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Conception d'un dispositif expérimental pour la mise à l'essai in vitro et ex vivo d'un pancréas bioartificielGauvin-Rossignol, Gabrielle 06 March 2024 (has links)
Le diabète de type 1 est un dysfonctionnement du système immunitaire qui provoque l’attaque des cellules insulino-sécrétrices du pancréas. Cette affection du système immunitaire fait l’objet de nombreuses recherches scientifiques en raison de son important impact négatif sur la santé de la population mondiale. Les groupes de recherche des professeurs Bégin-Drolet, Ruel et Hoesli utilisent la technologie d’impression tridimensionnelle d’encres fugitives pour vasculariser des matrices d’hydrogel ensemencées de cellules insulino-sécrétrices. L’encapsulation de ces cellules dans l’hydrogel permet de les isoler du système immunitaire et leur fournit une structure de support semblable à celle de la matrice extracellulaire naturelle. La vascularisation de l’hydrogel par le moulage d’encres sacrificielles est en mesure d’apporter, via la perfusion, les nutriments aux cellules réparties dans le gel. Elle permet aussi de retirer les déchets métaboliques et l’insuline produits par les cellules. Le projet présenté dans ce mémoire consiste en la conception d’un dispositif pour la mise à l’essai de cette approche par des expérimentations ex vivo et in vitro. Le dispositif constitue une preuve de concept quant à l’efficacité de la méthode pour l’obtention d’un pancréas bioartificiel vascularisé et actif. / Type 1 diabetes, an immune system dysfunction that causes the attack of insulin secretory cells, is the subject of many scientific researches because of its significant negative impact on the world’s population health. Bégin- Drolet, Ruel and Hoesli research groups use the 3D printing technology of sugar fugitive ink to build embedded vascular networks in hydrogel scaffolds seeded with insulin secretory cells. Cells encapsulation in hydrogel allows them to be isolated from the immune system and provides a tridimensional support structure that mimic the natural extracellular matrix. Vascular channels resulting from the rapid casting of fugitive inks, allows adequate perfusion of nutrients supply to encapsulated cells, and transportation of metabolic wastes and secreted insulin they produce. The aim of this project, presented in this thesis, consists in designing a device to test this approach by ex vivo and in vitro experiments. The device is the proof of concept that the method of sacrificial ink molding of cell seeded hydrogel scaffolds is effective and promising for the construction of a vascularized bioartificial pancreas.
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Development of Noninvasive Methods for Monitoring Tissue Engineered Constructs using Nuclear Magnetic ResonanceStabler, Cheryl Lynn 12 April 2004 (has links)
Implanted tissue engineered substitutes constitute dynamic systems, with remodeling mediated by both the implanted cells and the host. Thus, there exists a significant need for methods to monitor the function and morphology of tissue engineered constructs. Noninvasive monitoring using 1H Nuclear Magnetic Resonance (NMR) spectroscopy and imaging can prove to be the solution to this problem. Spectroscopy allows for assessment of cellular function through the monitoring of inherent metabolic markers, such as total-choline, while high resolution imaging enables the evaluation of construct morphology and interfacial remodeling. We applied these 1H NMR methods to monitor betaTC3 mouse insulinoma cells within hydrogel-based materials as a model pancreatic tissue substitute. In vitro research established a strong correlation between total-choline, measured by 1H NMR spectroscopy, and viable betaTC3 cell number, measured by MTT. Extending these methods to in vivo monitoring, however, was met with additional challenges. First, the implanted cells needed to be contained within a planar construct above a threshold density to allow for adequate quantification of the total-choline peak. Secondly, cell-free buffer zones between the implanted cells and the host tissue needed to be incorporated to prevent host tissue signal contamination. Finally, quantitative techniques needed to be developed to accurately account for contaminating signal from diffusing molecules. To overcome these challenges, a disk-shaped agarose construct, initially containing a minimum of 4 million betaTC3 cells and coated with an outer layer of pure agarose, was fabricated. Mathematical simulations aided the implant design by characterizing diffusive transport of nutrients and metabolites into and out of the construct. In vivo 1H NMR studies of these constructs implanted in mice established a strong correlation between total-choline, measured noninvasively using 1H NMR spectroscopy, and viable cell number, measured invasively using MTT. This study establishes total-choline as a reliable marker for noninvasively quantifying dynamic changes in viable betaTC3 cell number in vivo. 1H NMR imaging was used to monitor the implants structural integrity over time, while also assessing the hosts fibrotic response. We expect these studies to establish quantitative criteria for the capabilities and limitations of NMR methodologies for monitoring encapsulated insulinomas, as well as other tissue implants.
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Cryopreservation effects on a pancreatic substitute comprised of beta cells or recombinant myoblasts encapsulated in non-adhesive and adhesive alginate hydrogelsAhmad, Hajira Fatima 05 September 2012 (has links)
For clinical translation of a pancreatic substitute, long-term storage is essential, and cryopreservation is a promising means to achieve this goal. The two main cryopreservation methods are conventional freezing and vitrification, or ice-free cryopreservation. However, as both methods have their potential drawbacks for cryopreservation of a pancreatic substitute, they must be systematically evaluated in order to determine the appropriate method of cryopreservation. Furthermore, previous studies have indicated benefits to encapsulation in 3-D adhesive environments for pancreatic substitutes and that adhesion affects cell response to cryopreservation. Thus, the overall goal of this thesis was to investigate cryopreservation effects on model pancreatic substitutes consisting of cells encapsulated in non-adhesive and adhesive 3-D alginate hydrogels. Murine insulinoma betaTC-tet cells encapsulated in unmodified alginate hydrogels were chosen as the model pancreatic substitute in a non-adhesive 3-D environment. Murine myoblast C2C12 cells, stably transfected to secrete insulin, encapsulated in partially oxidized, RGD-modified alginate hydrogels were chosen as the model pancreatic substitute in a 3-D adhesive environment. With respect to cryopreservation effects on intermediary metabolism of betaTC-tet cells encapsulated in unmodified alginate, results indicate that relative carbon flow through the tricarboxylic acid cycle pathways examined is unaffected by cryopreservation. Additionally, insulin secretory function is maintained in Frozen constructs. However, vitrification by a cryopreservation cocktail referred to as DPS causes impairment in insulin secretion from encapsulated betaTC-tet cells, possibly due to a defect in late-stage insulin secretion. Results from Stable C2C12 cells encapsulated in RGD vs. RGE-alginate indicate that up to one day post-warming, cell-matrix interactions do not affect cellular response to cryopreservation after vitrification or freezing. Although there are differences in metabolic activity and insulin secretion immediately post-warming for DPS-vitrified RGD-encapsulated Stable C2C12 cells relative to Fresh controls, metabolic activity and insulin secretion are maintained at all time points assayed for Frozen constructs. Overall, due to results comparable to Fresh controls and simplicity of procedure, conventional freezing is appropriate for cryopreservation of betaTC-tet cells encapsulated in unmodified alginate or Stable C2C12 cells encapsulated in partially oxidized, RGD-modified alginate.
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Production of alginate beads : a project report [i.e. thesis] presented in partial fulfillment of the requirements for the degree of Master in Food Technology at Massey University, Auckland, New Zealand. EMBARGOED until 1 May 2011Ren, Lu Unknown Date (has links)
Content removed from thesis due to copyright restrictions: Winger, R.J. and L. Ren (2009). "Solubility of sodium and potassium iodates in saturated salt solutions." Food Chemistry 113: 600-601. / This paper was to improve the production of calcium-induced alginate gels manufactured by a company in Auckland. Problems encountered included yield and syneresis of the beads post-gelation. Essentially the alginate, sugars and other ingredients were dissolved in water at 80ºC. The pH of the solution was adjusted and the alginate beads were extruded into a 5% CaCl2 bath before being drained and dried. The chemical reaction between sodium alginate and calcium ions is dependent upon the solubility and availability of calcium ions. Some calcium salts (e.g., CaCl2, calcium lactate) were readily soluble and fully dissociated in water and resulted in an immediate gelation of the alginate. Dicalcium phosphate (DCP) was sparingly soluble at pH 7 and calcium ions were not released significantly until the pH reached about pH 4.2. Sodium hexametaphosphate (SHMP) is a chelating agent and this was used to soak up small quantities of Ca+2 to ensure no gelation occured while the alginate was being mixed. The optimum quantities of alginate, DCP and SHMP were defined in the laboratory trials. The use of SHMP, maltodextrin, and gums significantly affected the hardness and stickiness of gel beads. It was found that the combination of xanthan and alginate Protanal LF 120 gave the best results in terms of minimal stickiness and maximum yield after drying. Key words: alginate gel beads, syneresis, formula, pH, citric acid, gelation time, SHMP, setting time, yield rate, drying, hardness, stickiness, maltodextrin, xanthan gum, guar gum, stickiness by touching, leakage, apparent viscosity.
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Produção e caracterização de filmes de poli (3-hidroxibutirato) (PHB) com alginato de sódio esterificado e poli (etileno glicol) (PEG)Lopes, Jamilly Ribeiro 31 October 2016 (has links)
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / Alternative materials have long been studied and developed to replace conventional skin
dressings due to the emergence of new biopolymers and development of new polymeric
film fabrication techniques. As a new material for polymeric dressings, films of poly
(hydroxybutyrate) (PHB) blended with esterified alginate (ALG-e) and Poly
(ethyleneglycol) were studied. The esterification of sodium alginate (ALG-e) generated a
material with some amphiphilic characteristics and increased its compatibility with the
PHB. PEG was added as plasticizer in PHB/ALG-e films, since PEG is often used in
blends with PHB to improve its flexibility and reduce its hydrophobicity. At the amounts
studied, it was found that both PEG and ALG-e increase the degree of crystallinity, but a
decrease in the hydrophobic nature of PHB films was observed. At the maximum
concentration of ALG-e and PEG used an increase in water vapor permeability and a
decrease in tensile strength was reached due to the synergistic effect caused by better
homogenization of PEG and ALG-e in the PHB matrix. / Materiais alternativos têm sido estudados e desenvolvidos para substituir curativos de
pele convencionais devido ao surgimento de novos biopolímeros e o desenvolvimento de
novas técnicas de fabricação de filmes poliméricos. Como um novo material para
curativos poliméricos, filmes de poli (hidroxibutirato) (PHB) misturado com alginato
esterificado (ALG-e) e poli (etilenoglicol) foram estudados. A esterificação de alginato
de sódio (ALG-e) gerou um material com característica anfifílica e com uma
compatibilidade maior com o PHB. PEG foi adicionado como plastificante ao sistema
PHB/ALG-e, uma vez que PEG é muitas vezes utilizado em misturas com PHB para
melhorar a flexibilidade e reduzir a hidrofobicidade. Nas quantidades estudadas,
verificou-se que tanto PEG como ALG-e aumentaram o grau de cristalinidade, o entanto
foi observada uma redução na natureza hidrofóbica dos filmes de PHB. Nos filmes com
concentrações máximas de ALG-e e PEG um aumento na permeabilidade ao vapor de
água e uma diminuição na resistência à tração foram alcançadas devido ao efeito sinérgico
causado por uma melhor homogeneização de PEG e ALG-e na matriz de PHB.
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Produção e caracterização de micropartículas com multicamadas obtidas por gelificação iônica associada à interação eletrostática / Production and characterization of multilayer microparticlesNogueira, Gislaine Ferreira, 1988- 22 August 2018 (has links)
Orientador: Carlos Raimundo Ferreira Grosso / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Engenharia de Alimentos / Made available in DSpace on 2018-08-22T17:05:27Z (GMT). No. of bitstreams: 1
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Previous issue date: 2013 / Resumo: O objetivo deste trabalho foi produzir micropartículas com multicamadas contendo alto teor de proteínas, capazes de serem estáveis a condições adversas do meio e resistentes ao ambiente gástrico. Na primeira parte deste estudo, interações eletrostáticas entre o alginato e proteínas do concentrado proteico do soro do leite (WPC) foram avaliadas em relação às condições de pH (3,5 e 3,75) e proporções de polissacarídeo e proteína. A formação de coacervados com os biopolímeros alginato e WPC foi caracterizada quanto à aparência, tamanho médio e carga superficial. Esta análise permitiu definir as condições em que a interação entre proteínas e partículas de alginato pudesse ocorrer. Assim, micropartículas de alginato produzidas por gelificação iônica foram posteriormente recobertas por interação eletrostática com proteínas, utilizando soluções de diferentes concentrações de concentrado proteico do soro do leite, em dois pHs. Foram testadas três concentrações de proteína em solução para cada pH de recobrimento, sendo 0,6, 3 e 4% para o pH 3,5 e 1,7, 3 e 4% para o pH 3,75. As partículas obtidas foram caracterizadas com relação ao teor total de proteína, conteúdo de umidade, tamanho e morfologia. As maiores adsorções proteicas foram obtidas com a maior concentração de proteína em solução (4%) em ambos pHs. A partir deste estudo preliminar, selecionou-se a amostra de micropartículas com o maior teor de proteína adsorvida para se construir multicamadas em sua superfície através da interação eletrostática. Na segunda parte do estudo, foram produzidas multicamadas de alginato e proteínas do concentrado proteico do soro do leite sobre a superfície da partícula de alginato. Essas partículas foram caracterizadas igualmente as anteriores. A proteína total adsorvida na partícula foi alta, variou de 51,20% a 64,91%, sendo 33,24% dessa proteína encontrada na primeira camada (AlgPart1). Na terceira camada (AlgPart3), também foram encontradas elevados teores proteicos, variando de 17,96% a 31,67%. Uma relação proporcional entre a concentração de alginato e WPC com o aumento da adsorção proteica nesta camada foi observada. A formação das multicamadas (AlgPart1 e AlgPart3) sobre a superfície das partículas provocou uma diminuição significativa no teor de umidade das partículas (AlgPart), ao contrário do que foi observado com o tamanho. Observações realizadas por MEV revelaram que as camadas produzidas com alginato tendem a ter superfícies mais lisas, e com WPC, tendem a ser rugosas. A amostra de micropartículas com multicamadas que apresentou a maior adsorção proteica foi avaliada quanto à estabilidade em temperatura de esterilização (121 ºC, por 15 minutos),pH (2, 4, 6 e 8), concentração de sal (0, 50, 100, 150 e 200 mM) e em condições gastrointestinais (in vitro). Além disso, foram caracterizadas em relação ao tamanho médio, solubilidade proteica e morfologia. Partículas multicamadas úmidas permaneceram íntegras à temperatura de esterilização, apresentaram uma diminuição significativa de tamanho e um acréscimo significativo na solubilidade da camada proteica para o meio em pH 2, e permaneceram estáveis em pHs 4, 6 e 8. A perda de proteína das multicamadas da partícula aumentou significativamente com o aumento da força iônica do meio. As partículas com multicamadas se mostraram parcialmente resistentes às condições gástricas, com uma liberação de 30,5% da proteína presente na partícula e, foram sensíveis à atividade proteolítica em ambiente intestinal simulado promovendo a desintegração das multicamadas e a liberação de praticamente toda proteína da partícula. Considerando os resultados obtidos, conclui-se que é possível a formação de multicamadas de alginato e WPC sobre a superfície de partículas de gelificação iônica com alta adsorção proteica, capazes de serem estáveis em condições adversas do meio e parcialmente resistente às condições gástricas / Abstract: The objective of this work was to produce microparticles with multilayer containing high protein content, capable of being stable to harsh conditions of the environment and resistant to the gastric environment. In the first part of this study, the electrostatic interaction between the alginate and protein of concentrate whey protein (WPC) was evaluated in relation to pH conditions (3.5 and 3.75) and ratio of polysaccharide: protein. The formation of coacervates between the alginate and WPC was characterized as the visual appearance, medium size and surface charge. This analysis allowed us to define the conditions in which the interaction between proteins and alginate particles could occur. Thus alginate microparticles produced by ionic gelation were subsequently coated by electrostatic interaction with proteins, using solutions with different concentrations of whey protein at two pHs. Three concentrations were tested with respect to the protein concentration, being 0.6, 3 and 4% for pH 3.5 and 1.7, 3 and 4% for pH 3.75. The particles were characterized with respect to the total protein content, moisture content, size and morphology. The highest protein adsorption were obtained with the higher concentration of protein solution (4%) by both pH. From this preliminary study, we selected the particle with the highest level of protein adsorbed to construct multilayer using electrostatic interaction on its surface. In the second part of the study, were produced multilayers of alginate and WPC were produced on the surface of the particle of alginate. These particles were characterized in relation to protein adsorption, moisture content, medium size and morphology. The total protein adsorbed on the particle was high, varied from 51.20% to 64.91%, being 33.24% of this protein found in the first layer (AlgPart1). In the third layer (AlgPart3), were also found elevated protein levels, varying from 17.96% to 31.67%. A proportional relationship between the concentration of alginate and WPC with increased protein adsorption was observed in this layer. The formation of multilayers (AlgPart1 and AlgPart3) on the particle surface caused a significant decrease in moisture content of the particles (AlgPart), contrary to what was observed with the size. Observations made by SEM revealed that layers produced with alginate tend to have most smooth surfaces, and WPC tend to be rough. The particle multilayers that presented the highest protein adsorption was evaluated as to the stability at sterilization temperature (121 º C for 15 minutes), pH (2, 4, 6 and 8), salt concentration (0, 50, 100, 150 and 200 mM) and in gastrointestinal conditions. Furthermore were characterized with respect to medium size, protein solubility and morphology. Moist Multilayer particles have remained stable against the temperature of sterilization, showing a significant decrease in size and a significant increase in the solubility of the protein layer into the medium at pH 2, and remain stable at pH 4, 6 and 8. The loss of protein from multilayer particle increased as ionic strength increased. The particles with multilayer were partially resistant to gastric conditions, with a release of 30.49% of the protein in the particle, and were susceptible to proteolytic activity in simulated intestinal environment promoting the particle disintegration and the release of all protein recovering the particles. Considering the results obtained, it is concluded that it is possible the formation of multilayer alginate and WPC on the surface of particles obtained ionic gelation using high protein adsorption, capable of being stable in adverse conditions of the environment (temperature, pH, ionic strength) and resistant to gastric conditions / Mestrado / Consumo e Qualidade de Alimentos / Mestra em Alimentos e Nutrição
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Influencia do conteudo volumetrico das particulas de cargas nas propriedades mecanicas de diferentes materiais de moldagem / Mechanical properties of impression materials by volumetric filler contentCarlo, Hugo Lemes 24 July 2008 (has links)
Orientadores: Mario Alexandre Coelho Sinhoreti, Carlos Jose Soares / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba / Made available in DSpace on 2018-08-11T16:18:48Z (GMT). No. of bitstreams: 1
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Previous issue date: 2008 / Resumo: Baseado no entendimento incompleto de como o conteúdo de partículas de carga influencia nas propriedades mecânicas dos materiais de moldagem este estudo avaliou quantitativa e qualitativamente o conteúdo de partículas de carga inorgânicas presente em cinco marcas comerciais de alginatos (Jeltrate; Jeltrate Plus, Jeltrate Chromatic Ortho, Hydrogum e Ezact Krom) e nove marcas comerciais de siliconas de adição e/ou condensação nas consistências massa e/ou fluida (Clonage, Elite HD+ Light Body, Express Light Body, Flexitime, Optosil P Confort/Xantopren VL Plus, Oranwash L, Reprosil A+, Silon 2 APS e Virtual Extra Light Body). Foram realizados testes para determinar recuperação elástica e deformação sob compressão dos alginatos e dos elastômeros e estabelecer, dessa forma, uma correlação entre os resultados para partículas de carga e os testes mecânicos. O conteúdo volumétrico das partículas de carga foi determinado pesando-se as amostras submersas em água antes e após a queima das mesmas durante 3h a 450°C (alginatos) e a 600°C (siliconas). Quantidades determinadas de materiais não polimerizados foram lavadas em acetona e clorofórmio e recobertas com ouro para avaliação da morfologia e tamanho das partículas em M.E.V. A composição foi determinada por EDX. A recuperação elástica e a deformação sob compressão foram determinadas de acordo as especificações ? 1563 (alginatos) e 4823 (elastômeros) da ISO. O alginatos Jeltrate e Jeltrate Plus apresentaram os maiores valores médios para quantidade volumétrica de partículas de carga (%) enquanto o material Hydrogum apresentou os menores valores. A silicone de adição Flexitime Easy Putty apresentou os maiores valores de quantidade volumétrica de partículas, enquanto que a silicone de condensação Xantopren VL Plus apresentou os menores. As partículas de carga dos alginatos apresentaram-se, de forma geral, como objetos esféricos e com perfurações. O material Hydrogum apresentou forma de bastões cilíndricos e perfurados. As siliconas apresentaram morfologias variadas ¿ partículas trituradas, esféricas, esferóides, bastões cilíndricos perfurados e bastões misturados a partículas
usinadas. O alginato Ezact Krom apresentou os maiores valores médios de tamanho de partícula, enquanto que o alginato Hydrogum as menores. A silicone de condensação Clonage massa apresentou os maiores valores médios de tamanho de partícula, enquanto a silicone de adição Elite HD os menores. A análise da composição das partículas apresentou o silício como o elemento em maior quantidade. Com relação aos resultados de recuperação elástica, o alginato Ezact Krom e as siliconas Reprosil A+ massa e Flexitime fluida apresentaram os maiores valores de recuperação elástica, enquanto o alginato Jeltrate Plus e as siliconas Optosil P Confort e Clonage fluida apresentaram os menores. Os resultados de deformação sob compressão foram maiores para o alginato Jeltrate
Plus e para as siliconas Silon 2 APS massa e fluida. Os menores resultados foram apresentados pelo alginato Ezact Krom e as siliconas Reprosil A+ massa e Xantopren VL Plus. Todos os materiais estão em conformidade com a norma ISO ?1563, mas nem todos estão em relação à norma ?4823 / Abstract: Based on the incomplete understanding on how filler features influence the properties of elastomeric impression materials, the purpose of this study was to determine the inorganic filler fraction and size of five commercially available alginates (Jeltrate; Jeltrate Plus, Jeltrate Chromatic Ortho, Hydrogum e Ezact Krom) and nine addition/condensation silicones using the putty/light consistence (Clonage, Elite HD+ Light Body, Express Light Body, Flexitime, Optosil P Confort/Xantopren VL Plus, Oranwash L, Reprosil A+, Silon 2 APS e Virtual Extra Light Body). A SEM/EDX analysis was done to qualitatively characterize the materials. Soon afterwards elastic recovery and strain in compression of the alginates and some the silicones was carried. The inorganic particles volumetric fractions were accessed by weighing a previously determined mass of each material in water before and after burning samples for 3 hours at 450ºC (alginates) and 600ºC (silicones). Unsettled materials were soaked in acetone and chloroform and sputter-coated with gold for SEM evaluation of fillers¿ morphology and size. The filler composition was determined by EDX. Elastic recovery and strain in compression tests were conducted according to ISO specification number 1563 and 4823. Jeltrate and Jeltrate Plus presented the highest mean values of percentage content of inorganic particles in volume, while Jeltrate Chromatic Ortho presented the lowest values. Flexitime Easy Putty was the silicone with the highest mean value, while Xantopren VL Plus had the lowest value. The alginate fillers presented a circular appearance with helical form and various perforations. Hydrogum fillers looked like cylindrical, perforated sticks. SEM pictures of the silicone inorganic particles showed numerous morphologies ¿ lathe-cut, spherical, spherical-like, sticks, and sticks mixed to lathe-cut powder. Ezact Krom was the alginate with the highest values for diameter size, while Hydrogum had the lowest. Clonage Putty showed the highest values, while Elite HD+ Light Body presented the lowest
values. The component in higher concentration in the materials is silicon. The alginate Ezact Krom, and the addition cure silicones Reprosil A+ putty and Flexitime Correct Flow had the highest mean values of elastic recovery, while the alginate Jeltrate Plus and the condensation cured silicones Optosil P Confort and Clonage Putty presented the lowest values. Strain in compression test showed the alginate Jeltrate Plus and the condensation cured silicones Silon 2APS Putty and Fluid as the materials with the highest values. The alginate Ezact Krom and the silicones Reprosil A+ Putty and Xantopren VL Plus had lowest values. All materials are in conformity with the requirements of ISO specification number 1563, but not all materials are in conformity with the requirements of ISO specification number 4823 / Doutorado / Materiais Dentarios / Doutor em Materiais Dentários
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Alginate : a versatile biopolymer for functional advanced materials / Alginate : un biopolymère polyvalent pour des matériaux fonctionnels avancésPettignano, Asja 19 September 2016 (has links)
Les alginates, des polysaccharides produits par les algues brunes, sont des copolymères à blocs linéaires, formés d’unités mannuronate (M) et guluronate (G). En raison de leur abondance naturelle, prix et propriétés physicochimiques avantageuses, les alginates représentent une classe de biopolymères très intéressante et relativement inexplorée pour des applications dans le domaine des matériaux avancés. Dans ce contexte, le présent travail vise à enrichir la gamme des applications des matériaux dérivés d’alginates, en exploitant les propriétés de cette classe de polysaccharides naturels. En particulier, la préparation de matériaux à base d'alginate pour la catalyse, l'adsorption et le domaine biomédical a été étudiée, avec des résultats encourageants dans toutes les applications testées. L'utilisation bénéfique de l'acide alginique en catalyse hétérogène a été démontrée, en tant que promoteur de réaction et support pour l’hétérogénéisation d'un organocatalyseur. L'activité du catalyseur a été trouvée très dépendante de l'accessibilité des groupes fonctionnels, mettant en évidence l’avantage de l’emploi de formulations plus accessibles. La texturation des alginates a été aussi avantageuse dans la préparation de matériaux pour applications en flux. Des mousses d'acide alginique, avec une structure hiérarchique macro-mésoporeuse, ont été développées à cet effet. Une caractérisation précise des matériaux a été réalisée, afin d'optimiser la procédure de préparation et de corréler les propriétés texturales obtenues avec les paramètres utilisés. L'intérêt dans l’utilisation de mousses à base d'acide alginique a été démontré dans une application modèle, l'adsorption de bleu de méthylène à partir de solutions aqueuses, à la fois en batch et en flux. La possibilité de modifier facilement les groupes fonctionnels de l’alginate, couplée avec la nature biocompatible et biodégradable de ces biopolymères, a finalement été exploitée pour le développement de gels auto-réparants, obtenus grâce à la formation de deux types d'interactions covalentes dynamiques : base de Schiff et ester de boronate. Les deux systèmes examinés ont présenté une remarquable habilité à se reconstruire après un dégât, même si l'ampleur de la reconstruction et la stabilité des gels étaient fortement dépendantes des paramètres de préparation des gels et des conditions environnementales utilisées. Les résultats obtenus dans le cadre de cette étude démontrent clairement comment la compréhension et un emploi conscient des propriétés physico-chimiques des alginates peuvent maximiser le potentiel que cette ressource durable dans le domaine de la chimie des matériaux. / Alginates, polysaccharides produced by brown algae, are linear block-copolymers formed by mannuronate (M) and guluronate (G) units. Because of their huge natural abundance, cheapness and physicochemical properties, alginates represent a highly attractive and still relatively unexplored class of biopolymers for applications in the field of advanced materials. In this context, the present work aimed to enrich the range of possible applications of alginate-derived materials, making the most of the peculiar features of this class of natural polysaccharides. In particular, the preparation of alginate-based active materials to be employed in the catalysis, adsorption and biomedical field was studied, achieving encouraging results in all the tested applications. The beneficial use of alginic acid in heterogeneous catalysis, both as reaction promoter and as support for the heterogeneization of an organocatalyst, was demonstrated. The activity of the material was found highly dependent on the accessibility of the active functions, highlighting the advantage of employing more accessible alginate formulations. The texturation of alginates was further advantageous for the preparation of materials with improved flowability. Alginic acid foams, bearing a hierarchical macro-mesoporous structure were developed by means of a simple procedure. Accurate characterization was performed to optimize the preparation procedure and to correlate the textural properties of the obtained materials with the parameters used. The interest of the prepared alginic acid foams was demonstrated in a model application, the adsorption of methylene blue from aqueous solutions, both in batch and in flow conditions. The possibility to easily modify alginate functional groups, coupled with the biocompatible and biodegradable nature of alginates, was finally employed for the development of self-healing gels, thanks to the formation of two types of dynamic covalent interactions: Schiff base and boronate ester bonds. Both the examined systems presented a marked ability to recover after damage, even if the extent of the recovery and the stability of the gels was highly dependent on the preparation parameters and environmental conditions used. The results obtained in the course of this study clearly demonstrate how a full comprehension and conscious employment of alginate physicochemical properties can maximize the potential of this sustainable resource in the field of material chemistry.
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Uticaj farmaceutsko-tehnološke formulacije u obliku mikrovezikula sa alginatom na resorpciju gliklazida iz digestivnog trakta pacova / The effect of alginate microcapsules pharmaceutical formulation on gliclazide absorption in rat gastrointestinal tractĆalasan Jelena 24 April 2019 (has links)
<p>Gliklazid je jedan od najčešće korišćenih lekova u terapiji dijabetes melitusa tip 2. U poslednje vreme, utvrđeno je da gliklazid ispoljava i druge pozitivne farmakološke efekte kao što su imunomodulatorni i anti-koagulacioni efekti, ukazujući na njegovu potencijalnu primenu u terapiji dijabetes melitusa tip 1. Gliklazid se odlikuje varijabilnim stepenom apsorpcije nakon peroralne primene i iz tog razloga pretpostavlja se da bi tehnike njegove ciljane isporuke, kao što je mikroinkapsulacija, mogle da dovedu do poboljšanja njegove apsorpcije i njegove potencijalne primene u terapiji T1DM. Pokazano je da različite žučne kiseline, uključujući i holnu, imaju stabilizacione efekte u domenu primene mikrovezikula i kontrolisanog osobađanja lekova, te je moguće da bi njihov dodatak u mikrovezikularnu formulaciju gliklazida mogao dodatno da poboljša oslobađanje gliklazida, njegovu apsorpciju i antidijabetičke efekte. S tim u vezi, cilj ovog istraživanja je da se ispita hipoglikemijski efekat gliklazida primenjenog u obliku alginatnih mikrovezikula, sa ili bez dodatka holne kiseline na T1DM modelu pacova. Trideset šest pacova obolelih od T1DM indukovanog aloksanom i odgovarajuće zdrave kontrolne životinje su nasumično raspoređene u šest grupa (n=6) i tretirane jednokratnom dozom fiziološkog rastvora, suspenzijom gliklazida, gliklazidom u obliku alginatnih mikrovezikula, samo holnom kiselinom, i mikrovezikulama gliklazida sa ili baz dodatka holne kiseline. Uzorkovana je krv tokom 10 h nakon unete doze i merena je koncentracija glukoze u krvi I koncentracija gliklazida u serumu korišćenjem HPLC metode. Mikrovezikule gliklazida su ispoljile hipo-glikemijski efekat kod pacova obolelih od dijabetesa, uprkos njegovim smanjenim koncentracijama u serumu, dok je dodatak holne kiseline u mikrovezikularnu formulaciju smanjio hipoglikemijski efekat gliklazida. Ovo potvrđuje izostanak sinergističkog efekta između gliklazida i holne kiseline. Takođe, ni proces mikroinkapsulacije niti dodatak holne kiseline nisu doprineli poboljšanju apsorpcije gliklazida, što ukazuje na činjenicu da su njegovi hipoglikemijski efekti nezavisni od njegove apsorpcije i koncentracije u serumu. Stoga se može pretpostaviti da su hipoglikemijski efekti gliklazida pre pod uticajem crevno-metaboličke aktivacije nego ciljanog oslobađanja u digestivnom traktu sistemske apsorpcije. Mikrovezikule gliklazida ispoljavaju hipoglikemijski efekat kod pacova obolelih od T1DM nezavisno od insulina, te mogu imati potencijalnu primenu u terapiji T1DM. Ovaj rad su podržali: HORIZON 2020 MEDLEM projekat broj 690876; Projekat Sekretarijata naučnog i tehnološkog razvoja Vojvodine broj . 114-451-2072-/2016-02; Projekat Ministarstva obrazovanja, nauke i tehnološkog razvoja Republike Srbije broja 41012.</p> / <p><!--[if gte mso 9]><xml> <o:DocumentProperties> <o:Author>mladen</o:Author> <o:Version>16.00</o:Version> </o:DocumentProperties> <o:OfficeDocumentSettings> <o:AllowPNG/> </o:OfficeDocumentSettings></xml><![endif]--><!--[if gte mso 9]><xml> <w:WordDocument> <w:View>Normal</w:View> <w:Zoom>0</w:Zoom> <w:TrackMoves/> <w:TrackFormatting/> <w:PunctuationKerning/> <w:ValidateAgainstSchemas/> <w:SaveIfXMLInvalid>false</w:SaveIfXMLInvalid> <w:IgnoreMixedContent>false</w:IgnoreMixedContent> <w:AlwaysShowPlaceholderText>false</w:AlwaysShowPlaceholderText> <w:DoNotPromoteQF/> <w:LidThemeOther>EN-US</w:LidThemeOther> <w:LidThemeAsian>X-NONE</w:LidThemeAsian> <w:LidThemeComplexScript>X-NONE</w:LidThemeComplexScript> <w:Compatibility> 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Locked="false" Priority="71" Name="Colorful Shading Accent 2"/> <w:LsdException Locked="false" Priority="72" Name="Colorful List Accent 2"/> <w:LsdException Locked="false" Priority="73" Name="Colorful Grid Accent 2"/> <w:LsdException Locked="false" Priority="60" Name="Light Shading Accent 3"/> <w:LsdException Locked="false" Priority="61" Name="Light List Accent 3"/> <w:LsdException Locked="false" Priority="62" Name="Light Grid Accent 3"/> <w:LsdException Locked="false" Priority="63" Name="Medium Shading 1 Accent 3"/> <w:LsdException Locked="false" Priority="64" Name="Medium Shading 2 Accent 3"/> <w:LsdException Locked="false" Priority="65" Name="Medium List 1 Accent 3"/> <w:LsdException Locked="false" Priority="66" Name="Medium List 2 Accent 3"/> <w:LsdException Locked="false" Priority="67" Name="Medium Grid 1 Accent 3"/> <w:LsdException Locked="false" Priority="68" Name="Medium Grid 2 Accent 3"/> <w:LsdException Locked="false" Priority="69" Name="Medium Grid 3 Accent 3"/> <w:LsdException Locked="false" Priority="70" Name="Dark List Accent 3"/> <w:LsdException Locked="false" Priority="71" Name="Colorful Shading Accent 3"/> <w:LsdException Locked="false" Priority="72" Name="Colorful List Accent 3"/> <w:LsdException Locked="false" Priority="73" Name="Colorful Grid Accent 3"/> <w:LsdException Locked="false" Priority="60" Name="Light Shading Accent 4"/> <w:LsdException Locked="false" Priority="61" Name="Light List Accent 4"/> <w:LsdException Locked="false" Priority="62" Name="Light Grid Accent 4"/> <w:LsdException Locked="false" Priority="63" Name="Medium Shading 1 Accent 4"/> <w:LsdException Locked="false" Priority="64" Name="Medium Shading 2 Accent 4"/> <w:LsdException Locked="false" Priority="65" Name="Medium List 1 Accent 4"/> <w:LsdException Locked="false" Priority="66" Name="Medium List 2 Accent 4"/>
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