Level set method is a boundary tracking method that uses an implicit function to define the boundary location. By using the implicit function to define the structural boundary the level set method can be used for topology optimisation. The level set method has previously been used to solve a range of structural optimisation problems. The aim of this thesis is to extend the application of the level set method to additional applications of structural optimisation. A robust method of 3D level set topology optimisation is developed and tested. The use of a hole insertion method was found to be advantageous, but not vital, for 3D level set topology optimisation. The level set method is used to optimise the internal structure of a proximal femur. Similarities between the optimal structure and real internal trabecular bone architecture suggest that the internal bone structure may be mechanically optimal. Stress constrained level set topology optimisation is performed in 2D. Stress shape sensitivities are derived and interpolated to obtain smooth boundary sensitivity, resulting in feasible stress constrained solution in numerical examples. A new generic objective hole insertion method is used to reduce dependence on the initial solution. A level set method for optimising the design of fibre angles in composite structures is also introduced. Fibre paths are implicitly defined using the level set function. Sensitivity analysis is used to update the level set function values and optimise the fibre path. The method implicitly ensures continuous fibre paths in the optimum solution, that could be manufactured using advanced fibre placement.

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Após exodontia e instalação de implantes imediatos o sítio edêntulo sofre uma substancial remodelação óssea. O objetivo do presente estudo foi avaliar a remodelação dos tecidos moles e da tábua óssea vestibular em alvéolos pósexodontia e em implantes imediatos em cães com um biotipo periodontal fino, com a associação de um material de enxerto. Oito cães tiveram a espessura da gengiva de um lado da mandíbula reduzida, os pré-molares mandibulares extraídos em cirurgia sem retalho e 4 implantes foram instalados de cada lado à 1,5 mm da tábua óssea vestibular. Os demais alvéolos foram utilizados para o estudo da dinâmica de cicatrização alveolar. Os sítios foram aleatoreamente alocados em: GT (grupo teste) = gengiva fina; GT + ME (GT com material de enxerto); GC (grupo controle) = gengiva normal; e GC + ME (GC com material de enxerto). Espessura da tábua óssea vestibular (ETOV), espessura de gengiva queratinizada (EGQ), largura alveolar (LA), altura de retração gengival (RG) e profundidade de sondagem (PS) foram avaliados clinicamente. Após 12 semanas os cães foram sacrificados e as amostras processadas para as análises de micro-tomografia computadorizada, histologia, histomorfometria, fluorescência e imunohistoquímica. Uma ETOV fina foi observada em todos os cães. Os procedimentos pré-cirúrgicos reduziram a EGQ nos grupos teste, com alterações mínimas na LA. Não houve diferenças estatísticas significantes entre os grupos para os parâmetros clínicos. Em todos os grupos o alvéolo ou o gap vestibular foram preenchidos por osso neoformado e uma leve reabsorção da tábua óssea vestibular foi observada, sem diferença estatística entre os grupos. Nos alvéolos pós-exodontia uma taxa de mineralização numericamente maior foi observada nos grupos que receberam material de enxerto em 12 semanas. A espessura do osso vestibular foi um fator fundamental na reabsorção da tábua óssea vestibular, mesmo com cirurgia sem retalho. Diminuir a gengiva para uma espessura crítica ou a adição de um biomaterial, em um biotipo fino pré-existente, não influenciou os resultados. / After tooth extraction and immediate implant placement the edentulous site undergo marked bone remodeling. The aim of the present study was to evaluate soft tissues and buccal bone remodeling in fresh extraction sockets and immediate implants in dogs with a thin periodontal biotype, with the association of a graft material. The gingiva of 8 dogs was thinned at one side of the mandible, mandibular premolars were extracted without flaps, and 4 implants were installed on each side at 1.5 mm from the buccal bone. The remaining sockets were used for the study of the alveolar healing dynamic. The sites were randomly assigned into: TG (test group) = thin gingiva; TG + GM (TG with grafting material); CG (control group) = normal gingiva; and CG + GM (CG with grafting material). Buccal bone thickness (BBT), thickness of keratinized tissue (TKT), alveolar width (AW), gingival recession height (GR) and probing depth (PD) were clinically evaluated. After 12 weeks the dogs were sacrificed and the samples were processed for microtomographic, histological, histomorphometric, fluorescence and immunohistochemistric analysis. A thin BBT was observed in all the dogs. The pre-surgical procedures reduced gingival thickness in the test groups, with minimal changes of the AW. There were no statistically significant differences among the groups for the clinical parameters. In all the groups the socket or the buccal gap was filled with newly formed bone and a slight buccal bone loss was observed, with no statistical difference among the groups. In the extraction sockets a numerically higher mineralization rate was observed for the grafted groups at 12 weeks. The thickness of the buccal bone was a fundamental factor on buccal bone plate resorption, even with a flapless approach. To reduce the gingival thickness or the addition of a biomaterial, in a thin biotype, did not influence the results.

Research in the biomedical sciences is incredibly diverse and often involves the interaction of specialists in a variety of fields. In particular, quantitative, mathematical, and computational methods are increasingly playing significant roles in studying problems arising in biomedical science. This is particularly exciting for mathematical modeling as the complexity of biological systems poses new challenges to modelers and leads to interesting mathematical problems. On the other hand mathematical modeling can provide considerable insight to laboratory and clinical researchers. In this thesis we develop mathematical representations for three biological processes that are of current interest in biomedical science. A deeper understanding of these processes is desirable not only from the standpoint of basic science, but also because of the connections these processes have with certain diseases. The processes we consider are collective cell motility, bone remodeling, and injury response in articular cartilage. Our goals are to develop mathematical representations of these processes that can provide a conceptual framework for understanding the processes at a fundamental level, that make rigorous the intuition biological researchers have developed about these processes, and that help to translate theoretical and experimental work into information that can be used in clinical settings where the primary concern is in treating diseases associated with the process.

In cases of compromised bone remodeling like osteoporosis, insufficient osseointegration occurs and results in implant failure. Implant retention relies on proper secondary fixation, which is developed during bone remodeling. This process is disrupted in metastatic bone diseases like osteoporosis. Osteoporosis is characterized low bone mass and bone strength resulting from either accelerated osteoclast-mediated bone resorption or impaired osteoblast-mediated bone formation. These two processes are not independent phenomena. In fact, osteoporosis can be viewed as a breakdown of the cellular communication connecting bone resorption to bone formation. Because bone remodeling occurs at temporally generated specific anatomical sites and at different times, local regulators that control cross-talk among the cells of the BRU are important. Previous studies show Ti implant surface characteristics like roughness, hydrophilicity, and chemistry influence the osteoblastic differentiation of human MSCs and maturation of OBs. Furthermore, microstructured Ti surfaces modulate the production of factors shown to be important in the reciprocal communication necessary for the maintenance of healthy bone remodeling. Semaphorin signaling proteins are known to couple the communication of osteoblasts to osteoclasts and are capable of stimulating bone formation or bone resorption depending on certain cues. Implant surface properties can be optimized to exploit these effects to favor rapid osseointegration in patients with osteoporosis.

Orientador: Maria Aparecida Neves Jardini / Banca: Fabio da Silva Matuda / Banca: Andréa Carvalho de Marco / Banca: Mariéllen Longo Vilas Boas / Banca: Cibelle Barbosa Lopes / Resumo: A doença periodontal (DP) resulta de uma infecção polimicrobiana complexa, levando à destruição dos tecidos periodontais, como consequência da perturbação da homeostase entre a microbiota subgengival e os mecanismos de defesas do hospedeiro em indivíduos suscetíveis. A deficiência estrogênica (DE) é a causa mais comum de osteoporose. A osteoporose é definida como uma doença crônica, multifatorial, provenientes de uma desordem esquelética que promove fragilidade óssea pela redução de sua massa. Vários estudos experimentais têm demonstrado que a estimulação com Campo Eletromagnético Pulsátil (CEMP) pode promover a osteogênese e potencialmente aumentar a mineralização óssea e também, reduzir a inflamação aguda e crônica em tecidos moles e duros. Frente a isso, este estudo teve como objetivo, avaliar por meio da histomorfometria, imunoistoquímica e microtomografia computadorizada (MicroCT), a influência do CEMP na DP induzida em ratas ovariectomizadas e Sham. Para a pesquisa, foram utilizadas 60 ratas adultas (Rattus norvegicus, variação albinus, Wistar) com 3 meses de idade, pesando em torno de 300 gramas e em todos os animais a DP foi induzida. As ratas foram randomizadas em dois grupos experimentais, contendo 30 animais cada, classificados em ovariectomia simulada (Sham) e Ovariectomizada (Ovz), respectivamente. Os grupos foram divididos em dois subgrupos com 15 animais cada: Sham-S (n=15): não receberam terapia com CEMP e este foi nosso grupo controle. Sham-CEMP (n=15): receb... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract : Periodontal disease (PD) results from a complex polymicrobial infection, leading to the destruction of periodontal tissues as a consequence of the disturbance of homeostasis between the subgingival microbiota and the host defense mechanisms in susceptible individuals. Estrogen deficiency is the most common cause of osteoporosis. Osteoporosis is defined as a chronic, multifactorial disease from a skeletal disorder that promotes bone fragility by reducing its mass. Several experimental studies have shown that Pulsed Electromagnetic Field (PEMF) stimulation can promote osteogenesis and potentially increase bone mineralization and also reduce acute and chronic inflammation in soft and hard tissues. The aim of this study was to evaluate, through histomorphometry, immunohistochemistry and computerized microtomography (MicroCT), the influence of PEMF on PD induced in ovariectomized and Sham rats. For the research, 60 adult rats (Rattus norvegicus, albinus variant, Wistar) at 3 months of age, weighing around 300 grams were used and in all animals PD was induced. The rats were randomized into two experimental groups, containing 30 animals each, classified as simulated ovariectomy (Sham) and Ovariectomized (Ovz), respectively. The groups were divided into two subgroups with 15 animals each: Sham-S (n = 15): did not receive PEMF therapy and this was our control group. Sham-PEMF (n = 15): received PEMF therapy. Ovz-O (n = 15): did not receive PEMF therapy. Ovz-PEMF (n = 15): received PEMF therapy. The histomorphometric and MicroCT analyzes were performed and the data were submitted to analysis of variance (ANOVA) and Tukey's test, both with a 95% significance level and did not present any statistically significant difference. In the semiquantitative analysis for RANKL and OPG biomarkers, the Ovz-O subgroup showed higher expression of the RANKL biomarker and lower expression...(Complete abstract click electronic access below) / Doutor

A remodelação do processo alveolar após a exodontia é um fenômeno fisiológico que resulta em alterações das dimensões ósseas e que podem interferir na reabilitação protética. Para minimizar a perda óssea, estratégias de preservação do rebordo vêm sendo empregadas e a terapia por fotobiomodulação (TFBM) se destaca como uma opção de baixo custo e morbidade. Estudos prévios evidenciaram o impacto positivo da TFBM no reparo ósseo. O objetivo do presente trabalho foi avaliar o efeito TFBM no reparo alveolar. Vinte pacientes com indicação clínica de exodontia dos primeiros ou segundos molares bilateralmente foram selecionados e os lados direito e esquerdo de cada paciente distribuídos em um dos grupos experimentais: (1) TFBM, tratado com laser de baixa frequência, e (2) Controle, que recebeu o mesmo tratamento com o equipamento desligado; a aplicação foi realizada no pós-operatório imediato, 1, 2, 3, 4, 7 e 15 dias. Aos 45 dias pós-exodontia, espécimes de tecido do interior dos alvéolos foram coletados para análise microtomográfica e histológica. Os dados foram comparados utilizando o Teste-t pareado e o nível de significância foi de 5%. A análise morfométrica evidenciou diferenças estatisticamente significante entre os grupos para os seguintes parâmetros: superfície óssea (p=0,029), superfície óssea/volume total (p=0,028), número de trabéculas (p=0,025) e densidade de conectividade (p=0,029), maiores no grupo TFBM em relação ao Controle. O volume ósseo, volume ósseo/total, espessura e separação trabecular não apresentaram diferenças estatisticamente significantes (p=0,054; p=0,082; p=0,598 e p=0,109, respectivamente). Esses dados foram confirmados na análise histológica, onde foi identificado maior quantidade de tecido trabecular no grupo TFBM, enquanto no Controle fica evidente maior quantidade de tecido conjuntivo. Os resultados evidenciaram que a terapia de fotobiomodulação tem efeito positivo no reparo de alvéolos humanos. / The process of bone repair after tooth extraction is a physiological phenomenon which results in alterations of the bone dimensions and could interfere in prosthetic rehabilitation. To minimize bone loss, strategies for border preservation have been used and photobiomodulation therapy (TFBM) stands out as a low cost option and morbidity. Previous studies have shown the positive impact of TFBM on bone repair. The aim of this study was to evaluate the effect of TFBM on alveolar repair. Twenty patients with exodontia indication of the first or second molar bilaterally were chosen, right and left sides were distributed in one of the following experimental groups: (1) TFBM, treated with low frequency laser, and (2) Control group, who received the same treatment with the equipment off; besides, laser application was applied right after the post-operatory, after 1, 2, 3, 4, 7 and 15 days. After 45 days from the extraction, tissue samples from the alveoli were collected for micro-tomographic and histological analysis. Data were compared using the paired t-test and the accuracy level was 5%. A morphometric analysis showed statistically significant differences between the groups regarding the following parameters: bone surface (p = 0.029), bone surface / total volume (p = 0.028), trabeculae number (p = 0.025) and connectivity density (p = 0.029), higher in the TFBM group than in Control. The bone volume, bone / total volume, trabecular thickness and separation did not present statistically significant differences (p = 0.054, p = 0.082, p = 0.598 and p = 0.109, respectively). These data were confirmed in the histological analysis, where a greater amount of trabecular tissue was identified in the TFBM group, while in control group, a high amount of connective tissue was evident. The results showed that photobiomodulation therapy has a positive effect on the repair of human alveoli.

Thesis (M.S.)--University of Florida, 2003. / Title from title page of source document. Includes vita. Includes bibliographical references.

Osteocytes make up the largest cell population in bone and are believed to be the main mechanosensory bone cells. During mechanical disuse and overuse, osteocyte viability is compromised and is found to be co-localized with increased osteoclastic bone resorption. Osteoclasts are recruited to remodel sites of apoptosis or bone microdamage; however, it is unclear whether the apoptotic or neighbouring healthy osteocytes are responsible for targeted bone remodeling. I hypothesized that apoptotic osteocytes are: (a) directly responsible for initiating bone remodeling by recruiting osteoclast precursors and directing osteoclast differentiation, and (b) indirectly responsible by signaling to nearby healthy osteocytes that, in turn, regulate osteoclastogenesis. In this in vitro study, apoptotic osteocytes were found to increase osteoclast precursor migration and osteoclast formation. Inhibition of the osteoclastogenic protein, receptor activator of nuclear factor kappa B ligand (RANKL), in conditioned medium abolished the osteoclastogenic effect of apoptotic osteocytes. Healthy osteocytes surrounded by apoptotic regions were modeled by applying apoptotic osteocyte conditioned medium to healthy osteocytes. These cells also promoted osteoclastogenesis, and had increased expression of macrophage colony stimulating factor (M-CSF) and vascular endothelial growth factor (VEGF). Inhibition of these factors abrogated the pro-osteoclastic effect of healthy osteocytes conditioned by apoptotic osteocytes. These findings support the hypothesis that apoptotic osteocytes directly and indirectly, by signaling to nearby healthy osteocytes, initiate osteoclastogenesis. One limitation of our and other conventional in vitro models is the lack of real-time cell communication and physiologically-relevant mechanical environment. Using a microfluidics approach, a miniature fluid shear delivery system was created for in vitro osteocyte cultures. The purpose of this microsystem was to increase control of the cell microenvironment for subsequent integration into scalable screening platforms or co-culture systems for studying osteocyte mechanobiology under physiological loading conditions. Fluid shear stress was periodically applied without external pumping using a deflecting elastomer membrane, where up to 2 Pa of oscillating shear stress was possible by manipulating membrane dimensions. Osteocyte culture, viability and calcium response were demonstrated in the microdevice. Further studies should attempt to characterize calcium signaling in osteocytes which, using a conventional macro-scale system, was found to dependent on cell-cell communication.

Osteocytes make up the largest cell population in bone and are believed to be the main mechanosensory bone cells. During mechanical disuse and overuse, osteocyte viability is compromised and is found to be co-localized with increased osteoclastic bone resorption. Osteoclasts are recruited to remodel sites of apoptosis or bone microdamage; however, it is unclear whether the apoptotic or neighbouring healthy osteocytes are responsible for targeted bone remodeling. I hypothesized that apoptotic osteocytes are: (a) directly responsible for initiating bone remodeling by recruiting osteoclast precursors and directing osteoclast differentiation, and (b) indirectly responsible by signaling to nearby healthy osteocytes that, in turn, regulate osteoclastogenesis. In this in vitro study, apoptotic osteocytes were found to increase osteoclast precursor migration and osteoclast formation. Inhibition of the osteoclastogenic protein, receptor activator of nuclear factor kappa B ligand (RANKL), in conditioned medium abolished the osteoclastogenic effect of apoptotic osteocytes. Healthy osteocytes surrounded by apoptotic regions were modeled by applying apoptotic osteocyte conditioned medium to healthy osteocytes. These cells also promoted osteoclastogenesis, and had increased expression of macrophage colony stimulating factor (M-CSF) and vascular endothelial growth factor (VEGF). Inhibition of these factors abrogated the pro-osteoclastic effect of healthy osteocytes conditioned by apoptotic osteocytes. These findings support the hypothesis that apoptotic osteocytes directly and indirectly, by signaling to nearby healthy osteocytes, initiate osteoclastogenesis. One limitation of our and other conventional in vitro models is the lack of real-time cell communication and physiologically-relevant mechanical environment. Using a microfluidics approach, a miniature fluid shear delivery system was created for in vitro osteocyte cultures. The purpose of this microsystem was to increase control of the cell microenvironment for subsequent integration into scalable screening platforms or co-culture systems for studying osteocyte mechanobiology under physiological loading conditions. Fluid shear stress was periodically applied without external pumping using a deflecting elastomer membrane, where up to 2 Pa of oscillating shear stress was possible by manipulating membrane dimensions. Osteocyte culture, viability and calcium response were demonstrated in the microdevice. Further studies should attempt to characterize calcium signaling in osteocytes which, using a conventional macro-scale system, was found to dependent on cell-cell communication.