Submitted by MARIA ROSA FELIX DE SOUSA GOMIDE GUIMARÃES (DINTER) null (mariarosa@saolucas.edu.br) on 2016-11-25T14:46:15Z No. of bitstreams: 1 TESE DOUTORADO Maria Rosa Final.pdf: 1423380 bytes, checksum: 7002561449c42c6a10d037b7ac5e7381 (MD5) / Approved for entry into archive by Felipe Augusto Arakaki (arakaki@reitoria.unesp.br) on 2016-11-29T13:58:37Z (GMT) No. of bitstreams: 1 guimaraes_mrfsg_dr_araca.pdf: 1423380 bytes, checksum: 7002561449c42c6a10d037b7ac5e7381 (MD5) / Made available in DSpace on 2016-11-29T13:58:37Z (GMT). No. of bitstreams: 1 guimaraes_mrfsg_dr_araca.pdf: 1423380 bytes, checksum: 7002561449c42c6a10d037b7ac5e7381 (MD5) Previous issue date: 2016-11-22 / Objetivos: Analisar histologicamente e histometricamente o efeito do RTR® em defeitos ósseos cirúrgicos críticos em tíbias de ratos no processo de reparo ósseo. Materiais e Métodos: Defeitos ósseos críticos foram criados nas tíbias de 32 ratos Wistar divididos em dois grupos: Grupo Coágulo e Grupo RTR®. Após o período experimental de 30 e 90 dias, os animais foram sacrificados e as peças incluídas em parafina, cortadas e coradas com hematoxilina e eosina. Dois parâmetros foram analisados: a área óssea total neoformada (AON) e a área óssea da cortical neoformada (ACN). A análise estatística foi realizada nos dois períodos de observação pela análise de variância (ANOVA) e pelo Teste de Tukey. Resultados: Todos os grupos demonstraram reparo ósseo superior quando comparados ao Grupo Coágulo 30 dias nos dois parâmetros analisados. O Grupo RTR®, em 30 e 90 dias, apresentou reparo da cortical óssea e formações de tecido ósseo na região central do defeito maior do que no Grupo Coágulo de 90 dias, que apresentou reparo parcial da cortical óssea e poucas formações de tecido ósseo na região do defeito (p<0,05). Conclusões: O RTR® favoreceu a neoformação óssea no modelo experimental adotado podendo ser indicado em casos de cavidades ósseas de tamanho crítico. / Objectives: To analyze histologically and histometrically the effect of RTR® on critical surgical bone defects in rat tibiae in the bone repair process. Materials and Methods: Critical bone defects were created in the tibia of 32 Wistar rats divided into two groups: Clot Group and RTR® Group. After the experimental period of 30 and 90 days, the animals were sacrificed and the paraffin embedded pieces were cut and stained with hematoxylin and eosin. Two parameters were analyzed: total neoformed bone area (AON) and bone area of neoformed cortical (ACN). Statistical analysis was performed in the two observation periods by analysis of variance (ANOVA) and Tukey's test. Results: All groups demonstrated superior bone repair when compared to the Clot Group 30 days in the two analyzed parameters. The RTR® Group, in 30 and 90 days, presented repair of the cortical bone and bone tissue formations in the central region of the defect greater than in the 90-day Clot Group, which presented partial repair of the cortical bone and few bone tissue formations in the region of the defect (p <0.05). Conclusions: The RTR® favored the bone neoformation in the adopted experimental model and can be indicated in cases of bone of critical size.

Introdução: Com o aumento da expectativa de vida dos pacientes com Fibrose Cística (FC), a saúde óssea têm sido objeto de estudo a fim de otimizar a qualidade de vida desses pacientes. A prevalência de massa óssea baixa e os fatores de risco associados são altamente variáveis dependendo da população estudada. Objetivos: Determinar a prevalência de massa óssea baixa em pacientes adolescentes e adultos com FC e estudar os fatores potencialmente associados. Métodos: Densidade mineral óssea foi determinada por DXA na coluna lombar em todos os pacientes e no fêmur em pacientes ≥20 anos. Avaliações nutricionais, bioquímicas e pulmonares foram realizadas. Dados referentes ao tratamento farmacológico foram coletados. Resultados: 58 pacientes foram incluídos no estudo (25 homens/ 33 mulheres), média de idade de 23,9 anos (16-53). Massa óssea baixa foi verificada em 20,7% dos pacientes. Não houve histórico de fratura. Z-score da coluna lombar associou-se positivamente com IMC (r= 0,3; p= 0,022), VEF1% (r=0,415; p=0,001). A média do Z-score da coluna foi mais alta nas mulheres que nos homens (p=0,001), em pacientes que não possuíam insuficiência pancreática (p=0,02) e em pacientes que não haviam sido hospitalizados no período de três meses (p=0,032). Os fatores encontrados como preditores independentes de Z-score da coluna lombar foram sexo masculino e IMC. Conclusão: Massa óssea baixa é frequente em pacientes com FC e está associada ao IMC, o qual provavelmente reflete a severidade da doença, e ao sexo masculino. Esforços devem ser empreendidos com o objetivo de manter esses pacientes com perfil nutricional adequado. / Background: Survival of cystic fibrosis (CF) patients has increased, so bone health could be important for the quality of life of affected patients. Several studies described lower bone mass density (BMD) in patients with CF, which increased fracture risk. Objective: The aim of this study was to evaluate the prevalence of low BMD as well as to evaluate the factors associated with bone mass in these patients. Methods: BMD was measured by DXA in lumpar spine (L1-L4), in patients ≤19years-old, or lumbar spine and femur (total and neck) in patients ≥20years-old. Evaluations of nutritional status, biochemical parameters and lung function were performed. Medications were obtained from medical records Results: Fifty-eight patients were included in the study (25 males/33females), mean age 23.9 years (16-53). The prevalence of bone mass below the expected range for age at any site was 20.7%. None of the subjects had history of fracture. Lumbar spine Z-score in FC patients correlated positively with BMI (r= 0.3, p=0.001), and with FEV1 (%predicted) (r=0.415, p=0.022). Mean lumbar spine Z-score were higher in women (p=0.001), in patients with no pancreatic insufficiency (p=0.032), and in patients with no hospitalization in the last 3 months (p=0.02). BMI (p= 0.001) and sex (p=0.001) were independently associated with the Z-score in the lumbar spine. Conclusion: Low bone mass is a frequent problem in patients with CF, being associated with BMI, which could reflect disease intensity, and male sex. A larger effort should be made to keep these patients well-nourished.

Introdução: Com o aumento da expectativa de vida dos pacientes com Fibrose Cística (FC), a saúde óssea têm sido objeto de estudo a fim de otimizar a qualidade de vida desses pacientes. A prevalência de massa óssea baixa e os fatores de risco associados são altamente variáveis dependendo da população estudada. Objetivos: Determinar a prevalência de massa óssea baixa em pacientes adolescentes e adultos com FC e estudar os fatores potencialmente associados. Métodos: Densidade mineral óssea foi determinada por DXA na coluna lombar em todos os pacientes e no fêmur em pacientes ≥20 anos. Avaliações nutricionais, bioquímicas e pulmonares foram realizadas. Dados referentes ao tratamento farmacológico foram coletados. Resultados: 58 pacientes foram incluídos no estudo (25 homens/ 33 mulheres), média de idade de 23,9 anos (16-53). Massa óssea baixa foi verificada em 20,7% dos pacientes. Não houve histórico de fratura. Z-score da coluna lombar associou-se positivamente com IMC (r= 0,3; p= 0,022), VEF1% (r=0,415; p=0,001). A média do Z-score da coluna foi mais alta nas mulheres que nos homens (p=0,001), em pacientes que não possuíam insuficiência pancreática (p=0,02) e em pacientes que não haviam sido hospitalizados no período de três meses (p=0,032). Os fatores encontrados como preditores independentes de Z-score da coluna lombar foram sexo masculino e IMC. Conclusão: Massa óssea baixa é frequente em pacientes com FC e está associada ao IMC, o qual provavelmente reflete a severidade da doença, e ao sexo masculino. Esforços devem ser empreendidos com o objetivo de manter esses pacientes com perfil nutricional adequado. / Background: Survival of cystic fibrosis (CF) patients has increased, so bone health could be important for the quality of life of affected patients. Several studies described lower bone mass density (BMD) in patients with CF, which increased fracture risk. Objective: The aim of this study was to evaluate the prevalence of low BMD as well as to evaluate the factors associated with bone mass in these patients. Methods: BMD was measured by DXA in lumpar spine (L1-L4), in patients ≤19years-old, or lumbar spine and femur (total and neck) in patients ≥20years-old. Evaluations of nutritional status, biochemical parameters and lung function were performed. Medications were obtained from medical records Results: Fifty-eight patients were included in the study (25 males/33females), mean age 23.9 years (16-53). The prevalence of bone mass below the expected range for age at any site was 20.7%. None of the subjects had history of fracture. Lumbar spine Z-score in FC patients correlated positively with BMI (r= 0.3, p=0.001), and with FEV1 (%predicted) (r=0.415, p=0.022). Mean lumbar spine Z-score were higher in women (p=0.001), in patients with no pancreatic insufficiency (p=0.032), and in patients with no hospitalization in the last 3 months (p=0.02). BMI (p= 0.001) and sex (p=0.001) were independently associated with the Z-score in the lumbar spine. Conclusion: Low bone mass is a frequent problem in patients with CF, being associated with BMI, which could reflect disease intensity, and male sex. A larger effort should be made to keep these patients well-nourished.

Orientador: Roger William Fernandes Moreira / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba / Made available in DSpace on 2018-08-24T15:32:49Z (GMT). No. of bitstreams: 1 Rodrigues_DanilloCosta_D.pdf: 786712 bytes, checksum: 20e5c6c3c2775a5b2c547eae752381d0 (MD5) Previous issue date: 2014 / Resumo: O propósito do presente estudo foi avaliar comparativamente, através de teste de carregamento linear e análise fotoelástica, quatro métodos de fixação em fraturas simuladas em corpo de hemimandíbulas de poliuretano e resina fotoelástica. O trabalho foi dividido em quatro grupos: O grupo I, foi fixado com duas placas do sistema 2,0mm, uma na zona de tensão e outra na zona de compressão mandibular. No grupo II, utilizou-se uma placa do sistema 2,0mm na zona central da mandíbula e uma barra de Erich na zona dentada. O grupo III, foi fixado com uma placa do sistema 2,4mm na zona de compressão e uma barra de Erich na zona dentada. E no grupo IV, foi empregada uma placa do sistema 2,0mm na zona de tensão e uma placa do sistema 2,4mm na zona de compressão. Os métodos de fixação utilizados em cada grupo foram semelhantes em ambos os testes. Testes de carregamento linear foram realizados por meio da máquina para ensaio universal mecânica Instron®. Os valores foram analisados pelo teste de Shapiro-Wilk. Em seguida, foi aplicada a Análise de Variância (ANOVA), Kruskal-Wallis e posteriormente, o teste de Tukey e Mann-Whitney com correção de Bonferroni. Para a análise do teste fotoelástico, as hemimandíbulas em resina fotoelástica foram fotografadas quando a máquina de ensaio registrou o deslocamento final de 3mm e as franjas formadas no substrato foram avaliadas de forma qualitativa. Os resultados dos testes mecânicos indicaram que o grupo II apresentou menor resistência, seguido dos grupos I, IV e III. O teste fotoelástico confirmou a maior formação de tensão no grupo de menor resistência mecânica. Dessa forma concluiu-se que em fraturas lineares de corpo de mandíbula a utilização de placa do sistema 2,4mm apresentou maior resistência e que o emprego de apenas uma placa do sistema 2,0mm na zona central apresentou maior tensão / Abstract: The purpose of this study was to evaluate comparatively through linear load testing and photoelastic analysis, four methods of fixation in simulated fractures on polyurethane hemimandibles body and photoelastic resin. The study was divided into four groups: Group I was fixed with two plates of 2.0 mm system, one in the tension zone and another in compression zone. In Group II, it was used a 2.0 mm plate in the neutral zone and an Erich bar. Group III was fixed with a 2.4 mm plate in the compression zone and an Erich bar. The group IV was employed a 2.0 mm plate in tension zone and a 2.4 mm plate in the compression zone. The fixation methods used in each group were similar in both tests. Linear load testing was performed using an Instron® mechanical universal testing machine. After the tests, the values were analyzed by the Shapiro-Wilk test, Analysis of Variance (ANOVA), Kruskal -Wallis test and subsequently the Tukey test, and Mann-Whitney test with Bonferroni correction. For the analysis of photoelastic test, the hemimandibles were photographed in photoelastic resin when the testing machine recorded the final displacement of 3mm and the fringes formed on the substrate were evaluated qualitatively. The results of mechanical tests indicated that the group II had lower resistance, followed by the groups I, III and IV. The photoelastic test confirmed the increased formation of tension in the group of lower mechanical strength. Thus, it was concluded that in linear mandibular body fracture using the system board 2.4 mm presented more resistance and the use of only one 2.0 mm plante in the central area of the mandible showed higher tension / Doutorado / Cirurgia e Traumatologia Buco-Maxilo-Faciais / Doutor em Clínica Odontológica

Abstract This study focuses on the development of a bone collecting device for intra-oral bone harvesting and on the introduction of a new bone graft donor site, zygomatic bone. A bone collector was constructed and tested in vitro. This bone collector is suitable and efficient in dental implant related bone grafting surgery. It was also found to be more efficient and with a larger capacity in bone harvesting when compared to the two commercially available bone collectors. A zygomatic bone harvesting technique is introduced in this study. The safety and morbidity of the method was assessed in a cadaver and a prospective clinical study. In the cadaver study, 40 procedures were performed. The complications during the cadaver harvesting included 15 perforations into the maxillary sinus and 7 perforations into the infratemporal fossa. The only intra-operative complication in 32 clinical operations was perforation of the maxillary sinus in 33% of the zygomatic sites. None of these patients experienced any post-operative problems related to the perforation. Patients needed pain medication for a mean time of four days and they did not demonstrate any paresthesias or altered sensations in the donor area. The yield of the bone graft from zygomatic bone was quantified in cadaver and clinical studies. In the cadaver study, the average yield of the graft was 0.59 ml. In the clinical study the average graft volume was 0.90 ml. The required reconstructions were accomplished in all clinical cases. In the prospective clinical study, the bone grafts from the zygomatic bone were used simultaneously with one-stage dental implants placement. Bone grafting was employed at 72 of the 82 implant sites. Two of the bone grafted implants failed, yielding a survival rate of 97.2% for bone grafted implants and 97.6% for the whole study group. Grafted sites healed remarkably well, and no obvious signs of graft resorption were noted during the 26.9 months follow-up period. The bone collector developed in this study is an effective instrument in intra-oral bone harvesting. The zygomatic bone can be regarded as a safe bone harvesting donor site and the yield of bone graft from this area is sufficient for moderate defects in resorbed alveolar ridges.

Abstract Bone morphogenetic proteins (BMPs) constitute a large family of osteoinductive proteins. Different BMPs are widely used in animal experiments and increasingly in the field of bone surgery. However, the sterilization of BMPs and the choice of a suitable mode of delivery, which binds and slowly releases BMP molecules, are still under intensive investigation. The aims of this study were to evaluate the effects of ethylene oxide and gamma sterilizations and different delivery systems on the osteoinductivity of reindeer BMP extract by using heterotopic and orthopic animal models. Ethylene oxide gas (Steri-Vac 4XL, temperature 29 °C, exposure time 4 h, concentration 860 mg/l) and gamma (doses of 3.15 or 4.15 Mrad) sterilizations were used. The tested delivery systems for reindeer BMP were collagen (Lyostypt®), gelatine capsule (no.1) and composites containing collagen combined with tricalcium phosphate (TCP) or hydroxyapatite (HA) or biphasic tricalcium phosphate-hydroxyapatite (TCP/HA) or biocoral (NC) frames. The injectability of reindeer BMP was tested by using injections containing a saline or gelatine vehicle. Osteoinductivity was evaluated as ectopic bone formation in the thigh muscle pouches of mouse hind legs. The induced new bone was evaluated based on the incorporation of 45Ca or calcium yield, radiographs and histological examination three weeks after the operations. The effect of gamma sterilization on the bone healing capacity of reindeer BMP extract was evaluated in a rabbit radial bone defect model in comparison with non-sterilized reindeer BMP extract and recombinant BMP-2. Bone healing was evaluated after eight weeks based on radiographs, mechanical tests and peripheral computerized tomography (pQCT). All BMP implants induced new bone in vivo visible in radiographs, but no bone formation was seen in the control implants without reindeer BMP. Gamma sterilization did not decrease significantly the osteoinductivity of reindeer BMP extract, except when administered as an injection containing gelatine vehicle. Ethylene oxide sterilization decreased significantly the osteoinductivity of reindeer BMP extract and was significantly inferior compared to gamma sterilization. Reindeer BMP combined with collagen or composite containing collagen and TCP/HA frame induced new bone significantly better than reindeer BMP combined with composite containing collagen and TCP frame. BMP injections with gelatine or saline vehicles induced new bone effectively. Injections were easy to handle and well tolerated by the mice. Reindeer BMP extract administered with collagen carrier healed the bone defect of the rabbit radius significantly better than control implants without reindeer BMP or no treatment and its effect was comparable with rhBMP-2 treatment.

La vascularisation joue un rôle important dans la biologie de l’os. Les souris génétiquement modifiées sont devenues le modèle de choix dans ce champ de recherche ; cependant les outils permettant son exploration structurelle (réseau capillaire) et fonctionnelle (perfusion) dans ce modèle animal, demeurent imparfaits. Notre travail a consisté en une adaptation chez la souris de la technique d’histomorphométrie quantitative vasculaire des os longs, fondée sur le remplissage du réseau par du sulfate de baryum, précédemment développée chez le rat. Nous avons, par ailleurs, mis au point une technique reproductible de mesure de la perfusion osseuse dans le tibia en utilisant le Laser Doppler. En termes d’exploration structurelle, et grâce à une imagerie par microtomographie 3D (Synchrotron ou Nano scanner) nous montrons la supériorité du sulfate de baryum sur le Microfil®, (produit associant silicone et plomb) et sa compatibilité avec les colorations histologiques usuelles et les marquages immuno histochimiques de la paroi vasculaire. Nous établissons la reproductibilité de la technique et nous proposons une nomenclature. En termes de perfusion, après avoir optimisé le protocole en limitant les facteurs de variabilité, nous montrons que le Laser Doppler permet de mesurer de façon reproductible une perfusion strictement osseuse dans le tibia de souris. Sous réserve de recourir { des groupes d’animaux de taille suffisante, (n=15), il devient possible de réaliser des comparaisons intergroupes. Ces deux approches combinées et intégrées, menées sur des souris C57BL/6 et 129sv/Cd1 nous ont permis de montrer (1) qu’il n’y a pas de corrélation entre paramètres de perfusion et de densité vasculaire, (2) que lors du vieillissement chez les mâles, la cinétique d’évolution de la vascularisation osseuse diffère selon le fond génétique, et que la perte osseuse n’est pas accompagnée d’une diminution de la perfusion dans ce modèle, (3) que l’ovariectomie (OVX) induit une diminution de la vascularisation et de la perfusion osseuses qui précède la perte osseuse. Enfin, notre étude des effets vasculaires osseux structurels et fonctionnels de la parathormone 1-84 a montré qu’ils dépendent, à l’instar de ses effets sur la masse osseuse, de son mode d’administration, intermittent ou continu et qu’ils ne sont pas impactés par l’OVX / Vascularisation plays a major role in bone biology. Genetically modified mice became the most favorite model in this research field; however, the tools allowing bone vessel analysis on both structural (capillary network) and functional aspects (perfusion) in this animal model remain unsatisfactory. Our work consisted in adapting in mice the quantitative histomorphometry technique allowing the analysis of long bone vascularization, based on the infusion of barium sulfate, which was previously developed in the rat. In addition, we set up a reproducible Laser Doppler-Based technique for measurement of mouse tibia perfusion. In terms of structural analyses, and thank to 3D micro-Tomography imaging (Synchrotron or Nano scanner), we show the superiority of barium sulfate on a lead/silicon-Based contrast product (Microfil®)and its compatibility with common staining used in histology and with immuno-Histochemsitry of the vessel wall. We establish the reproducibility of the technique and propose a nomenclature. In terms of perfusion, we show, after having optimized the protocol by limiting the factors of variability, that Laser Doppler allows to measure, in a reproducible way, perfusion signals specific to bone. As long as the animal group size is appropriate (n=15), it becomes possible to carry out intergroup comparisons. These combined and integrated approaches, carried out on C57BL/6 and 129sv/Cd1 mice allowed us to show that (1) there is no correlation between perfusion and vascular density parameters (2) during ageing in males, the kinetics of bone vascularisation evolution differ according to the genetic background and that bone loss was not associated with decrease in perfusion in this model (3) that ovariectomy (OVX) induces a decrease in both bone vessel density and perfusion which precedes bone loss. Finally, we studied the structural and functional vascular effects of 1-84 parathyroid hormone and show that, as for its effects on bone mass, they depend on its mode of administration, intermittent or continuous and that they are not affected by OVX

Magister Scientiae Dentium - MSc(Dent) / Autologous bone grafting in conjunction with dental implant therapy is a well-accepted procedure in oral and maxillofacial rehabilitation. A variety of intraoral donor sites, such as the mandibular symphysis, the mandibular ramus and the maxillary tuberosity have been used in oral and maxillofacial reconstruction. However these sites are associated with complications. In order to reduce these complications, the anterior palate has been proposed as a potential donor site. However, the scientific literature in this regard is sparse, and larger studies are required to investigate the clinical potential of this proposed site. Aim: To determine the volume and density of available bone in the anterior palate that may be used for bone harvesting using cone-beam computed tomography (CBCT) in a select South African population. Materials and methods: One hundred previously acquired CBCT scans taken at the Diagnostic and Radiology Department of Tygerberg Oral Health Centre were analyzed for the required data. These were all acquired from a single CBCT machine (Newtom VGI®, Verona, Italy). The study sample included 52 females and 48 males ranging from ages 20 years to 80 years. The CBCT scans were divided into 3 different age groups. The first age group was between the ages of 20 and 39 years, the second age group was from 40 to 59 years and the third age group was ≥ 60 years. The volume and density of the anterior palate of the different age groups were analyzed using specific criterion. CBCT specific software (Simplant Pro Crystal®) Dentsply implants, Mannheim, Germany was used to standardize the data collection. All data was stored in a Microsoft Excel spreadsheet (Microsoft Corporation, Washington, USA). Results: The mean volume of the anterior palate in this study was 2.11 ± 0.55 cm3, with a minimum volume of 1.04 cm3 and a maximum volume of 3.82 cm3. There was no significant difference in the volume and density of the anterior palate between different age groups and no significant difference in the volume between males and females (p value = 0.227). Conclusions: The anterior palate affords a considerable amount of bone volume which is similar or even more than other intraoral donor sites. The anterior palate is a potential donor site for bone harvesting and CBCT may be regarded as an ideal tool to analyze the amount of bone available for harvesting.

[EN] Cortical bone tissue is the responsible of giving support and structure to vertebrates. For that reason, understanding and analyzing its behavior is needed from each different hierarchical level that composes it. The lower the structural scale is, the greater the complexity and scarcity of studies in literature. These studies are relevant for understanding, preventing and solving important health problems that affect human beings. From a mechanical point of view is interesting to evaluate and apply engineering numerical tools to analyze complex materials as biological tissues, increasing the state of the art in different disciplines that can be applied in numerous fields as material science, biomechanics, numerical methods, medicine and more. In this Thesis the mechanical behavior of cortical bone at microstructural level is analyzed, with finite element models of its basic structure, the osteon. The microstructure of osteons, composed of mineralized collagen fibrils in layers with different orientations disposed concentrically around blood vessels is considered in the models for the calculation of elastic properties and failure criteria definition. For obtaining elastic properties, the use of micromechanical finite element models is considered, with heterogeneous composition for both mineralized collagen fibrils (at nanostructural level) and lamellar level (at sub-microstructural level). The failure analysis for realistic geometries is applied after comparing different models that involve, on one hand the growth of microcracks with contact conditions and on the other, degradation of elastic material properties by user subroutines of the finite element code, the latter being the one that brings better results from a computational cost viewpoint. Therefore an interesting alternative is here presented that can be used to evaluate the damage propagation at three-dimensional level, which with other methods as X-FEM can be computationally unaffordable. Composite materials failure criteria are applied to osteon analysis and the results are related with experimental tests from bibliography, showing the relevance of shear stresses between lamellae for failure initiation and propagation. In a two-dimensional study it is also shown the important role of osteocyte lacunae in the failure initiation, what is interesting from a cellular mechanotransduction approach. / [ES] El tejido óseo cortical es el encargado de dar soporte y estructura a los vertebrados. Existe por tanto una necesidad de conocer y analizar mecánicamente su comportamiento desde los distintos niveles jerárquicos que lo componen, siendo mayor la complejidad y más escasos los estudios disponibles en la literatura cuanto más pequeña es la escala estructural que se analiza. Estos estudios son relevantes para comprender, prevenir y solucionar problemas de salud importantes que afectan al ser humano. Desde el punto de vista mecánico es interesante evaluar y aplicar herramientas numéricas ingenieriles para el análisis de materiales más complejos como son los biológicos, incrementando el estado del arte en distintas disciplinas que pueden ser aplicadas en numerosos campos como la ciencia de los materiales, la biomecánica, los métodos numéricos o la medicina, entre otras. En esta Tesis se analiza el comportamiento mecánico del hueso cortical a nivel microestructural, donde se modela mediante el método de los elementos finitos su unidad básica, la osteona. Para la obtención de las propiedades elásticas se considera en los modelos la microestructura compuesta por capas de colágeno mineralizado con diferentes orientaciones, dispuestas de manera concéntrica alrededor de los canales vasculares. Se incluye además la utilización de modelos micromecánicos de elementos finitos que tienen en cuenta la composición heterogénea tanto para el nivel del fibrilo de colágeno mineralizado (nivel nanoestructural) como para el nivel de lamela (nivel sub microestructural). El análisis del fallo para geometrías realistas se aplica tras comparar varios modelos que involucran por un lado el crecimiento de grietas mediante condiciones de contacto y por otro, degradación de las propiedades elásticas del material mediante subrutinas de usuario del código de elementos finitos, siendo este último el que mejores resultados presenta desde el punto de vista del coste computacional. De esta manera se presenta una alternativa interesante que permite evaluar la propagación del daño a nivel tridimensional, lo que con otros métodos como el X-FEM puede ser computacionalmente inabordable. Se aplican criterios de fallo utilizados para materiales compuestos en ingeniería estructural a las osteonas y los resultados se relacionan con los de los ensayos experimentales disponibles en la bibliografía, mostrando la relevancia de las tensiones de cortadura entre lamelas para la iniciación y propagación del daño. En un estudio bidimensional, también se muestra la participación importante en la fase de inicio de daño de las lagunas de osteocitos lo que es interesante desde un enfoque de mecanotransducción celular. / [CAT] El teixit ossi cortical és l'encarregat de donar suport i estructura als vertebrats. Existeix per tant una necessitat de conèixer i analitzar mecànicament el seu comportament des dels diferents nivells jeràrquics que ho componen, sent major la complexitat i més escassos els estudis disponibles en la literatura com més xicoteta és l'escala estructural que s'analitza. Aquests estudis són rellevants per a comprendre, prevenir i solucionar problemes de salut importants que afecten a l'ésser humà. Des del punt de vista mecànic és interessant avaluar i aplicar eines numèriques ingenieriles per a l'anàlisi de materials més complexos com són els biològics, incrementant l'estat de l'art en diferents disciplines que poden ser aplicades en nombrosos camps com la ciència dels materials, la biomecànica, els mètodes numèrics o la medicina, entre altres. En aquesta Tesi s'analitza el comportament mecànic de l'os cortical a nivell microestructural, on es modela mitjançant el mètode dels elements finits la seua unitat bàsica, la osteona. Per a l'obtenció de les propietats elàstiques es considera en els models la microestructura composta per capes de col·làgen mineralitzat amb diferents orientacions, disposades de manera concèntrica al voltant dels canals vasculars. S'inclou a més la utilització de models micromecànics d'elements finits que tenen en compte la composició heterogènia tant per al nivell del fibril de col·làgen mineralitzat (nivell nanoestructural) com per al nivell de lamela (nivell submicroestructural). L'anàlisi de la fallada per a geometries realistes s'aplica després de comparar diversos models que involucren d'una banda el creixement de clavills mitjançant condicions de contacte i per un altre, degradació de les propietats elàstiques del material mitjançant subrutines d'usuari del codi d'elements finits, sent aquest últim el que millors resultats presenta des del punt de vista del cost computacional. D'aquesta manera es presenta una alternativa interessant que permet avaluar la propagació del dany a nivell tridimensional, la qual cosa amb altres mètodes com el X-FEM pot ser computacionalment inabordable. S'apliquen criteris de fallada utilitzats per a materials compostos en enginyeria estructural a les osteones i els resultats es relacionen amb els de els assajos experimentals disponibles en la bibliografia, mostrant la rellevància de les tensions de cisallament entre lameles per a la iniciació i propagació del dany. En un estudi bidimensional, també es mostra la participació important en la fase d'inici de dany de les llacunes d'osteòcits el que és interessant des d'un enfocament de mecanotransducción cel·lular. / Arango Villegas, C. (2016). Study of the mechanical behavior of cortical bone microstructure by the finite element method [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/67570 / TESIS

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