Introdução: Materiais com modificações na formulação original do MTA, incluindo o NeoMTA Plus, têm sido desenvolvidos buscando melhorar suas propriedades físicoquímicas. O objetivo do presente estudo foi analisar a resposta do tecido ósseo de ratos Wistar frente ao implante de NeoMTA Plus em comparação com o MTA Angelus. Metodologia: 24 ratos foram anestesiados e uma broca de baixa rotação foi empregada para confeccionar três cavidades cirúrgicas no fêmur direito. As cavidades cirúrgicas foram preenchidas aleatoriamente com os materiais teste NeoMTA Plus e MTA Angelus ou deixada vazia (controle negativo). Após 7, 30 e 90 dias as características do reparo ósseo foram classificadas em escores com o auxilio de microscópio óptico. As comparações entre os grupos foram realizadas pelo teste de Friedman e as comparações entre os três períodos experimentais em cada grupo foram realizadas pelo teste de Kruskal-wallis, seguido pelo teste de Dunn. O nível de significância foi estabelecido em P<.05. Resultados: Não foram observadas diferenças estatísticas entre os materiais e o grupo controle nos 3 tempos experimentais. Em todos os grupos houve diferença estatisticamente significante entre os tempos de 7 e 30 dias e nenhuma diferença foi observada entre os tempos de 30 e 90 dias. Além disso, o reparo em 90 dias foi significativamente melhor do que em 7 dias nos grupos NeoMTA Plus e controle. Conclusões: O NeoMTA Plus demonstrou comportamento biológico satisfatório em contato direto com o tecido ósseo de ratos Wistar, apresentando resultados semelhantes aos grupos MTA Angelus e controle. / Introduction: Materials that alter the original formulation of MTA have been developed to improve physical-chemical properties, including NeoMTA Plus (NMTAP). The aim of the present study was to analyze bone tissue reactions to NMTAP compared to MTA Angelus (MTA-A). Methods: 24 animals were anesthetized and a slow-rotation bur was used to create three surgical cavities in their right femur. Surgical cavities were randomly designated to NMTAP, MTA-A and negative control (empty cavity) groups. After 7, 30, and 90 days histological analysis of the characteristics of bone repair were classified in scores. Friedman’s test performed intergroup comparisons and Kruskal-Wallis test, followed by the Dunn’s post hoc test, compared the three experimental periods in each group. The significance level was set at P<.05. Results: No differences were found between the materials and control group in each experimental period. In all groups, the bone tissue repair improved from 7 to 30 days and there was no difference from 30 to 90 days. Moreover, the repair at 90 days was significantly better than at 7 in NMTAP and control groups. Conclusions: NeoMTA Plus showed satisfactory biological behavior when in direct contact with rat bone tissue, presenting repair characteristics similar to those produced by MTA Angelus and by the control group.

Cortical bone tissue - one of the most intriguing materials found in nature - demonstrate some fascinating behaviours that have attracted great attention of many researchers from all over the world. In contrast to engineering materials, bone has its unique characters: it is a material that has both sufficient stiffness and toughness to provide physical support and protection to internal organs and yet adaptively balanced for its weight and functional requirements. Its structure and mechanical properties are of great importance to the physiological functioning of the body. Still, our understanding on the mechanical deformation processes of cortical bone tissue is rather limited. Penetration into a bone tissue is an intrinsic part of many clinical procedures, such as orthopaedic surgery, bone implant and repair operations. The success of bone-cutting surgery depends largely on precision of the operation and the extent of damage it causes to the surrounding tissues. The anisotropic behaviour of cortical bone acts as a distinctive protective mechanism and increases the difficulty during cutting process. A comprehensive understanding of deformation and damage mechanisms during the cutting process is necessary for improving the operational accuracy and postoperative recovery of patients. However, the current literature on experimental results provides limited information about processes in the vicinity of the cutting tool-bone interaction zone; while; numerical models cannot fully describe the material anisotropy and the effect of damage mechanisms of cortical bone tissue. In addition, a conventional finite-element scheme faces numerical challenges due to large deformation and highly localised distortion in the process zone. This PhD project is aimed at bridging the gap in current lack of understanding on cutting-induced deformation and fracture processes in the cortical bone tissue through experimental and numerical approaches. A number of experimental studies were accomplished to characterise the mechanical behaviour of bovine cortical bone tissue and to analyse deformation and damage mechanisms associated with the cutting process II along different bone axes in four anatomic cortices, namely, anterior, posterior, medial and lateral. These experiments included: (1) a Vickers hardness test to provide initial assessments on deformation and damage processes in the cortical bone tissue under a concentrated compressive load; (2) uniaxial tension and compression tests, performed to understand the effect of orientation and local variability of microstructure constituents on the macroscopic material properties of cortical bone; (3) fracture toughness tests, aimed at elucidating the anisotropic character of fracture toughness of cortical bone and its various fracture toughness mechanisms in relation to different orientations; (4) penetration tests, conducted to evaluate and validate mechanisms involved in bone cutting as well as orientation associated anisotropic deformation and damage processes at various different cortex positions. Information obtained in these experimental studies was used to assist the development of advanced finite-element models: (1) the effective homogenised XFEM models developed in conjunction with three-point bending test to represent a macroscopically, anisotropic elasticplastic fracture behaviour of cortical bone tissue; (2) three microstructured XFEM models to further investigate the effect of the randomly distributed microstructural constituents on the local fracture process and the variability of fracture toughness of cortical bone; (3) a novel finite-element modelling approach encompassing both conventional and SPH elements, incorporating anisotropic elastic-plastic material properties and progressive damage criteria to simulate large deformation and damage processes of cortical bone under penetration. The established models can adequately and accurately reflect large deformations and damage processes during the penetration in bone cutting. The results of this study made valuable contributions to our existing understanding of the mechanics of cortical bone tissue and most importantly to the understanding of its mechanical behaviours during the cutting process.

Bones are the principal structural components of a skeleton; they provide the body with unique roles, such as its shape maintenance, protection of internal organs and transmission of muscle forces among body segments. Their structural integrity is vital for the quality of life. Unfortunately, bones can only sustain loads until a certain limit, beyond which it fails. Usually, the reasons for bone fracture are traumatic falls, sports injuries, and engagement in transport or industrial accidents. The stresses imposed on a bone in such activities can be far higher than those produced during normal daily activities and lead to fracture. Understanding deformation and fracture behaviours of bone is necessary for prevention and diagnosis of traumas. Even though, in principle, studying bone's deformation and fracture behaviour is of immense benefit, it is not possible to engage volunteers in in-vivo investigations. Therefore, by developing adequate numerical models to predict and describe its deformation and fracture behaviours, a detailed study of reasons for, and ways to prevent or treat bone fracture could be implemented. Those models cannot be formulated without a set of experimental material data. To date, a full set of bone's material data is not implemented in the material data-base of commercial finiteelement (FE) software. Additionally, no complete set of data for the same bone can be found in the literature. Hence, a set of cortical bone's material data was experimentally measured, and then introduced into the finite-element software. A programme of experiments was conducted to characterise mechanical properties of the cortical bone tissue and to gain a basic understanding of the spatial variability of those properties and their link to the underlying microstructure. So, several types of experiments were performed in order to quantify mechanical properties of the studied bone tissue at macro- and microscales under quasi-static and dynamic loading regimes for different cortex positions called anterior, posterior, medial and lateral. Those experiments included: (1) uniaxial tension and creep tests to obtain its elastic, plastic and viscoelastic properties; (2) nanoindentation tests to characterise its microstructural elastic-plastic properties; (3) Izod tests to investigate its fracture properties under impact bending loading; (4) tensile-impact tests to characterise its impact strength and fracture force when exposed to a longitudinal loading regime. All the experiments were performed for different cortex positions and different directions (along the bone axis and perpendicular to it) when possible. Based on the results of those experiments, a number of finite-element models were developed in order to analyse its deformation and fracture using the extended finiteelement method (X-FEM) at different length scales and under various loading conditions. Those models included: (1) two-dimensional (2D) FE models to simulate its fracture and deformation at microscale level under quasi-static tensile loading. Additionally, the effect of the underlying microstructure on crack propagation paths was investigated; (2) 2D and three-dimensional (3D) FE models to simulate its fracture and deformation at macroscale level for the Izod impact test setup. In addition, the applicability of different constitutive material models was examined; (3) 3D FE models to simulate its fracture and deformation at macroscale level for tensile-impact loading conditions. The developed models provided high-quality results, and most importantly, they adequately reflected the experimental data. The main outcome of this thesis is a comprehensive experimental analysis and numerical simulations of the deformation and fracture of the cortical bone tissue at different length scales in response to quasi-static and dynamic loading. Recommendations on further research developments are also suggested.

Made available in DSpace on 2014-06-11T19:23:04Z (GMT). No. of bitstreams: 0 Previous issue date: 2005-07-26Bitstream added on 2014-06-13T18:09:15Z : No. of bitstreams: 1 werkman_c_me_sjc.pdf: 536599 bytes, checksum: 7def8f8672e76b8811df840d31139525 (MD5) / A osteoporose, doença caracterizada pela perda de massa óssea, tem sido alvo de estudos nos últimos anos. Fraturas decorrentes da osteoporose são muito comuns e podem apresentar consolidação mais lenta. O objetivo deste trabalho foi avaliar o efeito do risedronato (medicamento alopático) e da Calcarea phosphorica 6CH (medicamento homeopático) no processo de reparo ósseo em ratos machos com osteoporose induzida por castração. Para tanto, foram utilizados oitenta e quatro ratos de três meses de idade separados em quatro grupos de vinte e um animais, sendo três grupos submetidos à castração e um grupo a falsa cirurgia (sham). Um mês após, foram realizadas lesões ósseas monocorticais na tíbia de todos os animais e a partir do dia seguinte, os respectivos tratamentos foram iniciados de acordo com os seguintes grupos: CR - castrado/ risedronato (1mg/kg/dia); CCp - castrado/Calcarea phosphorica 6CH (três gotas/dia); CP - castrato/placebo e SP - sham/placebo que receberam apenas três gotas ao dia de água destilada. Os animais foram sacrificados aos sete, catorze e vinte e oito dias após o início do tratamento e as tíbias removidas. Radiografias digitais foram realizadas e avaliadas pelo programa Image Tool para obter a densidade óptica na área do defeito. Então as tíbias foram descalcificadas e processadas para a realização das análises histológicas. A histomorfometria mediu a porcentagem de osso formado utilizando um retículo graduado colocado no centro da lesão através do programa Image J. Para a análise estatística, os dados foram submetidos aos testes de ANOVA, Tukey e Dunnett, ao nível de 5%. Segundo a análise da densidade óptica, o grupo CCp apresentou os melhores resultados aos sete e catorze dias, mas foi superado pelo grupo CR aos vinte e oito dias. Segundo a histomorfometria o grupo SP apresentou o melhor resultado aos sete dias,... / Osteoporosis, a disease characterized by progressive bone loss, has been the target of several studies lately. It results in a much higher risk for fractures and might cause slower bone consolidation. The aim of this work was to study the effects of Risedronate (allopathic medicine) and Calcarea phosphorica 6CH (homeopathic medicine) to repair bone lesions in male rats with osteoporosis, induced by castration. For this, eighty-four three-months-old rats were used divided in four groups of twenty-one animals. Three groups where castrated and one group was submitted to Sham surgery. One month later, monocortical lesions were made in all animals' tibiae and after one day they began the different treatments according to the following groups: CR - castrated/Risedronate (1mg/kg/day); CCp - castrated/Calcarea phosphorica 6CH (3 drops/day); CP - castrated/placebo and SP - Sham/placebo that received 3 drops/day of distilled water. The animals were sacrificed at seven, fourteen and twenty-eight days after the beginning of treatment and had their tibiae removed. The tibiae's digital XR was analyzed in order to evaluate optical density, using the Image Tool program. Then, they were decalcified and processed for histologic analysis. Histomorphometric measures of bone percentual formation were evaluated using a graticule in the central area of the lesion, with the Image J program. Data was submitted to ANOVA, Tukey and Dunnett tests (5% level). According to the optical density, the CCp group showed the best results at seven and fourteen days, but it was surpassed by the CR group at the 28th day. The histomorphometrical analyses showed that the SP group had the best result at seven days but the CR group formed more bone than all the other groups at 14 and 28 days.Measuring the bony callus, the CR group had the thicker callus at seven and 28 days. It... Complete abstract, click electronic address below)

Introdução: Materiais com modificações na formulação original do MTA, incluindo o NeoMTA Plus, têm sido desenvolvidos buscando melhorar suas propriedades físicoquímicas. O objetivo do presente estudo foi analisar a resposta do tecido ósseo de ratos Wistar frente ao implante de NeoMTA Plus em comparação com o MTA Angelus. Metodologia: 24 ratos foram anestesiados e uma broca de baixa rotação foi empregada para confeccionar três cavidades cirúrgicas no fêmur direito. As cavidades cirúrgicas foram preenchidas aleatoriamente com os materiais teste NeoMTA Plus e MTA Angelus ou deixada vazia (controle negativo). Após 7, 30 e 90 dias as características do reparo ósseo foram classificadas em escores com o auxilio de microscópio óptico. As comparações entre os grupos foram realizadas pelo teste de Friedman e as comparações entre os três períodos experimentais em cada grupo foram realizadas pelo teste de Kruskal-wallis, seguido pelo teste de Dunn. O nível de significância foi estabelecido em P<.05. Resultados: Não foram observadas diferenças estatísticas entre os materiais e o grupo controle nos 3 tempos experimentais. Em todos os grupos houve diferença estatisticamente significante entre os tempos de 7 e 30 dias e nenhuma diferença foi observada entre os tempos de 30 e 90 dias. Além disso, o reparo em 90 dias foi significativamente melhor do que em 7 dias nos grupos NeoMTA Plus e controle. Conclusões: O NeoMTA Plus demonstrou comportamento biológico satisfatório em contato direto com o tecido ósseo de ratos Wistar, apresentando resultados semelhantes aos grupos MTA Angelus e controle. / Introduction: Materials that alter the original formulation of MTA have been developed to improve physical-chemical properties, including NeoMTA Plus (NMTAP). The aim of the present study was to analyze bone tissue reactions to NMTAP compared to MTA Angelus (MTA-A). Methods: 24 animals were anesthetized and a slow-rotation bur was used to create three surgical cavities in their right femur. Surgical cavities were randomly designated to NMTAP, MTA-A and negative control (empty cavity) groups. After 7, 30, and 90 days histological analysis of the characteristics of bone repair were classified in scores. Friedman’s test performed intergroup comparisons and Kruskal-Wallis test, followed by the Dunn’s post hoc test, compared the three experimental periods in each group. The significance level was set at P<.05. Results: No differences were found between the materials and control group in each experimental period. In all groups, the bone tissue repair improved from 7 to 30 days and there was no difference from 30 to 90 days. Moreover, the repair at 90 days was significantly better than at 7 in NMTAP and control groups. Conclusions: NeoMTA Plus showed satisfactory biological behavior when in direct contact with rat bone tissue, presenting repair characteristics similar to those produced by MTA Angelus and by the control group.

O Banco de Tecidos do Instituto de Ortopedia e Traumatologia do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo está desenvolvendo uma linha de estudos experimentais com o intuito de apresentar novos métodos de armazenamento de aloenxertos. Este estudo tem como objetivo comparar o método da criopreservação (- 80° C) com o da conservação em glicerol a 98% em temperatura ambiente. Foram analisadas tanto a capacidade de inibição de crescimento bacteriano e fúngico quanto às eventuais alterações histológicas. Para isso, foram estudadas 30 amostras de tecido ósseo trabecular coletadas de 10 pacientes submetidos à artroplastia total do quadril. Estas amostras foram divididas em três grupos de 10 espécimes, a saber: grupo controle, grupo criopreservado e grupo conservado em glicerol a 98% à temperatura ambiente. O período de armazenamento das amostras foi de um ano. Os resultados foram analisados estatisticamente pelo método de McNemar, com índice de significância de 0,10. No que diz respeito à preservação da matriz óssea, não houve variações significativas nos dois grupos estudados em relação ao grupo controle. Não ocorreu crescimento bacteriano ou de fungos nas amostras armazenadas durante um ano em glicerol a 98%. Por ser extremamente reduzido em relação à criopreservação, o custo do método da conservação em glicerol a 98% o indica para uso em Bancos de Tecidos de pequena monta. Contudo, são ainda necessários posteriores estudos sobre as propriedades biomecânicas, remoção do glicerol do tecido ósseo e o processo de integração biológica dos mesmos com o receptor. / The Tissue Bank of Instituto de Ortopedia e Traumatologia do Hospital das Clínicas da Universidade de São Paulo is developing a line of experimental studies with the intention to present new methods of allografts storage. This study has the objective to compare the method of cryopreservation (-80 ºC) with glycerol 98% preservation at room temperature. It even analyses, in such way, the inhibition capacity of bacterial and fungal growth and any eventual histological changes. For this, 30 samples of trabecular bone tissue have been collected from 10 patients submitted to total hip arthroplasty. These samples were separated in three groups of 10 specimens, as following: a control group, a cryopreserved group and a glycerol 98% preserved group at room temperature. They were stored during a period of one year. The results were analysed by the McNemar statistic method, with a significance of 0,10. Concerning to bone matrix, no significant changes occurred to the two studied groups compared to the control group. Bacterial and fungal growth do not occurred in the stored samples for one year in glycerol 98%. For being extremely reduced when compared with cryopreservation method, the preservation cost in glycerol 98% indicates its use on small sum tissue banks. However, posterior studies about biomechanical properties, glycerol removal of bone tissue and their biological process of integration with the receiver are necessary.

La reconstruction de lésions osseuses complexes reste un défi dans le domaine de la chirurgie orthopédique et maxillo-faciale. A ce jour, la technique de référence reste la greffe d’os autologue. Cependant cette technique présente de nombreuses limites (risque d’infection, morbidité au site de prélèvement). Dans ce contexte, l’ingénierie tissulaire peut apporter des solutions de reconstruction innovantes. En effet l’utilisation de matrices ostéoconductrices et ostéoinductrices permettrait de remplacer l’autogreffe. Le premier objectif de ce travail a été de mettre au point une matrice de polysaccharides, contenant des particules d’hydroxyapatite (HA) dopées avec du strontium (Sr), afin de stimuler à la fois la régénération osseuse, mais également l’angiogenèse. Les résultats obtenus in vitro et in vivo nous ont permis d’optimiser la formulation de cette matrice, en termes de quantités de particules d’hydroxyapatite dopées par différents taux de substitution en strontium, dispersées au sein de la matrice. La deuxième partie de ce travail a été consacrée à l’application de cette matrice à la technique de Masquelet afin de remplacer l’utilisation de l’autogreffe. Cette procédure chirurgicale en deux temps, basée sur la formation d’une membrane induite, est utilisée fréquemment en chirurgie orthopédique et maxillo-faciale. Le premier temps opératoire utilise un ciment chirurgical, le (poly(méthyl)méthalcrylate, PMMA) qui entraîne la formation d’une membrane induite vascularisée. Notre travail a été de remplacer ce ciment par du silicone et d’étudier l’influence de la radiothérapie sur la qualité et la fonction de la membrane ainsi formée. Les premiers essais d’évaluation de cette matrice ont été réalisés chez le rat après résection segmentaire du fémur, suivie d’une procédure de radiothérapie. Les perspectives de ce travail sont d’évaluer la performance de cette matrice dans une lésion mandibulaire de grand volume, après irradiation, chez le gros animal. / Reconstruction of large and complex bone defects remains a challenge for orthopaedic and maxillo-facial surgery. The gold standard strategy for bone reconstruction is the autologous bone graft. However, this approach still exhibits some limitations (infection risks, morbidity at the donor site). In this context, tissue engineering can provide innovative solutions for bone reconstruction. Indeed, the use of osteoconductives and osteoinductives matrices could replace autograft. Based on previous data obtained by our laboratory, the first objective of this work was to develop a composite matrix of polysaccharides containing hydroxyapatite (HA) particles doped with strontium (Sr), to stimulate both bone formation and angiogenesis. In vitro and in vivo results allow us to optimize the amount of HA particules and the ratio of Sr-substitution within the polysaccharide-based matrix. The second part of this work was to apply this biomaterial in the context of Masquelet approach. These two time procedure surgery, based on the formation of an induced membrane, is commonly used in orthopaedic and maxillo-facial surgery. The first chirurgical step uses a surgical cement (poly(methyl)methalcrylate, PMMA) to promote around it the formation of a vascularized membrane. Our work was to replace this cement by silicone and to study the influence of radiotherapy treatment on the quality and the function of this induced membrane. The first preclinical evaluation of this matrix has been performed on a rat femoral segmental bone defect, followed by a radiotherapy procedure. The perspectives of this work are to evaluate the performances of this matrix on irradiated segmental mandibular bone defect in large animal.

Plusieurs études rapportent l’intérêt de structures poreuses synthétiques reproduisant la micro-architecture osseuse pour obtenir une régénération des pertes de substance osseuses. La fusion laser sélective de titane permet de fabriquer des implants poreux aux propriétés mécaniques très proches de celles de l’os et au potentiel d’ostéointégration élevé. Néanmoins, la recolonisation osseuse des pores de ces implants peut être limitée par leurs propriétés élastiques que nous considérons surdimensionnées. Nous avons mis au point une étude expérimentale chez la brebis afin d’évaluer l’influence des propriétés élastiques de ces implants, utilisés dans des pertes de substance mandibulaires, sur leur recolonisation osseuse. Des implants poreux et contrôles permettant une reprise intégrale de la sollicitation mécanique ont été développés. Deux groupes de six brebis ont été équipés d’implants poreux et d’implants contrôles controlatéraux de raideur variable. La régénération osseuse au sein des implants a été évaluée par caractérisation mécanique des interfaces os–implant et par la mesure du volume osseux néoformé à partir d’acquisitions micro-CT. Les implants poreux ont permis une meilleure régénération osseuse que les implants contrôles. Les implants poreux à la raideur la plus basse ont montré une régénération osseuse significativement plus élevée que les autres implants poreux. Un modèle en éléments finis a été développé afin d’optimiser la fixation des implants et la transmission des contraintes aux interfaces os-implant. / Several articles report on the regeneration of bone defects using synthetic porous structures mimicking bone micro-architecture. Porous implants exhibiting mechanical properties close to that of bone tissue with enhanced osseointegration ability can be manufactured by means of selective laser melting of titanium. However, bone growth into the pores of such implant could be limited due to oversized elastic properties. We implemented an experimental study with ewes to assess the influence of the overall stiffness of these implants on bone ingrowth in critical-size mandibular defects. Fully load-bearing porous and control implants of varying overall stiffness were developed and implanted in two groups of six ewes. Bone ingrowth was assessed by mechanical characterization of bone-implant interfaces and by the measurement of the newly formed bone volume using micro-CT imaging. Higher bone ingrowth was identified in porous implants compared to control implants. Low-stiffness porous implants exhibited significantly higher bone ingrowth as compared to porous implants with stiffness closer to that of the missing bone. A finite elements model was developed to improve bone fixation of the implant and load transfer through the bone-implant interfaces.

Les conséquences de l’évolution démographique vers une population de plus en plus âgée ont un impact énorme sur l’économie en termes de santé. Vieillir en bonne santé est devenu un enjeu majeur et il est devenu primordial d’instaurer des politiques de prévention. La nutrition apparait comme l’une des stratégies préventives les plus prometteuses pour contrer la perte de masse osseuse liée à l’âge. Le couple Calcium/vitamine D ayant des effets limités,il est important de développer d’autres alternatives afin de préserver le capital osseux.L’étude de l’effet du collagène hydrolysé (H C) sur le tissu osseux est devenue une thématique montante ces dernières années. Plusieurs études in vivo ont permis de démontrer que l’ingestion de collagène hydrolysé améliorait le développement de la masse osseuse. L’objectif de cette thèse a été d’étudier la pertinence de l’utilisation du H C dans la mise au point de stratégies nutritionnelles pour la prévention de l’ostéoporose.Après avoir mis en évidence l’intérêt du H C sur l’activité d’ostéoblastes murins MC3T3-E1, nous avons évalué son effet in vivo sur des souris ovariectomisées : modèle d’ostéoporose post-ménopausique liée à une carence oestrogénique. Nous avons montré que le collagène hydrolysé d’origine bovine (B H C) contribue à limiter la perte osseuse induite par l'ovariectomie. Cette étude in vivo nous a permis de constater que la limitation de la perte osseuse induite est liée à un effet spécifique du B H C et dépendante de la longueur du peptide.La deuxième partie de nos travaux a consisté à mettre en lumière le rôle des métabolites de collagène sur l’activité des cellules osseuses. Ainsi, le BHC favorise la survie et la différenciation ostéoblastique et inversement pour les ostéoclastes en modulant le ratio OPG / RANKL.En résumé, nos résultats confirment le potentiel du collagène hydrolysé dans la prise en charge de la perte osseuse liée à l’âge et soulignent l’intérêt du collagène hydrolysé dans la conception de stratégies novatrices pour le management des troubles ostéoporotiques / Due to demographic changes healthy aging has become a major issue and interest in prevention has raised accordingly. In this context, nutrition has become one of the most promising strategies to counter age-related complications, including bone loss. Effects of hydrolyzed collagen (HC) on the bone tissue have focused attention in recent years. Several in vivo studies have demonstrated that hydrolyzed collagen ingestion may preserve bone mass. The aim of this thesis was to study the relevance of HC use in the development of nutritional strategies for osteoporosis prevention. The interest of HC was first investigated on the activity of murine osteoblasts MC3T3-E1. Then, we evaluated itseffect on ovariectomized mice: a postmenopausal osteoporosis model related to estrogenic deficiency. We have shownthat bovine hydrolyzed collagen (BHC) helps reducing bone loss induced by ovariectomy and that observed effect wasspecific and not related to protein content and that it was dependent on the mean molecular weight of the peptide. The second part of our work emphasizes the role of collagen metabolites on bone cell activity. We demonstrated that enreiched serum in BHC promotes osteoblast survival and differentiation, conversely inhibits osteoclastogenesis andmodulates the OPG / RANKL ratio. In summary, our results confirm the benefit of hydrolyzed collagen on bone and point out the value of hydrolyzed collagen in the design of innovative strategies for the management of osteoporotic disorders.

Non seulement la structure hiérarchisée du tissu osseux mais aussi son hétérogénéité, son anisotropie et les incertitudes expérimentales de mesures liées aux matériaux vivants rendent en pratique impossible la définition d'un modèle déterministe fiable de ses propriétés matérielles. Dans une démarche d'aide au diagnostic clinique, l'objectif de cette thèse est de développer une modélisation robuste desdites propriétés à l'échelle de l'organe en intégrant l'incertitude expérimentale de mesures.Pour ce-faire, nous avons développé un modèle multi-échelle stochastique basé sur le principe du maximum d'entropie et des méthodes d’homogénéisation en champs moyens (micromécanique) qui s'est montré capable de prédire les propriétés matérielles du tissu osseux à l'échelle de l'organe en prenant en compte les incertitudes expérimentales de données issues de l’imagerie. Dans la perspective d'identifier le mécanisme de propagation de l’incertitude à travers le modèle multi-échelle, plusieurs versions de ce modèle ont été analysées.Le modèle principal utilise comme variables primaires la fraction volumique des constituants essentiels (le minéral, l'eau et le collagène) pour lesquelles une discussion est proposée échelle par échelle en examinant leur effet sur les propriétés effectives à chaque échelle. Cette description est à l’image d'une matryoshka, plus communément appelée poupée russe, via l’aspect multi-échelle. Chaque matryoshka est une série de poupées de tailles décroissantes placées les unes à l'intérieur des autres. Grâce à cette analyse, cette version du modèle a pu être liée de façon directe aux mesures expérimentales issues de l’imagerie médicale que sont la densité minérale du tissu (TMD) et la porosité haversienne (HP) de l'os cortical lors d’une calibration à l’échelle millimétrique. Cette version a été validée en utilisant plusieurs méthodes numériques telles que la méthode aux éléments finis et la méthode de la transformée de Fourier rapide. On a ainsi pu non seulement évaluer la précision de la méthode proposée mais aussi analyser le processus de transfert d'incertitudes entre les échelles.Enfin, la modélisation stochastique de l'os cortical a été complétée en introduisant des champs de tenseurs d’élasticité des matériaux impliqués dans le processus d’homogénéisation pour l’obtention des propriétés effectives. L’incertitude est introduite via un tenseur aléatoire et se propage spatialement en respectant des longueurs de corrélation et en une suite de réalisations. Ici encore, cette approche peut être vue comme une déclinaison des matryoshka via les champs de tenseurs d’élasticité qui se déclinent dans la procédure stochastique / The hierarchical structure of bone tissues, as well as the heterogeneity and anisotropy of its physical properties and the uncertainty on in vivo experimental measures make it impossible to establish a deterministic reliable model of bone mechanical properties. Aiming at providing a valuable aide to diagnostics in orthopaedic, the purpose of this thesis is to develop a robust mechanical model able to account for the experimental uncertainty.Therefore we developed a multi-scale stochastic model, based on continuum micromechanics and maximum entropy principle which has proved effective predicting the heterogeneous and anisotropic elastic properties of bone tissue at the organ scale accounting for experimental uncertainty affecting image-based input data.Aiming to clarify the mechanism of propagation of these uncertainties through the chosen principal multi-scale model, others versions have been analyzed. First, the principal model, which uses the volume fractions of the essential constituents (mineral, water, collagen), as primary variables, has been analyzed scale-by-scale (mineral foam, ultra-structure, cortical bone). The effect of the chosen homogenization methods and volume fractions on the resulting composites (as layers of a random Matryoshka) have been discussed. Thanks to this analysis, this model has been simplified and relied directly to the measures straightly accessible form medical imaging of the bone: the tissue mineral density (TMD) and the haversian porosity (HP) and their calibration at millimeter scale. This version of the stochastic model, proved to be as accurate as the proceeding one and, more effective in the description of the bone.Finally, the stochastic model of bone has been completed with the direct modeling of the elastic tensors of the involved materials. For this purpose, the random matrix theory has been applied. This theory can be seen as another declination of the Matryoshka paradigm. In this case, the uncertainty on the random tensor propagate from the inside (random germ) to outside (each layer of random matrix) through a suitable sequence of nonlinear operations. Thanks to the proposed decomposition, at once, the isotropic material class of the resulting material and his spatial variability has been included in the model