O implante dental depende do osso de suporte para sua estabilidade e ongevidade funcional. O comportamento mecânico e a estrutura trabecular do osso afetam a interface com o implante. Tal conhecimento pode fornecer uma base para melhoramentos na função e desenho dos implantes atuais minimizando a reabsorção da crista óssea e falha na junção osso-implante. Desta forma a correta quantificação das forças que atuam sobre o sistema de implante e principalmente no osso de suporte ao qual ele está inserido é importante para o entendimento da biomecânica possibilitando que intervenções possam ser realizadas pelos profissionais visando assim à longevidade das próteses implanto-suportadas bem como dos implantes que as sustentam. Por essa razão, a proposta deste trabalho foi avaliar, com auxílio de extensômetros elétricos, se o processo laboratorial de confecção de coroas metalocerâmicas resulta em alterações das tensões no osso ao redor dos implantes. Para isto foi utilizado um modelo de poliuretano em forma de U simulando o osso mandibular com dois implantes de hexágono externo de 3,75mm de diâmetro por 13 mm de comprimento, nos quais foram fixados intermediários multi-unit. Os corpos de prova foram confeccionados com dois tipos de ligas odontológicas - Cobalto-Cromo e Paládio-Prata - e três tipos de cilindros protéticos calcinável, usinado de Cobalto-Cromo e usinado de Ouro. As leituras de deformação foram realizadas em dois momentos: 1- após a fundição das infra-estruturas e 2 após estas infra-estruturas terem recebido cobertura cerâmica. Os testes foram realizados parafusando os corpos de prova sobre os intermediários utilizando-se para isto um dispositivo eletrônico de torque com força máxima de 10 Ncm. Os resultados mostraram que, após a aplicação da cobertura cerâmica, ocorreu piora da condição de assentamento aos intermediários. O mesmo não foi detectado quando se avaliou a deformação do osso simulado, já que os valores de deformação não ndicaram diferenças antes e após a aplicação da cerâmica. / The dental implant depends on the supporting bone for its stability and functional longevity. Mechanical behavior and trabecular bone structure affect the interface with the implant. Such knowledge may provide a basis for improvements in the current implant function and design, decreasing bone crest resorption and failure at bone-implant junction. Adequate quantification of forces that act upon the implant system and mainly on the supporting bone is important for understanding the biomechanics, allowing the intervention by professionals with the purpose of achieving the longevity of implant-supported prostheses. Therefore, this work aims at evaluating, with the aid of strain gauges, whether the laboratorial process of metal ceramic crown fabrication results in changes of the tensions around the implants. A U-shaped polyurethane model simulating the mandibular bone with two 3.75-mm diameter and 13-mm length external hexagon implants were used with fixed multi-unit abutments. Specimens were prepared with two types of dental alloys - cobalt-chromium and silver-palladium - and three types of prosthetic cylinder castable plastic, prefabricated in cobalt-chromium or gold. The deformation readings were performed in two moments: 1- after framework casting and 2- after ceramic layering of the framework. The tests were performed with the framework screwed onto the abutments at 10Ncm using an electronic torque device. The results showed that the ceramic layering worsened the fit between the crowns and the abutments. The same was not detected when bone deformation was evaluated since the values were not statistically different.

A osteoporose, doença caracterizada pela redução da massa óssea e deterioração da microestrutura óssea, atinge a população idosa e afeta centenas de milhões de pessoas em todo mundo. Por manifestar-se sem causar sintoma visível, o diagnóstico da doença ocorre, na maioria dos casos após lesão ou fratura do osso. Na tentativa de detectar os sinais iniciais da doença, utilizam-se diferentes métodos de avaliação da qualidade óssea baseados na medida da densidade e da arquitetura óssea. Atualmente existe um grande interesse em estabelecer uma correlação entre as medidas de qualidade óssea com as propriedades mecânicas de resistência do osso. Uma estratégia para caracterizar o comportamento mecânico do osso consiste em obter as propriedades da macroestrutura óssea a partir das propriedades da sua microestrutura. Cowin (1985) propõe um modelo mecânico para materiais porosos elástico-lineares supondo que a função resposta mecânica do meio poroso elástico sob deformações infinitesimais é uma função isotrópica do tensor deformação infinitesimal, da fração volumétrica e do tensor textura que caracteriza a simetria do arranjo geométrico do meio poroso. Ao obter uma relação entre as componentes do tensor de elasticidade, as componentes do tensor textura e a fração volumétrica do meio poroso, o autor observa que o tensor de elasticidade obtido não fornece todos os tipos possíveis de simetria do material poroso, restringindo-se apenas à ortotropia e seus casos particulares, tais como a isotropia e a isotropia transversal. O tensor de elasticidade obtido por Cowin (1985) não descreve o comportamento local do meio poroso, pois depende explicitamente das componentes do tensor textura, o qual representa uma medida não local. Esta dissertação tem por objetivo estudar e analisar o modelo proposto por Cowin (1985). Propõe-se neste trabalho uma formulação para a função resposta de materiais porosos elástico-lineares para deformações infinitesimais que descreva o comportamento local do meio poroso. / Osteoporosis, a disease characterized by the reduction of bone mass and deterioration of bone microstructure deterioration, affects the elderly population and hundreds of millions of people worldwide. As a silent disease, its diagnosis occurs, in most cases, after injury, or, bone fracture. In an attempt to detect early signs of the disease, different methods of diagnostic imaging to obtain measures of density and bone architecture are used. Currently, there is great interest in establishing a correlation between the measurements of bone quality with the mechanical properties of bone strength. One strategy to characterize the mechanical behavior of bones is to obtain the properties of its macrostructure from the properties of its microstructure. Cowin (1985) proposes a mechanical model for porous materials by assuming that the mechanical response function of the material under infinitesimal deformation is a function of the infinitesimal deformation tensor, the volume fraction, and the texture tensor that characterizes the symmetry of the geometrical arrangement of the porous medium. By obtaining a relationship between the components of the elasticity tensor, the components of the texture tensor and the volume fraction of the porous medium, the author notes that resulting the elasticity tensor does not yield all possible types of symmetry of the porous material, being restricted to orthotropy and its particular cases, such as the isotropic and transverse isotropy. The elasticity tensor obtained by Cowin (1985) does not describe the local behavior of porous media, and depends explicitly on the fabric tensor components, which represent a non local measure. This dissertation aims to study and analyze the model proposed by Cowin (1985). A formulation for the response function of linear elastic porous materials under infinitesimal deformation that describes the local behavior of the porous medium is also proposed.

A osteoporose, doença caracterizada pela redução da massa óssea e deterioração da microestrutura óssea, atinge a população idosa e afeta centenas de milhões de pessoas em todo mundo. Por manifestar-se sem causar sintoma visível, o diagnóstico da doença ocorre, na maioria dos casos após lesão ou fratura do osso. Na tentativa de detectar os sinais iniciais da doença, utilizam-se diferentes métodos de avaliação da qualidade óssea baseados na medida da densidade e da arquitetura óssea. Atualmente existe um grande interesse em estabelecer uma correlação entre as medidas de qualidade óssea com as propriedades mecânicas de resistência do osso. Uma estratégia para caracterizar o comportamento mecânico do osso consiste em obter as propriedades da macroestrutura óssea a partir das propriedades da sua microestrutura. Cowin (1985) propõe um modelo mecânico para materiais porosos elástico-lineares supondo que a função resposta mecânica do meio poroso elástico sob deformações infinitesimais é uma função isotrópica do tensor deformação infinitesimal, da fração volumétrica e do tensor textura que caracteriza a simetria do arranjo geométrico do meio poroso. Ao obter uma relação entre as componentes do tensor de elasticidade, as componentes do tensor textura e a fração volumétrica do meio poroso, o autor observa que o tensor de elasticidade obtido não fornece todos os tipos possíveis de simetria do material poroso, restringindo-se apenas à ortotropia e seus casos particulares, tais como a isotropia e a isotropia transversal. O tensor de elasticidade obtido por Cowin (1985) não descreve o comportamento local do meio poroso, pois depende explicitamente das componentes do tensor textura, o qual representa uma medida não local. Esta dissertação tem por objetivo estudar e analisar o modelo proposto por Cowin (1985). Propõe-se neste trabalho uma formulação para a função resposta de materiais porosos elástico-lineares para deformações infinitesimais que descreva o comportamento local do meio poroso. / Osteoporosis, a disease characterized by the reduction of bone mass and deterioration of bone microstructure deterioration, affects the elderly population and hundreds of millions of people worldwide. As a silent disease, its diagnosis occurs, in most cases, after injury, or, bone fracture. In an attempt to detect early signs of the disease, different methods of diagnostic imaging to obtain measures of density and bone architecture are used. Currently, there is great interest in establishing a correlation between the measurements of bone quality with the mechanical properties of bone strength. One strategy to characterize the mechanical behavior of bones is to obtain the properties of its macrostructure from the properties of its microstructure. Cowin (1985) proposes a mechanical model for porous materials by assuming that the mechanical response function of the material under infinitesimal deformation is a function of the infinitesimal deformation tensor, the volume fraction, and the texture tensor that characterizes the symmetry of the geometrical arrangement of the porous medium. By obtaining a relationship between the components of the elasticity tensor, the components of the texture tensor and the volume fraction of the porous medium, the author notes that resulting the elasticity tensor does not yield all possible types of symmetry of the porous material, being restricted to orthotropy and its particular cases, such as the isotropic and transverse isotropy. The elasticity tensor obtained by Cowin (1985) does not describe the local behavior of porous media, and depends explicitly on the fabric tensor components, which represent a non local measure. This dissertation aims to study and analyze the model proposed by Cowin (1985). A formulation for the response function of linear elastic porous materials under infinitesimal deformation that describes the local behavior of the porous medium is also proposed.

O implante dental depende do osso de suporte para sua estabilidade e ongevidade funcional. O comportamento mecânico e a estrutura trabecular do osso afetam a interface com o implante. Tal conhecimento pode fornecer uma base para melhoramentos na função e desenho dos implantes atuais minimizando a reabsorção da crista óssea e falha na junção osso-implante. Desta forma a correta quantificação das forças que atuam sobre o sistema de implante e principalmente no osso de suporte ao qual ele está inserido é importante para o entendimento da biomecânica possibilitando que intervenções possam ser realizadas pelos profissionais visando assim à longevidade das próteses implanto-suportadas bem como dos implantes que as sustentam. Por essa razão, a proposta deste trabalho foi avaliar, com auxílio de extensômetros elétricos, se o processo laboratorial de confecção de coroas metalocerâmicas resulta em alterações das tensões no osso ao redor dos implantes. Para isto foi utilizado um modelo de poliuretano em forma de U simulando o osso mandibular com dois implantes de hexágono externo de 3,75mm de diâmetro por 13 mm de comprimento, nos quais foram fixados intermediários multi-unit. Os corpos de prova foram confeccionados com dois tipos de ligas odontológicas - Cobalto-Cromo e Paládio-Prata - e três tipos de cilindros protéticos calcinável, usinado de Cobalto-Cromo e usinado de Ouro. As leituras de deformação foram realizadas em dois momentos: 1- após a fundição das infra-estruturas e 2 após estas infra-estruturas terem recebido cobertura cerâmica. Os testes foram realizados parafusando os corpos de prova sobre os intermediários utilizando-se para isto um dispositivo eletrônico de torque com força máxima de 10 Ncm. Os resultados mostraram que, após a aplicação da cobertura cerâmica, ocorreu piora da condição de assentamento aos intermediários. O mesmo não foi detectado quando se avaliou a deformação do osso simulado, já que os valores de deformação não ndicaram diferenças antes e após a aplicação da cerâmica. / The dental implant depends on the supporting bone for its stability and functional longevity. Mechanical behavior and trabecular bone structure affect the interface with the implant. Such knowledge may provide a basis for improvements in the current implant function and design, decreasing bone crest resorption and failure at bone-implant junction. Adequate quantification of forces that act upon the implant system and mainly on the supporting bone is important for understanding the biomechanics, allowing the intervention by professionals with the purpose of achieving the longevity of implant-supported prostheses. Therefore, this work aims at evaluating, with the aid of strain gauges, whether the laboratorial process of metal ceramic crown fabrication results in changes of the tensions around the implants. A U-shaped polyurethane model simulating the mandibular bone with two 3.75-mm diameter and 13-mm length external hexagon implants were used with fixed multi-unit abutments. Specimens were prepared with two types of dental alloys - cobalt-chromium and silver-palladium - and three types of prosthetic cylinder castable plastic, prefabricated in cobalt-chromium or gold. The deformation readings were performed in two moments: 1- after framework casting and 2- after ceramic layering of the framework. The tests were performed with the framework screwed onto the abutments at 10Ncm using an electronic torque device. The results showed that the ceramic layering worsened the fit between the crowns and the abutments. The same was not detected when bone deformation was evaluated since the values were not statistically different.

Orientadores: Mônica Barbosa de Melo, José Paulo Cabral de Vasconcellos / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-25T15:53:03Z (GMT). No. of bitstreams: 1 Oliveira_MarianaBorges_M.pdf: 6901699 bytes, checksum: b84b4ac92949fdb082625b01ad6c66a1 (MD5) Previous issue date: 2014 / Resumo: O glaucoma engloba um grupo de doenças que têm como característica comum a atrofia progressiva do disco óptico com alteração correspondente de campo visual, decorrente da perda de células ganglionares da retina. O aumento da pressão intraocular (PIO) é o principal fator de risco para o desenvolvimento do glaucoma, mas tem sido sugerida a existência de outros aspectos relevantes, tais como alterações no metabolismo do óxido nítrico, na regulação do fluxo vascular, sinais de estresse oxidativo e alterações no sistema imunológico. O glaucoma primário de ângulo aberto (GPAA), a forma mais prevalente entre os glaucomas, está associado a uma série de fatores de risco para sua instalação e desenvolvimento, além da PIO. Os demais fatores de risco são: idade (relação direta), raça (mais frequente e grave em indivíduos da raça negra), miopia e história familiar de glaucoma. A maioria dos casos de GPAA apresenta um padrão complexo de hereditariedade, em que variantes de suscetibilidade contribuem para a gravidade da doença. O objetivo deste estudo do tipo caso-controle foi avaliar o papel de polimorfismos nos genes da interleucina alfa (IL1A), interleucina beta (IL1B) e fator de necrose tumoral alfa (TNFA) em relação à suscetibilidade ao GPAA. Após avaliação oftalmológica, foram recrutados 214 indivíduos não relacionados portadores de GPAA. A análise molecular foi realizada por meio de técnicas de PCR e sequenciamento direto. Neste estudo observou-se que o alelo C do polimorfismo -31 C/T, presente na região promotora do gene IL1B, confere risco para o glaucoma (p=0,002). Este alelo está contido em um "TATA" box, influenciando na transcrição deste gene. Existe um desequilíbrio de ligação entre os SNPs -31 C/T e -511 T/C do gene IL1B e este último também está associado a um risco aumentado para o glaucoma (p=0,006). Com relação aos demais SNPs estudados (+3954 C/T do gene IL1B, -889 C/T e +4845 G/T do gene IL1A e -238 G/A e -308 G/A do gene TNFA), não houve associação com o glaucoma. Este estudo sugere que há relação das variantes "C" do SNP -31 C/T e "T" do SNP -511 T/C do gene IL1B com a etiologia do GPAA em uma amostra da população brasileira / Abstract: Glaucoma comprises a group of diseases characterized by progressive atrophy of the optic disc and corresponding visual field loss, as consequence of retinal ganglion cells death. Augmented intraocular pressure (IOP) is the main risk factor for glaucoma development, but it has been suggested that there are other relevant aspects that may lead to neuronal and trabecular meshwork (TM) damage and contribute to the development of glaucoma, including alterations in nitric oxide metabolism, oxidative stress and vascular and immune system dysregulations. Primary open angle glaucoma (POAG), the most prevalent form of glaucoma, is associated with several risk factors to its initiation and progression besides IOP. The additional risk factors are: age (direct correlation), race (more frequent in black subjects), myopia and family history of glaucoma. The majority of POAG cases presents a complex pattern of heritability, in which susceptibility variants contribute to disease severity. The aim of this case-control study was to evaluate the role of single nucleotide polymorphisms (SNPs) in the interleukin alpha (IL1A), interleukin beta (IL1B) and tumor necrosis factor alpha (TNFA) genes in relation to POAG susceptibility. After ophthalmologic evaluation, 214 unrelated subjects with POAG were recruited. The molecular analysis was performed by PCR and direct sequencing techniques. In this study it was observed that the C allele of the -31 C/T promoter polymorphism of the IL1B gene confers risk for glaucoma (p=0.002). This allele disrupts a "TATA" box, influencing the transcription of the IL1B gene. There is linkage disequilibrium between the -31 C/T e -511 T/C SNPs, and the latter is also associated with an increased risk for glaucoma (p=0.006). Regarding the others studied SNPs (+3954 C/T of the IL1B gene, -889 C/T and +4845 G/T of the IL1A gene and -238 G/A and -308 G/A of the TNFA gene), there is no association with glaucoma. This study suggests the relationship of the "C" variant of -31C/T and "T" variant of -511T/C of IL1B gene with POAG etiology in a sample of the Brazilian population / Mestrado / Oftalmologia / Mestra em Ciências Médicas

Clinicians have described the success rates of dental implants. The use of implants is projected to increase in the future. With a 5-10% failure rate, it is unclear the exact factors that are associated with implant failures. To improve upon these success rates, it is critical to understand parameters associated with implant failure including: periodontitis, peri-implantitis, systemic diseases, site preparation, dental history of the implant site, bone quality, materials, occlusion, and treatment timelines. While bone quality is associated with failure, objective measures to assess bone quality and characteristics are scarce. Therefore, the aim of this study is to determine whether possible comorbidities, associated dental parameters, and measurable bone quality are possible predictors of implant failure. In this study, we utilized the electronic health record system axiUm® to retrospectively investigate non-failed (NF) and failed (F) dental implants from a patient cohort with 149 implants placed between 2012-2015 at Virginia Commonwealth University School of Dentistry. A chart review was conducted extracting information on age, gender, systemic diseases, smoking, occlusal trauma, parafunction, bone grafting history, treatment timelines, implant site/type/placement protocol, infection, torque at placement, bone quality and microarchitecture assessed by the novel, innovative technology: trabecular bone score (TBS). A total of 149 implants, 46 failures and 105 non-failed controls, were selected based on similar implant sites. Preliminary data obtained from analysis suggests that average time from implant placement to failure was 6.6 months (0.55 years). Parafunction habit (p=0.0202) and increased number of implants (p=0.0478) were found to be associated with increased implant failure.

La red trabecular es una estructura situada en la cámara anterior del ojo cuya función es drenar el humor acuoso. Alteraciones en ella pueden producir aumentos de la presión intraocular (IOP) los cuales pueden provocar pérdidas en el campo visual y por lo tanto cegueras parciales o totales (glaucoma).El objetivo de esta tesis doctoral se basa en el estudio de la fisiología de la red trabecular con el fin de tener un mayor conocimiento de sus funciones y así poder entender mejor su papel regulador dentro de la evacuación del humor acuoso. Dado que el ATP y otros derivados purinérgicos se encuentran presentes en el humor acuoso, en la realización de este proyecto se han estudiado los receptores purinérgicos en la red trabecular y el papel del ATP y derivados dinucleósidos polifosfato en la modulación de la evacuación del humor acuoso.Se ha evaluado el efecto del ATP mediante el estudio de los incrementos de Ca2+ con el fluoróforo fura-2. Este nucleótido provoca incrementos rápidos del Ca2+ intracelular que disminuyen lentamente hasta los valores basales. El porcentaje de respuesta frente a éste y otros agonistas muestra un perfil de respuesta (ATP = UTP > ATP--S >> ADP = UDP) corresponde al receptor purinérgico P2Y2, el cual es sensible al antagonista suramina.El Ca2+ movilizado tras la estimulación de los receptores P2Y procede de los depósitos citoplasmáticos y las vías de señalización intracelular involucran una proteína Gq/11 que estimula la fosfolipasa C- y produce IP3 con la subsiguiente estimulación de receptores de IP3.Experimentos de inmunocitoquímica y western-blot confirman la existencia de un receptor P2Y2 además de la coexistencia con los subtipos P2Y1 y P2Y4.Se ha estudiado como el ATP extracelular modula corrientes de K+ mediadas por el canal de alta conductancia dependiente de calcio BKCa. La estimulación con ATP extracelular provoca un aumento significativo de la corriente de salida de K+ mediante la participación del receptor P2Y2 en la corriente y los aumentos de corriente dependen del Ca2+ intracelular para activarse.Por otro lado, Las células trabeculares poseen la capacidad de liberar ATP frente a estímulos hipotónicos y la cantidad de ATP liberado es proporcional a la hipotonicidad utilizada.Finalmente, se ha estudiado el ATP en la regulación de la facilidad de evacuación de humor acuoso(C). Para ello se utilizó la técnica de perfusión de segmentos anteriores oculares en condiciones de cultivo de órgano obteniéndose valores de C (l/min/mmHg). El ATP no muestra ningún efecto sobre la C. El análogo no hidrolizable del ATP, el ATP--S, el cual es resistente a la acción de las ectonucleotidasas tampoco varia la C, indicando que quizá la el ATP estimula diferentes tipos de receptor.En el segundo objetivo del trabajo de tesis se han estudiado los análogos estructurales del ATP dinucleósidos polifosfato ya que estos activan receptores purinérgicos y además se ha demostrado que varían la IOP.Los efectos de los dinucleótidos polifosfato son similares a los mostrados por el ADP. El dinucleótido Up4U muestra una dinámica semejante a la observada por el ATP con incrementos más sostenidos en el [Ca2+]i. Las concentraciones a las que se producen estos incrementos de Ca2+ son grandes y a concentraciones fisiológicas sus efectos son muy bajos. Los dinucleótidos Ap3A y Ap4A producen un aumento en la C y su efecto está mediado por la activación del receptor P2Y1. El aumento provocado por el Ap4A se previene al prefundir juntamente con el antagonista del receptor P2Y1. El agonista selectivo del P2Y1 aumenta la C y su efecto no se produce en presencia del antagonista del P2Y1. / SUBJECT: Functional involvement of purinergic activation in trabecular meshwork.TEXT: The understanding of the physiology of the trabecular meshwork has advanced in the last few years, however purinergic receptors have not been characterized in this tissue and their role have not been determined.In this work it is shown that trabecular meshwork express three diferent subtypes of purinergic receptors: P2Y1, P2Y2 and P2Y4. They are activated by different purinergic agonists and depending on the subtype their response on the intracellular calcium levels are diferent.The activation of P2Y2 and P2Y4 leads Ca2+ mobilisations greater than the P2Y1 activation and their stimulation does not produce changes in outflow facility.On the other hand, the stimulation of P2Y1 receptor by compounds selective for the receptor or some dinucleosides polyphosphate lead an increase in the outflow facility. The increments do not seem to involve calcium signalling and perhaps the intracellular mechanisms could involve second messengers like cAMP.

Additive manufacturing technologies are enabling newfound degrees of geometrical complexity to be realised, particularly with regards to internal structures. All of these manufacturing technologies are dependant on their prior design in an appropriate electronic form, either by reverse engineering, or, primarily, by computer-aided design. Within these emerging applications is the design of scaffolds with an intricate and controlled internal structure for bone tissue engineering. There is a consensus that ideal bone scaffold geometry is evident in biological trabecular structures. In their most basic topological form,these structures consist of the non-linear distribution of irregular interconnecting rods and plates of different size and shape. Complex and irregular architectures can be realised by several scaffold manufacturing techniques, but with little or no control over the main features of the internal geometry, such as size, shape and interconnectivity of each individual element. The combined use of computer aided design systems and additive manufacturing techniques allows a high degree of control over these parameters with few limitations in terms of achievable complexity. However, the design of irregular and intricate trabecular networks in computer aided design systems is extremely time-consuming since manually modelling an extraordinary number of different rods and plates, all with different parameters, may require several days to design an individual scaffold structure. In an attempt to address these difficulties, several other research efforts in this domain have largely focussed on techniques which result in designs which comprise of relatively regular and primitive shapes and do not represent the level of complexity seen biologically. Detailed descriptions of these methods are covered in chapter 1. An automated design methodology for trabecular structures is proposed by this research to overcome these limitations. This approach involves the investigation of novel software algorithms, which are able to interact with a conventional computer aided design program and permit the automated design of geometrical elements in the form of rods, each with a different size and shape. The methodology is described in chapter 2 and is tested in chapter 3. Applications of this methodology in anatomical designs are covered in chapter 4. Nevertheless, complex designed rod networks may still present very different properties compared to trabecular bone geometries due to a lack detailed information available which explicitly detail their geometry. The lack of detailed quantitative descriptions of trabecular bone geometries may compromise the validity of any design methodology, irrespective of automation and efficiency. Although flexibility of a design methodology is beneficial, this may be rendered inadequate when insufficient quantitative data is known of the target structure. In this work a novel analysis methodology is proposed in chapter 5, which may provide a significant contribution toward the characterisation and quantification of target geometries, with particular focus on trabecular bone structures. This analysis methodology can be used either to evaluate existing design techniques or to drive the development of new bio-mimetic design techniques. This work then progresses to a newly derived bio-mimetic automated design technique, driven by the newly produced quantitative data on trabecular bone geometries. This advanced design methodology has been developed and tested in chapter 6. This has demonstrated the validity of the technique and realised a significant stage of development in the context and scope of this work.

L’os subit perpétuellement des contraintes mécaniques et physiologiques, ainsi sa qualité et sa résistance à lafracture évoluent constamment au cours du temps à travers le processus de remodelage osseux. Cependant,certaines pathologies osseuses comme l’ostéoporose ou la maladie de Paget altèrent cette dernière et conduisent àune augmentation du risque de fracture osseuse. La qualité osseuse est non seulement définie par la densitéminérale osseuse (DMO) mais également par les propriétés mécaniques ainsi que la microarchitecture. Au total, onévalue en France à environ 3 millions le nombre de femmes et 1 million le nombre d’hommes souffrantd’ostéoporose, pour un coût estimé à 1 milliard d’euros. La prévention par le développement d’outils de diagnosticest nécessaire. Le diagnostic doit permettre d’estimer la qualité osseuse (propriétés mécaniques, activitéscellulaires, architecture). Ces travaux de thèse proposent un modèle innovant permettant de combiner lesdifférents facteurs agissant sur le remodelage osseux, à savoir : (i) le comportement mécanique, (ii) l’activitécellulaire, (iii) le processus de transduction ; visant à traiter les différentes informations d’origines mécanique etbiochimique. Les lois de comportement mécaniques et cellulaires sont issues de modèles validés dans la littératureet la stratégie d’unification voit sa justification à travers différents travaux sur les mécanismes de transduction.Ainsi, l’implémentation de ces trois acteurs du remodelage dans une analyse par éléments finis permet d’obtenirun modèle mécano-biologique du remodelage de l’os trabéculaire. Le modèle est applicable à différentes échelles etpermet d’étudier le niveau de remodelage local modulé par l’activité physique et la concentration de certains agentsbiochimiques. L’application du modèle sur un volume virtuel de fémur selon différents scénarios cliniques donnedes résultats conformes aux observations faites en imagerie médicale. / By continuously undergoing mechanical and physiological stresses, bone quality and bone strength evolve throughremodeling process. However, osteoporosis and Paget’s disease for instance alter bone quality and increase the risk of bone fracture. Bone quality is mainly defined by its Bone Mineral Density (BMD) but mechanical properties and microarchitecture have also to be taken into account for a proper definition. About 3 million of women and 1 million of men suffer from osteoporosis which costs approximately 1 billion Euros per year in France. This highlights the necessity to develop diagnostic tools in order to enable proper bone quality characterization (mechanical properties, cellular activity and architecture).This thesis proposes an original model combining the main bone remodeling constituents which are : (i) the mechanical behavior, (ii) the cellular activity, (iii) the transduction phase ; enabling mechanical and biochemical information processing. Mechanical and cellular behavior models are taken from already published work and the transduction phase model unifying mechanical and biological information is inspired from the literature. Consequently, the implementation of these three main bone remodeling constituents into a finite element analysis gives a plausible mechano-biological model of trabecular bone remodeling. The developed model can be used at different scales in order to study the local amount of bone remodeled, magnified by physical activity and the concentration of some biochemical agents. Its application on virtual volume of femora under different clinical scenarios gives good results in respect to medical images observations.

Le glaucome est défini par une dégénérescence du nerf optique dont le principal facteur de risque est l’hypertension oculaire due à des altérations du tissu trabéculaire. Les traitements incluent des agonistes du récepteur FP, les agonistes du récepteur EP2 pouvant également avoir des effets bénéfiques.Au cours de cette thèse, un modèle de cellules trabéculaires primaires humaines a été défini et les effets du latanoprost, un agoniste FP, et du butaprost, un agoniste EP2, ont été étudiés, d'une part, sur la survie des cellules trabéculaires, et d’autre part, sur la transition myofibroblastique. Il a été montré que l’activation du récepteur EP2 permet de protéger les cellules trabéculaires d’un stress du réticulum endoplasmique par une diminution de l’accumulation de p53 qui résulte en l’inhibition de l’expression de Puma. Enfin, le butaprost entraîne l’augmentation de l’expression de Bcl-2 et la phosphorylation de Bad qui participent à l’inhibition de l’apoptose.D’autre part, le latanoprost induit une contraction des cellules trabéculaires tandis que le butaprost inhibe la contraction induite par le TGF-B2. En revanche, les deux agonistes inhibent la déposition du collagène.En conclusion, indépendamment de leur effet hypotenseur connu, le latanoprost favoriserait l’acquisition par les cellules trabéculaires d’un phénotype contractile et l’activation du récepteur EP2 pourrait limiter le développement de la dysfonction trabéculaire en protégeant de la mort cellulaire et en favorisant une relaxation. Ces résultats suggèrent que la stimulation du récepteur EP2 pourrait limiter le développement du glaucome et serait plus favorable que les agonistes du récepteur FP. / Glaucoma is defined as an optic neuropathy whose main risk factor is ocular hypertension due to alterations of the trabecular meshwork (TM). The first-line therapies for glaucoma are agonists of the FP receptor. Agonists of the EP2 receptor could also present beneficial effects.During the thesis project, a model of primary human TM cells has been defined and the effects of latanoprost, an FP agonist, and butaprost, an EP2 agonist, have been studied on, firstly, the survival of TM cells and, secondly, on the myofibroblast transition.We have shown that activation of the EP2 receptor protects TM cells from an endoplasmic reticulum stress by a decreased accumulation of p53 which results in the inhibition of Puma transcription. Finally, butaprost mediates an increased expression of Bcl-2 and an elevation of Bad phosphorylation which contribute to protection against TM cell death.Moreover, latanoprost induces TM cell contraction while butaprost inhibits TGF-B2-dependent contraction. On the other hand, both agonists inhibit collagen.In conclusion, independently of their hypotensive effects, latanoprost would favor the acquisition by TM cells of a contractile phenotype while stimulation of EP2 receptor could limit TM dysfunction by protecting against TM cell death and relaxing the tissue. These results suggest that activation of EP2 receptor could slow down or inhibit the course of glaucoma progression and would be more favorable than the FP agonists currently used.