Made available in DSpace on 2014-06-11T19:27:11Z (GMT). No. of bitstreams: 0 Previous issue date: 2010-07-26Bitstream added on 2014-06-13T20:55:48Z : No. of bitstreams: 1 ruiz_slm_me_bauru.pdf: 2192479 bytes, checksum: 69f94a0515d295047a14f126eaa6fb64 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / O crescente aumenta na expectativa de vida da população tem resultado numa igual demanda e procura por biomateriais metálicos. Biomateriais metálicos são utilizados na substituição ou recuperação de ombros, joelhos, quadril e cotovelos. As ligas a base de Ti são materiais promissores para tais fins, pois apresentam uma excelente biocompatibilidade, ótima resistência à corrosão em meio biológico. Essas características são grandemente influenciadas pela presença de elementos substitucionais e oxigênio intersticial e a técnica do atrito interno constitui um aliado bastante importante na análise dos resultados deste trabalho. Dessa forma, o objetivo deste trabalho é analisar a influência do exigênio intersticial nas propriedades das ligas Ti-8Ta e Ti-16Ta (% em peso). As medidas de atrito interno foram utilizadas para obtenção do módulo de elasticidade dinâmico das ligas estudadas, pois esta grandeza está experimentalmente associada ao amortecimento das vibrações livres do sistema, a dissipação de energia elástica e a frequencia de oscilação do sistema. Para tais medidas empregou-se um Pêndulo de Torção com frequencia de oscilação de aproximadamente 30Hz e temperatura na faixa de 230 a 350K. As ligas estudadas passaram por processos de tratamento térmico e dopagens com oxigênio e foram caracterizadas por medidas de densidade, difração de raios X e posterior refinamento de Rietveld, microdureza, módulo de elasticidade e testes de citotoxicidade in vitro. Os testes iniciais de biocompatibilidade mostram que não houve nenhuma resposta citotóxica, originando resposta celular satisfatória. As medidas de microdureza apresentam valores menores que os encontrados na literatura e as medidas de raios X mostram picos característicos da fase 'alfa' do titânio. Na análise de Rietveld verificou-se a presença de estrutura martensítica 'alfa' e fase 'beta' para... / The accelerating increase in life expectancy of the population has resulted in greater demand and more searches for metallic biomaterials. Metallic are extensively used in the replacement or restoration fo shoulders, knees, hips and elbows. Ti-based alloys are promising materials for such purposes, because they present excellent biocompatibility, a great mechanical strengh/density relation and a high corrosion resistance in a biological medium. These characteristics are greatly influenced by the presence of substitutional elements and interstitial oxygen. The internal friction technique is a very important ally in the analysis of the results of this work. Thus, the purpose of this work is to analyze the influence of insterstitial oxygen on the properties of Ti-8Ta and Ti-16Ta alloys (wt%). Internal friction measurements were used to obtain the dynamic elasticity modulus of the alloys studied, because this quantity is experimentally associated with the damping of free vibration of the sytem, which is related to the elastic energy dissipation and the oscillation frequency of the system. For such measurements, a torsion pendulum was employed, with an oscillation frequency of approximately 30 Hz and temperature in the range of 230-350 K. The alloys underwent heat treatment and oxygen doping processes, and were characterized by density, x-ray diffraction and subsequent refinement of Rietveld, microhardness and elasticity modulus measurements, and in vitro cytotoxicity tests. The initial biocompatibility tests showed that there was no cytotoxic answer, giving origin to a satisfactory cellular response. Microhardness measurements had values less than found in the literature, and x-rays showed characteristic peak of the titanium 'alfa' phase. In the Rietveld analysis, observed were the presence of martensitic 'alfa' structure and a 'beta' phase for all sample and conditions studied. The ... (Complete abstract click electronic access below)

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En chirurgie reconstructive osseuse les biomatériaux remplacent le tissu osseux manquant et dans le cas de pathologies ils peuvent également délivrer des molécules actives. L’élément semi-métallique, gallium (Ga), est utilisé dans le traitement de différentes pathologies liées à la résorption accélérée de l’os dû à son effet inhibiteur sur les ostéoclastes (cellules résorbantes de l’os). Le Ga peut être incorporé dans la structure des biomatériaux osseux et nous nous sommes intéressés aux propriétés biologiques de ces derniers. In vitro, en présence de Ga nous avons mis en évidence une diminution de la différentiation des ostéoclastes, ainsi qu’une sur-expression de plusieurs marqueurs des ostéoblastes (cellules formatrices d’os). In vivo, le modèle murin de comblement du défaut osseux a montré une augmentation de la quantité de tissu osseux néoformé avec un biomatériau chargé en Ga vs. contrôle. Ces données démontrent que les biomatériaux chargés en Ga sont compatibles avec la survie et la prolifération des cellules osseuses et que le Ga peut améliorer la reconstruction osseuse. D’autre part, étant donné que des effets anti-tumoraux du Ga sont largement décrits, nous avons étudié ces effets sur une lignée cellulaire cancéreuse, choisie pour son affinité pour le tissu osseux. Nous avons montré que le Ga réduit la prolifération et probablement le potentiel tumoral de cette lignée, mais aussi la différentiation ostéoclastique induite par les cellules cancéreuses. Ces effets inhibiteurs observés dans un contexte tumoral indiquent que le Ga est un candidat intéressant pour le couplage avec des biomatériaux destinés au comblement osseux après une résection tumorale. / In bone reconstructive surgery biomaterials commonly replace the missing tissue and in case of pathologies can also serve as vectors for drug delivery. The semi-metallic element gallium (Ga) is used for the treatment of several disorders associated with accelerated bone resorption, due to its inhibitory action on bone-resorbing cells (osteoclasts). Since Ga can be incorporated into the structure of bone biomaterials, we embarked on characterising the biological properties of novel Ga-loaded materials. In vitro, we observed a decrease in osteoclast differentiation and the upregulated expression of several osteoblastic markers (bone-forming cells) in the presence of Ga-loaded biomaterial. In vivo, using a rat bone defect model, we showed an increase in newly formed bone tissue in implants filled with Ga-loaded biomaterial vs. control. Taken together, our data indicate that Ga-loaded biomaterials provide biocompatible substrates allowing bone cells survival and improved bone reconstruction in vivo. Taking into account antitumoral effects of Ga, largely described in literature, we also investigated its impact on a bone metastatic model. Using an aggressive human cancer cell line selected for its ability to invade bone tissue, we showed that Ga could reduce cancer cell proliferation and viability and reverse excessive osteoclastogenesis in bone metastatic environment. Moreover, we demonstrated that Ga modulated the expression of several marker genes hindering the tumour-propagating potential of cancer cells. Thus, due to its inhibitory action on cancer cells, Ga could represent an attractive additive to biomaterials used for tissue reconstruction after tumour resection.

Le premier objectif de notre travail est de caractériser l'évolution temporelle de proprié-tés structurales et mécaniques de matériau osseux régénéré et immature sur un grand volume.Nous avons étudié ce tissu en évolution lors de sa genèse dans un environnement mécanique contrôlé. Pour caractériser l'évolution temporelle des propriétés mécaniques de ce tissu, à partir d'un modèle animal, nous mettons en place une étude couplant essais mécanique d'indentation,observations macroscopiques et étude histologique. Cette méthodologie combinée donne des informations complémentaires à différentes échelles : macroscopique par simple observation,mésoscopique avec les tests d'indentation et microscopique avec l'histologie. Le tissu osseux ré-généré évolue d'un matériau homogène, visqueux et souple vers un matériau hétérogènes, plus rigide et moins visqueux. D'un point de vue biologique, l'organisation cellulaire part d'un amas de nombreuses cellules et progresse vers une structure plus proche de celle de l'os. Mécanique et biologie révèlent une évolution similaire : d'abord le régénérat grossit, puis il se différencie en tissu ostéochondral et finalement, la calcification commence. Les résultats biologiques confirment les études de la littérature et les résultats mécaniques donnent les premières valeurs de caractéristiques mécaniques de ce tissu avec le module d'Young réduit.Le deuxième objectif de cette étude est de développer une bioprothèse avec un biomatériau biodegradebable afin de régénérer un défaut d'os de taille critique. Notre étude est originale carelle propose d'utiliser le biomatériau comme tuteur de la régénération. Une étude préliminaire a été menée avec un modèle animal et un biomatériau céramique phosphocalcique. De premiers résultats encourageant ont été obtenus mais le processus clinique reste à concrétiser. / The first objective of our work was to experimentally characterise the temporal evolutionof the structural and mechanical properties of large volume immature regenerated tissues. Westudied these evolving tissues from their genesis in controlled mechanical conditions. To characterizethe temporal evolution of mechanical properties, based on animal model, we carried outindentation tests coupled with macroscopic examinations and histological studies. This combinedmethodology yielded a range of information on osteogenesis at different scales : macroscopic bysimple observation, mesoscopic by indentation test and microscopic by histological study. Resultsallowed us to identify different periods, providing a link between biological changes and materialproperty evolution in bone tissue regeneration. The regenerated tissue evolves from a viscous,homogeneous, soft material to a heterogeneous stiffer material endowed with a lower viscosity.From a biological point of view, cell organization progresses from a proliferated cell clot to a maturestructure closer to that of the bone. During the first seven days, mechanical and biologicalresults revealed the same evolution : first, the regenerated tissue grew, then, differentiated into anosteochondral tissue and finally calcification began. While our biological results confirm those ofother studies, our mechanical results provide the first experimental mechanical characterizationby reduced Young's modulus of such tissue.In a second time,we develop a bioprothesis with a biodegradebable biomaterial to regenerate acritical size bone defect. Our study is original because it proposes to use the biomaterial to initiatethe regeneration. A study was performed with an animal model and phosphocalcic ceramic.First observation gave some encouraging results but the clinical process should be realized

This thesis presents the work conducted during a three year research project in the field of Control Systems and Biomaterials Engineering. The findings are presented over seven chapters, starting with a thorough literature review of the existing methods and key technologies, and following through by highlighting the existing problems with the current methods and how they have been overcome. The data is presented in tables, figures and photographs to enhance understanding and clarification. The research focuses on two relatively new manufacturing methods in the field of Tissue Engineering. Both of the methods are used for creating materials for regeneration of human and animal tissue, with the aim of replacing the current surgical methods. The methods are viewed from a control systems perspective and improvements have been made with the implementation of new technologies and methods. Additionally, further advancements are presented on the theoretical modelling field of control systems, where the shortfalls of existent modelling methods are highlighted and solutions proposed.

L’accident vasculaire cérébral (AVC) représente une des plus importantes causes d’handicap acquis de l’adulte. A l’heure actuelle, après les premières heures de l’AVC, aucun traitement efficace en dehors de la rééducation n’est disponible, renforçant l’importance de la recherche des traitements alternatifs. La thérapie de reperfusion à la phase aigüe est conditionnée par une détection et une prise en charge très précoce. Pour cette raison, seulement environ 10% des patients peuvent en bénéficier. L’application des nouvelles techniques d’imagerie cérébrale peut être de grande utilité dans la compréhension des mécanismes de l’ischémie aiguë et l’identification des candidats potentiels à la reperfusion. Dans le cadre de notre première étude dans un modèle expérimental d’ischémie cérébrale chez le rat (par occlusion de l’artère cérébrale moyenne oACM), nous avons caractérisé les altérations micro-vasculaires, hémodynamiques et la saturation locale en oxygène (StO2) à la phase aigüe de l’AVC (dans la première heure) par IRM multiparamétrique. Les résultats de cette étude ont montré le potentiel de la cartographie par IRM de la StO2 dans la détection du cœur ischémique sans l’inclusion d’aucune zone potentiellement récupérable.Au-delà de la phase aigüe, le réel besoin de disposer de thérapies avec une fenêtre thérapeutique plus étendue s’impose. La thérapie cellulaire présente un potentiel dans le traitement de l’AVC. La thérapie cellulaire semble promouvoir une réduction du handicap après un AVC par des mécanismes de neuroprotection et de régénération du tissu cérébral. Malgré ces résultats encourageants, l’importante mort cellulaire quand les cellules exogènes sont administrées dans la cavité de l’infarctus doit être améliorée. Nous avons évalué un biomatériau hydrogel in vivo et son potentiel à protéger les cellules greffées à long terme. Dans notre étude pilote chez le rat sain, nous avons démontré que l’hydrogel à base d’acide hyaluronique (HA) HyStemTM-HP (Sigma-Aldrich, France) pouvait rester dans le tissu cérébral pendant 28 jours sans être dégradé, ce qui représente une protection potentielle pour des cellules greffées.La greffe intracérébrale de HA combinée à des cellules souches mésenchymateuses humaines (CSMh) issues de la moelle osseuse), 7 jours après l’oACM, a favorisé la survie cellulaire et a augmenté les marqueurs angiogéniques. Les cellules RECA1+ (marqueur des cellules endothéliales vasculaires) ont été augmentées. Les cellules Collagen-IV+ (membrane basale des vaisseaux) étaient également augmentées par le traitement. L’angiogenèse est un processus clé dans la récupération post-AVC. Malgré ces effets pro-angiogéniques bénéfiques, aucun des traitements (CSMh+HA ou CSMh seules) n’a permis une récupération fonctionnelle 3 semaines après l’injection (évaluation par deux test sensori-moteurs: échelle d’évaluation neurologique (mNSS) et test du retrait d’adhésif). / As the leading cause of disability in adulthood, stroke remains an important subject of study because no effective treatments except by rehabilitation are currently available after the first hours. The acute phase therapy reperfusion is conditinated to a rapid detection and management. For this reason, just around 10% of patients benefit of this. The application of new brain imaging techniques can be relevant for the comprehension of acute stroke mechanism and for a more accurate identification of candidates for acute phase reperfusion therapies. In our first study in a rat model of ischemic stroke (by occlusion of middle cerebral artery, MCAo) we characterized the microvascular, hemodynamic and local saturation in oxygen (StO2) alterations in the acute phase (around one hour after stroke onset), using multiparametric MRI. We demonstrated the potential of StO2 MRI map for detecting the ischemic core without the inclusion of any reversible ischemic damage.Therapeutic approaches that can be applied beyond acute phase are urgently needed. Most evidences suggest that cell therapies have the potential to reduce post-stroke disability through neuroprotection and brain remodelling mechanism. Despite of beneficial effects were demonstrated, some issues need to be addressed, such as the important loss of grafted cells reported when cells are administrated into infarct cavity. We evaluated an innovating biomaterial hydrogel in vivo and their potential to promote long term protection of grafted cells. In a pilot study, we demonstrated that hyaluronic acid-based hydrogel (HA) HyStemTM-HP (Sigma-Aldrich, France) presented a long lasting (over 28 days) in healthy brain suggesting to be a good candidate for cell therapy.When co-administrated by intracerebral route combined with human Mesenchymal Stem Cells (hMSC from bone marrow) seven days after MCAo, the HAhydrogel promoted an increase of hMSC survival and improved angiogenic process. In the immunohistological study, RECA1+ (vessel endothelial cells makers) were increased. Collagen-IV+ cells (vessel basal membrane) were also increased. Post stroke angiogenesis is a key process for brain recovery. No difference in lesion volume was detected among the ischemic groups by in vivo MRI. Despite the pro-angiogenic beneficial effect, neither hMSC+HA nor hMSC alone were able to improve functional results 3 weeks after intracerebral injection (assessed by modified neurological severity score (mNSS), and adhesive removal test).

Submitted by Luciana Daniele Trino (lucianadtrino@gmail.com) on 2018-06-08T15:40:25Z No. of bitstreams: 1 Tese_Luciana_Daniele_Trino_POSMAT.pdf: 6699069 bytes, checksum: be06e9652268b5025a7ed7d568576862 (MD5) / Approved for entry into archive by Lucilene Cordeiro da Silva Messias null (lubiblio@bauru.unesp.br) on 2018-06-08T17:37:31Z (GMT) No. of bitstreams: 1 trino_ld_dr_bauru.pdf: 6603946 bytes, checksum: dacabdf3e79f4b7c7de3dc9da7bdaa1f (MD5) / Made available in DSpace on 2018-06-08T17:37:31Z (GMT). No. of bitstreams: 1 trino_ld_dr_bauru.pdf: 6603946 bytes, checksum: dacabdf3e79f4b7c7de3dc9da7bdaa1f (MD5) Previous issue date: 2018-04-19 / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / O titânio e suas ligas são utilizados em diversas aplicações, dentre elas em implantes ortopédicos e dentários devido à sua reconhecida biocompatibilidade. No entanto, falhas e subsequentes efeitos colaterais clínicos ainda são recorrentes em implantes. Neste contexto, melhorias podem ser alcançadas projetando biomateriais nos quais o bulk e a superfície do titânio são independentemente modificadas. Deste modo, filmes finos nanoestruturados de óxidos metálicos, tais como TiO2 e ZnO, podem melhorar as propriedades físico-químicas, a biocompatibilidade e a resistência à corrosão dos implantes de titânio. Além disso, a conjugação de biomoléculas, como peptídeos derivados da proteína da matriz dentinária 1 (DMP1), na superfície dos óxidos metálicos pode melhorar sua bioatividade, acelerando o processo de osteointegração. Dessa forma, o objetivo deste trabalho foi funcionalizar óxidos metálicos com diferentes moléculas bifuncionais e investigar as propriedades físico-químicas de grupos silano, amino, ácido carboxílico, tiol e hidroxila que atuaram como espaçadores entre os óxidos metálicos e os peptídeos da DMP1. Além disso foram realizadas análises de biocompatibilidade, mineralização, resistência à corrosão e à tribocorrosão das superfícies bio-funcionalizadas com os peptídeos da DMP1. Neste trabalho, filmes de TiO2 e ZnO nanométricos foram sintetizados pelo método sol-gel e depositados pela técnica spin coating em substratos de titânio. Posteriormente, os filmes finos de óxidos metálicos foram funcionalizados com (3-aminopropil) trimetoxissilano (APTMS), ácido 3- (4-aminofenil) propiônico (APPA), ácido 3-mercaptopropiônico (MPA) ou polietilenoglicol (PEG), que atuam como espaçadores entre os óxidos metálicos e os peptídeos da DMP1. As análises físico-químicas por XPS, microscopia confocal, AFM, ângulo de contato e energia de superfície revelaram a efetiva modificação das superfícies dos óxidos metálicos com APTMS, APPA, MPA e PEG. Após a bio-funcionalização as análises físico-químicas confirmaram a presença dos peptídeos da DMP1 na superfície dos óxidos metálicos. Além disso, testes biológicos indicaram que os peptídeos puderam modular a afinidade, proliferação e diferenciação de células mesenquimais humanas. Para a amostra contendo o dióxido de titânio, foram observados melhores resultados para o TiO2 funcionalizado com MPA e os peptídeos da DMP1. Já para o óxido de zinco, melhores resultados de biocompatibilidade foram observados para ZnO funcionalizado com APPA e os peptídeos. Além disso, a imobilização dos peptídeos da DMP1 através dos espaçadores APPA e MPA, para ambos os óxidos, levou à formação de biominerais de apatita. Os resultados eletroquímicos indicaram um aumento da resistência à corrosão nos materiais bio-funcionalizados, sendo que melhores resultados foram observados para o TiO2 quando comparado ao ZnO. Além disso a análise de tribocorrosão apresentou menor perda de massa para as amostras de TiO2 bio-funcionalizadas. Considerando os aspectos de biocompatibilidade, diferenciação osteogênica, mineralização, resistência à corrosão e à tribocorrosão a amostra de TiO2 funcionalizada com MPA e os peptídeos da DMP1 foi a que apresentou melhores resultados. Portanto, os resultados obtidos sugerem que a bio-funcionalização de óxidos metálicos é capaz de projetar implantes de melhor qualidade aplicados à medicina regenerativa. / Titanium and its alloys are used in a variety of applications, including orthopedic and dental implants because of their recognized biocompatibility. However, failures and subsequent clinical side effects are still recurrent in implants. In this context, improvements can be achieved by designing biom aterials in which the bulk and surface of the titanium are independently tailored . Thus, nanostructured metal oxides thin films , such as TiO 2 and ZnO, can improve the physicochemical properties, biocompatibility and corrosion resistance of titanium implant s. In addition, the conjugation of biomolecules, such as peptides derived from the dentin matrix 1 protein (DMP1), on the surface of the metal oxides can improve their bioactivity, accelerating the os t eointegration process. Therefore, the objective of thi s work was to functionalize metal oxides with different bifunctional molecules and to investigate the physicochemical properties of silane, amino, carboxylic acid, thiol and hydroxyl groups that act as spacers between metal oxides and DMP1 peptides. In add ition, biocompatibility, mineralization, corrosion and tribocorrosion resistance of the bio - functionalized surfaces were performed. In this work, nanosized TiO 2 and ZnO thin films were synthesized by sol - gel method and deposited by spin coating technique o n titanium substrates. Subsequently, the thin films of metal oxides were functionalized with (3 - aminopropyl) trimethoxysilane (APTMS), 3 - (4 - aminophenyl) propionic acid (APPA), 3 - mercaptopropionic acid (MPA) or polyethylene glycol (PEG), which acted as spac ers between the metal oxides and the DMP1 peptides. The physicochemical analyzes by XPS, confocal microscopy, AFM, contact angle and surface energy revealed the effective modification of the metal oxides surfaces with APTMS, APPA, MPA and PEG. After the bi o - functionalization the physicochemical analyzes confirmed the presence of the DMP1 peptides on the surface of the metal oxides. In addition, biological tests indicated that the peptides could modulate the affinity, proliferation and differentiation of hum an mesenchymal stem cells. For the sample containing the titanium dioxide, better results were observed for the TiO 2 functionalized with MPA and the DMP1 peptides. On the other hand, better biocompatibility results were observed for ZnO functionalized with APPA and peptides. In addition, the immobilization of the DMP1 peptides through the APPA and MPA spacers for both oxides led to the formation of apatite biominerals. The electrochemical results indicated an increase in corrosion resistance in the bio - func tionalized materials, and better results were observed for TiO 2 when compared to ZnO. In addition, the tribocorrosion analysis presented lower mass loss for the bio - functionalized TiO 2 samples. Considering the aspects of biocompatibility, osteogenic differ entiation, mineralization, resistance to corrosion and tribocorrosion, the TiO 2 functionalized with MPA and DMP1 peptides presented the best results. Therefore, the results suggest that the bio - functionalization of metal oxides can design better quality im plants applied to regenerative medicine / 2014/01713-3

Submitted by Maria Medeiros (maria.dilva1@ufcg.edu.br) on 2018-06-28T13:41:53Z No. of bitstreams: 1 ROSANA ARAÚJO ROSENDO - TESE (PPGCEMat) 2016.pdf: 6730629 bytes, checksum: c33c7810f9b205ef693b160c3fbaa042 (MD5) / Made available in DSpace on 2018-06-28T13:41:53Z (GMT). No. of bitstreams: 1 ROSANA ARAÚJO ROSENDO - TESE (PPGCEMat) 2016.pdf: 6730629 bytes, checksum: c33c7810f9b205ef693b160c3fbaa042 (MD5) Previous issue date: 2016-02-29 / Os sistemas de liberação controlada de fármaco apresentam inúmeras vantagens quando comparados a outros de dosagem convencional e, dentre os polissacarídeos mais empregados no desenvolvimento desses sistemas destaca-se a quitosana que, por ser biocompatível e biodegradável, tem despertado o interesse na comunidade científica para sua utilização no desenvolvimento de estruturas onde possam ser incorporados fármacos. A espécie vegetal Cissus verticillata (L.) Nicolson & C.E. Jarvis é conhecida popularmente como insulina e, diversos estudos farmacológicos têm indicado a sua ação hipoglicemiante, justificando-se assim sua aplicabilidade na terapia de pacientes com diabetes. Sendo assim, este trabalho objetivou desenvolver e caracterizar scaffolds de quitosana com diferentes concentrações de Cissus verticillata (L.) Nicolson & C.E. Jarvis, a fim de avaliar sua possível utilização em pacientes portadores de diabetes melito tipo 2. O método consistiu na solubilização da quitosana em ácido acético, adição da droga vegetal, e obtenção dos scaffods através da técnica de freeze drying. As amostras foram caracterizadas através das técnicas de Espectroscopia na Região de Infravermelho com Transformada de Fourier (FTIR), Difração de Raios X (DRX), Microscopia Eletrônica de Varredura (MEV), Espectroscopia de Energia Dispersiva (EDS), Microscopia Ótica (MO), Teste de Molhabilidade, Teste de Compressão, Análise Termogravimétrica (TG) e de Calorimetria Exploratória Diferencial (DSC), Grau de Intumescimento com PBS e saliva artificial e Ensaio de Biodegradação Enzimática. O estudo químico realizado através do FTIR identificou todas as bandas características dos materiais estudados e o estudo morfológico revelou, nos scaffolds, a formação de uma estrutura tridimensional com poros interconectados. A técnica de EDS indicou a presença dos elementos químicos Carbono, Oxigênio e Nitrogênio, além de Magnésio, Silício e Cálcio presentes na droga vegetal. O grau de intumescimento demonstrou que as médias das massas foram correspondentemente mais elevadas na forma intumescida do que na condição seca, sendo esse intumescimento maior quando as amostras foram imersas na saliva artificial, quando comparado com a solução de Phosphate Buffered Saline (PBS). O teste de molhabilidade demonstrou que os scaffolds tiveram sua hidrofilicidade aumentada com a incorporação da droga vegetal e, o teste de compressão, confirmou uma maior resistência à deformação dos mesmos. As análises de TG/DTG demonstraram que a droga vegetal diminuiu a estabilidade térmica dos scaffolds. A partir do ensaio de biodegradação, constatou-se que os scaffolds sofreram uma maior degradação em contato com a solução de PBS do que em PBS/Lisozima; e que, nos períodos de avaliação, a saliva artificial não promoveu biodegradação às estruturas. A incorporação da droga vegetal aos scaffolds foi confirmada por meio dos resultados obtidos nos ensaios de FTIR, DRX, MEV, MO, Grau de intumescimento, testes de molhabilidade e de compressão, TG/DTG e DSC. Desta forma, pode-se concluir que houve a formação de scaffolds com propriedades morfológicas e físico-químicas favoráveis para a obtenção de um sistema para liberação controlada de fármacos. / The systems of controlled clearance of pharmaco present several advantages when compared to others of conventional dosages and, among the most used polysaccharides in the development of these systems can be highlighted the chitosan which, due to being biocompatible and biodegradable, has aroused the interest of the scientific community for its use in the development of structures where pharmaco may be incorporated. The plant species Cissus verticillata (L.) Nicolson & C.E. Jarvis is popularly known as insulin and, several pharmacological studies have indicated its hypoglycemic action, thereby justifying its applicability in the care of patients with diabetes. Thus, this work aimed to develop and characterize chitosan scaffolds with different concentrations of Cissus verticillata (L.) Nicolson & C.E. Jarvis, in order to access its possible use in patients with type 2 diabetes mellitus. The method consisted in the solubilization of the chitosan in acetic acid, addition of the vegetal drug, and obtaining of the scaffolds by means of the freeze drying technique. The samples were characterized by the analysis of Fourier transformed infrared spectroscopy (FTIR), X-ray Difractometry (XRD), Scanning Electron Microscopy (SEM), Energy Dispersive X-ray Spectrometer (EDS), Optical Microscopy (OM), Wettability Test, Compression Test, Thermogravimetric Analysis (TGA) and the Differential Scanning Calorimetry (DSC), Degree of swelling with PBS and artificial saliva and Enzymatic Biodegradation Test. The chemical study was carried out by the FTIR identified all the bands characteristic of the studied materials and the morphological study revealed, in the scaffolds, the formation of a tridimensional structure with interconnected pores. The EDS technique revealed the presence of the chemical elements Carbon, Oxygen and Nitrogen, in addition to Magnesium, Silicon and Calcium present in the vegetable drug. The degree of swelling demonstrated that the averages of the masses were correspondingly higher in the swollen form than in the dry condition, being this swelling greater when the samples were immersed in artificial saliva, when compared to the PBS solution. The wettability test demonstrated that the scaffolds had their hydrophilicity increased with the incorporation of the vegetal drug and, the compression test, confirmed their greater resistance to deformation. The TG/DTG analysis demonstrated that the vegetal drug reduced the thermal stability of the scaffolds. From the biodegradation test, was found that the scaffolds suffered a greater degradation in contact with the PBS solution than in PBS/Lysozyme; and that, in the assessment periods, the artificial saliva did not promote biodegradation to the structures. The incorporation of the vegetable drug to the scaffolds was confirmed by means of the results obtained in the de FTIR, DRX, MEV, OM, Degree of swelling, wettability and compression tests, TG/DTG and DSC tests. Therefore, it can be concluded that there was the formation of scaffolds with favorable morphological and physicochemical properties for obtaining a system of controlled clearance of pharmaco.

Submitted by Maria Medeiros (maria.dilva1@ufcg.edu.br) on 2018-09-12T13:24:10Z No. of bitstreams: 1 ROSEMARY SOUSA CUNHA LIMA - TESE (PPGEP) 2010.pdf: 3173555 bytes, checksum: eb43e3b3de3d9ad75369a30da4e18a31 (MD5) / Made available in DSpace on 2018-09-12T13:24:10Z (GMT). No. of bitstreams: 1 ROSEMARY SOUSA CUNHA LIMA - TESE (PPGEP) 2010.pdf: 3173555 bytes, checksum: eb43e3b3de3d9ad75369a30da4e18a31 (MD5) Previous issue date: 2010-12-22 / A utilização de biomateriais surgiu em função de pessoas que nascem com problemas em órgãos/tecidos ou os adquirem por traumas. Sua demanda foi enfatizada pelo aumento da expectativa de vida dos seres humanos; recentemente, a área de biomateriais encampou muitos estudos, a exemplo da pesquisa com liberação controlada de fármacos, biosensores e dispositivos biomédicos. Uma das doenças crônicas de grande abrangência na contemporaneidade é o Diabetes mellitus tipo 1, cujo tratamento consiste em administração subcutânea diária de insulina. O objetivo deste trabalho foi desenvolver biofilmes compostos de quitosana e insulina, na perspectiva de administrar o fármaco por uma via alternativa a injetável, em sistemas de liberação controlada, contribuindo para uma maior adesão ao tratamento. Os biofilmes foram desenvolvidos a partir da quitosana adquirida em dois fornecedores diferentes e a insulina utilizada foi a NPH em duas concentrações diferentes. A caracterização foi feita pelas técnicas de Molhabilidade, Espectroscopia na Região do Infravermelho com Transformada de Fourier (FTIR), Difração de Raios X (DRX), Calorimetria Exploratória Diferencial (DSC), Termogravimetria (TG), Microscopia Eletrônica de Varredura (MEV), Biodegradação Enzimática, Avaliação da Viabilidade Celular dos Macrófagos e Determinação da Produção de Óxido Nítrico. Foram constatadas pequenas diferenças de hidrofilicidade das amostras, através das análises de molhabilidade. Através dos resultados de FTIR e DRX foi evidenciada a formação do biofilme quitosana/insulina. A morfologia do biofilme não foi modificada consideravelmente, independentemente da presença da insulina, das concentrações e do tipo de quitosana utilizada, sendo a morfologia característica de polímeros de natureza fibrosa, típica da quitosana. Os ensaios realizados por DRX demonstraram variação da cristalinidade nas preparações sendo constatada maior cristalinidade para a preparação de quitosana a 1%, Sigma Aldrich®, GD 75% (B2.1) e menor para a preparação de quitosana a 1,5% Sigma Aldrich®, GD 85% / 50UI de insulina, (B1.4). O DSC acusou três eventos térmicos mostrando que a presença insulina nas preparações de baixa massa molar se equivaleu aos efeitos constatados nas preparações de alta massa molar. A TG constatou maior perda de massa nas preparações de quitosana sem insulina. Os ensaios de biodegradação foram aplicados aos biofilmes de quitosana Sigma Aldrich® a 1%, resultando numa maior degradação para a composição a 1% / 50 UI de insulina (B1.3) e menor para a composição de quitosana a 1 % sem insulina (B1.1). Os ensaios de toxicidade demonstraram nas composições B, a viabilidade da utilização deste sistema como alternativa viável para o tratamento do Diabetes mellitus. / The use of biomaterials was induced to help people borned with problems in organs / tissue or people that acquired them by traumas. This demand was increased by the human beings prolonged life expectance. Recently in the area of biomaterials, many studies have been published, such as researches on drug delivery systems, biosensors and biomedical devices. One of the high incidences of chronic diseases in contemporary society is Diabetes mellitus type 1, which treatment consists of daily subcutaneous administration of insulin. The aim of this study was to develop biofilms composed of chitosan and insulin, towards an alternative to the injectable drug administration, using drug delivery systems to increase adherence to the treatment. Biofilms were developed from chitosan from two different suppliers and NPH insulin was used in two different concentrations. The films were characterized by the techniques of Wettability, Fourier Transform Infrared Spectroscopy (FTIR), X-ray Diffraction (XRD), Differential Scanning Calorimetry (DSC), Thermogravimetry (TG), Scanning Electron Microscopy (SEM), Enzymatic Biodegradation, Assessment of Viability and Determination of Macrophage Nitric Oxide Production. We found small differences in hydrophilicity of the samples observing wettability analysis. The results of FTIR and XRD confimed the formation of biofilms chitosan / insulin. The biofilms morphology didn’t change substantially, regardless the presence of insulin concentrations and the type of chitosan used, presenting a nature fibrous polymer characteristic morphology, typical for chitosan. Tests conducted by XRD showed a variation of crystallinity in the samples. The highest crystallinity was found for the chitosan (1%), Sigma Aldrich ®, 75% GD (B2.1) preparation and lowest for the chitosan (1.5%), Sigma Aldrich ®, GD 85%, plus 50 IU of insulin, (B1.4) preparation. The DSC observed three thermal events showing that insulin presence in preparations of low molecular weight was equivalent to the effects of that in preparations of high molecular weight. The TG showed a higher weight loss for preparations of chitosan without insulin. The biodegradation tests were applied to chitosan from Sigma Aldrich® 1% biofilms, and showed the highest degradation for the composition of 1% / 50 IU of insulin (B1.3) and the lowest for the composition of chitosan 1% without insulin ( B1.1). The toxicity tests showed the feasibility to use this system as a viable alternative for the treatment of Diabetes mellitus.

Les gels de fibrine présentent un fort intérêt en médecine régénérative, puisqu’ils miment la matrice temporaire créée lors de la cicatrisation. Cependant, quand préparés à concentration physiologique, ils ne sont pas manipulables, ni conservables à sec. Pour contrer ces désavantages, ils peuvent être associés à un autre réseau de polymères, dans une architecture de Réseaux Interpénétrés de Polymères (RIP). Cette approche a été utilisée pour associer à un réseau de fibrine, un coréseau semi-synthétique d’albumine de sérum bovin (BSA) et de poly(oxyde d’éthylène) (POE), obtenu par photopolymérisation de BSA et PEG modifiés avec des fonctions méthacrylate (BSAm, PEGDM).Il a été démontré par des tests ex vivo et in vitro que ces matériaux ont de multiples applications potentielles, puisqu’ils supportent à leur surface, la croissance de nombreux types cellulaires. De plus, il a été observé que ces matériaux peuvent servir comme vecteurs pour la délivrance de molécules d’intérêt thérapeutique.La technologie a d’ailleurs été optimisée, en utilisant non plus des précurseurs modifiés avec des fonctions méthacrylate, mais acrylate. Cette modification a permis de réduire la toxicité du procédé de synthèse, tout en conservant les performances des matériaux. Il a également été démontré que divers matériaux optimisés ont des mécanismes de dégradation différents, et contrôlables par leur formulation initiale.Enfin, deux nouvelles familles de RIPs à base de fibrine ont été développées, en associant à un réseau de fibrine, un autre réseau de protéine, la fibroïne de soie. Des RIPs parfaitement manipulables ont été obtenus, supportant à leur surface la culture de fibroblastes. Ces matériaux sont donc prometteurs pour l’ingénierie tissulaire de la peau et d’autres applications. / Fibrin gels are of interest in regenerative medicine, as they mimic the provisory matrix synthesized during wound healing process. However, when prepared at physiologic concentration, these gels cannot be handled, nor stocked in dry state. To face these drawbacks, they can be associated with another polymer network, in an Interpenetrating Polymer Network (IPN). This strategy was used to associate to a fibrin network, a semi-synthetic conetwork composed of bovine serum albumin (BSA) and poly(ethylene oxide) (PEO), obtained by photopolymerization of methacrylate-modified BSA and PEG.It was demonstrated through ex vivo and in in vitro experiments that these materials have numerous potential applications, as they support on their surface, the culture of numerous cell types. Moreover, it was observed that they may be used as drug carrier for drug release applications.Moreover, the technology was optimized by modifying the methacrylate functions on the precursors for acrylate functions. This modification allowed to reduce the toxicity of the process, while preserving materials performances. It was also demonstrated that these optimized materials have different degradation mechanisms, which are controllable by their initial formulation.Finally, 2 new groups of fibrin-based IPNs were developed, by associating to a fibrin network, another protein network, the silk fibroin. Perfectly handable IPNs were obtained, which support on their surface the culture of fibroblasts. These materials are then very promising for skin tissue engineering, and most likely other applications.