome in order to facilitate large scale manufacturing of devices are costly back-end processes. Among these, bonding presents some of the most obvious difficulties and is often associated with structural deformation and surface modification. Off-stoichiometric thiol-ene (OSTE) is a relatively new material and hasn’t yet achieved the same level of adoption as Polydimethylsiloxane (PDMS) which has been the go-to material in the field of microfluidics for over two decades. OSTE offers an alternative to PDMS and promises bonding without surface treatment as well as a hydrophilic surface, removing a step in the manufacturing process. In this work, the property of OSTE to bond with a variety of commonly used thermoplastic materials were tested as well as its suitability for use in pharmaceutical devices such as Lab-on-a-chip. In addition to untreated OSTE, a surface modifier was used to examine the potential for surface modification when using OSTE as a microfluidics material. From the testing performed, we demonstrated OSTE’s capacity to form robust bonds with a range of thermoplastic materials as well as comparable biocompatibility to PDMS. / Bland de största hindren som industrin ännu ej löst när det kommer till storskalig produktion av mikrofluidiska produkter är kostsamma ”back-end” processer. Av dessa presenterar bindingsprocesser några av de mest uppenbara svårigheterna och medför ofta deformationer av finstrukturer samt ändringar i ytkemi. Off-stoichiometric thiolene (OSTE) är ett relativt nytt material och har ännu inte blivit lika utbrett i sin använding som Polydimethylsiloxane (PDMS) vilket har varit standardmaterialet i mikrofluidik i över två årtionden. OSTE erbjuder ett alternativ till PDMS, med bindingsprocesser som ej kräver ytterligare ytmodifikationer och en hydrofil yta, vilket eliminerar ett steg i tillverkningsprocessen. I detta arbete undersöktes egenskapen av OSTE att binda till en rad ofta använda thermoplaster samt dess lämplighet i medicinskt bruk, i system som ”Lab-on-a-chip”. Förutom obehandlad OSTE, så användes en ytmodifierare för att undersöka möjligheten för ytmodifiering vid användingen av OSTE i mikrofluidik. Resultaten av våra tester visade OSTE’s förmåga att forma robusta bindingar till en rad thermoplaster så väl som en jämförbar biokompatibilitet till PDMS.

<p> Cell encapsulation aims at the delivery of a therapeutic protein to a patient from transplanted cells. Conventional approaches involve immune-isolating cell lines that have been genetically modified to express a therapeutic protein, in alginate-based microcapsules. The long-term success of this approach hinges on the structural stability of the microcapsules, as well as their ability to maintain an environment suitable for the long-term survival of encapsulated cells. The most commonly studied type of microcapsule is the alginate-poly-Llysine-alginate (APA) microcapsule. However, the main concern with AP A microcapsules is the Joss of structural integrity during long-term implantation due to the exchange of calcium ions with other physiological ions, as well as the loss of the polyelectrolyte overcoats. </p> <p> In order to increase the structural stability of the microcapsules, we developed and characterized a number of synthetic polyelectrolytes that undergo phase separation upon complexation, and which are capable of forming covalent cross-links. These reactive polyelectrolytes are designed to take the place of poly-L-lysine and the outer alginate layer. We also explored combining cross-linkable synthetic polyanions with sodium alginate to strengthen the Ca Alginate core, by forming a core cross-linked network extending throughout the microcapsules. The polyelectrolyte complexes, encapsulation processes and microcapsule properties were studied in detail using extensive characterization techniques, including collaborative work on cell viability and host-immune response. </p> <p> Overall, this thesis describes a novel approach and prom1smg materials for cell encapsulations that offer enhanced microcapsule resistance to chemical and mechanical stresses, while preserving the desired biocompatibility. These materials may ultimately be useful for clinical immunosuppressive therapies. </p> / Thesis / Doctor of Philosophy (PhD)

No description available.

<p>This study is focused on synthesizing Nitinol by additive manufacturing that can provide desirable mechanical properties for orthopedic implants and adding functionally gradient coating that can enhance both safety and biocompatibility for orthopedic implant applications.</p> <p><br></p> <p>The characteristics of additively manufactured Nitinol, by using the direct energy deposition (DED) technique, were experimentally studied. Because of a unique layer-by-layer manufacturing scheme, the microstructure and associated properties (mechanical and thermo-mechanical properties) of the DED Nitinol is different compared to conventionally produced Nitinol. Both the feasibility of manufacturing defect-free microstructure and the precise control of chemical composition were demonstrated. Effects of chemical compositions and post heat-treatment conditions on the phase transformation temperatures of the DED Nitinol were systematically analyzed and compared with those of conventional Nitinol. More precise control of phase transformation temperature from DED Nitinol was possible due to incoherent precipitate formation during aging heat treatment. In a similar way, the mechanical properties of the DED Nitinol were less sensitive to its chemical compositions and post heat-treatment conditions. The feasibility of the precise control of both mechanical and thermo-mechanical properties of the DED Nitinol was demonstrated which can broaden its applications. </p> <p><br></p> <p>The bulk polycrystalline properties of the NiTi phase were studied via molecular dynamics (MD) simulations. Thermo-mechanical properties that are highly sensitive to chemical composition were not precisely predicted from previous reports and studies. In this study, realistic boundary conditions were applied to calculate bulk polycrystalline properties. Thermally driven phase transitions of NiTi between martensite and austenite are simulated with external stresses in both normal and shear directions. It is shown that phase transformation temperatures are affected by applied external stresses, and realistic values compared to experimental data are correctly predicted only when external stresses in both normal and shear directions are similar to the experimentally observed values of 0.05 – 0.1 GPa. The experimentally observed grain orientation and grain boundary thickness were applied to simulation domains for the prediction of the elastic moduli. The elastic moduli of polycrystalline NiTi structure was calculated as 52 GPa which is close to the experimentally reported value of 20-40 GPa while other studies predicted over 85 GPa. </p> <p><br></p> <p>Lastly, pure titanium gradient layers were coated on the Nitinol surface for orthopedic implant applications to eliminate potentially toxic Ni ion release. Using the DED technique, both the core Nitinol and titanium gradient layers were manufactured with high purity and without microstructural defects. An additional biomedical coating of Hydroxyapatite (HA) was deposited on the outer surface using the cold spray technique. The resultant bonding strength was determined to be 26 MPa which exceeded the requirement of the ISO-13779 standard (15 MPa). The <em>in vitro</em> test of the Ni release rate from the entire gradient Nitinol structure was very low, which was comparable to drinking water.</p>

Les cellules dérivées de la moelle osseuse, principalement les cellules endothéliales progénitrices, sont réduites chez les patients souffrant de maladies cardiovasculaires. Leur mobilisation et leur incorporation aux sites de lésion vasculaire sont des évènements prépondérants dans l’accélération des processus de réendothélialisation. Dans un modèle murin, le 17β-estradiol favorise les processus de guérison vasculaire par la mobilisation et le recrutement des cellules endothéliales progénitrices dérivées de la moelle osseuse. Il existe présentement plusieurs stratégies afin d’augmenter la mobilisation des cellules progénitrices ainsi que leur incorporation à la paroi vasculaire. Cependant, peu d’études privilégient la livraison locale d’un nombre élevé de cellules progénitrices fonctionnelles par un véhicule biodégradable et leur maintien au site de lésion afin de favoriser la réendothélialisation ciblée. Un polymère d’intérêt pour cette application s’avère être le chitosan. Ce biopolymère non toxique et biodégradable est couramment utilisé dans l’ingénierie tissulaire et, depuis peu, est utilisé dans la guérison vasculaire. Le chitosan complexé à la phosphorylcholine voit sa solubilité s’accroître dans les solutions aqueuses ainsi que sa biocompatibilité cellulaire en condition physiologique. Le projet de ce mémoire visait donc : 1) à étudier in vitro, la capacité d’un polymère de chitosan complexé à la phosphorylcholine à influencer l’adhésion, la survie, la différenciation et la fonctionnalité cellulaire dans un modèle murin de culture mixte de cellules dérivées de la moelle osseuse et 2) de déterminer l’impact de la présence du 17β-estradiol sur ces mêmes comportements cellulaires. Nos travaux démontrent que la matrice de chitosan-phosphorylcholine s’avère compatible avec notre modèle de culture cellulaire. En effet, ce polymère est capable de promouvoir l’organisation et le développement des cellules dérivées de la moelle osseuse de façon comparable à la matrice normalement utilisée dans la croissance in vitro des cellules endothéliales progénitrices, la fibronectine. De plus, ce polymère n’a nullement compromis l’activité migratoire des cellules, laissant supposer qu’il pourrait éventuellement être un véhicule approprié pour effectuer une livraison cellulaire à un site de lésion. Il s’avère que le 17β-estradiol, lorsqu’ajouté au milieu de culture ou complexé au polymère de chitosan phosphorylcholine, est capable de moduler le comportement cellulaire, et ce, de façon différente. Le 17β-estradiol complexé au polymère de chitosan-phosphorylcholine démontre, par rapport à sa forme soluble, une plus grande aptitude à accroître le nombre de cellules hématopoïétiques ainsi que des cellules endothéliales progénitrices dérivées de la moelle osseuse in vitro. De plus, le 17β-estradiol complexé au polymère de chitosan-phosphorylcholine permet une amplification marquée des cellules endothéliales progénitrices et leur offre un support adéquat afin de favoriser la guérison vasculaire. L’ensemble de nos travaux suggère que le polymère de chitosan complexé à la phosphorylcholine en présence ou non de 17β-estradiol est une matrice compatible avec les cellules progénitrices dérivées de la moelle osseuse in vitro. Le 17β-estradiol complexé au polymère est toutefois plus efficace que sa forme soluble à promouvoir l’amplification du nombre de cellules progénitrices. Ce polymère représente un outil thérapeutique attrayant et une matrice de livraison d’agent bioactif prometteuse pour le recrutement cellulaire dans l’accélération de la guérison vasculaire. / Bone marrow derived cells, including endothelial progenitor cells, are reduced in numbers in patient with cardiovascular disease or risk factors. Mobilization and incorporation of these cells at the vascular lesion site are important events in the reendothelialization process. 17β-estradiol was shown in a mouse model of injury, to favour this healing process through mechanisms which involve the mobilization and incorporation of endothelial progenitor cells derived from the bone marrow. At the moment, there are many strategies to increase endothelial progenitor cells mobilization as well as recruitment into the vascular wall. However, few studies favour local delivery of a large number of functional progenitor cells on a biodegradable scaffold and to maintain them at the lesion site in order to promote reendothelialization. An interesting biopolymer for this application is chitosan. This non toxic and biodegradable biopolymer is commonly used in tissue engineering and was recently used in vascular healing. Phosphorylcholine modified chitosan can increase the water solubility and cell biocompatibility of the biopolymer in physiological condition. This master project was thus designed to :1) evaluate, in vitro, the capacity of phosphorylcholine modified chitosan to influence cell adhesion, survival, differentiation and functionality in a mouse model of bone marrow mixed culture and 2) determine the impact of 17β-estradiol on these cell behaviours. Our results suggest an adequate biocompatibility of phosphorylcholine modified chitosan with our cell culture system. Indeed, this polymer was able to promote cell organization and development of bone marrow derived cells in the same way that fibronectin, the most commonly matrix used in the progenitor cells in vitro culture. Moreover, cell migratory activity was not compromised by the chitosan polymer. It appears that 17β-estradiol, when added to cell culture media or attached on phosphorylcholine modified chitosan is able to modulate differently cell behaviour. Our data suggest that 17β-estradiol coupled to the chitosan polymer was superior to increase the number of haematopoietic and endothelial progenitor cells derived from bone marrow in vitro compared to the soluble form. 17β-estradiol coupled to the polymer of phosphorylcholine modified chitosan allowed an increased amplification of progenitor cell number and provided adequate scaffold to favour vascular healing. We propose that phosphorylcholine modified chitosan in presence or not of 17β-estradiol is a compatible matrix with bone marrow derived progenitor cells in vitro. 17β-estradiol enhances the amplification of progenitor cell in vitro when associated to the polymer compared to its soluble form. This biopolymer may be an attractive matrix and a promising vehicle in a drug delivery therapeutic system for progenitor cells recruitment and to promote vascular healing.

L'absorption des biomolécules, en particulier des protéines, sur les implants médicaux joue un rôle important dans le processus d'acceptation de l'implant dans le corps humain. L'activation des surfaces polymères par polymérisation plasma à pression atmosphérique et traitement plasma sont des méthodes utilisées dans les laboratoires des recherches pour modifier la cinétique d'adsorption et la quantité d'adsorbant. Le but de cette thèse est de mieux comprendre les mécanismes d'absorption des molécules biologiques sur des surfaces polymères modifiées par plasma à pression atmosphérique ou par autoassemblage, d'établir les mécanismes à l'interface et aussi d'établir la liaison entre la conformation des molécules adsorbées et les propriétés de biocompatibilité. / The objective of this thesis is to better understand the absorption mechanisms of biological molecules on surfaces obtained in plasma at atmospheric pressure or by self-assembly, to establish mechanisms at the interface and also establish the link between conformation of proteins adsorbed and the properties of biocompatibility.We studied a discharge at atmospheric pressure to obtain thin films of polyethylene glycol (PEG) and polyethylene glycol (PEG) with polystyrene copolymer. The characterization of thin polymer films was made using techniques atomic force microscopy (AFM), scanning electron microscopy (SEM), the contact angle measurements, infrared spectroscopy with Fourier transform (FTIR ) and X-ray photoelectron spectroscopy (XPS). The surfaces were analyzed in terms of biomolecules absorption with atomic force spectroscopy and quartz crystal microbalance.Studies of the ions and amino acids diffusion through functionalized mesoporous structures by low-pressure plasma are presented. After functionalization, we demonstrate the selectivity of the membrane for a particular class of amino acid, those which have a hydrophilic character.The mechanisms of self-assembly and stabilization of the G type molecules inside of the porous silicon are shown. Because the optical properties of these types of surfaces it can be observed the differences in stability of these molecules on the ionic strength of the different ion which form the structures.

En odontologie, la perte d'éléments naturels est palliée par l'utilisation de biomatériaux de reconstruction d'origine métallique ou céramique, celle-ci connait actuellement un fort développement avec une propension à supplanter le métal pour n'avoir que du « tout céramique ». Ces matériaux sont, par leur fonction, amenés à séjourner durablement dans le milieu buccal favorisant l'apparition de phénomènes corrosifs. La salive est un électrolyte efficace auquel viennent s'ajouter les variations de pH, de température, le polymétallisme, augmentant la vitesse de corrosion et le relargage des éléments constituants. L'étude porte sur cinq alliages couramment utilisés en odontologie prothétique : un précieux, un semi précieux et trois non précieux, et des céramiques d'infrastructure, visant à remplacer les alliages : zircone, alumine et disilicate de lithium. Tous les échantillons subissent en statique une attaque salivaire, et en dynamique une combinaison d'action salivaire et d'usure grâce à une machine unique, simulant le plus précisément possible les mouvements cuspidiens en présence constante de salive artificielle reproduisant de très près les conditions intra-buccales. L'analyse des échantillons au M.E.B.et les résultats de la spectrométrie montrent au niveau alliage un excellent comportement du Cr Co et du titane. Les céramiques montrent aussi des propriétés remarquables sur le plan biologique infirmant pour certaines les ressentis cliniques. Par contre une usure importante des dents naturelles antagonistes ne leur confère pas une biocompatibilité parfaite / In dentistry, the loss of natural elements is made up for by the use of reconstruction biomaterials of metal or ceramic origin. The use of the latter is now fastly developing and tends to supersede metal, to have only "all ceramic" elements. All these materials will remain in the mouth of the patients for a long time, which creates optimal conditions for the appearance of corrosion phenomena. Saliva is indeed an effective electrolyte. The variations in pH, temperature and polymetalism increase the speed of corrosion and the release of the component elements. The present study concerns five alloys usually used in prosthetic dentistry: one noble, one high noble, three basic alloys and several ceramics of infrastructure to replace alloys: zirconia, alumina and lithium disilicate. All the samples undergo a salivary attack in statics, and a combination of salivary action and wear in dynamics thanks to a unique machine, simulating as exactly as possible the buccal conditions. The analysis of the samples in the S.E.M., as well as the spectrometry results, suggest that the Co-Cr alloy and titanium present an excellent behaviour. Ceramics also show remarkable properties on the biological plan, in spite of certain people's clinical experience. However, an important wear of the opposing natural teeth does not give them a perfect biocompatibility