Les poly (3-hydroxyalcanoates) (PHAs) sont des polyesters aliphatiques produits et accumulés par des bactéries en tant que réserve de carbone et d'énergie. Ils sont constitués d'unités β-hydroxyesters et possèdent des chaînes latérales de longueur variable, pouvant être fonctionnalisées. Ils possèdent des propriétés de biodégradabilité et de biocompatibilité; ceci leur confère de vastes possibilités d'utilisation dans le domaine biomédical, notamment pour la mise au point de systèmes de libération contrôlée de principes actifs. Dans cette optique, nous nous sommes intéressés à la synthèse de copolymères amphiphiles de différentes architectures à base de PHAs, ainsi qu'à l'étude de leurs propriétés d'auto-association en milieu aqueux. Une méthode simple et efficace permettant le greffage d'oligomères de poly (éthylène glycol) (PEG) a tout d'abord été mise au point grâce à l'utilisation de la chimie " click ". Une série de copolymères diblocs bien définis PHA-b-PEG a ainsi pu être synthétisée par cycloaddition de Huisgen catalysée par le cuivre (CuAAC). Les copolymères diblocs à base de PHAs à moyennes chaînes latérales (PHA-mcl) ont montré leur capacité à s'auto-associer en milieu aqueux et à former des micelles monodisperses présentant une concentration micellaire critique très faible. Par la suite des copolymères de type greffés PHOU-g-PEG ont été synthétisés par addition thiol-ène. Les analyses par cryo microscopie électronique à transmission (cryo-TEM) ont montré que dans ce cas les copolymères s'auto-associaient en structures vésiculaires, ou polymersomes. Enfin, la synthèse de copolymères amphiphiles greffés porteurs de chaînes perfluorées PHOU-g-(F;PEG) a permis l'obtention de structures auto-associées plus complexes. Le cryo-TEM a en effet révélé la formation de micelles multicompartimentées, c'est à dire possédant un coeur présentant une séparation de phase entre les domaines hydrophobes et les domaines fluorés. Des tests biologiques préliminaires ont montré la cytocompatibilité de ces micelles

Cell adhesion is the first step of cell response to materials and the extracellular matrix (ECM), and is essential to all cell behaviours such as cell proliferation, differentiation, migration and apoptosis for anchor-dependent cells. Therefore, studies of cell attachment have important implications to control and study cell behaviours. During many developed techniques for cell attachment, the manipulation of surface chemistry is a very important method to control initial cell attachment. To control cell adhesion on a two-dimensional surface is a simple model to study cell behaviours, and is a fundamental topic for cell biology, tissue engineering, and the development of biosensors. From the engineering point of view, the preparation of a material with controllable surface chemistry can help studies of cell behaviours and help scientists understand how surface features and chemistry influence cell behaviours. During the fabrication, the challenge is to create a surface with heterogeneous surface properties in the micro scale and subsequently to guide cell initial adhesion. In order to control cell adhesion in a spatial and temporal manner, a photochemical method to control surface chemistry was employed to control the surface property for cell adhesion in this project. Two photocleavable derivatives of the nitrobenzyl group were tried on two types of surfaces: a model self-assembled monolayer (SAM) with alkanethiol-gold surface and biodegradable chitosan. Reactive functional groups on two different surfaces can be inactivated by covalent binding with these photocleavable molecules, and light can be further introduced into the system as a stimulus to recover their reactivity. By simply applying a photomask with diffe

Poly Brominated Diphenyl Ethers (PBDEs) are known flame retardants with highly persistent and lipophilic in nature. The continued usage of PBDE in various products amplifies the human burden of PBDEs. It is therefore, important to study the potential toxicological and/or biological effects of PBDE exposure in human. In this study we investigated the mode of action of PBDE induced toxicity in human liver by exposing human hepatocarcinoma cells in a time (24-72h) and dose (0-100μM) dependent manner. The highest test dose caused an inhibition in cell viability up to 50% after 72h, whereas lower doses (<50μM) showed slight increase in cell viability. Likewise, higher doses caused significant accumulation of intracellular ROS over time. Further, increase in caspase-3 enzyme levels and DNA fragmentation showed that, lower brominated PBDEs induce liver toxicity through accumulation of toxic metabolites and reactive oxygen species over time leading to caspase-mediated apoptotic cell death.

Citrate-coated gadolinium trifluoride (Cit-GdF3) and poly(acrylic acid)-coated nanoparticles (PAA-GdF3 NPs) were synthesized, the former reproduced from literature (though using more refined conditions), the latter through a new, two-step, ligand exchange method. Diamagnetic nanoparticle analogs (Cit-YF3 NPs) were prepared to investigate citrate interactions with the nanoparticle surface using NMR. Citrate was found to bind in numerous conformations, with a total of between 29 – 46 % bound at 0 ºC. Exchange studies revealed short residence lifetimes of one and twelve seconds respectively for bound and free forms of citrate (0 ºC), perhaps explaining the colloidal instability of these nanoparticles. PAA-GdF3 NPs were synthesized by first producing their Cit-GdF3 counterparts, and then exchanging citrate for PAA. The impetus behind this latter synthesis was the relative enhancement in stability and relaxivity attainable by these nanoparticles. The displacement of citrate by PAA was verified using diffusion NMR studies.

Recent biosensors using glucose oxidase enzyme to detect glucose (“blood sugar”) were made with intrinsic conducting polymers such as poly pyrrole (PPY) to mediate the reaction. PPY coated electrodes were difficult to employ via eletropolymerization because PPY is only soluble in solvents potentially damaging to enzymes. Nano crystalline cellulose – poly pyrrole (NCC-PPY) colloid circumvents this by forming natural, enzyme compatible, and hydrophilic films mechanically bound to electrodes using easy-to-disperse colloids. NCC-PPY was studied as mediator to investigate use in biosensor applications. Using NCC-PPY film casted on microfabricated interdigitated electrodes, a glucose biosensor with sensitivity factor of 20 was achieved. NCC-PPY showed enhanced catalysis with no enzyme inactivation and a total current of 2mA. Enhanced sensitivity was attributed to resistance changes of doped PPY, redox mediation, and compatibility of cellulose with enzyme.

Citrate-coated gadolinium trifluoride (Cit-GdF3) and poly(acrylic acid)-coated nanoparticles (PAA-GdF3 NPs) were synthesized, the former reproduced from literature (though using more refined conditions), the latter through a new, two-step, ligand exchange method. Diamagnetic nanoparticle analogs (Cit-YF3 NPs) were prepared to investigate citrate interactions with the nanoparticle surface using NMR. Citrate was found to bind in numerous conformations, with a total of between 29 – 46 % bound at 0 ºC. Exchange studies revealed short residence lifetimes of one and twelve seconds respectively for bound and free forms of citrate (0 ºC), perhaps explaining the colloidal instability of these nanoparticles. PAA-GdF3 NPs were synthesized by first producing their Cit-GdF3 counterparts, and then exchanging citrate for PAA. The impetus behind this latter synthesis was the relative enhancement in stability and relaxivity attainable by these nanoparticles. The displacement of citrate by PAA was verified using diffusion NMR studies.

Recent biosensors using glucose oxidase enzyme to detect glucose (“blood sugar”) were made with intrinsic conducting polymers such as poly pyrrole (PPY) to mediate the reaction. PPY coated electrodes were difficult to employ via eletropolymerization because PPY is only soluble in solvents potentially damaging to enzymes. Nano crystalline cellulose – poly pyrrole (NCC-PPY) colloid circumvents this by forming natural, enzyme compatible, and hydrophilic films mechanically bound to electrodes using easy-to-disperse colloids. NCC-PPY was studied as mediator to investigate use in biosensor applications. Using NCC-PPY film casted on microfabricated interdigitated electrodes, a glucose biosensor with sensitivity factor of 20 was achieved. NCC-PPY showed enhanced catalysis with no enzyme inactivation and a total current of 2mA. Enhanced sensitivity was attributed to resistance changes of doped PPY, redox mediation, and compatibility of cellulose with enzyme.

This essay aims to examine what subject positions are possible within the discourse of relationship anarchy. Through semi-structured interviews with four people who define themselves as relationship anarchists I've made a discourse analysis to determine how these relationship anarchists explain what, in the discourse they’re in, is described as an relationship anarchistic way of being, what isn’t and how they relate to this. Relationship anarchy is described as an ideology based on freedom. It is about the right to define their relationships as they like, as something constantly changing and that does not hold a specific value based on its label. But it is apparent that the freedom is relative when it occurs in a discourse where other standards are created. Based on these standards, both the hegemonic discourse, where being a couple is the relationship standard, and the counter-hegemonic relationship anarchist discourse, the respondents are positioning themselves as something different from that, and that their way of practicing relationships are based on responsibility and communication. Based on this I find that there are three possible subject positions within relationship anarchy: the idealogical, the player and the responsible.

This thesis develops a novel photopatterning strategy for biomimetic scaffolds that enables spatial and biochemical control of engineered cellular architectures, such as the microvasculature. Intricate tools that allow for the three dimensional (3D) manipulation of biomaterial microenvironments will be critical for organizing cellular behavior, directing tissue formation, and ultimately, developing functional therapeutics to treat patients with critical organ failure. Poly(ethylene glycol) (PEG) based hydrogels, which without modification naturally resist protein adsorption and cellular adhesion, were utilized in combination with a two-photon laser patterning approach to covalently immobilize specific biomolecules in custom-designed, three-dimensional (3D) micropatterns. This technique, known as two-photon laser scanning lithography (TP-LSL), was shown in this thesis to possess the capability to micropattern multiple different biomolecules at modular concentrations into a single hydrogel microenvironment over a broad range of size scales with high 3D resolution. 3D cellular adhesion and migration were then explored in detail using time-lapse confocal microscopy to follow cells as they migrated along micropatterned tracks of various 3D size and composition. Further, in a valuable modification of TP-LSL, images from the endogenous microenvironment were converted into instructions to precisely direct the laser patterning of biomolecules within PEG-based hydrogels. 3D images of endogenous microvasculature from various tissues were directly converted into 3D biomolecule patterns within the hydrogel scaffold with precise pattern fidelity. While tissue engineers have previously demonstrated the formation of vessels through the encapsulation of endothelial cells and pericyte precursor cells within PEG-based hydrogels, the vessel structure had been random, uncoordinated, and therefore, ultimately non-functional. This thesis has utilized image guided TP-LSL to pattern biomolecules into a 3D structure that directs the organization of vessels to mimic that of the endogenous tissue vasculature. TP-LSL now stands as a valuable tool to control the microstructure of engineered cellular architectures, thereby providing a critical step in the development of cellularized scaffolds into functional tissues. Ultimately, this thesis develops new technologies that advance the field of regenerative medicine towards the goal of engineering viable organs to therapeutically treat the 18 patients who die every day waiting on the organ transplant list.

A key part of the development of new polymeric materials focuses on the use of flame-retardant additives, which help to reduce the inherent flammability of polymers and the production of smoke and toxic gases. The aim of this thesis was the preparation, characterization and application of new polymeric flame-retardant additives, which can lead to intumescent systems when mixed with ¨commodity¨ polymers. The synthesis of this kind of additives was carried out by chemical modification of different polymeric structures (alcohols, polyketones, polyaziridines) with phosphorous moieties, previously described as promoting flame retardance structures, and/or nitrogen containing moieties. The efficacy of some of these additives was tested by blending with polypropylene, one of the most commonly used thermoplastic. Flame retardancy behaviour of the blends, as well their compatibility and mechanical properties were studied, in order to observe how the flame retardant additives may affect the substrate properties. / Una parte fundamental del desarrollo de nuevos materiales poliméricos se centra en la utilización de agentes retardantes a la llama, los cuales contribuyen a reducir la inherente combustibilidad de los polímeros y la producción de humos y de gases tóxicos. El objetivo del presente trabajo ha sido la preparación, characterización y aplicación de nuevos aditivos retardantes a la llama de tipo polimérico que pueden dar lugar al mezclarse con polímeros termoplásticos de gran consumo a sistemas de tipo intumescente. La síntesis de estos additivos se ha llevado a cabo por modificación química de diferentes estructuras polimericas (alcoholes, policetonas, poliaziridinas) con compuestos fosforados, descritos previamente como promotores de retardancia a la llama y/o compuestos con nitrogeno. La eficacidad de algunos de estos additivos ha sido estudiada por mezclarse con polipropileno, uno de los más utilizados termoplasticos.