Homeostasis of hematopoietic stem cells (HSC) in the mammalian bone marrow stem cell niche is regulated by signals of the local microenvironment. Besides juxtacrine, endocrine and metabolic cues, paracrine and autocrine signals are involved in controlling quiescence, proliferation and differentiation of HSC with strong implications on expansion and differentiation ex vivo as well as in vivo transplantation. Towards this aim, a cell culture analysis on a polymer microcavity carrier platform was combined with a partial least square analysis of a mechanistic model of cell proliferation. We could demonstrate the discrimination of specific autocrine and paracrine signals from soluble factors as stimulating and inhibitory effectors in hematopoietic stem and progenitor cell culture. From that we hypothesize autocrine signals to be predominantly involved in maintaining the quiescent state of HSC in single-cell niches and advocate our analysis platform as an unprecedented option for untangling convoluted signaling mechanisms in complex cell systems being it of juxtacrine, paracrine or autocrine origin.

<p>Tumor angiogenesis is critical to tumor growth and metastasis, yet much is unknown about the role vascular cells play in the tumor microenvironment. A major outstanding challenge associated with studying tumor angiogenesis is that existing preclinical models are limited in their recapitulation of in vivo cellular organization in 3D. This disparity highlights the need for better approaches to study the dynamic interplay of relevant cells and signaling molecules as they are organized in the tumor microenvironment. In this thesis, we combined 3D culture of lung adenocarcinoma cells with adjacent 3D microvascular cell culture in 2-layer cell-adhesive, proteolytically-degradable poly(ethylene glycol) (PEG)-based hydrogels to study tumor angiogenesis and the impacts of neovascularization on tumor cell behavior. </p><p>In initial studies, 344SQ cells, a highly metastatic, murine lung adenocarcinoma cell line, were characterized alone in 3D in PEG hydrogels. 344SQ cells formed spheroids in 3D culture and secreted proangiogenic growth factors into the conditioned media that significantly increased with exposure to transforming growth factor beta 1 (TGF-β1), a potent tumor progression-promoting factor. Vascular cells alone in hydrogels formed tubule networks with localized activated TGF-β1. To study cancer cell-vascular cell interactions, the engineered 2-layer tumor angiogenesis model with 344SQ and vascular cell layers was employed. Large, invasive 344SQ clusters developed at the interface between the layers, and were not evident further from the interface or in control hydrogels without vascular cells. A modified model with spatially restricted 344SQ and vascular cell layers confirmed that observed 344SQ cluster morphological changes required close proximity to vascular cells. Additionally, TGF-β1 inhibition blocked endothelial cell-driven 344SQ migration. </p><p>Two other lung adenocarcinoma cell lines were also explored in the tumor angiogenesis model: primary tumor-derived metastasis-incompetent, murine 393P cells and primary tumor-derived metastasis-capable human A549 cells. These lung cancer cells also formed spheroids in 3D culture and secreted proangiogenic growth factors into the conditioned media. Epithelial morphogenesis varied for the primary tumor-derived cell lines compared to 344SQ cells, with far less epithelial organization present in A549 spheroids. Additionally, 344SQ cells secreted the highest concentration of two of the three angiogenic growth factors assessed. This finding correlated to 344SQ exhibiting the most pronounced morphological response in the tumor angiogenesis model compared to the 393P and A549 cell lines. </p><p>Overall, this dissertation demonstrates the development of a novel 3D tumor angiogenesis model that was used to study vascular cell-cancer cell interactions in lung adenocarcinoma cell lines with varying metastatic capacities. Findings in this thesis have helped to elucidate the role of vascular cells in tumor progression and have identified differences in cancer cell behavior in vitro that correlate to metastatic capacity, thus highlighting the usefulness of this model platform for future discovery of novel tumor angiogenesis and tumor progression-promoting targets.</p> / Dissertation

Objetivo: Avaliar as modificações estruturais do pericárdio bovino após hidrólise seletiva de grupos carboxiamidas em carboxílicos e resposta biológica em defeitos ósseos reparados com as matrizes de colágeno aniônico. Material e métodos: Amostras das matrizes modificadas foram comparadas com amostras de pericárdio bovino nativo através de microscopia óptica e de microscopia eletrônica de varredura. A resposta biológica foi avaliada implantando fragmentos das matrizes em trepanações criadas em tíbias de ratos. O reparo dos defeitos foi estudado 3, 7, 15 e 30 dias pós-implantação usando-se microscopia óptica. Resultados: O processo de hidrólise seletiva de grupos carboxamidas em carboxílicos removeu completamente as células intersticiais do pericárdio bovino e transformou a estrutura compacta e fibrilar do colágeno nativo em uma estrutura esponjiforme. Além disso, foi observado que as matrizes modificadas permitiram o reparo das trepanações ósseas com a formação de osso trabecular, sem induzir nenhuma reação adversa. Conclusões: A hidrólise utilizada aplicada ao pericárdio bovino produz uma matriz acelular com poros distribuídos na sua estrutura. Essas matrizes são biocompatíveis, não induzem reação inflamatória e permitem o reparo de trepanações ósseas experimentalmente induzidas. / Objective: Evaluate the structural modifications in the bovine pericardium after selective hydrolysis of carboxiamides groups into carboxilic and the biological response in bone defects repaired using the anionic collagen matrices. Material and methods: Samples of the modified matrices were compared to samples of native bovine pericardium using light microscopy and scanning electron microscopy. The biological response were evaluated implanting fragments of the matrices into defects made in rat tibias. The repair of the defects were evaluated 3, 7, 15, and 30 days after implantation using light microscopy. Results: The process of selective hydrolysis of carboxiamides groups into carboxilic completely removed the interstitial cells of the bovine pericardium and turned the compact and fibrilar structure of native collagen into a sponge-like structure. Besides, it was observed that the modified matrices allowed the repair of the bone defects through the formation of cancellous bones, without any side reaction. Conclusions: The used hydrolysis applied to bovine pericardium produces a acellular matrix with pores distributed along its structure. These matrices are biocompatible, they do not induce any inflammatory reaction and allow the repair of experimentally induced bone defects.

A contaminação dos implantes e seus componentes protéticos por patógenos específicos, ainda é um problema a ser resolvido na Implantodontia. Nanoestruturas associadas à prata, aplicadas em superfície de titânio, têm sido investigadas e vêm demonstrando inibir significativamente a adesão, crescimento e colonização de uma vasta gama de microrganismos patogênicos, inclusive os resistentes a antibióticos. O objetivo deste experimento foi verificar a presença de toxicidade de nanoestruturas associadas à prata, aplicadas à superfície de titânio, frente a cultura de osteoblastos, visando desenvolver um material biocompatível, promissor na corrida pela prevenção da colonização bacteriana dos implantes. Discos de titânio comercialmente puro foram revestidos com três tipos diferentes filmes nanoestruturados. As amostras foram expostas a culturas de linhagens imortalizadas de osteoblastos (MC3T3-E1) e submetidas a ensaios de toxicidade direta (MTT), após 24h, 48h e 72h de incubação, a fim de determinar a taxa de proliferação e redução da viabilidade celular. Além disso, para verificar adesão e morfologia celular, foi realizada Microscopia Eletrônica de Varredura (MEV) após 24h de incubação. No ensaio de toxicidade celular MTT, após 48h de incubação, as superfícies nanoestruturadas, nomeadas TiAg, TiAA e SiO2, comportaram-se de maneira muito similar ao grupo controle de titânio puro (Ti) (p<0,05). O grupo SiO2 registrou maior absorbância em 24h, com diferença relevante em relação a todos os outros grupos (testes e controles). Em MEV foram verificadas uma morfologia celular compatível com viabilidade e presença de adesão dos osteoblastos em todas as superfícies testadas, similar aos grupos controles. Dessa forma, verificou-se que os três filmes nanoestruturados demonstraram biocompatibilidade a osteoblastos. / Contamination of implants and their prosthetic components by specific pathogens is still a problem to be solved in Implantology. Nanostructures associated to silver applied on titanium surface have been investigating, and have showing to inhibit significantly the adhesion, and growth of a broad range of pathogenic microorganisms, including antibiotic-resistant ones. The aim of this experiment was to verify the presence of toxicity in nanostructures associated to silver applied to titanium surface against osteoblast culture, in order to develop a biocompatible promising material in the race for prevention on implants bacterial colonization. Each commercially pure titanium disk received one of three different nanostructured films: SiO2, TiAg, and TiAA. Samples have exposed to cultures of immortalized lines osteoblasts (MC3T3-E1), and submitted to direct toxicity assay (MTT) after 24h, 48h and 72h of incubation to determine the proliferation rate and cell viability reduction. Furthermore, to verify adhesion and cell morphology, Scanning Electron Microscopy (SEM) has performed after 24h incubation. The 48h MTT cell toxicity assay showed similarity in results among test surfaces and pure titanium control group (Ti) (p <0.05). The SiO2 group registered higher absorbance in 24h, with significant difference regarding to all other groups (tests and controls). SEM exhibited cell morphology indicative of viability, and presence of osteoblast adhesion on all test surfaces, similar to control groups. Thus, it found of that three nanostructured films demonstrated osteoblasts compatibility.

Orientador: Rui Seabra Ferreira / Resumo: Desenvolvido em 1990 por um grupo de pesquisadores do Centro de Estudo de Venenos e Animais Peçonhentos (CEVAP), no Estado de São Paulo, Brasil, o Biopolímero de Fibrina (BPF) possuía o principal objetivo de ser um adesivo à base de fibrina sem o uso de sangue humano, a fim de evitar a transmissão de doenças infecciosas por meio deste insumo. Após diversas pesquisas com o BPF, comprovou-se não somente sua capacidade adesiva, como também sua ação coagulante, sua ação como auxiliar no reparo ósseo e cartilaginoso e sua função como arcabouço para células-tronco mesenquimais (CTMs), devido ao fato de que o BPF possui uma estrutura tridimensional adequada. Em estudos recentes e ao exercer essa função, tal material não afetou o microambiente biológico das células, ou seja, permitiu a adesão, proliferação e diferenciação celular, e aderência e crescimento destas. Tais características, apresentadas pelo BPF, são desejáveis na maioria dos biopolímeros utilizáveis, o que ressalta a importância do aprofundamento das pesquisas com BPF e suas interações em experimentos in vivo. Assim, no capítulo 1 realizamos uma ampla revisão na literatura sobre biopolímeros de fibrina, células-tronco e reparação de tecido ósseo. No capítulo 2 é apresentado o artigo científico “Arcabouço de fibrina para células-tronco mesenquimais como potencial osteogênico”. / Abstract: Developed in 1990 by a group of researchers from the Center for the Study of Venomous and Poisonous Animals (CEVAP) in the State of São Paulo, Brazil, the Fibrin Biopolymer (GMP) had the main objective of being a fibrin-based adhesive without the use of human blood in order to avoid the transmission of infectious diseases by means of this input. After several investigations with BPF, it was verified not only its adhesive capacity, but also its coagulant action, its action as an aid in bone and cartilage repair and its function as a framework for mesenchymal stem cells (MSCs), due to the fact that the BPF has an adequate three-dimensional structure. In recent studies and in carrying out this function, such material did not affect the biological microenvironment of the cells, that is, it allowed cell adhesion, proliferation and differentiation, and adhesion and growth of these cells. These characteristics, presented by BPF, are desirable in most usable biopolymers, which underscores the importance of deepening GMP research and its interactions in in vivo experiments. Thus, in Chapter 1 we conducted a broad review in the literature on biopolymers of fibrin, stem cells and repair of bone tissue. In chapter 2 the scientific paper "Fibrin scaffold for mesenchymal stem cells as osteogenic potential" is presented. / Doutor

O titânio comercialmente puro (Ti-Cp) e suas ligas destacam-se como biomateriais metálicos devido a sua biocompatibilidade sendo amplamente utilizados. Buscando aprimorar o sucesso clínico dos implantes de Ti-Cp em longo prazo, é necessário revestir a sua superfície, proporcionando uma eficiente ancoragem mecânica do implante com o tecido ósseo. Dentre os diversos revestimentos superficiais destacam-se os revestimentos híbridos orgânicos-inorgânicos à base de precursores alcóxidos de silício, obtidos via processo sol-gel. Para que ocorra uma satisfatória adesão do revestimento no substrato, precisa-se levar em consideração a natureza e a preparação da superfície metálica antes da aplicação deste revestimento. Na etapa inicial do trabalho, pré-tratamentos superficiais foram propostos previamente à aplicação dos revestimentos buscando aumentar a aderência entre o titânio e este revestimento híbrido. Utilizou-se três diferentes pré-tratamentos na superfície do Ti-Cp: o "piranha" (ácido sulfúrico e peróxido de hidrogênio), o "kroll" (ácido fluorídrico, ácido nítrico e água) e o "hidróxido de sódio". Em sequência, aplicou-se por processo de dip-coating sobre as superfícies tratadas, um revestimento híbrido produzido a partir dos precursores alcóxidos de silício tetraetoxisilano (TEOS) e metiltrietoxisilano (MTES), obtido pelo processo de sol-gel. Em uma segunda etapa, sobre a superfície do Ti-Cp com o pré-tratamento superficial que proporcionou uma maior aderência do revestimento híbrido ao titânio, aplicou-se por dip-coating, um revestimento híbrido à base de precursores alcóxidos de silício TEOS e MTES com adição de partículas de hidroxiapatita buscando aprimorar a diferenciação celular sobre o revestimento híbrido. O pré-tratamento com o hidróxido de sódio promove o melhor resultado dentre os pré-tratamentos, pois o revestimento híbrido aplicado posteriormente apresenta recobrimento regular e adesão ao substrato de Ti-Cp. Os resultados morfológicos por MEV-FEG mostraram um revestimento híbrido com boa dispersão da hidroxiapatita e um recobrimento regular e adesão ao substrato de Ti-Cp. Nos resultados biológicos Ti-Cp revestido com TEOS/MTES com a presença de partículas de hidroxiapatita obteve uma adesão celular semelhante ao Ti-Cp sem tratamento. Porém este mesmo revestimento não propiciou a proliferação e diferenciação celular. Os resultados indicaram que a combinação de fatores como a sua superfície hidrofóbica (91°) e a presença da hidroxiapatita no revestimento tornou a superfície desorganizada, acarretando em uma superfície com comportamento desfavorável para o desenvolvimento das células-tronco mesenquimais. / Commercially pure titanium (cp-Ti) and its alloys stand out among the metallic materials due to their biocompatibility being widely used in biomaterials. In order to improve the clinical success of cp-Ti implants in the long term, it is necessary to coat the surface, providing an efficient mechanical anchoring of the implant with the bone tissue. Among the various surface coatings are the hybrid coatings based on silicon alkoxide precursors, obtained by the sol-gel process, however, considering the nature and the preparation of the metal surface prior to the application of this coating. In the initial stage of the work, surface pre-treatments were proposed prior to the application of the coatings seeking to increase the adhesion between the titanium and this hybrid coating. Three different pretreatments were used on the cp-Ti surface: "piranha" (sulfuric acid and hydrogen peroxide), "kroll "(hydrofluoric acid, nitric acid and water) and "sodium hydroxide". Subsequently, a hybrid coating produced by the tetraethoxysilane silicon (TEOS) and methyltriethoxysilane (MTES) precursors obtained by the sol-gel process was applied by the dip-coating process onto the treated surfaces. In a second step, on the surface of the cp-Ti with the surface pretreatment that gave a greater adhesion of the hybrid coating to the titanium, dip-coating, a hybrid coating based on precursors silicon alkoxides TEOS and MTES with the addition of hydroxyapatite particles to enhance cell differentiation on the hybrid coating. Pretreatment with sodium hydroxide promotes the best result among the pre-treatments, since the hybrid coating applied afterwards presents regular coating and adhesion to the cp-Ti substrate. The morphological results by SEM-FEG showed a hybrid coating with good dispersion of the hydroxyapatite and a regular coating and adhesion to the cp-Ti substrate. In the biological results Ti-Cp coated with TEOS / MTES with the presence of hydroxyapatite particles obtained a cell adhesion similar to Ti-Cp without treatment. However, this same coating did not promote cell proliferation and differentiation. The results indicated that the combination of factors such as its hydrophobic surface (91°) and the presence of the hydroxyapatite encapsulated in the coating rendering the surface disorganized led to a surface with unfavorable behavior for the development of mesenchymal stem cells.

Dans le cas d'une tumeur pancréatique, la chirurgie d'exérèse est le traitement de première intention lorsqu'elle est possible. Les pancréatectomies sont des actes à haut risque, entraînant un taux de morbidité de 50%. L'une des complications les plus graves est l'apparition de fistules pancréatiques (FP) qui surviennent dans 15 à 20 % des cas, pour lesquelles il n'existe aucune solution de prévention. Cette thèse porte sur l'élaboration d'un biomatériau pour la prévention des FP. Le cahier des charges, défini avec l'équipe chirurgicale, nous a orienté vers un dispositif médical sous forme de pansement absorbant, présentant des propriétés mécaniques adaptées, ainsi qu'une résistance aux enzymes pancréatiques serait intéressant. Un biomatériau constitué de deux couches a été imaginé : 1) une matrice absorbante constituée d'un complexe polyélectrolyte (PEC) sous forme de film, 2) une couche supérieure imperméable permettant de limiter la diffusion des enzymes pancréatiques dans le milieu péritonéal ; afin de répondre aux spécifications demandées par l'équipe médicale. La première partie de ce travail a porté sur l'optimisation de la mise en forme de la matrice sous forme de film à partir de PEC d'alginate (ALG) et de chitosane (CHI) présentant différents ratio de polymères (ALG-CHI 50/50 et ALG-CHI 63/37). L'influence de la technique d'homogénéisation des PEC, sous ultra-turrax (UT) ou au Stephan (ST) a été étudiée sur les propriétés physico-chimiques des films obtenus. Les propriétés de biodégradation, de gonflement et de cytotoxicité sont principalement influencées par le ratio des polymères. En revanche, leurs structure et propriétés mécaniques sont essentiellement influencées par la technique d'homogénéisation utilisée lors de l'élaboration du PEC. Au vu de ces résultats, le choix de la matrice au contact de l'anastomose ou de la tranche pancréatique s'est arrêté sur le PEC ALG-CHI 63/37 UT. La deuxième partie de cette thèse a été consacrée à l'incorporation d'une couche imperméable à la surface supérieure du film. Deux polymères ont été testés : l'acide polylactique (PLA) et le polycaprolactone (PCL). Ils ont été incorporés après fonctionnalisation de la surface du film. La matrice ALG-CHI 63/37 UT recouverte de PLA présente une surface plus hydrophobe, des propriétés mécaniques adaptées, une bonne résistance aux enzymes pancréatiques tout en possédant des propriétés de gonflement intéressantes. Le biomatériau ainsi obtenu est un bon candidat qui répond au cahier des charges d'un pansement indiqué pour la prévention des fistules pancréatiques. / Resection surgery is the first-line treatment indicated for pancreatic tumor. The morbidity of this surgery is high with a complication rate around 50%. One of the most serious complications is the occurrence of pancreatic fistula (PF), which occurs in 15-20% of cases. To date, no biomaterial available on the market is indicated for the prevention of the onset of PF following pancreatectomy. This project focuses on the development of a biomaterial for the prevention of PF. Specifications identified by the surgical team oriented us to ward an absorbent dressing with sufficient mechanical properties and pancreatic enzymes resistance. A biomaterial made up of two layers was designed: 1) an absorbent matrix, in the form of a film, constituted by a polyelectrolyte complex (PEC), 2) an impermeable backing layer expected to limit the diffusion of the pancreatic enzymes into the peritoneal medium; to meet surgeons' specifications. The first part of this work focused on the optimization of the preparation of the matrix, composed of alginate (ALG) and chitosan (CHI) PECs films with different polymer ratios (ALG-CHI 50/50and ALG-CHI 63/37). The influence of the technique of homogenization of PEC, ultra-turrax (UT) or Stephan (ST) was studied on the physicochemical properties of the films. Biodegradation, swelling and cytotoxicity were shown to be mainly influenced by the ratio of polymers used. On the other hand, structure and mechanical properties are mainly influenced by the homogenization technique. With these results, the choice of the matrix to pancreatic application was set as the PEC ALG-CHI 63/37 UT. The second part of the present work was devoted to the incorporation of an impermeable backing layer on the upper film surface. Two polymers were evaluated: polylactic acid (PLA) and polycaprolactone (PCL). They were incorporated after the functionalization of the film surface. The PLA-coated ALG-CHI 63/37 UT matrix led to more hydrophobic surfaces, as well as adaptated mechanical properties and resistance to pancreatic enzymes with interesting swelling properties. The obtained biomaterial is a promising candidate responding to the specifications for a dressing indicated for the prevention of PF.

"Bacterial infections persist as a public threat due to the ease by which bacteria adapt to commonly used antibiotics. In addition, bacteria on surfaces develop protective communities called biofilms that hinder the ability of antibiotics to completely eliminate the pathogens. The rapid development of bacterial resistance to antibiotics has made pharmaceutical companies reluctant to fund new antibiotics research. Hence, novel approaches to prevent and treat infections are needed. The development of infections can be divided into three steps: adhesion, invasion and multiplication. Antibiotics target at the latter two step and are prone to bacterial resistance as passive strategies. Bacterial adhesion to host cells/implanted medical devices is the first step leading to following invasion and multiplication. However, fundamental understanding of bacterial adhesion process is still lacking. The current studies are aimed to systematically investigate biological interactions between pathogenic bacteria and host cell, proteins and biomaterials with both macro and micro scale approaches. The macro scale methods include bacterial adhesion assay, viability studies, and thermodynamic modeling. The micro scale methods include direct adhesion force measurements, ultra surface visualization via atomic force microscopy (AFM) and surface structure modeling. Our work combines experiments and modeling aimed at understanding the initial steps of the bacterial adhesion process, focusing on two case studies: 1) Mechanisms by which cranberry can prevent urinary tract infections through interfering with bacterial adhesion; and 2) Design of anti-adhesive and antimicrobial coatings for biomaterials. We make direct adhesion force measurements between bacteria and substrates with an atomic force microscope (AFM), and combine such experiments with thermodynamic calculations, in order to develop a set of tools that allows for the prediction of whether bacteria will attach to a given surface. These fundamental investigations of the bacterial adhesion process help elucidate the underlying mechanisms behind bacterial adhesion, thus leading to improved clinical outcomes for a number of biomedical applications. "

A ortopedia e a odontologia têm especial interesse às tecnologias biocompatíveis que apresentam a fase alfa do fosfato tricálcico (α-TCP), pois estas são capazes de formar hidroxiapatita deficiente em cálcio, similar à óssea. Porém, a baixa resistência mecânica limita sua aplicação. A fim de superar essa limitação, foi agregada acrilamida ao cimento α-TCP, com redutor de líquido, originando o cimento α-TCP de dupla pega. A partir disso foram desenvolvidos compostos à base de cimento de α-TCP e α-TCP de dupla pega agregados dos fármacos sulfato de gentamicina, cloridratos de lidocaína, bupivacaína e levobupivacaína e testada sua funcionalidade como sistemas de liberação de fármacos. Não existem dados bibliográficos sobre liberação de fármacos por sistemas de cimento α-TCP de dupla pega. A metodologia utilizada foi qualiquantitativa. Para as diferenças analíticas considerou-se o intervalo de confiança de 95% com nível de significância menor que 5% (p<0,05). O estudo compreendeu três fases. Na Fase 1 foram elaborados corpos de prova à base de cimento α-TCP e α-TCP de dupla pega com e sem (grupo-controle) adição de fármacos. Na Fase 2 os biomateriais estudados foram caracterizados por difração de raios X, espectroscopia de absorção no infravermelho com transformada de Fourier, microscopia eletrônica de varredura, resistência mecânica a compressão axial, densidade, porosidade e absorção de líquido; sendo também proposta a análise da porosidade por meio de imagens. A Fase 3 corresponde ao estudo da cinética da liberação dos fármacos in vitro, onde os corpos de prova foram imersos em solução tampão fosfato pH 7,0 e as amostras analisadas por meio de UV-vis. A liberação do antibiótico também foi avaliada por Espectroscopia de Impedância Eletroquímica (EIS), como proposta inovadora. Conforme os resultados, ambos os cimentos funcionaram como sistemas de liberação dos fármacos. Tanto o sistema hidrogel, quanto os fármacos não modificaram as propriedades estruturais do cimento. O sistema com hidrogel apresentou melhor resistência mecânica. A difusão Fickiana foi o principal mecanismo envolvido no processo de liberação dos fármacos, com menor influência do relaxamento das cadeias. A técnica de EIS mostrou-se promissora para avaliação de liberação de fármacos. / To better regulate it is necessary to know the new Technologies. Orthopedics and dentistry have demonstrated special interest in biocompatible technologies that present the alpha phase of tricalcium phosphate (α-TCP), whit can form calcium-deficient hydroxyapatite (like bone hydroxyapatite). However, its application is limited by the low mechanical resistance. To overcome this limitation, acrylic hydrogel containing liquid reducer was added to the α-TCP cement, resulting in the α-TCP double setting cement. From this, composites of α-TCP and α-TCP double setting cements aggregates of the drugs gentamicin sulfate, lidocaine, bupivacaine and levobupivacaine hydrochlorides were developed and the functionality drug delivery systems was tested. There isn't bibliographic data about drugs release systems by α-TCP double setting cement. Qualitative and quantitative methodologies were applied. For the analytical differences, we considered the 95% confidence interval with a level of significance lower than 5% (p <0.05). It comprised three different phases. In Phase 1, an α-TCP and α-TCP double setting cement specimens were prepared with and without (control group) drugs addition. In Phase 2, the studied biomaterials were characterized by X-ray diffraction, Fourier transform infrared spectroscopy, scanning electron microscopy, compression mechanical resistance, density, porosity and liquid absorption, being also proposed of the porosity analysis by images. The Phase 3 corresponds to the study of the in vitro drug release kinetics. The specimens were immersed in phosphate buffer solution pH 7.0 and the samples analyzed by UV-vis. As an innovative proposal, drug release was also assessed using Electrochemical Impedance Spectroscopy (EIS). According to the results, both cements functioned as controlled drug delivery systems. The hydrogel improved the properties of cement moreover the drugs did not impair these properties. Fick diffusion was the main mechanism involved in the process of drug release by composites, with a minor influence of polymer chain relaxation. The EIS technique proved to be promising for the evaluation of drug release.

Tese (doutorado)—Universidade de Brasília, Faculdade de Tecnologia, Departamento de Engenharia Mecânica, 2018. / Este trabalho apresenta pesquisa pioneira voltada para a redução de consumo energético em edificações utilizando materiais provenientes da flora e fauna brasileira, os bioPCMs. Nos capítulos iniciais, características identificadas como essenciais a um material de mudança de fase são confrontadas contra aquelas encontradas em ácidos graxos e derivados, permitindo o entendimento do potencial destes como alternativa aos materiais tradicionais. Observou-se, nesse momento, que bioPCMs são capazes de atuar de forma semelhante a materiais de mudança de fase tradicionais, porém reduzindo consideravelmente a pegada carbônica associada à sua produção. Há, porém, uma carência local de metodologias e aparatos capazes de identificar possíveis bioPCMs, ponto diretamente abordado pela pesquisa. Desenvolveu-se, assim, uma rede de procedimentos que se inicia pela caracterização do material, que por sua vez é submetido a uma análise de transferência de calor e, finalmente, a uma simulação de operação em condições de uso. A análise das propriedades termo-físicas foi realizada para cinco candidatos, segundo procedimento conhecido como T-history. Os resultados foram satisfatórios, permitindo que parâmetros como calor latente de fusão, calor específico, temperatura de mudança de fase, temperatura de sub-resfriamento e condutividade fossem caracterizados. Identificou-se, ali, o óleo de coco como o material com maior potencial para as aplicações pretendidas. Para o estudo de transferência de calor, optou-se por analisar um caso baseado no problema clássico de Stefan, onde o material é armazenado em um reservatório retangular. Desenvolvidos a partir de técnicas utilizadas por outros autores, como Viskanta, Campbell e Kamkari, a metodologia e aparato experimental apresentados permitiram a observação e caracterização do fronte de fusão e solidificação do material de mudança de fase.Finalmente, o óleo de coco foi inserido em um sistema de carregamento e descarregamento energético que simula condição de operação similar ao encontrado em aplicações de resfriamento noturno em locais de clima tropical de savana. Ao final do processo, observou-se que, apesar de cada estágio anterior ser capaz de cumprir seu propósito individual, seja ele de caracterização do material ou do processo de transferência de calor, apenas ao combinar os resultados que a compreensão plena da aplicabilidade do elemento estudado foi obtida. Por exemplo, normalmente estudos de caracterização limitam-se a definir dados como temperatura de fusão ou calor latente de mudança de fase. Apesar de importante, observou-se que esses dados poderiam levar a problemas de dimensionamento de um sistema contendo ácidos graxos, por desconsiderar o impacto que o sub-resfriamento teria na capacidade e velocidade de armazenamento energético. / In the current thesis, a research on the identification and characterization of phase change materials (PCMs) produced from renewable sources, the bioPCMs, is introduced. The document dedicates its initial chapters to the bibliographic review on the study of PCMs used for building thermal demand control. The characteristics identified as essential to a PCM are compared against those found in fatty acids and derivatives, allowing an understanding of their potential as an alternative to traditional materials. It was observed that bioPCMs are able to act similarly to paraffins. Additionally, bioPCMs can be extracted from pre-existing production chains, as a by-product or as waste, greatly reducing the environmental impact of their adoption. There is, however, a local lack of methodologies and devices capable of identifying possible bioPCMs, a point directly addressed by the research. A chain of procedures was developed that begins with the characterization of the material, which in turn is subjected to a heat transfer analysis and, finally, to a practical simulation of operational conditions. The analysis of the thermo-physical properties was performed for seven candidates, according to a procedure known as T-history. The results were satisfactory, allowing parameters such as enthalpy of fusion, specific heat, melting temperature, sub-cooling temperature and conductivity to be characterized. For the study of heat transfer, a classical Stefan problem, where the material is stored in a rectangular container,was chosen. Based on techniques used by other authors such as Viskanta, Campbell and Kamkari, the developed methodology and experimental apparatus allowed the characterization of the melting and solidification fronts of a non-renewale PCM,the n-eicosane, used as reference, and a bioPCM, the coconut oil. The oil was then inserted into an energy loading and unloading system that simulates night cooling operating conditions.At the end of the process it was observed that, although each stage was able to fulfill its individual purpose, be it characterization of the material or of the heat transfer process, only by combining the results that the full understanding of the material applicability was obtained. For example, typically, characterization studies are limited to defining data such as melting temperature or enthalpy of fusion. Although important, it was observed that these data alone could lead to energy system design issues such as disregarding the impact that sub-cooling would have on the energy storage capacity and response time.