Ce travail porte sur l'étude du polyglyoxylate d'ethyle (PGEt) : sa synthèse, sa caractérisation et sa dégradation. Le PGEt a été obtenu par polymérisation anionique. Les conditions optimales font intervenir un amorçage par NE3 dans le CH2Cl2 à une température inférieure à -20°C. L'existence d'une température plafond (Tp = 310K pour [M]0 = 1M) nécessite l'utilisation d'agents de terminaison (phényl isocyanate ou bromure de 2-bromo-2-méthyl propionyle) afin d'obtenir des PGEt stables. La dégradation par hydrolyse in vitro du PGEt a été étudiée par RMN 1H, CES... Le mécanisme fait intervenir des coupures de chaines et des hydrolyses des esters. Les produits ultimes de dégradation identifiés sont l'éthanol et l'hydrate d'acide glyoxylique. Le caractère biodégradable du PGEt a été confirmé par respirométrie. Des études préliminaires de toxicité (sur des hématies, le nématode C. Elegans, et la croissance des plantes) n'ont pas révélé d'effet nocif du PGEt et de ses produits de dégradation. / This work focuses on the study of poly(ethyl glyoxylate) (PRtG), from its synthesis and its characterization to its degradation to some biological applications. The chosen conditions for PEtG's synthesis were initiated by an anionic way (NEt3) in presence of CH2Cl2. Because the ceiling temperature of the monomer (EtG) is low (7°C), it is necessary to block the hydroxyl ended groups generated in situ. The use of PhNCO leads to stables PEtG. The PEtG can be used as a macroinitiator of atom transfer radical polymerization (ATRP if it is wisely done. The copolymerization of styrene is then controlled. The degradation by in vitro hydrolysis of PEtG mainly led to ethanol and glyoxylic acid hydrate release. The biodegradable character of PGEt was assessed by a respirometric test and a preliminary study of toxicity (on red blood cells, worms and plants) revealed no significant effect at the concentrations generally used.

The developmental stress hypothesis predicts that an aversive condition, such as decreased food intake, predation, and social isolation, in the early developmental stage could have long term effects on behaviors and brain development of an animal. In nature, bird nestlings are susceptible to various factors, such as malnutrition, infections, and parasites. Effects of early life stress on adulthood have been extensively studied with some stressors including malnutrition. However, immune challenges as an early life stressor and their long-term programming effects on adult behaviors are yet to be studied in detail. The goal of the current study was to investigate changes in growth rate, personality, mate selection behaviors and brain development in zebra finch nestlings after injection with a viral infection mimicking agent, Polyinosinic: polycytidylic acid (Poly I:C). By using Poly I:C, it was possible to isolate long-term effects to the immune response of the bird. After Poly I:C injection on post-hatch day (PD) 14, morphological measures were conducted to detect changes in body growth rate. When birds became sexually mature (> ~PD 200), behaviors of birds were observed in different conditions to detect changes associated with the personality traits of animals. In mate choice trials, both attractiveness of males and mate selection behaviors of males and females were investigated. Finally, the development and neuronal activity of specific brain nuclei involved in courtship (i.e., HVC and RA) and social/sexual behaviors (nucleus taeniae of the amygdala, TnA) were investigated. The results showed that nestlings’ growth rate was not affected. However, Poly I:C injection had some effects on certain, but not all, personality traits observed in the study. Such effects were found only in female zebra finches, suggesting that there was a limited sex-specific influence of an early life immune challenge on personalities of adults. The results also showed that Control females tended to choose untreated males over Poly I:C injected males in mate choice trials. Finally, Poly I:C injection negatively affected the overall development of targeted brain nuclei. In addition, neuronal activity in TnA was higher in Poly I:C injected birds. Results of the present study suggest that one time injection with Poly I:C early in the life causes long term effects on adulthood. These findings are further discussed regarding their relevance to the developmental stress hypothesis.

Cells have the ability to sense the rigidity of the extracellular matrix which directly affects the control of cellular functions in development, wound healing and malignant transformation. Polydimethylsiloxane elastomers are useful model biomaterials for mechanotransduction studies because they possess several advantages including ease of fabrication, tunable elasticity and modifiable surface chemistry. In this work, we are investigating the influence of matrix stiffness on adhesion strength and the mechanosensory structures that regulate these processes. In addition, the effect of surface modifications to this elastic substrate system on other physical properties such as local stiffness and topography will be analyzed. Based on previous research, we hypothesized that cell adhesion dependent processes will be regulated by matrix stiffness, but that surface chemistry influences on protein adsorption could provide overriding regulatory signals. The results of this research will provide insight into the interconnected processes of mechanosensing and cell adhesion strengthening, and reveal criteria for designing instructive biomaterials with specific mechanical and chemical properties.

Une voie originale de recyclage des films de PET / PVDC est proposée par leur transformation chimique avec des alcoxydes de titane par procédé d'extrusion réactive à l'état solide. Les réactions d'échanges entre ces composés organo-métalliques et le PET ont été mises en oeuvre à des températures entre 250 et 280° C à l'échelle du laboratoire et ont permis de segmenter les chaînes de PET, en de petits oligomères avec des températures de fusion basses, sur des temps de réaction très courts de l'ordre de quelques minutes. Ces oligomères peuvent être post-fonctionnalisés avec des diols. Le transfert technologique de ces réactions d'échange à l'échelle de l'extrudeuse bi-vis pilote a été optimisé afin de permettre la transformation des films de PET / PVDC à des températures comprises entre 160 et 180 °C pour ne pas dégrader le PVDC. Les alcoxydes de titane permettent de stabiliser les dégagements d'acide chlorhydrique (HCl) lors de la dégradation thermique de ce polymère halogéné. La revalorisation de ces oligomères dans différents systèmes polyuréthanes a ensuite été étudiée et a démontré la compatibilité des oligomères de PET avec ces matrices avec l'amélioration de certaines propriétés physiques et mécaniques / An original way for recycling PET / PVDC films is proposed by their chemical transformation with titanium alkoxydes by reactive extrusion process in the solid state. The exchange reactions between these organo-metallic species and the PET were carried out at temperatures between 250 and 280°C at laboratory scale and they have allowed to shorten the PET's chains, in short oligomers with low melting temperatures, in a range of reaction time of few minutes. These oligomers could be post-functionalized with diols. The technologic transfert of these exchange reactions to the twin screw extruder scale was optimized in order to transform PET / PVDC films at temperatures between 130 and 180°c without degrading the PVDC. The titanium alkoxydes allow to stabilize the release of hydrochloric acid (HCl) during thermal degradation of this halogenated polymer. The reuse of these oligomers into different polyurethane systems were then studied and demonstrated the compatibility of PET oligomers with these matrix with improvements of some physical and mechanical properties

Acrolein is an electrophilic α, β-unsaturated aldehyde. Additionally, acrolein is a metabolite of the antineoplastic alkylating agent cyclophosphamide and is implicated in off-target effects, including to bladder hemorrhagic cystitis and cyclophosphamide-induced cardiotoxicity, both of which have led to serious secondary iatrogenic injury during and following chemotherapy. At low concentrations acrolein inhibits cell proliferation without inducing apoptosis, while at high concentrations may result in secondary apoptosis promotion. This investigation assessed the role of the enzyme poly (ADP-ribose) polymerase (PARP) in acrolein induced toxicity using the established toxicological H9c2 (2-1) cardiomyoblast in vitro model. H9c2 (2-1) cells were plated in 24-well plates at 75,000 cells per well three days prior to testing, followed by acrolein dosing at concentrations between 10 µM and 1000µM for either 30 or 55 minutes. PARP activity was quantitatively measured in total cell lysates using a biotin-avidin-conjugated horseradish peroxidase-TMB reporter system in a 96-well microplate formate. The lowest effective dose of toxicity at 30 minute dosing was found at 25 μM (PARP Activity 1.65-fold control) which returned to baseline at 100 μM; concentrations at or above 250 μM results in significant PARP activity reductions (≤ 0.46-fold control). Biomarkers were further characterized for cytotoxicity (AST presence), and viability (MTT reduction) in order to facilitate mechanistic characterization of PARP-mediated acrolein cardiotoxicity. Investigation of a PARP inhibitor was assessed to explore the intervention for acrolein induced cardiac tissue damage.

Drug-induced cardiotoxicity has resulted in a thorough evaluation of patient doses, treatments, and rehabilitation. One of the most commonly prescribed chemotherapeutic agents is cyclophosphamide. The active metabolite, acrolein, is one of the most potent inducers of cardiomyopathy. In this study, research was conducted on the H9c2 (2-1) cardiomyocyte cell line derived from the embryonic myocardium of rattus norvegicus to assess its competency for evaluation of the change in poly (ADP-ribose) polymerase (PARP) activity. The application of this model to study the effects of acrolein on PARP activation was chosen as an ideal determinant of cell damage produced by nitrogen mustards. To verify the legitimacy of this model, cardiomyocytes were exposed to acrolein in varying concentrations and time durations with a subsequent protein concentration measurement determined through the BCA Protein Assay. After the normalization of samples through volume adjustments and verification of sufficient protein, other aliquots were subjected to a PARP Assay in order to measure PARP activity. PARP was activated at exposure concentrations of 75 μM in all trials, with an average detection of 0.00569 ± 0.001 mU/200ng protein. Other concentrations showed varying degrees of PARP activation, verifying the model’s competency. PARP activation implies the potential use of this model for further research into targeted molecular therapy of PARP inhibition. Therefore, this model has the ability to be used as an assessment tool for the combined use of PARP inhibitors and chemotherapeutic agents; it can be useful for future research investigating the use and efficacy of PARP inhibitors in reducing drug-induced cardiotoxicity.

This thesis describes the synthesis of soluble Polymer of Intrinsic Microporosity (PIM-1), fluoro-endcapped PIM-1 (F-PIM-1) and copolymers of F-PIM-1 with poly(ethylene glycol) monomethyl ether (MeOPEG). The main aim of the project was to alter the porosity of microporous PIM-1 in three ways: (a) synthesis of copolymers of F-PIM-1 with MeOPEG (b) blending of PIM-1 with MeOPEG in various proportions; and (c) adsorption of MeOPEG from aqueous solution byPIM-1. PIM-1 and F-PIM-1 were synthesized by step growth polymerization of tetrafluoroterephthalonitrile (TFTPN) with 5,5',6,6'-tetrahydroxy-3,3,3',3'-tetramethyl-1,1'-spirobisindane (THSB), using the conventional method and a newly reported high shear mixing method. F-PIM-1 oligomers were then coupled to poly(ethylene glycol) monomethyl ether (MeOPEG). The products were analyzed by NMR, IR, MALDI ToF MSS, TGA and polystyrene based GPC as well as multidetector GPC techniques. The high shear technique generally produced high molar mass products and yields. This method was also more successful for copolymerization.Blending of PIM-1 and MeOPEG in different proportions resulted in macrophase separation. Copolymer products were used to facilitate mixing of blends (as compatibilizers), however only 5% of MeOPEG could be solubilised into a PIM-1 phase. The effect of compatibilizer was found to be affected by interaction between PIM-1 and copolymer. However, N2 adsorption studies showed that after thermal removal of MeOPEG, PIM-1 regained stable porosity with significant BET surface area.Fluorescence studies were aimed at applications of PIM-1 and copolymers in sensors. PIM-1 and copolymers, spin-coated on the polyester-based substrate Melinex, were studied with and without methanol treatment in an environment of different solvent vapours. The effect of time and volume on wavelength shift and change in intensity was studied. Polar solvents tended to cause a red shift with decrease in intensity while less polar solvents behaved otherwise. Based on fluorescence experiments, solvent profiles for PIM-1 and copolymers were established.

Les polyesters aliphatiques dégradables tels que la poly(e-caprolactone) (PCL), le poly(glycolide) (PGA) ou le poly(lactide) (PLA) présentent de nombreuses applications dans le domaine biomédical. Lors de leur utilisation comme implant, le contrôle des propriétés de surface des polyesters est d'un intérêt considérable. En effet, les interactions avec le milieu vivant ont lieu aux interfaces. Ce travail de thèse vise donc le développement d'une méthode simple et généralisable de couplage de petites molécules, macromolécules et biomolécules sur des surfaces de PLA, en évitant sa dégradation. Cette méthode est basée sur une stratégie en deux étapes, initialement développée en solution sur la PCL et comprenant une activation anionique dans des conditions spécifiques, suivie de la fonctionnalisation par un groupe propargyle afin d'obtenir une surface de PLA « clickable ». Cette méthodologie a ensuite été utilisée pour synthétiser des surfaces de PLA (bio)actives anti-bactériennes et visibles en IRM. Les stratégies ont été initialement développées et optimisées en milieu homogène avec la PCL. Ensuite, les surfaces de PLA ont été modifiées, en milieu hétérogène, par CUAAC de poly(ammonium quaternaire)s fonctionnalisés azoture et d'un complexe de gadolinium fonctionnalisé azoture. / Biodegradable aliphatic polyesters such as poly(e-caprolactone) (PCL), poly(glycolide) (PGA) or poly(lactide) (PLA) are widely used in biomedical applications. When employed as an implantable material, the control of the surface properties of polyesters is of great interest because biochemical reactions occur on the surface or at interfaces. This work proposes a simple and versatile method to immobilize simple molecules, macromolecules, and biomolecules on PLA surfaces while preventing polymer degradation. The method is based on a one-pot, two-step procedure, first developed in solution with PCL and comprises an anionic activation under selected conditions followed by propargylation to form a ¡°clickable¡± PLA surface. This methodology is then employed to generate bioactive surfaces, namely antibacterial PLA surfaces and MRI-visible PLA surfaces. In a first place, chemical strategies are developed and optimized in homogeneous systems using PCL. Subsequently, PLA surfaces are modified, under heterogeneous conditions, by grafting of well-defined ¦Á-azido-functionalized poly(quaternary ammonium)s and an ¦Á-azido-functionalized complex of gadolinium to the propargylated PLA surface using "click" chemistry.

Orientador: Watson Loh / Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Quimica / Made available in DSpace on 2018-08-07T11:45:40Z (GMT). No. of bitstreams: 1 Anselmo_AleteiaGarcia_M.pdf: 1348079 bytes, checksum: 03480ee468bf0185ae57c464c2020046 (MD5) Previous issue date: 2006 / Resumo: Neste trabalho estudou-se a partição do poli (óxido de propileno), PPO, poli (N - isopropilacrilamida), PNIPAM, poli (N-vinil-2- pirrolidona), PVP, e poli (óxido de etileno), PEO em sistemas líquidos bifásicos, entre as fases aquosa e orgânica (CHCI3, CH2Cl2 e C6H5CI). Os resultados obtidos indicaram que a partição do PPO, polímero hidrofóbico, é preferencial para as fases orgânicas em todos os sistemas bifásicos estudados, enquanto que para os polímeros hidrofílicos, tais como, o PVP e PNIPAM, a partição ocorre preferencialmente para a fase aquosa. As entalpias de transferência, da fase aquosa para a fase orgânica para estes polímeros, foram determinadas através da técnica de titulação calorimétrica isotérmica e revelaram que para todos os sistemas estudados o processo de transferência é endotérmico. Isto sugere que a solvatação dos polímeros pela fase aquosa é mais energética que quando comparada com a solvatação dos polímeros pela fase orgânica, e que, portanto, para o PPO, o processo de transferência é entropicamente dirigido. Spitzer e colaboradores observaram resultados similares para a partição do poli (óxido de etileno), PEO, em sistemas bifásicos contendo CHCl3 e CH2Cl2, (Spitzer et aI.; J. Phys. Chem. B 2002, 106, 12448). Em comparação com o PEO, os valores de entalpia de transferência obtidos para o PPO são mais positivos, o mesmo pode ser observado para o coeficiente de partição. A partição do PPO pode ser explicada em termos de efeito hidrofóbico, o qual propõe a liberação das moléculas de água que estariam solvatando o polímero quando este é transferido para a fase orgânica. / Abstract: In this work the partitioning of poly (propylene oxide), PPO, poly (Nisopropylacrylamide), PNIPAM, poly (vinyl pyrrolidone), PVP and poly (ethylene oxide), PEO between aqueous and organic phases (CHCI3, CH2Cl2 and C6H5CI) was investigated. The results reveal that for all biphasic systems the partitioning of PPO, a hydrophobic polymer, to organic phase is predominant, while for PVP and PNIPAM, hydrophilic polymers, partitioning is always preferential towards the aqueous phase. The enthalpies of transfer for these polymers from aqueous to organic phases were calorimetrically determined and revealed an endothermic process for all the systems investigated, suggesting that solvatation of polymers in aqueous phase is more energetic than organic phase and, therefore, the process of transfer must be entropically driven for PPO. Spitzer and coworkers observed similar results for the partitioning of PEO in biphasic systems containing CHCl3 and CH2Cl2, (Spitzer et aI.; J. Phys. Chem. B 2002, 106, 12448). In comparison with PEO, the enthalpies of transfer of PPO are more positive, the same being observed for the partition coefficients. These data indicate that partitioning of PPO can be explained within the framework of the hydrophobic effect, whereby water molecules that were originally solvating the polymer are released when this is transferred to the organic phase. / Mestrado / Físico-Química / Mestre em Química

Orientadores: Lucia Helena Innocentini Mei, Marcos Akira D'Avila / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Engenharia Química / Made available in DSpace on 2018-08-26T15:02:32Z (GMT). No. of bitstreams: 1 Santos_LarissaGiorgettidos_M.pdf: 23548686 bytes, checksum: e066ca702d1acefc2c3a72890d4456f5 (MD5) Previous issue date: 2014 / Resumo: Biomateriais nanofibrosos, obtidos com polímeros sintéticos biodegradáveis pela técnica de eletrofiação (electrospinning), com ou sem a presença de bioativos, são scaffolds promissores para aplicação na engenharia de tecidos devido a similaridade com matrizes extracelulares (ECM) naturais. O poli (ácido lático) (PLA) é um polímero de grande interesse tecnológico devido às suas propriedades para aplicação nessa área. Sedum dendroideum é um fitoterápico conhecido cientificamente por suas propriedades antiinflamatórias e cicatrizantes, e amplamente utilizado pela medicina popular. Neste trabalho, membranas de PLLA foram obtidas através do processo de eletrofiação, com variação da concentração do polímero (2,5%, 5%, 7,5% 10% e 12,5% m/v) e variação da taxa de vazão da solução no processo (2ml/h, 4ml/h e 6ml/h), buscando uma membrana com um menor diâmetro de fibra. A caracterização da massa molar, da isomeria, dos grupos químicos e do comportamento térmico do PLLA, foram feitas pelas técnicas de cromatografia de permeação (GPC), polarimetria, espectrometria no infravermelho (FT-IR), calorimetria diferencial de varredura (DSC) e Termogravimetria (TGA), respectivamente. O objetivo deste trabalho foi, além de obter membranas nanoestruturadas de PLLA por eletrofiação e caracterizá-la morfologicamente, foi incorporar extrato de S. dendroideum na membrana de menor diâmetro de fibra (7,5%) e investigar sua utilização no processo de cicatrização, com o intuito de otimizar as propriedades in vivo do material. Para tanto, foram realizados testes in vitro para análise do perfil de liberação do fitoterápico, no qual ficou constatado a libração do mesmo, e in vivo para verificar os efeitos da membrana como suporte na regeneração tecidual. Este estudo apresenta a eficácia das membranas de PLLA como suporte para liberação controlada do extrato de S. dendroideum e a sua capacidade em promover o reparo tecidual em lesões excisionais na pele do dorso de ratos Wistar. Os animais foram aleatoriamente divididos em cinco grupos: controle (C), animais tratados com membranas de PLLA (M), animais tratados com o extrato de S. dendroideum dissolvido em solução salina (F), animais tratados com membranas de PLLA com 10% de S . dendroideum (MF10), animais tratados com membranas de PLLA com 25% S. dendroideum (MF25). As amostras de tecidos foram colhidas no 2º, 6º e 10º dia após a cirurgia e foram submetidas a análise estrutural e morfológica. As observações experimentais mostraram a eficácia do fitoterápico incorporado na membrana, que promoveu um aumento significativo do número de células inflamatórias, a porcentagem de fibras colágenas maduras e birrefringentes e na espessura do epitélio em lesões cutâneas excisionais em ratos Wistar. Foi também demonstrado a aplicação das membranas de PLLA, sem o extrato, que promoveram respostas semelhantes no tecido lesionado, comprovando sua eficácia na aplicação como suporte para o crescimento de tecidos / Abstract: Nanofibrosos biomaterials, obtainde with biodegradable synthetic polymers through the electrospinning method, with or without bioactive molecules, are promising scaffolds in tissue engineering because of similarity to extracellular matrix (ECM) natural. Poly (lactic acid) (PLA) is a polymer of great interest due to its technological applications in this area. Sedum dendroideum is a herbal scientifically known for its anti-inflammatory and healing properties, and widely used in folk medicine. In this study, a PLLA membranes were obtained by electrospinning process, varying the polymer concentration (2.5%, 5%, 7.5% and 12.5% 10% w / v) and varying the flow rate solution in the process (2 ml / h, 4 ml / h and 6 ml / h) seeking a membrane with a smaller fiber diameter. The characterization of the molecular weight, of isomerism, chemical groups and the thermal behavior of PLLA were made by techniques permeation chromatography (GPC), polarimetry, infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC) and thermogravimetry (TGA), respectively. The aim of this work was in addition to getting nanostructured membranes of PLLA by electrospinning and morphologically characterize it, was incorporate S. dendroideum extract in the membrane of smaller fiber diameter (7.5%) and investigate their use in the healing process, in order to optimize the in vivo properties of the material. Therefore, in vitro tests were done to analyze the herbal release in which it was found the liberation of the same, and in vivo to check the effects of the membrane as support in tissue regeneration. This study shows the effectiveness of PLLA membranes as support for controlled release of the S. dendroideum extract and its ability to promote tissue repair in skin lesions excised from the back of Wistar rats. The animals were randomly divided into five groups: control (C) animals treated with PLLA membrane (M), animals treated with the extract of S. dendroideum dissolved in saline (F), animals treated with PLLA membranes with 10% S. dendroideum (MF10), animals treated with PLLA membranes with 25% S. dendroideum (MF25). Tissue samples were collected at 2nd, 6th and 10th days after surgery and underwent structural and morphological analysis. Experimental observations have shown the effectiveness of membrane embedded with herbal, which caused a significant increase in the number of inflammatory cells, the percentage of mature collagen fibers and birefringent and the thickness of epithelium in excising skin lesions in rats. It was also demonstrated the application of PLLA membranes without the extract, which promoted similar responses in the injured tissue, proving its effectiveness in application as support for tissue growth / Mestrado / Ciencia e Tecnologia de Materiais / Mestra em Engenharia Química