Šio magistro darbo tikslas – verslo procesų modelius, specifikuotus grafine BPMN (Business Process Modelling Notation) notacija, transformuoti į formalius PLA (Piece-Linear Aggregates) modelius, naudojantis sudarytomis transformavimo taisyklėmis ir pasirinktomis technologijomis. Darbe apibendrinti modelių transformacijų ir verslo procesų modeliavimo sričių pagrindiniai teoriniai principai; suformuluotos BPMN notacija aprašytų verslo procesų modelių transformavimo į PLA modelius priežastys; sudaryti realios leidyklos verslo procesų modeliai, naudojant BPMN ir PLA specifikacijas; naudojantis sudarytais modeliais ir abiejų specifikacijų metamodeliais, sudaryta BPMN ir PLA elementų atitikmenų aibė; suformuluotos pagrindinės transformavimo taisyklės; naudojantis šiomis taisyklėmis ir XML bei STX technologine erdve, programiškai realizuotas BPMN modelių transformavimas į PLA modelius. Pasiektas rezultatas: realizuotas pagrindinių BPMN konstrukcijų automatinis transformavimas į PLA konstrukcijas, naudojant tarpinio atvaizdavimo transformavimo metodą, t. y. modelius atvaizduojant tarpiniu XML formatu ir atliekant XML dokumentų transformacijas. Transformavimo rezultatas – PLA modelis XML formatu. / The main purpose of this work is to transform business process models specified in graphical BPMN (Business Process Modelling Notation) notation into PLA (Piece-Linear Aggregates) models, using stated transformation rules and selected technologies. There are summarized main principles of models transformations and business process modeling domains; reasons of transformation of business process models specified in BPMN to PLA models are stated; designed the business process models of real publishing house using BPMN and PLA; using these models and metamodels of both specifications the set of equivalents of elements was made; main rules of transformation are stated. Using these rules and XML and STX technologies the transformation of BPMN models to PLA models is implemented. Result: using method if intermediate representation, the automated transformation of main BPMN constructs to PLA was made. The resulta of this transformation – PLA model in XML.

L’ingénierie tissulaire est une méthode de reconstruction d’organes et de tissus vivants. Elle consiste à ensemencer et faire coloniser un implant spécifique appelé scaffold par des cellules. Ce scaffold est un matériau architecturé doté d’une géométrie adaptée à l’organe à reconstruire. Sa fonction est de servir de guide et de support de régénération au tissu. Afin d’éviter les conséquences à long terme de la présence d’un implant synthétique dans l’organisme (risque de rejet, inflammation ...) l’idéal est d’utiliser un matériau biorésorbable qui, se dégradant au fur et à mesure de la reconstruction, laisse place aux néo-tissus formés. Les polymères biorésorbables sont, grâce à la vaste gamme de propriétés qu’ils proposent, les meilleurs candidats pour ce genre d’applications. Un polymère biorésorbable particulièrement intéressant est le PLA-b-PEG-b-PLA. En effet, celui-ci est biocompatible et possède, par sa structure tribloc, une potentielle vaste gamme de propriétés physiques et mécaniques. La réussite de la reconstruction tissulaire nécessite une parfaite connaissance du comportement mécanique du matériau constituant le scaffold ainsi que son évolution au cours de la dégradation.L’objectif de cette thèse est la caractérisation expérimentale et la modélisation du comportement mécanique des polymères PLA-b-PEG-b-PLA au cours de leur dégradation. L’intérêt est de fournir des outils de dimensionnement de scaffolds biorésorbables pour l’ingénierie tissulaire. Dans un premier temps, des essais de traction-relaxation ont été conduits sur un PLA-b-PEG-b-PLA à différents temps de dégradation. Afin de réaliser ces essais dans des conditions proches de celles rencontrées in vivo, un dispositif expérimental permettant d’accomplir des essais mécaniques en milieu immergé à une température de 37°C a été mis au point. A partir de ces essais, un modèle viscoélastique linéaire capable de prendre en compte la variation des propriétés mécaniques au cours de la dégradation pour de faibles déformations a été réalisé. Dans un second temps, afin de modéliser le comportement mécanique dans une gamme plus large de déformations, un modèle viscoélastique non-linéaire a été développé. Il s’agit d’un modèle quasi-linéaire viscoélastique adaptatif capable de prédire les courbes de traction-relaxation à différents niveaux de déformation ainsi que la perte de propriétés mécaniques au cours de la dégradation. Lors de la troisième partie, des PLA-b-PEG-b-PLA de compositions et masses molaires différentes ont été caractérisés afin d’étudier l’influence de la structure originelle du polymère sur leurs propriétés mécaniques et leur évolution au cours de la dégradation. La capacité du modèle viscoélastique linéaire précédemment développé à prédire le comportement des différents polymères a alors été discutée. Dans une dernière partie, le modèle viscoélastique linéaire dégradable a été utilisé pour simuler numériquement le comportement mécanique d’un tricot potentiellement utilisable en ingénierie tissulaire. / Tissue engineering is an interdisciplinary field that applies the principles of engineering and biological science toward the development of biological substitutes that restore, maintain or improve the development of a whole organ by tissue reconstruction. It consists in seeding an implant called scaffold with cells taken from the patient and cultivated in vitro. The cells will then colonize and recreate tissue that takes the shape of the scaffold. The scaffold is an architecture biomaterial specifically designed for a considered organ. The knowledge of mechanical properties of the scaffold is particularly important. Indeed, it often must be used as a mechanical substitute to the injured organ. Moreover, its mechanical properties must be compatible with those of the host tissue to allow a good tissue regeneration. The main advantage of using biodegradable materials is their degradation along the regeneration process. It means that the material no longer remains in the body at long term avoiding toxicity and inflammation risks. Among biodegradable materials, polymers are particularly interesting due to their large range of properties. A very good candidate for tissue engineering applications is the PLA-b-PEG-b-PLA biodegradable triblock copolymer. This polymer is biocompatible and possesses a good properties modulation. To allow a good tissue reconstruction, the knowledge of the mechanical properties of the scaffold as well as their evolution during degradation is essential.The aim of this work is to characterize experimentally and model the mechanical behavior of the PLA-b-PEG-b-PLA and its evolution during degradation. The interest is to provide tools to size and simulate biodegradable scaffolds for tissue engineering applications. At first, tensile-relaxation tests has been realized on the polymer during different degradation times. In order to realize the mechanical tests in conditions closed to in vivo ones, a specific experimental device has been designed that allows From this tests, a linear viscoelastic model able to take into account the variations of mechanical properties during degradation for small strain has been developed. Then, in order to model the mechanical behavior in a larger range of strain, a non-linear viscoelastic model was realized. In a third part, different polymers PLA-b-PEG-b-PLA with different initial composition has been mechanically characterized in order to study the influence of the original structure on mechanical properties and their evolution during degradation. To finish, the degradable linear viscoelastic model will be used to simulate numerically the mechanical behavior of a knitted textile for potential applications in tissue engineering.

Made available in DSpace on 2014-06-11T19:32:09Z (GMT). No. of bitstreams: 0 Previous issue date: 2007-04-04Bitstream added on 2014-06-13T20:23:05Z : No. of bitstreams: 1 mainardes_rm_dr_arafcf.pdf: 1864850 bytes, checksum: f49ab7e28e985faad2f32205305f0de3 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / Universidade Estadual Paulista (UNESP) / A zidovudina (AZT) é um fármaco amplamente usado no tratamento da síndrome da imunodeficiência adquirida. O AZT apresenta baixa biodisponibilidade oral pois sofre rápido e extenso metabolismo de primeira passagem hepática, além de curto t1/2. Sendo assim, altas e freqüentes doses são requeridas para se manter concentrações plasmáticas efetivas e, dessa maneira, apresenta graves efeitos colaterais, dose-dependentes, que limitam o seu uso em determinados tipos de pacientes. As nanopartículas são eficientes sistemas poliméricos que contribuem para a redução da toxicidade de fármacos, pois são capazes de liberá-los de maneira prolongada, proporcionando maior tempo de contato do fármaco com o plasma e tecidos. A via de administração intranasal é uma rota interessante, quando se deseja evitar o metabolismo de primeira passagem e, também, pode oferecer um ótimo perfil de absorção para nanopartículas. Neste trabalho, estudouse a incorporação de AZT em nanopartículas de PLA e de blendas de PLA-PEG com diferentes razões molares. A caracterização físico-química demonstrou que a presença do PEG influenciou a forma, o diâmetro médio, a eficiência de encapsulação, assim como o potencial de superfície das partículas. O diâmetro médio e a eficiência de encapsulação das nanopartículas aumentaram com o aumento crescente da razão molar de PEG na blenda. A forma geral e a apresentação das partículas variaram em função da concentração de PEG, sendo que os melhores resultados foram obtidos com as menores razões molares deste na blenda. Os experimentos de liberação in vitro mostraram que a liberação do AZT a partir das nanopartículas foi mais lenta em relação ao AZT em solução. A presença do PEG nas nanopartículas alterou o perfil de liberação do AZT, tornando... / Zidovudine (AZT) is a drug widely used in the treatment of acquired immunodeficiency syndrome. AZT shows low bioavailability because it suffers fast and extensive by pass hepatic metabolism, besides of low t1/2. High and frequent doses are requested to achieve effective plasmatic concentrations, and thus, it shows serious and dosedependents side effects that limit its use in certain kind of patients. Nanoparticles are efficient polymeric systems that contributes to reduce the drug toxicity, because maintain prolonged drug release, making longer the contact between drug and plasma/tissues. The intranasal way is a very interesting route to avoid the by pass metabolism, and also offers a great absorption profile to nanoparticles. In the present work, the AZT encapsulation in PLA e PLA-PEG blends nanoparticles was studied. The physico-chemical characterization showed that the presence of PEG influences the nanoparticles shape, mean diameter, encapsulation efficiency and superficial charge. The mean diameter and encapsulation efficiency increase with increasing PEG proportion in the blend. The nanoparticles shape varied in function of PEG concentration, the better results being obtained with the lowest PEG concentration. In vitro experiments showed that AZT release from nanoparticles was slower than that of AZT solution. The presence of PEG in nanoparticles altered the AZT release profile, making it faster than that from PLA nanoparticles. The ex vivo phagocytosis experiments demonstrated that PLA-PEG blends nanoparticles were more efficient in avoiding the activation of phagocytic cells. The intranasal bioavailability in rats shows that blend PLA-PEG nanoparticles demonstrated longer plasmatic circulating times than that those make of PLA alone. These results demonstrate that PLA and PLA-PEG blends nanoparticles can be used as an efficient intranasal drug delivery system.

Submitted by Luiza Santos (lukgsantos@gmail.com) on 2018-09-17T21:17:37Z No. of bitstreams: 2 Luiza Gouvêa Santos - Dissertação.pdf: 10565562 bytes, checksum: 13492cd06232cc330f2ba1e52264b916 (MD5) BCO carta comprovante autoarquivamento.pdf: 568109 bytes, checksum: a2c43c4628375f2a395644298e50473d (MD5) / Approved for entry into archive by Eunice Nunes (eunicenunes6@gmail.com) on 2018-09-17T23:25:23Z (GMT) No. of bitstreams: 2 Luiza Gouvêa Santos - Dissertação.pdf: 10565562 bytes, checksum: 13492cd06232cc330f2ba1e52264b916 (MD5) BCO carta comprovante autoarquivamento.pdf: 568109 bytes, checksum: a2c43c4628375f2a395644298e50473d (MD5) / Approved for entry into archive by Eunice Nunes (eunicenunes6@gmail.com) on 2018-09-17T23:33:12Z (GMT) No. of bitstreams: 2 Luiza Gouvêa Santos - Dissertação.pdf: 10565562 bytes, checksum: 13492cd06232cc330f2ba1e52264b916 (MD5) BCO carta comprovante autoarquivamento.pdf: 568109 bytes, checksum: a2c43c4628375f2a395644298e50473d (MD5) / Made available in DSpace on 2018-09-17T23:33:27Z (GMT). No. of bitstreams: 2 Luiza Gouvêa Santos - Dissertação.pdf: 10565562 bytes, checksum: 13492cd06232cc330f2ba1e52264b916 (MD5) BCO carta comprovante autoarquivamento.pdf: 568109 bytes, checksum: a2c43c4628375f2a395644298e50473d (MD5) Previous issue date: 2018-07-20 / Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) / Poly (lactic acid) (PLA) is a non-toxic, transparent and biodegradable aliphatic polyester, produced from renewable raw materials. This polymer meets several requirements for packaging applications, but is fragile and has lower gas and water vapor barrier properties, compared to polymers currently used in this application. The formation of PLA blends with poly (ethylene-co-vinyl alcohol) (EVOH), which has transparency and good gas barrier properties, is an advantageous alternative to modify this biodegradable polymer, in order to obtain better mechanical and barrier properties without loss of transparency. This research objective was to develop biodegradable PLA/EVOH nanoblends, for packaging application, through reactive extrusion followed by the production of films. EVOH was added in 3, 5 and 10 wt%. Two compatibilization systems, containing epoxy as the reactive group, and a catalyst of the reaction between epoxy and hydroxyl, were used for interfacial modification. The influence of the dispersed phase content, the use of different compatibilizers and the presence of the catalyst in the thermal, mechanical, rheological, optical and barrier properties, as well as the the morphology of the blends, were analyzed. It was possible to observe a reduction in the diameter of the dispersed EVOH particles in the PLA matrix through reactive extrusion and addition of compatibilizing systems. The reduction was even more significant with the use of the catalyst, reaching values very close to the nanometric scale, but resulted in the degradation of the PLA matrix. The blends compatibilized with GMA and peroxide presented the best mechanical performance, however still very close to the PLA matrix. The barrier properties of all blends were higher than those of PLA. The blends showed transparency when the film is positioned close to the object, thus presenting sufficient optical property for packaging application. / O poli (ácido láctico) (PLA) é um poliéster alifático, atóxico, transparente e biodegradável, produzido a partir de matérias-primas renováveis. Este polímero atende a vários requisitos para aplicação em embalagens, porém é frágil e apresenta propriedades menores de barreira a gases e ao vapor de água, em comparação a polímeros utilizados atualmente nesta aplicação. A formação de blendas de PLA com o poli (etileno-co-álcool vinílico) (EVOH), que possui transparência e boas propriedades de barreira a gases, apresenta-se como uma alternativa vantajosa para modificar esse polímero, a fim de se obter melhores propriedades mecânicas e de barreira, sem a perda da transparência. Esta pesquisa teve como objetivo o desenvolvimento de nanoblendas PLA/EVOH biodegradáveis para aplicação em embalagens por meio de extrusão reativa seguida da produção de filmes. O EVOH foi adicionado em 3, 5 e 10% em massa. Dois sistemas de compatibilização, contendo o grupo reativo epóxi, além de um catalisador da reação entre o epóxi e a hidroxila, foram utilizados para modificação interfacial. A influência do teor da fase dispersa, do uso dos diferentes compatibilizantes e da presença do catalisador nas propriedades térmicas, mecânicas, reológicas, ópticas e de barreira, assim como na morfologia das blendas, foi analisada. Foi possível observar redução no diâmetro das partículas dispersas de EVOH na matriz de PLA, através de extrusão reativa e adição dos sistemas compatibilizantes. A redução foi ainda mais significativa com o uso do catalisador ZnSt2, atingindo valores muito próximos à escala nanométrica, porém resultou na degradação da matriz PLA. As blendas compatibilizadas com GMA e peróxido apresentaram o melhor desempenho mecânico, entretanto ainda muito próximo ao da matriz PLA. As propriedades de barreira de todas as blendas foram superiores à do PLA. As blendas apresentaram transparência quando o filme é posicionado próximo ao objeto, apresentando assim propriedade óptica suficiente para aplicação em embalagens. / CNPq: 134655/2016-8

Made available in DSpace on 2015-05-14T13:00:14Z (GMT). No. of bitstreams: 1 arquivototal.pdf: 1937147 bytes, checksum: c7c7a7218440d8aec73885dba794fe24 (MD5) Previous issue date: 2010-08-31 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / The anatomy and physiology of the eye, together with its protective barriers represent challenges to effective ocular drug delivery systems. The pharmacological treatment of eye diseases had been limited to conventional drug formulations, which are not satisfactory for diseases affecting the posterior segment of the eye. The delivery of therapeutic doses at tissues from the posterior segment in order to minimize adverse systemic and regional effects is the main goal in the treatment of ocular diseases. With this aim, several studies have been conducted to develop new ocular drug delivery systems, such as those involving ocular implants. These implants are prepared using a variety of different polymers that can be either biodegradable or non-biodegradable. Polymers derived from lactic and glycolic acid have revealed to be promising materials for the formulation of ocular implants, mainly due to their biocompatibility and biodegradability. In this study, two different biodegradable indomethacin implants formulated based on a copolymer of lactic/glicolic acid (PLGA 50:50) and D,L-lactic acid (D,L-PLA) were characterized by differential scanning calorimetry (DSC), in vitro release using dissolution apparatus and scleral diffusion (from rabit´s eye) using Franz chambers. The study was done in collaboration with 3T Biopolymers (São Paulo, Brazil) that provided samples of the polymers and implants for analyses. The results of the validation of the HPLC method for indomethacin quantification were within the limits set forth by Brazilian legislation (RE 899, 2003, ANVISA). The results of DSC analysis revealed absence of any evidence of physico-chemical interactions between the drug and polymer. The suppression of the indomethacin melting peak is probably due to changes from the crystalline to the amorphous state of the drug following lyophilization or by dilution effects. Preliminary in vitro release data revealed a triphasic profile for indomethacin release from the PLGA-based implants and a biphasic one for the PLA implants. The implants formulated with PLGA promoted a faster release of indomethacin (103.64%) compared with implants formulated with PLA (49.9%) during the thirty days of the experiment. The release profile of indomethacin was determined by the rate of degradation of polymers, which also determined the scleral diffusion of indomethacin from PLGA and PLA (1.7 x 10-5 cm / s and 0.24 x 10-5 cm / s, respectively). The scleral diffusion experiments using Franz difusion chambers have shown that the rabit sclera is permeable to indomethacin and polarized light microscopy revealed that the structure of the scleral collagen fibers were not significantly altered during the diffusion experiments. The drug-release systems studied were able to release indomethacin in a sustained fashion, serving as a model for the formulation of indomethacin implants that could be used in the future for the treatment of ocular diseases such as the cystoid macular edema. / A anatomia e fisiologia do olho e suas barreiras protetoras representam um desafio para o desenvolvimento de sistemas de transporte de drogas oftálmicas efetivos. O tratamento farmacológico de doenças oculares tem se limitado às formas convencionais de administração que não são satisfatórias para o tratamento de doenças que acometem o segmento posterior do bulbo do olho. O transporte de doses terapêuticas para os tecidos do segmento posterior do olho, que minimize os efeitos colaterais sistêmicos e locais, é o principal objetivo no tratamento de doenças oculares. Visando atingir este objetivo, estudos têm sido feitos no sentido de desenvolver novos sistemas de liberação de fármacos para o olho, entre estes estão os implantes. Esses implantes são preparados a partir de diferentes polímeros, os quais podem ser biodegradáveis ou não biodegradáveis. Os polímeros derivados dos ácidos lático e glicólico têm se revelado bastante promissores devido, principalmente, às suas características de biocompatibilidade e biodegradabilidade. Neste trabalho, dois diferentes implantes de indometacina formulados a partir do copolímero ácido lático / ácido glicólico (PLGA 50:50) e do polímero derivado do ácido D,L-lático (PLA), através de liofilização da mistura polímero-fármaco, foram fornecidos pela empresa 3T Biopolímeros (São Paulo - SP) e avaliados através de DSC, estudos de liberação in vitro usando aparato de dissolução e estudos de difusão através de esclera de coelho utilizando câmaras de Franz. Os resultados da validação do método CLAE para quantificação da indometacina apresentaram-se dentro dos limites estabelecidos pela legislação brasileira (Resolução RE 899, 2003, ANVISA). As análises de DSC mostraram a ausência aparente de interações químicas e físicas entre o fármaco e os polímeros, sendo sugerido que o desaparecimento do pico de fusão da indometacina tenha ocorrido pela amorfização do fármaco durante o processo de liofilização ou pela diluição do fármaco no polímero. Os estudos preliminares de liberação in vitro demonstraram um perfil trifásico para os implantes formulados com PLGA e um perfil bifásico para àqueles formulados com PLA. Os implantes formulados com PLGA promoveram uma liberação mais rápida da indometacina (103,64%) quando comparado com os implantes formulados com PLA (49,9%) durante os trinta dias de experimento. O perfil de liberação da indometacina foi determinado pela velocidade de degradação dos polímeros, que também determinou a difusão escleral da indometacina a partir do PLGA e do PLA (1,7 x 10-5 cm/s e 0,24 x 10-5 cm/s, respectivamente). Os estudos de difusão escleral mostraram que a esclera de coelho é permeável à indometacina e a microscopia de luz polarizada mostrou que a estrutura das fibras colágenas da esclera não foram significativamente alteradas durante o estudo de difusão nas câmaras de Franz. Os sistemas de liberação de fármacos avaliados foram capazes de liberar a indometacina de forma prolongada, servindo como um modelo para formulação de implantes de indometacina que podem ser futuramente utilizados para tratamento de doenças como edema macular cistóide.

Neste trabalho compósitos foram obtidos a partir da blenda comercial 100% biodegradável Ecovio® C2224 da BASF, uma blenda formada por 55% em massa de um copoliéster biodegradável, o Ecoflex® (poli[(adipato de butileno)-co-(tereftalato de butileno)]) e 45% em massa de PLA poli(ácido láctico). Como carga, utilizaram-se dois tipos de argilas comerciais do grupo das esmectitas, ambas predominantemente montmorilonitas: Cloisite Sódica® e Cloisite 30B®. Também foi utilizado como carga a sílica coloidal comercial Aerosil 200®, com área superficial de 200 m2/g e diâmetro médio de partícula 12nm. Os compósitos estudados, ambos contendo 5% e 10% em massa de cargas, foram preparados em uma extrusora de rosca dupla, acoplada a um reômetro de torque. O estudo foi dividido em três etapas: 1ª) etapa: Obtenção e caracterização dos compósitos de Ecovio®/ argila e Ecovio® / sílica; 2ª) etapa: Avaliação da fotodegradação do Ecovio® puro e dos compósitos obtidos; 3ª) etapa: Avaliação da biodegradabilidade do Ecovio® puro e dos compósitos após exposição em câmara de UV. As propriedades mecânicas dos compósitos antes e depois de serem submetidos à exposição em câmara de UV foram avaliadas por ensaios de resistência à tração e resistência ao impacto Izod. Os resultados obtidos na 1ª etapa deste trabalho indicaram aumento nos valores de módulo de elasticidade de todos os compósitos, em relação à blenda pura. Destacam-se as composições com 5% e 10% em massa de sílica coloidal, que apresentaram aumentos de até 115% nos valores de módulo de elasticidade, sem perdas significativas em resistência à tração, alongamento e resistência ao impacto, quando comparadas à fase matriz. Na 2ª etapa, a partir de 20 dias de exposição, todas as composições (blendas e compósitos) apresentam redução nas propriedades mecânicas em função do aumento do tempo de exposição à radiação UV. Na 3ª etapa, independente do tipo ou teor de carga presente na blenda, todas as composições apresentaram índices de biodegradabilidade, depois de 120 dias, de 40 a 60%, devido à prévia exposição à radiação UV. / In this work, composites were prepared with 100% biodegradable commercial blend Ecovio® C2224 BASF, a polymer blend composed of 55 wt% of a biodegradable copolyester, the Ecoflex®, poly [(butylene adipate) -co- (butylene terephthalate)], and 45 wt% of PLA poly(lactic acid). Two types of commercial clays of the smectite group, predominantly montmorillonites, were used as fillers: Cloisite Na+® and Cloisite 30B®. The commercial colloidal silica Aerosil 200®, with a surface area of 200 m2/g and an average particle diameter of 12 nm, was also used as filler. The composites containing 5 and 10 wt% of filler were obtained in a twin screw extruder coupled to a torque rheometer. This study was divided in three steps: 1st) Preparation and characterization of Ecovio®/clay and Ecovio®/silica composites; 2nd) Evaluation of the photodegradation of pure Ecovio® and of the composites; 3rd) Biodegradability assessment of pure Ecovio® and composites after exposure to UV chamber. The mechanical properties of the composites before and after the exposition to UV were evaluated by tensile and Izod impact strength. The results obtained in the 1st step showed an increase in the tensile modulus of all blends, especially for the compositions with 5 and 10 wt% of colloidal silica, which presented an increase of 115% in their tensile modulus values without significant reduction in impact and tensile strength and elongation, when compared to the pure blend. In the 2nd step, from 20 UV exposure days, all compositions (blends and composites), presented a significant reduction in the mechanical properties as a function of the increase of the UV radiation exposure time. In step 3, regardless of the filler type or content, all blend compositions showed biodegradability index, after 120 days, of 40 to 60%, due to the prior UV exposure.

Introdução: A obesidade se caracteriza como um processo oxidativo e inflamatório, que predispõe adolescentes, de modo precoce, a eventos até recentemente pouco frequentes nessa faixa etária. Assim, a ação da enzima Fosfolipase A associada às lipoproteínas (Lp-PLA ), que reduz fosfolipídios oxidados e gera lisofosfolipídios, bem como a disponibilidade de antioxidantes plasmáticos, representam um importante tema de pesquisa no contexto cardiovascular. Objetivo: Verificar se a atividade da LP-PLA 2 2 e a concentração de antioxidantes lipossolúveis se associam com os principais marcadores de risco cardiovascular em adolescentes. Métodos: Duzentos e quarenta e dois adolescentes (10 a 19 anos), de ambos os sexos foram distribuídos, segundo o índice de massa corporal (IMC), em três grupos: Eutróficos (n=77), Sobrepeso (n=82) e Obesos (n=83). A amostra foi caracterizada através de parâmetros sócio-econômicos, estado de saúde, uso de medicamentos, antedecentes familiares de doenças crônicas e prática de atividade física. Foram avaliados ainda os dados antropométricos (peso, altura e composição corporal - bioimpedância), e o consumo alimentar por meio de três recordatórios 24 h. A partir de uma amostra de sangue coletada após jejum (12h), realizaram-se as análises da atividade da Lp-PLA , LDL(-) e seus auto-anticorpos, perfil lipídico (colesterol total, LDL-C, HDL-C e triglicerídeos), tamanho da HDL, proteína transportadora de éster de colesterol (CETP), ácidos graxos não esterificados (NEFAs), adipocitocinas, assim como antioxidantes (retinol, licopeno, -tocoferol e -caroteno) no plasma. Resultados: Artigo 1: Lp-PLA maybe an important cardiovascular biomarker in obese adolescents. Verificou-se que o perfil lipídico, insulina, HOMA-IR (resistência à insulina) e LDL(-) evidenciaram um maior risco cardiovascular nos adolescentes obesos. A atividade da enzima Lp-PLA 2 mostrou uma variação proporcional ao IMC, circunferência da cintura e porcentagem de gordura. Essa tendência foi, ainda, reforçada pelas associações positivas entre a enzima e HOMA-IR, glicose, insulina e as variáveis lipídicas. Adicionalmente, associação negativa foi encontrada para ApoAI. As associações mais relevantes foram observadas para ApoB e Apo B / Apo AI (=0,293; P<0,001, =0,343; P<0,001, respectivamente). O melhor modelo preditor para a atividade da enzima incluiu Apo B/Apo AI (= 0,327; P<0,001), tamanho da HDL (=-0,326; P<0,001), circunferência da cintura (=0,171; P=0,006) e glicose (= 0,119; P=0,038). A análise de Odds Ratio mostrou que a mudança de uma unidade na razão entre Apo B/Apo AI esteve associada a 73.5 maior risco para elevada atividade de Lp-PLA 2 . Conclusão: A enzima Lp-PLA , em adolescentes, varia em função do estado nutricional e está relacionada a vários marcadores de risco cardiovascular, especialmente a Apo B/Apo AI. Assim, a atividade da enzima pode representar um importante biomarcador de risco cardiovascular na adolescência. Artigo 2: Antioxidant, and inflammatory aspects of phospholipase A 2 associated to lipoprotein (Lp-PLA ): A review. Esta revisão descreve os principais aspectos relacionados à enzima Lp-PLA 2 e seu impacto no perfil inflamatório e oxidativo da doença aterosclerótica. Artigo 3: Plasma antioxidants, but not the dietary ones, are associated with cardiometabolic risk in adolescents. Neste artigo, observou-se que 2 os antioxidantes -caroteno, licopeno, retinol e -tocoferol variam em função do IMC. Verificou-se que -caroteno e -tocoferol apresentaram valores reduzidos para o grupo obeso em comparação ao eutrófico e ao sobrepeso. Para o -caroteno, verificou-se que essa diferença pôde ser observada inclusive quando comparados sobrepesos e eutróficos. Quando esses antioxidantes foram ajustados pelo colesterol total ou pelo LDL-C essas diferenças se mantiveram. Correlações importantes foram obtidas entre os antioxidantes ajustados por colesterol ou por LDL-C e as variáveis de risco cardiometabólico (perfil lipídico (colesterol total e frações, CETP), resistência à insulina (HOMA-IR, insulina, glicose) e LDL(-)). A obesidade representou um importante fator para a existência dessas correlações, pois após o ajuste por IMC foram reduzidas. Apesar desses resultados, os antioxidantes availados pelo recordatório de 24h não apresentaram nenhuma correlação com os fatores de risco cardiometabólico. Conclusão: Antioxidantes plasmáticos estão relacionados ao risco cardiometabólico em adolescentes, sendo que o IMC desempenha um papel importante para a existência dessas correlações. Tais biomarcadores representam uma melhor maneira de estimar a influência de um padrão dietético sobre o risco cardiometabólico em adolescentes do que a avaliação do inquérito alimentar / Introduction: Obesity is characterized as an oxidative and inflammatory process, which precociously predisposes adolescents to events until recently uncommon in this age group. Thus, the action of Lipoprotein-associated phospholipase A (LpPLA ), which reduces oxidized phospholipids and generates lysophospholipids, as well as the availability of plasma antioxidants, represent important subjects of cardiovascular research. Objetive: To evaluate if the activity of Lp-PLA 2 and the concentration of fat-soluble antioxidants are associated with the most important cardiovascular risk markers in adolescents. Methods: 242 adolescents (10 to 19 years old), from both sexes, were distributed according to Body mass index (BMI) in three groups: Health Weigth (HW, n=77), Overweigth (OV, n=82) and Obeses (OB, n=83). The sample was characterized by socioeconomic parameters, health condition, use of medications, family history of chronic diseases and physical activity. It were evaluated also the anthropometric data (weigth, heigth, body composition - bioimpedance) and the food intake through three 24h-recall. From a blood sample collected after fasting (12h), were analized the Lp-PLA activity, the levels of LDL(-) and it antibodies, the lipid profile (total cholesterol, LDL-C, HDL-C and triglycerides), HDL-size, Non-Esterified Fatty Acids (NEFAs), Cholesteryl Ester Transfer Protein (CETP), adipocytokines, as well as plasma antioxidants (retinol, licopene, -tocopherol e -carotene). Results: Article 1: Lp-PLA as an important biomarker of cardiovascular risk in obese adolescents. It was observed that the lipid profile, the insulin, the HOMA-IR (insulin resistance) and the LDL(-) represented a higher cardiovascular risk in obese adolescents. The activity of Lp-PLA 2 has shown a variation proportional to BMI, waist circumference and fat mass percentage. This tendency was reinforced by positive associations of the enzyme with HOMA-IR, glucose, insulin and lipid variables. Additionaly, a negative association was observed for Apo AI. The most relevant associations were observed for ApoB and Apo B / Apo AI (=0,293; P<0,001, =0,343; P<0,001, respectively). The best predictor model for the enzyme activity included Apo B/Apo AI (= 0,327; P<0,001), HDLsize (=-0,326; P<0,001), waist circumference (=0,171; P=0,006) and glucose (= 0,119; P=0,038). The Odds Ratio analysis showed that the change of one unit in the ratio of Apo B/Apo AI was related to a 73.5 times higher risk of elevated Lp-PLA activity. Conclusion: The enzyme Lp-PLA , in adolescents, varies in function of the nutritional status and it is related to several cardiovascular risk markers, especially to Apo B/Apo AI. Thus, this enzyme activity may represent an important biomarker of cardiovascular risk in adolescence. Article 2: Antioxidant and inflammatory aspects of phospholipase A 2 2 associated to lipoprotein (Lp-PLA ): a review. This review describes the main aspects related to the enzime Lp-PLA 2 and its impact to inflammatory and oxidative profiles of atherosclerotic disease. Article 3: Plasma antioxidants, but not the dietary ones, are associated with cardiometabolic risk in 2 adolescents. It was observed that the antioxidants -carotene, licopene, retinol and -tocopherol vary in function of BMI. It was verified that -carotene and - tocopherol presented reduced values for the OB group in comparison with the HW and OV groups. For -carotene, it was observed that this difference was also verified when OB and OV were compared. These differences remained alike when the antioxidants were adjusted by total cholesterol or by LDL-C. Important correlations were obtained between the antioxidants adjusted by total cholesterol or by LDL-C, and cardiometabolic risk variables (lipid profile (total cholesterol and fractions, CETP), insulin resistance (HOMA-IR, insulin, glucose) and LDL(-)). The obesity represented an important factor to the occurrence of these correlations, since they were reduced after BMI adjustment. Despite these results, the antioxidants evaluated by 24h-diet recall did not show any correlations with cardiometabolic risk. Conclusion: Plasma antioxidants are related to cardiometabolic risk in adolescents, where the BMI represents an important factor. These biomarkers are better than the food intake to estimate the influence of a dietary pattern on the cardiometabolic risk in adolescents

Les mousses de calage en plastique utilisées dans les emballages sont très volumineuses et beaucoup de travaux s'intéressent à limiter leur production et à les remplacer par des matériaux qui soient biosourcés et/ou compostables mais avec des propriétés mécaniques comparables aux mousses en plastique pétrochimique. Ainsi vient l'idée de ce projet de recherche qui consiste à développer des mousses de calage à base d'amidon par extrusion réactive, en étudiant les relations : formulation – process – structure – propriétés. L'un des objectifs de ce travail de recherche est de comprendre et d'optimiser le procédé de fabrication des plaques de mousses de calage à base d'amidon afin d'assurer la stabilité et la reproductibilité du procédé. Dans le cadre de cette étude, nous avons déterminé la combinaison idéale « procédé/matière » en étudiant l'effet des différents ingrédients de la formulation sur les propriétés mécaniques et structurales des mousses résultantes. Les mousses ayant obtenu les meilleures propriétés de calage ont été caractérisées et leurs performances mécaniques, en termes d'absorption, d'amortissement et de transmission du choc lors du transport, ont été comparées à celles des mousses de calage traditionnelles d'origine pétrochimique. Nous avons également étudié le vieillissement, la biodégradabilité et la stabilité des propriétés des mousses à différentes conditions climatiques. Ces études nous ont permis de déterminer la stabilité des mousses dans le temps et leur comportement selon que l'on soit dans une région tempérée, tropicale ou autres. Dans le but d'améliorer les propriétés et les performances mécaniques des mousses et de réduire leur sensibilité à l'humidité, nous avons rajouté des fibres naturelles, des biopolymères et des charges minérales à la formulation de base et étudié leurs effets sur les propriétés des mousses résultantes. Le développement des mousses à base d'amidon par extrusion réactive a alors été optimisé. Les mousses extrudées ont obtenu des propriétés physiques et un pouvoir amortissant comparables aux mousses en plastique traditionnelles, type polyéthylène expansé, leur permettant d'être utilisées dans diverses applications dont principalement les calages qui, à l'issu de ces travaux de recherche, va être développé à l'échelle industrielle. / Foam cushions used in packaging are very light and bulky and a lot of efforts have been made to limit their production and to replace them with materials that are from renewable resources but with comparable mechanical properties to the current petroleum plastic foams. Consequently, the aim of this project, which consists of developing starch-based foam cushions by reactive extrusion, is to study the relationship between formulation, process, structure and properties. One of the research goals was to understand and optimize the manufacturing process of starch-based foam sheets to ensure the stability and the repeatability of the process. In this study, we determined the perfect « process / material » combination by studying the effects of the various ingredients of the formulation on the mechanical and structural properties of the resulting foams. The foams with the best cushioning properties were characterized and their mechanical performances in terms of absorption, cushioning and shock transmission during transport were compared to those of petrochemical foam cushions. We also studied the aging, biodegradability and stability of the foam properties at different climatic conditions. These studies allowed us to determine the long-term stability of the material and their behavior depending on their storage conditions. In order to improve the mechanical properties of the foams and to reduce their moisture sensitivity, we added natural fibers, mineral fillers and biopolymers to the formulation and studied their effects on the resulting properties. Thus, the development of starch-based foams by reactive extrusion has been optimized. The extruded foams have comparable physical properties with the conventional plastic foams, like expanded polyethylene, allowing them to be used in various applications, especially as cushioning materials, which is now ready to be developed at industrial scale.

Detta examensarbete har ämnat konstruktionen av en strimlare för att sönderdela kasserad PLA-plast från 3d-skrivarna i verkstaden på Mälardalens universitet. Målet med detta arbete var att underlätta återvinning men även möjliggöra återbruk av materialet genom att skapa nytt filament av den sönderdelade plasten som åter kan användas av 3d-skrivarna och därmed minska behovet av att köpa in nytt filament. För att planera detta arbete har projektgruppen använt sig av ett Gantt schema som skapades under arbetets tidiga fas.   Projektgruppens arbete har bestått av att utvärdera befintliga lösningar så som en granulator och strimlare för att sedan välja ut den bäst lämpade maskinen att konstruera för ändamålet. Under arbete utfördes även en fallstudie för att skapa en uppfattning om hur stor kraft som behövs för att sönderdela PLA-plast.   I detta uppdrag har projektgruppen använt sig av utvärderingsmetoden FMEA tillsammans med föreskrifter från arbetsmiljöverket för att konstruera bort eller minimera risker som kan orsaka skada på maskin och användare.   För att verifiera den framtagna konstruktionens hållbarhet har FEM analys använts i ett flertal fall med syftet att undersöka säkerhetsfaktorer och spänningsfördelningar under belastning.   Resultatet av detta arbete presenteras som en CAD modell i formen av en strimlare med tillhörande elektronik. Till största del möter den slutliga konstruktionen de förbestämda kraven specificerade av kunden med ett undantag gällande den önskade vikten som överskreds på grund utav den tunga snäckväxeln som implementerades i konstruktionen för att möta det utmätta kraftbehovet. Arbetet anses har skapat en grund för fortsatt arbete att byggare vidare på och vidareutveckla med nya idéer och lösningar. / This thesis consists of the construction of a shredder to shred discarded PLA-plastic from the 3d-printers in the workshop at Mälardalens University. The aim of this assignment was to ease the recycling process, but also enable the possibility to reuse the shredded plastic to make new filament that can be used by the 3d-printers and thereby decrease the need to purchase new filament.  To plan this project, the project group used a Gantt chart that was created during the project's infancy.   The work has consisted of evaluating existing solutions such as a granulator and a shredder in order to pick the best-suited machine to construct. During the assignment, a case study was also conducted with the aim of creating an understanding of how much force is needed to shred PLA-plastic.   In this assignment, the project group has used the evaluation method FMEA together with regulations from The Swedish Work Environment Authority to remove or minimize risks that can cause damage the machine or harm the user.   To verify the durability of the machine, FEM analysis was implemented in multiple cases with the purpose of examining safety factors and material stress under load.   The result for the work produced is presented as a CAD model in the form of a shredder together with the electronics. For the most part, the finished machine meets the pre-determined requirements except for the desired weight, which was exceeded because of the heavy worm gear that got implemented in the construction to meet the measured power demands. The work is considered to have created a foundation to develop further with innovative ideas and solutions.

Lignin är, med undantag för cellulosa, den av de naturliga polymererna det finns mest av på jorden och den ledande källan till fenolföreningar. De träväxterna som existerar idag, innehåller ca 30 % av just denna biopolymer. Lignin har länge ansetts vara svår att utnyttja i materialapplikationer, i jämförelse med de polymererna som existerar i lignocellulosa biomassa, nämligen cellulosa och hemicellulosa. Konventionella metoder som innefattar lignin-extraktion leder ofta till strukturell skada på polymeren, men också, blir ofta resultatet en försämrad, modifierad produkt med få användningsområden. Mikrovågsextraktion är en nyare process som är både effektiv och selektiv. I denna rapport har tre typer av lignin-innehållande växter använts som biomass-råvara, nämligen barrträ, lövträ och halm för att utforska möjligheterna att isolera lignin med mikrovågs-assisterad extraktion. Utspädd svavelsyra har använts som lösningsmedel i denna extraktion. Olika kombinationer av parametrar har använts med avseende på temperatur (180-200 °C), processtid (5-20 minuter) samt koncentration av svavelsyra (0.2 M och 1 M). Syftet med extraktionen var att avlägsna cellulosa samt hemicellulosa. Även förbehandling av biomassan har undersökts med fokus på malningsprocessen och torkningsförhållandena. Den kvarvarande fasta fasen, förhoppningsvis syra-olösligt lignin, har analyserats med FTIR, TGA, HSQC-, 31P- samt 1H-NMR. Den lösliga fasen (potentiellt syra-lösligt lignin samt polysackarider) har analyserats med hjälp av 13C-NMR. Lignin, utvunnet från tall (mjukträ) vid 190 °C, 0.2 M svavelsyra under 15 respektive 20 minuter visade sig ha de mest önskvärda egenskaperna (högre lignin-innehåll). För provet med den lägre processtiden användes olika tillvägagångssätt för att utvinna mer produkt per mikrovågsextraktion vilket ledde till sämre resultat. På grund av tidsbegränsningen av arbetet, blandades de nya proven för att uppnå en lämplig mängd lignin för att fortsätta utvärdera de möjliga material-applikationerna. Det utvunna ligninet acetylerades för att förhoppningsvis förbättra kompatibilitet med den mer hydrofoba polymeren polylaktid (PLA). Därefter, blandades lignintyperna med PLA var för sig till 10 vikt% vardera. Nästa steg involverade filament-extrudering för att förbereda materialen för 3D-printing. Dessvärre, lyckades endast ett prov med en enhetlig extrudering, nämligen ligninet från den kortare mikrovågsprocessen, PLA/Lignin15. PLA extruderades för att kunna jämföra egenskaperna med lignin/PLA blandningen. Båda materialen 3D printades till en hundbenssliknande form och undersöktes med dragprovning. Resultatet var ett material med 10 vikt% lignin blandat med PLA med en lägre töjning vid brott (%) och med liknande maximal dragspänning (MPa) än PLA. / Lignin is, second after cellulose, the most abundant natural polymer on earth and the leading natural source of phenolic compounds. Woody plants that exist today consist of ∼30 % of this biopolymer. Lignin has long been seen as a difficult material to utilize in material applications in comparison to the other two main polymers existing in woody biomass- cellulose and hemicellulose. Conventional methods of extraction of lignin often result in a structurally damaged polymer, often highly degraded, modified or condensed lignin with finite usages. Microwave extraction is a more novel process contributing to efficient and selective processing. Softwood, hardwood and straw have been utilized as biomass sources in this study to evaluate the possibility of isolating lignin by microwave-assisted extraction. Diluted sulphuric acid was used as solvent in this extraction. Different parameters have been investigated- a temperature range of 180 °C-200 °C, a reaction duration varying from 5-20 minutes and a concentration of sulphuric acid of 0.2 M or 1 M. The aim of the extraction was to remove cellulose and hemicellulose. The remaining solid phase, expectantly lignin, was  analyzed by FTIR, TGA, HSQC-, 31P-, and 1H-NMR. The liquid phase after extraction was analyzed by 13C-NMR. The samples with the more favorable properties (higher lignin content) appeared to be lignin extracted from Pine (Softwood) with the processing temperature of 190 °C with 0.2 M sulphuric acid with a time of 15 and 20 minutes. For the sample with the lower processing time different approaches were used to achieve more product per microwave extraction but this led to inferior results. Due to the limit of time, the new samples were blended to achieve an appropriate amount of lignin for further evaluation in material applications. More product from the lignin with the longer extraction time was also needed and resulted in more similar lignin properties. The goal was to blend the most suitable lignin (the sample with the more distinct lignin structure /highest lignin content based on the analysis) with PLA. The extracted lignin was acetylated to hopefully achieve better compatibility with the more hydrophobic PLA. Thereafter, filament extrusion took place prior to 3D printing. Extrusion of PLA with the modified lignin sample with a processing time of 20 minutes failed (PLA/Lignin19). The other blend on the other hand, PLA/Lignin15, was more successful leading to successful filament extrusion and 3D printing being performed. Also, neat PLA was extruded successfully and 3D printed for comparison in tensile testing. The result was a material with 10 wt. % of lignin incorporated in PLA. The material had a decrease in elongation at break (%) but similar tensile strength (MPa) compared to PLA.