O desenvolvimento de dispositivos microfluídicos biomiméticos, \"órgãos-em-chip\", tem permitido melhores respostas em ensaios que carecem de uma correlação fisiológica mais próxima da in vivo. Explorando as tecnologias da microfluídica e microfabricação, esses dispositivos recapitulam aspectos específicos de estruturas e funções dos órgãos. Ainda, os avanços obtidos em culturas tridimensionais de células, modelos de matrizes extracelulares e tecnologias direcionadas às células tronco, têm consolidado os órgãos-em-chip como uma ferramenta fundamental para a compreensão de diversas respostas biológicas do corpo humano frente às aplicações biomédicas, farmacêuticas, químicas e ambientais. Com os avanços da nanotecnologia e ciência dos materiais, inúmeros progressos têm sido alcançados na farmácia e na medicina. Devido à redução da escala, propriedades que se diferenciam substancialmente daquelas encontradas na escala macro são obtidas. As nanopartículas de dióxido de titânio (NPs TiO2) têm apresentado múltiplas aplicações na medicina e na indústria. Em vista disso, faz-se necessário a investigação dos efeitos tóxicos dessas nanopartículas, seja na saúde ou no meio ambiente. É bem documentado que as NPs TiO2 podem chegar à corrente sanguínea e alcançar vários órgãos, causando reações inflamatórias e interações celulares que podem ser patogenicamente relevantes. Assim, o presente trabalho propõe o estudo dos efeitos das NPs TiO2 em células endoteliais (HUVEC) cultivadas em um dispositivo microfluídico fabricado em poliéster-toner (PT), uma tecnologia simples que alia rapidez e baixo custo de produção. A viabilidade do uso dos microchips de PT foi avaliada por meio do teste MTT e produção de NO e verificou-se serem adequados para a cultura de células endoteliais. As células no sistema microfluídico foram expostas às NPs TiO2, e os resultados comparados a um sistema estático (placas de cultura de células) submetido às condições semelhantes. Os sobrenadantes de ambos os sistemas foram utilizados para determinação da produção de VEGF-A. Ademais, foram avaliadas a produção de aníon superóxido e a indução de apoptose. Os resultados esclarecem os mecanismos de toxicidade das NPs TiO2 e são correlacionados com as patologias que eventualmente estão associadas a esses efeitos. Por meio deste estudo, demonstrou-se o grande potencial dos microchips de PT para estudos em biologia celular, os quais podem fornecer a base para ensaios pré-clinicos com maior poder preditivo, alternativos ao uso de animais e cobaias na pesquisa científica. / The development of biomimetic microfluidic devices, \"organ-on-chips\", has allowed better responses in assays that need a closer in vivo physiological correlation. Exploring the technologies of microfluidics and microfabrication, these devices recapitulate specific aspects of structures and functions of the organs. In addition, the progress made in 3D cell cultures, extracellular matrix models, and stem cells technologies, have consolidated the organ-on-chips as a key tool for understanding various biological responses of the human body in face of biomedical, pharmaceutical, chemical, and environmental applications. With the advances in nanotechnology and materials science, much progress has been made in pharmacy and medicine. Due to the scale reduction, properties that differ substantially from those found on the macro scale are obtained. Titanium dioxide nanoparticles (TiO2 NPs) have found many applications in medicine and industry. In view of this fact, it is necessary to investigate the toxic effects of nanoparticles, either on health or in the environment. It has been well documented that TiO2 NPs can reach the bloodstream and affect various organs, causing inflammatory reactions and cellular interactions that can be pathogenetically relevant. Thus, this work proposes the study of the effects of TiO2 NPs in endothelial cells (HUVEC) cultured in a microfluidic device made of polyester toner (PT), a simple technology that combines speed and low cost of production. The viability of the use of PT microchips was evaluated by MTT assay and production of NO and we found that it is suitable for culturing of endothelial cells. The HUVEC in the microfluidic system were exposed to TiO2 NPs and the results compared to a static system (cell culture plates) subjected to similar conditions. Supernatants from both systems were used for determining the production of the VEGF-A. Furthermore, we have evaluated superoxide anion production and induction of apoptosis. The results clarify the mechanisms of toxicity of NPs TiO2 and are correlated with the pathologies that eventually are associated with these effects. Through this study, we demonstrated the great potential of PT microchips for studies in cell biology, which may provide the basis for pre-clinical trials with greater predictive power, alternative to the use of animals in scientific research.

A utilização de biomassa vegetal como matéria-prima para a obtenção de produtos químicos exige pré-tratamentos que levem à desestruturação do complexo lignocelulósico, sendo o principal desafio a remoção seletiva e quantitativa da lignina. O bagaço de cana-de-açúcar, como todo material lignocelulósico, é composto por celulose, polioses e lignina, como principais componentes macromoleculares, e vem sendo alvo de pesquisas para produção de bioetanol e produtos com maior valor agregado. A heterogeneidade das ligninas obtidas como subprodutos dos processos de deslignificação é uma das responsáveis pela limitação de possíveis aplicações industriais. Contudo, os recentes desenvolvimentos no etanol celulósico levarão a um aumento da quantidade de lignina disponível numa base global. Estas considerações futuras têm renovado o interesse no isolamento e conversão de lignina em produtos químicos de maior valor agregado. Neste sentido, o isolamento e a caracterização destas ligninas são de fundamental importância. Neste trabalho apresentamos os resultados de estudos de deslignificação do bagaço de cana-de-açúcar pela aplicação de diferentes processos de polpação (processos Soda, Sulfito e Organossolve etanol/água). Estes processos foram avaliados segundo o rendimento do pré-tratamento e seletividade frente aos componentes macromoleculares dos materiais lignocelulósicos. A segunda etapa do trabalho descreve a caracterização das ligninas obtidas nos diferentes processos de polpação, visando posteriores modificações e aplicações como derivados oxidados e na preparação de novos materiais poliméricos termoplásticos e/ou termorrígidos. Os processos produziram diferentes ligninas, sendo essas diferenças observadas na distribuição de massas molares, quantidade de hidroxilas, estabilidade térmica, quantidade de impurezas, etc. A utilização do fracionamento por solventes foi efetivo na obtenção de diferentes massas molares e menores polidispersividades. As condições empregadas nas poliesterificações produziram polímeros com características diferentes, como viscosidade, temperatura de transição vítrea e estabilidade térmica. / The use of plant biomass as a feedstock for the production of chemicals requires pre-treatments which lead to disruption of the lignocellulosic complex, the main challenge being selective and quantitative removal of lignin. Sugarcane bagasse is a lignocellulosic material composed of cellulose, lignin and polyoses as major macromolecular components, and has been the subject of research for bioethanol production and products with higher added value. The heterogeneity of lignins obtained as byproducts of delignification processes is one reason for the limitation of possible industrial applications. However, recent developments in cellulosic ethanol will raise the amount of lignin available on a global basis. These forward-looking statements have renewed interest in the isolation and conversion of lignin in chemical products with higher added value. In this sense, the isolation and characterization of lignins is of fundamental importance. We present the results of studies of delignification of sugarcane bagasse by applying different pulping processes (Soda, Sulfite and organosolv ethanol / water processes). These processes were evaluated according to the performance of pre-treatment and selectivity against macromolecular components of lignocellulosic materials. The second stage of the work describes the characterization of lignins obtained in different pulping processes, aiming to further modifications and applications as oxidized derivatives and the preparation of new polymeric materials thermoplastic and / or thermosetting. Processes produced different lignins, and these differences in distribution of molecular weight, amount of hydroxyls, thermal stability and amount of impurities. The use of solvent fractionation was effective in getting different molar masses and lower polydispersities. The conditions employed in esterification reaction produced polymers with different characteristics, such as viscosity, glass transition temperature and thermal stability.

As space exploration has advanced, time spent in space has increased. With the building of the International Space Station and plans for exploration missions to the Moon and Mars, astronauts will be staying in space for longer periods of time. With these increased stays in space comes an increase in fire safety concerns. One area of fire safety interest is flammability. While current flammability test procedures are in place, they are all performed on the ground and may not be representative of flammability in microgravity. In addition to this, limited research into the severity of skin burn injury in a microgravity environment has been performed. <p>An apparatus was designed to be flown on a low gravity parabolic aircraft flight to assess the flammability of cotton and 50% cotton/50% polyester fabrics and the resulting skin burn injury that would occur if these fabrics were to ignite. The apparatus, modelled after a Canadian General Standards Board standard flammability test, was also used on the ground for experiments in 1-g. Variables examined in the tests include gravity level, fabric type, air gap size, oxygen concentration, apparatus orientation, ignition source, and method used to secure the specimen. Flame spread rates, heat fluxes, and skin burn predictions determined from test results were compared. <p>Results from test in 1-g indicated that the orientation of the apparatus had a large effect on flame spread rate, heat flux and predicted skin burn times. Flame spread rates and heat fluxes were highest when the fabric was held in the vertical orientation, which resulted in the lowest predicted times to produce skin burns. Flame spread rates and heat fluxes were considerably lower in microgravity than in 1-g, which resulted in higher predicted times to produce skin burns.

As space exploration has advanced, time spent in space has increased. With the building of the International Space Station and plans for exploration missions to the Moon and Mars, astronauts will be staying in space for longer periods of time. With these increased stays in space comes an increase in fire safety concerns. One area of fire safety interest is flammability. While current flammability test procedures are in place, they are all performed on the ground and may not be representative of flammability in microgravity. In addition to this, limited research into the severity of skin burn injury in a microgravity environment has been performed. <p>An apparatus was designed to be flown on a low gravity parabolic aircraft flight to assess the flammability of cotton and 50% cotton/50% polyester fabrics and the resulting skin burn injury that would occur if these fabrics were to ignite. The apparatus, modelled after a Canadian General Standards Board standard flammability test, was also used on the ground for experiments in 1-g. Variables examined in the tests include gravity level, fabric type, air gap size, oxygen concentration, apparatus orientation, ignition source, and method used to secure the specimen. Flame spread rates, heat fluxes, and skin burn predictions determined from test results were compared. <p>Results from test in 1-g indicated that the orientation of the apparatus had a large effect on flame spread rate, heat flux and predicted skin burn times. Flame spread rates and heat fluxes were highest when the fabric was held in the vertical orientation, which resulted in the lowest predicted times to produce skin burns. Flame spread rates and heat fluxes were considerably lower in microgravity than in 1-g, which resulted in higher predicted times to produce skin burns.

The compound 2,6-anthracenedicarboxylic acid is used as a comonomer for the synthesis of poly(ethylene terephthalate). The resulting copolymers are characterized and further functionalized by Diels-Alder grafting or crosslinking through the anthracenate unit. Diels-Alder reaction is used to graft small molecules and oligomers endcapped with maleimide as dienophiles on to poly(ethylene terephthalate-co-2,6-anthracenedicarboxylate),PET-co-A. Maleimide-capped poly(ethylene glycol) is grafted onto PET-co-A to improved its hydrophilicity. 2,6-Anthracenedicarboxylic acid is also incorporated into the known liquid crystalline polymer, LCP, poly(4-oxybenzoate-co-1,4-phenylene isophthalate), HIQ40. The resulting copolymer, poly(4-oxybenzoate-co-1,4-phenylene isophthalate-co-2,6-phenylene anthracenate), HIQ40-co-A, shows LCP behavior. These HIQ40-co-A copolymers are grafted with maleimide end-capped monomers and polymers andcrosslinked with bismaleimides through a Diels-Alder mechanism.

Three series copolyesters [poly(butylene succinate-co-propylene succinate) (PBPSu), poly(butylene succinate-co-2-methyl-1,3-propylene succinate) (PBMPSu) and poly(ethylene succinate-co-butylene succinate) (PEBSu)] and their homopolyesters [poly(butylene succinate) (PBSu), poly(ethylene succinate) (PESu), poly(propylene succinate) (PPSu) and poly(2-methyl-1,3-propylene succinate) (PMPSu)] were synthesized by a two-step reaction (esterification and polycondensation) with titanium tetraisopropoxide as the catalyst. Molecular weights of all synthesized polyesters were determined by intrinsic viscosity and gel permeation chromatography (GPC) measurements. The values of intrinsic viscosity (0.97 ~ 1.62 dL/g) and relative molecular weight (2.4x10000 ~ 11.9x10000 g/mol) indicate that these polyesters can be made into films without complications. Compositions and sequence distributions of copolyesters were determined by analyzing the spectra of 1H NMR and 13C NMR. The randomness values of these copolyesters are closed to 1.0 that represents random sequence distribution of the comonomers. Thermal properties and stabilities were characterized using differential scanning calorimeter (DSC) and thermogravimetric analyzer (TGA), respectively. All copolyesters exhibited a single glass transition temperature (Tg). For PBPSu copolyesters, incorporating propylene succinate units to PBSu not only narrows the window between Tg and melting temperature (Tm), but also retards the cold crystallization ability, thereby lowering the crystallinity to a considerable extent. This phenomenon also occurred in PBMPSu and PEBSu copolyesters when the 2-methyl-1,3-propylene succinate (MPS) and butylene succinate (BS) units were incorporated into PBSu and PESu, respectively. Tstart is the temperature of first detectable deviation from the derivative curve of weight loss. Tstarts of all synthesized polyesters around 240 £jC, higher than the temperature of polycondensation reaction (220 £jC), demonstrates that there is no necessity of using a thermal stabilizer during the synthesis of these polyesters. Additionally, the thermal stability does not vary significantly with compositions in the same series polyester. Wide-angle X-ray diffractograms (WAXDs) at room temperature were obtained from polyesters crystallized isothermally at a temperature around 5-20 £jC below their melting temperatures. WAXD patterns of two series polyesters elucidated that the incorporation of PS or MPS units into PBSu markedly inhibits the crystallization behavior of PBSu. The phenomenon also occurred in PEBSu copolyesters when BS units were incorporated into PESu. Results of WAXD and DSC measurements showed that PMPSu is a amorphous polyester. The retarding effect on crystallization by methyl substituents on the polymer chain is efficient.

Capillary electrophoresis chip has gradually ripe along with the development of MEMS technology. However, such these electrophoresis chips was design closed-channel form whose process including the micro-channel forming and chip bonding and so on, so the cost is higher. In addition, if these chips use repeated will cause some pollution problems such as obstruction or difficult to clean in the closed-channel. Therefore, to fabricate a non-closed microfluidic chip system will resolve the issues above listed. In this study has successful developed a convenient and low-cost thread microfluidic system, the thin polyester thread is instead of the traditional closed separation channel. And to avoid the cross contaminations that the separation channel can free replace a new electrophoresis separation channel by the roller equipment. Thread microfluidic systems can take advantage of capillary action to move, as a disposable chromatography flow channel, and the electric field is applied to this system for electrophoresis separation and electrochemical detection in the backend. This research develop an novel process technology, the hot embossing technology shape from concave embossing and metal coating procedure in PMMA, the salient pillow-electrode structure has be produced in PMMA board, the salient electrode structure set up the polyester fiber thread, the polyester fiber thread is as the electrophoresis separation channel, and electrochemical detect samples in back-end. In this study take plasma treatment to improve wettability and surface roughness of the polyester fiber thread, in order to improve the operational effectiveness of the thread microfluidic systems. The cyclic voltammetry measure potassium ferricyanide samples and the results showed that the performance of thread microfluidic system significantly increase after the plasma treatment, the measuring current value is 10 times greater than without the plasma treatment, and the estimated detection limit of potassium ferricyanide is around 6.25 £gM in the plasma treatment one. In addition, the thread microfluidic devices with plasma treatment has successful separation and detection the mixing samples of 0.3 mM chlorine, bromine and iodine ions, and the signal of the S/N ratio is 6 times higher than the without plasma treatment one, and the number of theoretical plates of electrophoresis separation also enhance to 28% in the plasma treatment one. In addition, in order to further enhance the detection sensitivity of the thread microfluidic systems, the study design and fabricate the concave-shaped three-dimensional electrode structure, and to achieve greater contact area between thread and the electrode. Thread microfluidic system with plasma treatment detect in concave-shaped three-dimensional electrode and flat electrode respectively, the results showed that concave-shaped electrodes in the potassium ferricyanide detection limit that measured current value is 10 times greater than flat electrode, and a mixture of dopamine and catechol sample are electrophoresis separated that concave-shaped 3D electrode whose measured S/N ratio is 5 times higher than flat electrode, and the number of theoretical plates is 1.5 times higher than the flat electrode. This study develops a novel thread microfluidic system that will provide a simple process and low-cost, and can solve the shortcomings of conventional closed-channel electrophoresis chips. In future, in this study develop the thread microfluidic system architecture will have contribute for fast electrophoresis separation and detection.

L'objectif de cette étude est de synthétiser de nouveaux polymères aux propriétés spécifiques, en utilisant pour la première fois comme monomère un aldocétène : l'éthylcétène. La synthèse de l'éthylcétène a été entreprise en utilisant deux procédés distincts :d'une part la méthode de McCarney, qui a permis de le préparer dans un solvant par entraînement à la vapeur, et d'autre part le craquage de l'anhydride butyrique à 575°C sous 40mbar.La polymérisation ionique de l'éthylcétène a ensuite été réalisée, dans différentes conditions de solvant, de température et avec plusieurs amorceurs. La polymérisation anionique a abouti uniquement à la formation d'un polyester amorphe, tandis que la polymérisation cationique a conduit exclusivement à un polymère de structure polycétone,d'une grande stéréorégularité avec une cristallinité moyenne de 0,34. Une caractérisation fine de ces polymères a été effectuée par IRTF-ATR, RMN, TGA, DSC, GPC et diffraction desRX.

This study was conducted to investigate the effects of organoclay type and concentration on the nanocomposites synthesized by &ldquo / In-Situ Polymerization&rdquo / and &ldquo / Prepolymerization&rdquo / methods. In-Situ Polymerization Method was in fact a new route which consisted of dispersing the monomers / propylene glycol, maleic anhydride and o-phthalic anhydride into the galleries of montmorillonite followed by subsequent polymerization. The Prepolymerization Method involved the addition of montmorillonite to the previously synthesized unsaturated polyester. As the first step, all the compositions were prepared by Cloisite 30B, and then for comparison of clay type, nanocomposites containing 3 wt.% of Cloisite 15A and Cloisite 25A were also synthesized. The efficiency of the two methods were compared with regards to their structural, thermal and mechanical properties. According to the results of XRD analysis, in both methods, maximum intercalation was observed when Cloisite 30B was used. An exfoliated structure was obtained in the Prepolymerization Method at 3 wt. % Cloisite 30B content. In all clay types, the increase in the d-spacings of the organoclays was higher when the Prepolymerization Method was applied. With Cloisite 30B, maximum improvement in the impact strength was obtained at 3 wt. % organoclay loading and the In-Situ Method yielded better results leading to a 77% increase in the impact strength at this organoclay loading. Among the organoclay types, Cloisite 15A was found to give rise to maximum increase in the impact strength. With the Prepolymerization Method higher improvement in flexural strength and flexural modulus was obtained owing to the lower styrene content in the crosslinking medium. The elongation at break values followed a decreasing trend with increasing clay content but did not show any significant difference when the clay types were compared.

ABSTRACT CORNEA ENGINEERING ON BIODEGRADABLE POLYESTERS Zorlutuna, Pinar M. Sc., Department of Biotechnology Supervisor: Prof. Vasif Hasirci Co-Supervisor: Asst. Prof. AySen Tezcaner January 2005, 66 pages Cornea is the outermost layer of the eye and has an important role in vision. Damage of cornea due to injuries or infections could lead to blindness lowering the quality of life of the patient severely. In such cases, transplantation or artificial corneas have been used for treatment but both had drawbacks. The novel approach for corneal replacements is the tissue engineering of the cornea, a promising method which would be free of these drawbacks, if successful. In this study, carriers for tissue engineering of the cornea were designed and tested in vitro. Blends of biodegradable and biocompatible polyesters of natural (PHBV8) and synthetic (PLLA) origin were used to construct these carriers. For the epithelial layer of the cornea, PLLA-PHBV8 micropatterned films were prepared with solvent casting and seeded with D407 (retinal pigment epithelial) cells. In order to achieve proper cell growth, the films were coated with fibronectin. For the stromal layer of the cornea, highly porous foams of PLLA-PHBV8 were prepared by lyophilization and seeded with 3T3 cells (fibroblasts). A new approach was developed to create a combination of the film and the foam to obtain a surface patterned, 3 dimensional cell carrier. These carriers were seeded with Saos-2 cells (osteosarcoma cells) in the preliminary optimization studies and with D407 and 3T3 cells in further studies. The cell numbers on the carriers were quantified by using MTS assay (non-radioactive cell proliferation assay) and the cell proliferation on polymeric carriers was significantly higher than that of control (Tissue culture polystyrene) by the day 14. Characterization of these cells and the carrier was done using a variety of microscopic methods. The micrographs showed that the foam had a highly porous structure and the pores were interconnected. 3T3 cells were found to be distributed quite homogeneously at the seeding site, but due to the high thickness of the foam, the cells could not sufficiently populate the core (central parts of the foam) during the given incubation time. The micropatterned film allowed multilayer formation of D407 cells. The functionality of the cells seeded on the carriers was examined by immunohistochemistry. These analyses proved that the cells retained their phenotype during culturing. D407 cells formed tight junctions characteristic of epithelial cells, and 3T3 cells deposited collagen type I into the foams. Based on the results, it can be concluded that the 3-D PLLA-PHBV8 construct with surface patterns have a serious potential for use as a tissue engineering carrier for the reconstruction of the cornea. Key words: Tissue engineering, cornea, polymeric carrier, biodegradable, polyester.