Le contrôle de la qualité des ressources en eau nécessite des outils de détection en continu et in situ. Dans ce contexte, les biocapteurs sont prometteurs dans le développement de nouveaux systèmes pour une détection précoce. On peut citer deux exemples dans des domaines aussi variés que la détection précoce de corrosion bactérienne ou la détection de la formation d'espèces biologiques responsables de maladies dégénératives.Ce travail propose la conception et la réalisation d'un biocapteur pour la détection de molécules d'intérêt biologiques. La réalisation de ce biocapteur est basée sur le dépôt de matériaux hybrides organiques/inorganiques à la surface d'un transducteur piézoélectrique.La première étape consiste à développer des matériaux fonctionnalisés innovants permettant l'encapsulation d'espèces biologiques. Pour cela deux voies ont été étudiées. La première passe par l'utilisation d'un acrylate type "acide aminé" le N-acryloyglycine (NAGly) permettant la synthèse de matériaux sous forme de film. La seconde utilise un autre type d'acrylate, le N-acryloxysuccinimide (NAS) couplé au 2-hydroxyethylacrylate (HEA) aboutissant un hydrogel fonctionnalisé. Les différentes mesures montrent que dans tous les cas, ces réseaux sont interpénétrés et permettent l'encapsulation de biomolécules.Pour la détection de ces espèces, un biocapteur piézoélectrique est développé dans la deuxième étape. Un dispositif expérimental développé au laboratoire assure la mesure et le suivi de l'évolution des propriétés viscoélastiques d'un matériau en contact avec un transducteur piézoélectrique. En effet, ces propriétés caractéristiques sont extraites à partir d'un modèle électrique original tenant compte simultanément des évolutions électriques et mécaniques du matériau. Ce capteur (transducteur + matériau déposé en surface) mis au contact avec les biomolécules permet leur détection et quantification.Les résultats montrent une corrélation entre le module visqueux du biocapteur et la concentration en biomolécules du milieu en contact. Cette corrélation est une première étape vers le développement d'un biocapteur piézoélectrique pour la détection et la quantification sélective de différentes espèces biologiques en solution. / The control of the quality of water resources requires tools for continuous and in-situ detection. In this context, biosensors are interesting in the development of new systems for early detection. For examples we can note the interest in the early detection of bacterial corrosion or the formation of biological species responsible of degenerative diseases.This work proposes the design and implementation of a biosensor for the detection of biological molecules. The realization of this biosensor is based on the deposition of organic/inorganic materials on the surface of a piezoelectric transducer.The first step is the development of innovative functionalized materials for encapsulation of biological species. For this, two approaches have been studied. The first involves the use of an "amino acid" acrylate, the N- acetylglycine (Nagly) for the synthesis of thin film. The second uses an other acrylate, the N- acryloxysuccinimide (NAS) copolymerized with 2- Hydroxyethyl acrylate (HEA) to form a functionalized hydrogel. The different measures show that in all cases, these networks are interpenetrating and allow the encapsulation of biomolecules.For the detection of these species, a piezoelectric biosensor is developed in the second step. An experimental device, developed in the laboratory, measures and monitors the evolution of the viscoelastic properties of a material in contact with a piezoelectric transducer. Indeed, these characteristics are extracted from an original electric model that take into account simultaneous electrical and mechanical changes in the material. This sensor (transducer and material deposited on the surface) in contact with biomolecules, enables the detection and quantification of these biomolecules.The results show a correlation between the viscous modulus of the biosensor and the concentration of biomolecules in contact. This correlation is a first step in the development of a piezoelectric biosensor for detection and selective quantification of different biological species in solution.

Le phénomène de biofouling affecte toute surface immergée dans un milieu aqueux, le recouvrant par un biofilm que ce soit dans le milieu médical ou marin. Afin de lutter contre ce phénomène, lors de ce travail, des matériaux biosourcés à base d’alginate ont été élaborés. Pour des applications dans le milieu médical, des films d’hydrogel de surface lisse ou poreuse et des films déposés sur acier par électrophorèse ont été élaborés. La présence de cuivre et zinc sous leur forme ionique Cu2+ et Zn2+ a été démontrée. Tous les films à base de cuivre et de zinc ont montré des propriétés antibactériennes contre des souches de bactéries pathogènes. Des volumes d’hydrogel d’alginate à base de calcium, cuivre et zinc ont été aussi élaborés pour des applications dans le monde marin. La stabilité des différents matériaux a été étudiée dans différents milieux et à différentes températures. La propriété antimicrobienne de ces hydrogels a été démontrée sur deux souches de microalgues ainsi que sur quatre souches de bactéries marines sans toxicité. Finalement, le retardement de la formation de biofilms sur la surface d’acier inoxydable a été étudié par la méthode d’OCP en présence de matériaux à base de zinc. / Biofouling is a phenomenon that affects every surface that is immersed in an aquatic medium covering it by a biofilm either in the medical or marine field. In order to prevent this phenomenon, in this work, biosourced alginate materials were elaborated. For applications in the medical field, hydrogel films of smooth or porous surface and films coating stainless steel by electrophoresis were elaborated. The presence of copper and zinc in their ionic form Cu2+ and Zn2+ was demonstrated.All the copper and zinc based films showed antibacterial properties on pathogenic bacterial strains.Alginate hydrogels in bulk based on calcium, copper and zinc were also elaborated for applications in the marine field. Stability of the different materials was studied in different mediums and at different temperatures. The antimicrobial property of these hydrogels based on copper and zinc was demonstrated on two microalgae stains as well as on four marine bacteria strains with no sign of toxicity. Finally, the delay in the formation of biofilms on stainless steel surfaces was studied by the OCP method in the presence of zinc based materials.

Submitted by Aline Lins de Lima (alineodontoufpb@yahoo.com.br) on 2018-08-07T17:00:06Z No. of bitstreams: 1 Tese ALLima.pdf: 1544888 bytes, checksum: abad9299fa11bc8ebf7e2fcbbc8c6aff (MD5) / Approved for entry into archive by Silvana Alvarez null (silvana@ict.unesp.br) on 2018-08-16T13:18:18Z (GMT) No. of bitstreams: 1 lima_al_dr_sjc.pdf: 1544888 bytes, checksum: abad9299fa11bc8ebf7e2fcbbc8c6aff (MD5) / Made available in DSpace on 2018-08-16T13:18:19Z (GMT). No. of bitstreams: 1 lima_al_dr_sjc.pdf: 1544888 bytes, checksum: abad9299fa11bc8ebf7e2fcbbc8c6aff (MD5) Previous issue date: 2018-06-08 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / A estomatite protética é uma das afecções mais comuns e recorrentes em pacientes portadores de próteses totais. O fungo do gênero Candida, promotor dessa patologia, além de resistente se torna ainda mais complexo de ser combatido devido à dificuldade da ação de fármacos tópicos que só conseguem permanecer por um curto período no local da infecção, em virtude da dinâmica da cavidade bucal. O processo de Solution Blow Spinning permite a obtenção de fibras ultrafinas que podem ser aplicadas em vastas áreas, inclusive na bioengenharia. Uma das aplicabilidades das fibras ultrafinas é sua utilização para liberação controlada de fármacos de forma eficiente e duradoura. Dessa forma, o intuito do presente trabalho foi incorporar Cinamaldeído (CA), composto que possui propriedades antimicrobianas, a mantas de Poli(ácido lático) e Poli(etileno glicol) (PLA/PEG) e avaliá-las quanto à produção e caracterização por, Microscopia eletrônica de varredura (MEV), Termogravimetria (TGA), Calorimetria Exploratória Diferencial (DSC), Espectroscopia de infravermelho por transformada de Fourier (FTIR), Espectroscopia no ultravioleta visível (UV/vis), ensaios mecânicos e ação antifúngica. Para realização dos experimentos, foram fiadas as seguintes mantas: PLA, PLA/PEG e PLA/PEG 23,8% CA. As micrografias obtidas por MEV mostraram, que os diâmetros das fibras que não continham CA, apresentaram diâmetros semelhantes entre si, PLA (354±160 nm)a e PLA/PEG (428±250nm)a, sendo esses diâmetro menores dos que encontrados nas fibras de PLA/PEG 23,8% CA (749±370 nm)b . O ângulo de contato e tensão superficial não puderam ser verificados em virtude da proporção de polímeros nas blendas que apresentaram alta afinidade pelos solventes utilizados no teste. No ensaio de TGA, a curva de PLA/PEG com acréscimo de 23,8% CA exibiu uma maior estabilidade térmica. No teste de DSC o ponto de transição vítrea das mantas contendo 23,8% CA foi o que apresentou menor valor. A liberação de CA foi satisfatória ocorrendo até o 12° dia. No teste de ensaios mecânicos, o acréscimo de CA às mantas aumentaram significativamente o Módulo elástico (24,94±4,45) e a Tensão máxima de ruptura (0,99±0,16 MPa) com relação às mantas puras de PLA/PEG (18,74±3.41 MPa) and (0,85±0.09 MPa), esse acréscimo ainda promoveu redução estatisticamente significante (p˂ 0,05%) em mais de 50% nos biofilmes monotípicos de C. albicans e C. krusei e no multiespécie de C. albicans, C. krusei e C. glabrata. Mediante os resultados encontrados pode-se depreender que é possível se obter mantas de fibras ultrafinas de PLA/PEG contendo 23,8% de CA com propriedades antifúngicas e capacidade de liberação do agente antimicrobiano por cerca de 12 dias. / Denture stomatitis is one of the most common and recurrent conditions in patients with total dentures. The fungal of the genus Candida, the causer of this pathology, besides being resistant, becomes even more complex to be combated due to the difficulty of the action of topical drugs that can only remain for a short time at the site of infection due to the dynamic of the oral cavity. The Solution Blow Spinning process allows the production of ultrafine fibers that can be applied in large areas, including bioengineering. One of the applications of ultrafine fibers is their use for controlled release of drugs in an efficient and long-lasting manner. Thus, the aim of the present work was to incorporate Cinnamaldehyde (CA), a compound that has antimicrobial properties, to Poly (lactic acid) and Poly (ethylene glycol) blankets (PLA / PEG) and to evaluate them for the production and characterization by Scanning Electron Microscopy (SEM), Thermogravimetric (TGA), Differential Scanning Calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), Ultraviolet–visible (UV/vis) spectroscopy, mechanical properties and antifungal action. Antifungal activity was verified against C. albicans, C. krusey and C. glabrata by broth microdilution test, disk diffusion and anti-biofilm activity, in both multi-species and mono-species biofilms. For the experiment, three types of meshes were spun: pure PLA, PLA/PEG and PLA / PEG 23.8% CA. The micrographs obtained by SEM showed that the fibers that did not contain CA had similar diameters to each other and smaller than the fibers containing PLA / PEG 23, 8% CA. The contact angle and surface tension could not be measured by virtue of the proportion of polymers in the blends which showed high affinity for the solvents used in the test. In the TGA assay, the PLA/PEG curve with 23.8% CA increase exhibited a higher thermal stability while in the DSC test the glass transition point of the meshes containing 23.8% CA it was the one with the lowest value. The release of CA was satisfactory occurring until the 6th day. PLA membranes with fibres of diameter exhibited the lowest fibre diameter (354 ±160 nm)a followed by PLA/PEG (428±250nm)a and PLA/PEG/CA (749±370 nm)b. Addition of CA resulted in an increase in mechanical properties of the membranes from (24.94±4.85 MPa) the elastic modulus and (0.99±0.16 MPa) tensile strength in comparison to PLA/PEG (18.74±3.41 MPa) and (0,85±0.09 MPa). CA incorporation increased improved the thermal stability, with release of CA of 0.10 µg/mL over a 12 days period. The PLA/PEG CA membranes presented antifungal activities, showing reductions in more than 50% of the biofilm biomass, being statistically significant (p<0.05%) to the control group. Fibrous membranes of PLA/PEG/CA ultrathin fibres were produced by SBS that exhibited antifungal properties and release over a 12-day period.

La projection par plasma de suspension d’hydroxyapatite, d’oxyde de titane et de zircone yttriée permettant d’obtenir des revêtements biocompatibles, des barrières thermiques ou encore des surfaces photo-catalytiques est étudiée. Les revêtements sont projetés à l’aide d’une torche plasma SG-100. La puissance électrique se situe entre 27 et 40 kW et les distances de projection entre 40 et 70 mm, selon le type de matériau projeté. La stabilité de la suspension est déterminée par des mesures de potentiels Zeta. Les propriétés mécaniques des revêtements d’hydroxyapatite après projection et après immersion dans un fluide physiologique sont comparées. Il en résulte que la dureté augmente avec la durée d’immersion. Pour les revêtements de titane, l’essai de rayure a confirmé la bonne adhérence et la bonne cohésion de ce type de revêtement. Nous avons également observé que les revêtements testés montrent de meilleures propriétés photo-catalytiques que les revêtements commerciaux Pilkington Active™ glass. L’étude des revêtements à base d’oxydes de zircone s’est focalisée sur les propriétés mécaniques et le transport thermique. L’indentation instrumentée confirme les très bonnes propriétés mécaniques de ces revêtements, jusque 3.5 GPa pour la dureté et jusque 130 GPa pour le module d’élasticité. Nous avons aussi observé que les valeurs de conductivité thermique des revêtements testés sont plus faibles que celles des revêtements projetés avec des méthodes conventionnelles.En conclusion, les revêtements obtenus par projection plasma présentent des propriétés qui les rendent utilisables dans de nombreuses applications. / The basics of thermal spraying were presented. Suspension plasma spraying method was described and also possible applications, as biocompatible coatings, thermal barrier or photo-catalytic surfaces were presented. Instrumented indentation test was characterized. In work hydroxyapatite, titanium dioxide, yttria stabilized zirconia and yttria with ceria stabilized zirconia were used. Set-up of plasma spray installation was presented. The stability of suspension was determined by zeta potential measurements. Coatings were sprayed with plasma torch SG-100. Electric power was in range from 27 to 40 kW and spray distance varying from 40 to 70 mm, depending on type of sprayed material.Mechanical properties of hydroxyapatite coatings as-sprayed, as well as soaked in simulated body fluid were tested. Influence of soaking time on coatings hardness was noted, which increases with increasing time of soaking. In case of titania coatings, mechanical and photo-catalytic properties were estimated. Scratch test confirmed high values of cohesion and adhesion. Tested coatings exhibit better photo-catalytic properties than commercial Pilkington Active™ glass. Investigation of coatings based on zirconium oxide concerned on mechanical and thermal transport properties. Instrumented indentation test confirmed very good mechanical properties, up to 3.5 GPa and up to 130 GPa for hardness and elastic modulus, respectively. Values of thermal conductivity of tested coatings were lower than coatings sprayed with conventional methods. Based on conducted studies was found that suspension plasma sprayed coatings exhibit properties, which made possible its application on different fields of technique.

Os objetivos do trabalho foram caracterizar as biocerâmicas a base de hidroxiapatita (HA), -fosfato tricálcio (TCP) e o compósito HA/TCP na proporção 60:40 pela análise microestrutural e por Espectrometria de Energia Dispersiva de Raios-X (EDS) ao microscópio eletrônico de varredura, e comparar histomorfometricamente o processo de reparo ósseo de defeitos cranianos perenes tratados com essas três diferentes cerâmicas e o enxerto autógeno nos períodos de 0, 30, 90 e 180 dias pós-operatório. Microestruturalmente, a HA apresentou superfície irregular com concavidades, fendas e grande quantidade de microporos; o TCP exibiu superfície irregular e baixa resistência mecânica; a HA/TCP apresentou superfície lisa com raras concavidades e ausência de porosidades. As cerâmicas estavam constituídas pelos elementos O, P e Ca, sendo que a relação Ca/P seguiu a ordem: HA/TCP > HA > TCP. Morfometricamente, o volume inicial enxertado foi aproximadamente de 60 mm3 para todos os tratamentos. Entre 30 e 180 dias, o volume total da região do enxerto (Vtre) e do material enxertado (VM) manteve-se constante nos defeitos tratados com osso autógeno (Vtre = 53,61 mm³, VM =20,11 mm³), HA (Vtre = 60,13mm³, VM = 32,72 mm³), HA/TCP (Vtre = 57,60mm³, VM = 31,61 mm³), TCP (Vtre = 38,27mm3, VM = 10,07 mm³). Aos 30 dias, o volume de tecido ósseo no grupo autógeno foi de 22,06 mm³, ocupando quase a totalidade dos espaços entre as partículas, enquanto que, nos grupos HA e HA/TCP foi de apenas 7,62 mm³, sendo parte dos espaços (19,10 mm3), constituído por tecido conjuntivo fibroso. Entre 30 e 180 dias, o volume de tecido ósseo não apresentou diferenças estatísticas significantes (p>0,05). O número absoluto de osteoblastos e osteócitos no grupo autógeno foi, respectivamente, de 118,57 x102 e 178,57 x102 células, aos 30 dias, diminuindo 40,16% e 29,09% aos 90 dias, decorrente do processo de remodelação óssea. Nos grupos HA e HA/TCP, o número absoluto de osteoblastos e osteócitos foram similares e permaneceram constantes dos 30 aos 180 dias, com uma média de 39,13 x102 e 132,20 x102 células, respectivamente. Com relação ao grupo TCP, o volume de tecido ósseo foi de 4,16mm3 aos 30 dias e aumentou 70,27% aos 90 dias, passando a ocupar 13,93 mm³ do Vtre. Concomitantemente, o número absoluto de osteoblastos e osteócitos passaram, respectivamente, de 5,64 x102 e 37,01 x102 células, aos 30 dias, para 67,46 x102 e 166,13 x102 células, aos 90 dias. Baseados nos resultados aqui obtidos, concluímos que, no modelo experimental de defeitos cranianos em ratos, o enxerto autógeno é ainda, o padrão ouro para reconstrução óssea, enquanto que, dentre as cerâmicas analisadas, o TCP é o melhor biomaterial ósseo-substituto. / The aim of the work was to characterize the ceramics: hydroxyapatite (HA), -tricalcium phosphate (TCP) and the composite HA/TCP (60:40) through scaning electron microscope - energy dispersive system (SEM-EDS) analysis and to compare histomorphometrically the repair of perennial skull defects treated with these three different ceramics and autogenous graft at 0, 30, 90 and 180 days post-operatively. Microstructurally, HA showed irregular surface with concavities, cracks and several pores. TCP also presented irregular surface and low mechanical strength. HA/TCP showed smooth surface with rare concavities and pores. The ceramics were constituted by the elements O, P and Ca, and the relation Ca/P follow the order: HA/TCP > HA > TCP. Morphometrically, the initial graft volume was approximately 60 mm3 for all treatments. Between 30 and 180 days, the total volume of the grafted area (Vtga) and of the implanted material (Vim) were constant in the following groups: autogenous (Vtga = 53,61 mm³; Vim = 20,11 mm3), HA (Vtga = 60,13mm³; Vim = 32,72 mm3), HA/TCP (Vtga = 57,60mm³; Vim = 31,61 mm3) and TCP (Vtga = 38,27mm³; Vim = 10,07 mm3). At 30 days, the bone tissue volume was of 22,06 mm3 in the autogenous group, occupying totally the space among the particles, while in the HA and HA/TCP groups was only 7,62 mm3. At 30 and 180 days, the bone tissue volume did not show statistical differences (p>0.05). The total number of osteoblasts and osteocytes in the autogenous group was respectively, 118, 57 x 102 and 178,57 x 102 cells, at 30 days, reducing 40,16% e 29,09%, at 90 days, due to bone remodeling. In the HA and HA/TCP groups, a similar and stable number of osteoblasts and osteocytes were observed during all periods, with mean of 39,13 x 102 and 132,20 x 102 cells, respectively. In the TCP group, the bony tissue volume was of 4,16 mm3, at 30 days, increasing 70,27% at 90 days. Concomitantly, the total number of osteoblasts and osteocytes was respectively, 5,64 x 102 and 37,01 x 102 cells, at 30 days, achieving 67,46 x 102 and 166,13 x 102 cells, at 90 days. Based in the results obtained here, we concluded that in the rat skull defect model the autogenous bone is yet the good standard graft material for bone reconstruction and that among the tested ceramics, the TCP is the best bone graft substitute.

A perda do osso alveolar como resultado de doença periodontal ou secundariamente à cirurgia são fontes de inúmeras complicações para os cirurgiões dentistas, e a solução para tal problema se baseiam em procedimentos regenerativos. A regeneração é feita através de enxertos ósseos que estabelecem um arcabouço para a reparação tecidual, aumentando os tecidos ósseos nos defeitos resultantes de trauma ou cirurgias, preenchendo os alvéolos após extração para preservar a altura e espessura do rebordo alveolar e aumentando e/ou reconstruindo o rebordo alveolar. Estes procedimentos são realizados através da utilização de enxertos autógenos, alógenos, aloplásticos ou xenogênicos, tendo cada um suas características e indicações. Com o desenvolvimento dos implantes osseointegrados, viu-se a necessidade de manter uma boa quantidade e qualidade óssea. Este projeto tem como objetivo avaliar a resistência a tração e módulo de elasticidade do osso mineralizado e desmineralizado de calvária de ratos, a fim de determinar padrões iniciais (máximos e mínimos) para comparações com possíveis biomateriais de preenchimento de osteoindução e osteocondução. Foram utilizados 24 animais divididos em 2 grupos. O grupo 1 (n=12): módulo de elasticidade sendo que utilizaremos as duas parietais do animal, possibilitando 24 espécimes, subdividido em mineralizado (n=12) e desmineralizado (n=12). O grupo 2 (n=12): microtração, sendo que 12 hemicalvária foram utilizado para o sub-grupo desmineralizado e as outras 12 hemicalvária para o sub-grupo mineralizado. Após a morte dos animais, os espécimes serão coletados e tratados de acordo com o subgrupo (mineralizado e desmineralizado). Os testes foram realizados numa máquina de teste universal (Vitrodyme, V1000). As médias de resistência a tração do mineralizado foi 129,814 ± 34,921 MPa e o desmineralizado foi 18,547 ± 3,682 MPa. Para o módulo de elasticidade obtivemos os valores de 1377,792 ± 208,331 MPa para o grupo mineralizado e 49,669 ± 11,204 MPa para o grupo desmineralizado, ao compararmos o módulo de elasticidade e resistência a tração entre os subgrupo desmineralizado e mineralizado observa-se uma diferença estatisticamente significante para o grupo mineralizado (p<0,001). Conclui-se que o teste de microtração pode ser utilizado para avaliar as propriedades mecânicas nesse modelo experimental biológico. / The loss of the alveolar bone as resulted of periodontal illness or second to the surgery is sources of innumerable complications for the surgeons dentists, and the solution for such problem if it bases on regenerative procedures. Regeneration is made through bone grafts that establish one scaffold for the tecidual repairing, increasing bone fabrics in the resultant defects of trauma or surgeries, filling the alveolous after extraction to preserve the height and thickness of the alveolar rigde and being increased and/or reconstructing the alveolar rigde. These procedures are carried through the use of autogenous, alografts, aloplastic or xenogenics grafts, having each one its characteristics and indications. With the development of the osseointegrated implants, it was seen necessity to keep a good amount and bone quality. This project has as objective to evaluate the resistance the traction and modulus of elasticity of the mineralized bone and desmineralized.of calvarium of rats, similar to determine initial standards (maximum and minimum) for comparisons with possible biomateriais of fulfilling of osteoinduction and osteoconduction. 24 animals divided in 2 groups had been used. Group 1 (n=12): modulus of elasticity being that we will use the two parietals of the animal, having made possible 24 specimens, subdivided in mineralized (n=12) and desmineralized (n=12). Group 2 (n=12): microtraction, being that 12 hemi-calvarium had been used for 12 the desmineralized sub-group and the others hemi-calvarium for the mineralized sub-group. After the death of the animals, the specimens will be collected and treated in accordance with the sub-group (mineralized and desmineralized). The tests had been carried through in a machine of universal test (Vitrodyme, V1000). The resistance averages the traction of the mineralized one was mineralized 129,814 ± 34.921 MPa and the desmineralized one was 18,547 ± 3,682 MPa. For the modulus of elasticity we got values of 1377,792 ± 208.331 MPa for the mineralized group and 49,669 ± 11,204 MPa for the desmineralized group, when comparing the resistance and modulus of elasticity the traction between the desmineralized and mineralized sub-group observes a estatistical significant difference for the mineralized group (p<0,001). Concluded that the microtraction test can be used to evaluate the mechanical properties in this biological experimental model.

Conjugated macrocycles have emerged as novel structural motifs that modulate the electronic properties of organic molecules because of their strained and contorted structures. Cycloparaphenylenes, known as nanohoops, are a particularly attractive scaffold for the design of new types of carbon nanomaterials because of their size-selective synthesis, radially oriented π-systems and tunable electronic properties. The development of modular syntheses of nanohoops over the past decade should enable the preparation of substituted derivatives that can be tuned for applications in biology and materials science. Chapter I provides a brief overview of conjugated macrocycles recently reported in the literature with a discussion of the structural effects that are responsible for the remarkable properties of this class of molecules. Chapter II highlights a scalable and mild synthetic approach developed in our lab to prepare nanohoop conjugated macrocycles and expands the generality of this methodology with the formal synthesis of natural product Acerogenin E. Chapter III describes the synthesis of cycloparaphenylenes with versatile functional handles and uncovers the reactivity of the strain nanohoop backbone under reaction conditions that promote the formation of radical cations. Chapter IV takes advantage of the functional groups described in chapter III to develop the first example of nanohoops as a new class of biocompatible fluorophores. Chapter V details a novel synthetic approach that enables the incorporation of the linear acene pentacene into the nanohoop backbone and reports our findings on the impact that the macrocyclic structure has on the properties of this organic semiconductor. In summary, the findings discussed in this dissertation provide synthetic strategies for the selective functionalization of nanohoops and highlight this class of molecules as a novel scaffold for the design of new types of carbon nanomaterials. This dissertation includes previously published and unpublished co-authored material.

Com a evolução do Biomateriais houve melhorias nas opções de tratamentos e atualmente são utilizados em substituição de partes do corpo que foram perdidas e promovem a recuperação de funções biológicas. Dentre eles existem as chamadas Biocerâmicas, que incluem alumina, zircônia e derivadas de fosfato de cálcio. A hidroxiapatita possui composição e estrutura minerais semelhantes à fase mineral óssea e apresenta como propriedades a biocompatibilidade, osteocondutividade e bioatividade. O trabalho avaliou a viabilidade celular em cerâmica de hidroxiapatita experimental de origem bovina em comparação com dois tipos de zircônia comerciais e liga de titânio comercialmente puro, para que futuramente possa ser utilizada como material base para implantes dentários. A avaliação in vitro foi realizada por meio de testes nos quais células pré-osteoblásticas cultivadas de linhagem murina MC3T3-E1 foram colocadas em contato indireto e direto com estes materiais. Para viabilidade celular (n=8) foram feitos testes de ensaio MTT e Cristal Violeta em duplicata e após 24, 48 e 72 horas os níveis de absorbâncias foram analisados por meio de espectrofotometria no leitor de Elisa. Para as analises por microscopia eletrônica de varredura (n=6) as células foram plaqueadas diretamente sobre as superfícies dos discos, fixadas em vapor de tetróxido de ósmio 2% após 24 e 48 horas, seguido da metalização após 48 horas da fixação das células para análise em Microscópio Eletrônico de Varredura. Os resultados para viabilidade indireta foram submetidos ao teste paramétrico ANOVA, seguido de teste de Tukey (p<0,05). Tanto no teste de MTT quanto no Cristal Violeta, de acordo com o grupo controle positivo, todos os grupos apresentaram resultados satisfatórios. A cerâmica de hidroxiapatita não apresentou diferença estatística significante, demonstrando não ser um material citotóxico. Pelas imagens geradas no MEV do teste de viabilidade direta, verificou-se que houve adesão e proliferação das células nos dois períodos sobre as superfícies dos materiais. Portanto, pode-se afirmar que a cerâmica de hidroxiapatita apresentou-se como um material biocompatível. / With the evolution biomaterials there were improvements in treatment options, and are currently used in replacement body parts that were lost and promote the recovery of biological functions. Among them are the bioceramic which include alumina, zirconia and calcium phosphate derivative. Hydroxyapatite has mineral composition and structure similar to bone mineral phase and can be used as a biomaterial having biocompatibility, osteoconductivity and bioactivity. The study evaluated the cell viability in experimental hydroxyapatite ceramic bovine compared the two types of commercial zirconia and titanium alloy commercially pure, so that in future it can be used as base material for dental implants. In vitro evaluation was carried by means of tests in which the pre-osteoblastic cells MC3T3-E1 murine lineage cultured were placed in indirect and direct contact with these materials. For cell viability (n=8) were carried MTT assay and Crystal Violet tests in duplicate and after 24, 48 and 72 hours the absorbance levels were analyzed by spectrophotometry Elisa reader. For analysis by Scanning Electron Microscope variable pressure (n = 6) cells were plated directly on the discs surfaces, fixed in osmium tetroxide steam 2% after 24 and 48 hours, followed by metallization after 48 of cells fixation. The results for the cell viability were submitted to parametric test ANOVA, followed by Tukey test (p<0.05). Both in the MTT assay as Crystal Violet all groups exhibited satisfactory results absent cytotoxicity. By means of the SEM images produced, it was found that there was adhesion and proliferation of cells on the materials surfaces in the two periods. Therefore, it can be stated that the hydroxyapatite ceramic was presented as a biocompatible material.

Resumo: Proposição: Avaliar a resposta tecidual ao enxerto xenógeno inorgânico de osso bovino, por meio de análise histomorfológica e histomorfométrica. Material e método: O enxerto foi obtido da costela de boi resfriada após 8 horas de sacrifício do animal e processado da seguinte maneira: imersão por 60 minutos em água oxigenada a temperatura ambiente, com trocas a cada 15 minutos; imersão em água oxigenada aquecida, a uma temperatura de 100ºC, por 30 segundos e resfriamento imediato com água destilada a uma temperatura variando de 6º a 8ºC; enxague em água destilada corrente por 6 horas; imersão em álcool 70º, 90º e 100º, respectivamente, sendo 15 minutos em cada álcool; esterilização em autoclave. Em seguida, 10 coelhos brancos (Nova Zelândia) foram utilizados, originando dois grupos: Grupo I - enxerto inserido no pavilhão auricular e Grupo II - enxerto inserido e fixado em tíbia. Decorridos 180 dias, foi realizado sacrifício dos animais por injeção excessiva de anestésico. Resultados: No Grupo I, o enxerto apresentou-se em íntimo contato com tecido subcutâneo. No Grupo II, o enxerto apresentou-se em justaposição com o leito ósseo receptor. E nos dois grupos havia espaços medulares preenchidos por medula óssea ativa e osso neoformado, além da ausência de osteócitos no osso bovino e presença destas células no osso neoformado, próximo aos espaços medulares. Conclusão: Em razão dos resultados obtidos o enxerto xenógeno inorgânico de osso bovino demonstrou biocompatibilidade, capacidade osteocondutora e discreta perda de volume, preenchendo requisitos importantes do material ideal para reconstrução óssea. / Abstract: Objective: To evaluate tissue response to inorganic bovine bone xenograft by histomorphological and histomorphometrical analyses. Material and methods: The bone grafts was obtained from cooled bovine rib 8 hours after slaughtering and were processed as follows: 60-minute immersion in hydrogen peroxide at room temperature, with changes at 15-minute intervals; 30-second immersion in hydrogen peroxide at 100ºC; immediate cooling with distilled water at temperatures ranging from 6º to 8ºC; rinsing in running distilled water for 6 hours; immersion in alcohol grades of 70º, 90º and 100ºGL (15-minute in each solution); autoclaving. Thereafter, 10 white New Zealand rabbits were distributed into two groups: Group I - graft inserted in the ear pavilion and Group II - graft inserted and fixed in the tibia. After 180 days, the animals were sacrificed by anesthetic overdose. Results: In Group I, the graft was in intimate contact with the subcutaneous tissue, while in Group II the graft was juxtaposed to the recipient site. Both groups presented medullar spaces filled with active bone marrow and newly formed bone. In addition, osteocytes were absent in the bovine bone graft and present in the newly formed bone, close to the medullar spaces. Conclusion: From the obtained results, the inorganic bovine bone xenograft showed biocompatibility. / Orientador: Wilson Roberto Poi / Coorientador: Idelmo Rangel Garcia Júnior / Banca: Osvaldo Magro Filho / Banca: Roberta Okamoto / Banca: José Luiz Rodrigues Leles / Banca: Eleonor Álvaro Garbin Júnior / Doutor

A perda do osso alveolar como resultado de doença periodontal ou secundariamente à cirurgia são fontes de inúmeras complicações para os cirurgiões dentistas, e a solução para tal problema se baseiam em procedimentos regenerativos, que é realizada através de enxertos ósseos que estabelecem um arcabouço para a reparação tecidual, aumentando os tecidos ósseos nos defeitos resultantes de trauma ou cirurgias, preenchendo os alvéolos após extração para preservar a altura e espessura do rebordo alveolar e aumentando e/ou reconstruindo o rebordo alveolar. Este projeto tem como objetivo determinar a resistência à tração do osso neoformado com a utilização de diferentes biomateriais. Foram utilizados 60 animais divididos em 3 grupos. O grupo 1A (n=10): GenO; Grupo 1B (n=10): GenMix; Grupo1C (n=10): Bio-Oss; Grupo 2a (n=10): PerioGlas; Grupo 2b (n=10): Polímero de mamona e Grupo 3 (n=10): coágulo. Após 3 meses de nascimento os animais foram submetidos a anestesia intraperitonial e confecção de defeito não critico (3mm de diâmetro) na calvária dos animais, que foram preenchidos com os biomateriais correspondentes a cada grupo. Após 6 meses da cirurgia foi realizada a morte dos animais, os espécimes foram coletados e submetidos ao teste em uma máquina de teste universal. Observa-se que o grupo que obteve maior média de resistência à tração foi o grupo de polímero de mamona (10,932±4,529MPa). Consequentemente, obteve-se uma comparação descrescente na seguinte ordem: Coágulo (9,563±3,74MPa), Bio-Oss (8,706±4,087MPa), GenMix (8,587±3,602MPa), GenOx (7,709±2,416MPa), PerioGlas (7,185±6,837MPa), não notando-se diferença estatisticamente significante entre os grupos. Nas microscopias eletrônicas de varredura na maioria dos grupos observou-se presença de fibras colágenas ao redor do tecido ósseo neoformado e dos remanescentes de enxerto. Conclui-se que o material foi indiferente para o resultado final da resistência à tração, demonstrando uma boa qualidade dos materiais utilizados, tanto quando comparamos os produtos quanto a sua origem (xenogênica, polimérica ou coágulo), ou a sua procedência de fabricação (nacional ou importado). / The loss of alveolar bone as a result of periodontal disease or secondary to surgery are numerous sources of complications for the dentists, and the solution to this problem are based on regenerative procedures, which is conducted through bone grafts that provide a scaffold for tissue repair by increasing the bone tissues in the defects resulting from trauma or surgery, filling the alveoli after extraction to preserve the height and thickness and increasing the alveolar ridge and/or reconstructing the alveolar ridge. This project aims to determine the tensile strength of newly formed bone with the use of different biomaterials. We used 60 animals divided into three groups. Group 1A (n = 10): GenOx; Group 1B (n = 10): GenMix; Group 1C (n = 10): Bio-Oss; Groups 2a (n = 10): PerioGlas; Group 2b (n = 10): castor bean polymer; Group 3 (n = 10): clot. After 3 months of birth the animals were anesthetized intraperitoneally and making non critical defect (3mm diameter) in the calvaria of the animals, which were filled with biomaterials for each group. After 6 months of surgery was performed the animals\' death, the specimens were collected and tested in a universal testing machine. It is observed that the group had a higher average tensile strength was the castor oil polymer group (10.932 ± 4.529 MPa). Consequently, we obtained a comparison descended in the following order: Clot (9.563 ± 3.74 MPa), Bio-Oss (8.706 ± 4.087 MPa), GenMix (8.587 ± 3.602 MPa), GenOx (7.709 ± 2.416 MPa), PerioGlas (7.185 ± 6.837 MPa), not noticing a significant difference between the groups. In scanning electron microscopies in most groups there was presence of collagen fibers around the newly formed bone and remaining graft. It is concluded that the material was irrelevant to the final result of the tensile strength, showing a good quality of materials used, both when comparing products as their source (xenogenic, polymeric or clot), or its origin of manufacture (national or imported).