Replacing a diseased disc with a tissue engineered disc has the potential to restore normal spinal biomechanics. However, recreating the interface between annulus fibrosus (AF) and vertebral bone (VB) will be necessary to facilitate proper function of the implant in vivo. This study characterizes the native bovine AF-VB interface and assesses adult human discs. The AF insertion site in humans and cows is uniquely differentiated from other soft tissue-bone interfaces, as AF collagen fibers anchor into the calcified region of vertebral endplate through a zone of hyaline cartilage and have a different organization in inner and outer AF. Mineralization-associated proteins are present in this region and the chondroid tissue undergoes calcification over time. Based on these observations an in vitro AF culture system was developed and demonstrated that AF cells can induce mineralization. Understanding mechanism(s) regulating AF mineralization will help develop conditions to ensure proper integration of bioengineered AF.

Tissue engineering the annulus fibrosus (AF) for use in a functional intervertebral disc replacement is a promising alternative to current treatments of degenerative disc disease. Polycarbonate urethane (PU) scaffolds have demonstrated the ability to support AF cell attachment and matrix synthesis and are suitable for tissue engineering the AF. The present study investigates the effects of the physical and biochemical environment on AF cells grown on aligned nanofibrous PU scaffolds. First, the effect of dynamic spinner flask culture and fibronectin pre-coating on tissue formation was analyzed and then the role of scaffold fibre tension on annulus fibrosus cells was examined using a tailored culture system. The results of these studies demonstrated that AF cells are sensitive to differences in biochemical cues at the scaffold surface and their physical environment and respond by altering their cellular responses and, potentially by manipulating their microenvironments, including the physical characteristics of the PU-ADO scaffolds.

Tissue engineering the annulus fibrosus (AF) for use in a functional intervertebral disc replacement is a promising alternative to current treatments of degenerative disc disease. Polycarbonate urethane (PU) scaffolds have demonstrated the ability to support AF cell attachment and matrix synthesis and are suitable for tissue engineering the AF. The present study investigates the effects of the physical and biochemical environment on AF cells grown on aligned nanofibrous PU scaffolds. First, the effect of dynamic spinner flask culture and fibronectin pre-coating on tissue formation was analyzed and then the role of scaffold fibre tension on annulus fibrosus cells was examined using a tailored culture system. The results of these studies demonstrated that AF cells are sensitive to differences in biochemical cues at the scaffold surface and their physical environment and respond by altering their cellular responses and, potentially by manipulating their microenvironments, including the physical characteristics of the PU-ADO scaffolds.

In this study, a long annulus bonded to a rigid cylinder containing an axisymmetric circumferential crack of width (d-c) at the midplane is considered. The material of the annulus is assumed to be linearly elastic and isotropic. The external surface of the annulus is free of stress. Surfaces of the crack are subject to distributed compressive loads. The Fourier and Hankel transform techniques are used to solve the governing equations which are reduced to a singular integral equation for crack surface displacement derivative. This integral equation is converted to a system of linear algebraic equations which are solved numerically by using Gauss-Lobatto and Gauss-Jacobi quadrature formulas. Then, the stress intensity factors at the edges of the crack are calculated. Results are presented in graphical form.

In several cases, current therapies available to treat a large number of musculoskeletal system diseases are unsatisfactory as they provide only temporary or partial restoration of the damaged or degenerated site. In an attempt to maintain a high standard of life quality and minimise the economic losses due to the treatments of these frequently occurring ailments and subsequent lost working days, alternative therapies are being explored. Contrary to the current treatments, tissue engineering aims to regenerate the impaired tissue rather than repair and alleviate the symptoms; thus offering a definitive solution. The annulus fibrosus (AF) of the intervertebral disc (IVD) is a musculoskeletal system component frequently subjected to degeneration and rupture, characterised by predominance of anisotropically arranged collagen fibres. In the present thesis, electrospinning technology is used to fabricate polycaprolactone (PCL) scaffolds intended to replicate the anisotropic structure of the AF.

Sub-endocardial fibres line the inner surface of both ventricles and are responsible for longitudinal oscillations of the mitral annulus, such oscillations may be measured using tissue Doppler echocardiography (IDE). During systole the annulus descends and during early diastole (ETDE) and atrial systole (ATDE) itascends. This thesis examined whether changes in the velocity of the annulus ineach of these phases of oscillation, measured using tissue Dopplerechocardiography (TDE), could determine the nature of increases in left ventricular size (pathological or physiological). Study one examined differences at rest in longitudinal velocities between individuals with hypertrophic cardiomyopathy (HCM), hypertension (HT), weightlifters, runners and controls, (n = 15 all groups) and all groups were aged between 20 - 36 years. The results demonstrated that both pathological groups had systolic and ETDE velocities significantly lower than groups with physiological hypertrophy (weightlifters or runners) or controls p < 0.05. AIDE however was not significantly different between groups. Additionally runners also demonstrated a significantly higher ETDE than either weightlifters or controls (p < 0.05). Binomial logistic regression identified longitudinal systolic velocity < 9 cm s" 1 and ETDE velocity < 11 cm s" 1 as the best combination of variables to predict pathological increases in heart size. Study two examined older subjects in order to determine whether the criteria set out in study one were applicable to senior athletes. The subject groups were the same as in study one however all subjects were aged between 36-55. In this case systolic annular velocity was significantly lower in groups with pathological LVH but ETDE < 9 cm s" 1 was a better differentiator. Binomial logistic regression identified ETDE < 9 cm s" 1 and a mitral E / A ratio < 1 as the best combination of variables to predict pathological LVH. Study three examined the age related changes in long axis function using the pooled data from studies one and two. This demonstrated that in the pathological LVH groups only ETDE / ATDE ratio was significantly correlated with age (r = - 0.5 p < 0.05) suggesting that there appears to be no summation of the effects of pathology and age on mitral annular velocities. The control groups demonstrated a significant age related reduction in all long axis variables (systolic velocity r = - 0.7 p < 0.05; ETDE r = - 0.6 p < 0.01; ATDE r = 0.5 p < 0.05; ETD E / ATDE r = - 0.5 p< 0.01). Weightlifters however did not demonstrate an age related decline in either systolic or diastolic annular velocities. Runners had no age related decline in systolic annular velocities, and whilst they had an age dependent fall in ETDE ( r = - 0.62 p < 0.05) the older runners ETDE were still significantly faster (p < 0.05) than that seen in control subjects. Study four investigated relationship between mitral annular velocity and VOiruK in runners, weightlifters and controls. These results demonstrated peak exercise E TDE strongly correlated to VO^PEAK (r = 0.8 p < 0.01). ConclusionsTaken together these data suggest that longitudinal velocities of the mitral annulus may be useful in determining the nature of increases in heart size, in addition the increased performance of endurance - trained athletes is due in part to functional changes of the long axis.

A exploração de petróleo em alto mar traz consigo desafios crescentes com o aumento da lâmina d’água e do grau de agressividade dos contaminantes presentes no fluido produzido. Sendo a produção no País majoritariamente escoada do poço para as unidades de produção por dutos flexíveis, faz-se necessária a realização de estudos aprofundados da influência destas condições na vida em fadiga destes equipamentos. Tais condições quando associadas ao alagamento da região anular dos dutos flexíveis, pode favorecer a corrosão das armaduras de tração, responsáveis por conferir resistência axial ao duto. Este fato compromete a integridade da estrutura, levando a operação à uma condição não segura. Com o intuito de elevar o grau de conhecimento sobre estes mecanismos de degradação, o presente estudo tem por objetivo estabelecer uma relação entre os parâmetros construtivos e operacionais destes dutos, com o seu desempenho em campo frente a carregamentos cíclicos e na condição de anular alagado Para tal, tendo como base a literatura disponível no tema, foram selecionados parâmetros de estudo para, a partir destes, determinar fatores de redução de vida em fadiga (FRVFs). Estes fatores foram quantificados e estudados através de correlações numéricas e experimentais, sendo validadas através da realização de um ensaio em escala real de um duto flexível com anular alagado com água do mar sintética saturada com dióxido de carbono. Como resultados foram obtidos fatores de redução de vida em fadiga para as condições estudadas. Ainda, foi estabelecida uma metodologia para a determinação destes e sua utilização para o cálculo do dano acumulado de fadiga nestes dutos. / Offshore oil exploration involves growing challenges as water depth increases and aggressive oil contaminants are present in production fluid. As Brazilian production is conducted from the well to the production units mostly through flexible pipes, studies regarding the influence of this conditions on fatigue life of these structures are necessary. When the annulus is flooded with seawater the above conditions turns the environment corrosive for tensile armor wires, that are responsible to provide axial strength to the pipe. This fact compromises the integrity of the structure as a whole turning the operation unsafe. To increase the knowledge regarding these degradation mechanisms this study aims to stablish a relationship between constructive and operational parameters with field performance considering dynamic loadings and flooded annulus conditions. For such, using the literature data available it was selected some relevant parameters and from these it was determined fatigue life reduction factors (FRVFs). The FRVF was quantified and studied using numeric and experimental relations and validated through a full scale fatigue test in flooded annulus condition with synthetic seawater saturated with CO2. As a result, it was obtained the FRFV to explored conditions. Even more, it was stablished a methodology for its determination and applicability for calculation of cumulative fatigue damage in flexible pipes.

A exploração de petróleo em alto mar traz consigo desafios crescentes com o aumento da lâmina d’água e do grau de agressividade dos contaminantes presentes no fluido produzido. Sendo a produção no País majoritariamente escoada do poço para as unidades de produção por dutos flexíveis, faz-se necessária a realização de estudos aprofundados da influência destas condições na vida em fadiga destes equipamentos. Tais condições quando associadas ao alagamento da região anular dos dutos flexíveis, pode favorecer a corrosão das armaduras de tração, responsáveis por conferir resistência axial ao duto. Este fato compromete a integridade da estrutura, levando a operação à uma condição não segura. Com o intuito de elevar o grau de conhecimento sobre estes mecanismos de degradação, o presente estudo tem por objetivo estabelecer uma relação entre os parâmetros construtivos e operacionais destes dutos, com o seu desempenho em campo frente a carregamentos cíclicos e na condição de anular alagado Para tal, tendo como base a literatura disponível no tema, foram selecionados parâmetros de estudo para, a partir destes, determinar fatores de redução de vida em fadiga (FRVFs). Estes fatores foram quantificados e estudados através de correlações numéricas e experimentais, sendo validadas através da realização de um ensaio em escala real de um duto flexível com anular alagado com água do mar sintética saturada com dióxido de carbono. Como resultados foram obtidos fatores de redução de vida em fadiga para as condições estudadas. Ainda, foi estabelecida uma metodologia para a determinação destes e sua utilização para o cálculo do dano acumulado de fadiga nestes dutos. / Offshore oil exploration involves growing challenges as water depth increases and aggressive oil contaminants are present in production fluid. As Brazilian production is conducted from the well to the production units mostly through flexible pipes, studies regarding the influence of this conditions on fatigue life of these structures are necessary. When the annulus is flooded with seawater the above conditions turns the environment corrosive for tensile armor wires, that are responsible to provide axial strength to the pipe. This fact compromises the integrity of the structure as a whole turning the operation unsafe. To increase the knowledge regarding these degradation mechanisms this study aims to stablish a relationship between constructive and operational parameters with field performance considering dynamic loadings and flooded annulus conditions. For such, using the literature data available it was selected some relevant parameters and from these it was determined fatigue life reduction factors (FRVFs). The FRVF was quantified and studied using numeric and experimental relations and validated through a full scale fatigue test in flooded annulus condition with synthetic seawater saturated with CO2. As a result, it was obtained the FRFV to explored conditions. Even more, it was stablished a methodology for its determination and applicability for calculation of cumulative fatigue damage in flexible pipes.

Theoretical and experimental studies of particle deposition in turbulent pipe flow have been carried out for over forty years, but some of the most important transport mechanisms are still not well understood. The first part of this thesis is concerned with the calculation of particle density when using Lagrangian methods to predict inertial particle transport in two-dimensional laminar fluid flows. Traditionally, Lagrangian calculations involve integrating the particle equations of motion along particle pathlines, and the particle density is obtained by applying a statistical averaging procedure to those pathlines which intersect a particular computational grid cell. Unfortunately, extremely large numbers of particles are required to reduce the statistical errors to acceptable levels, and this makes the method computationally expensive. Recently, the Full Lagrangian approach has been developed, which allows the direct calculation of the particle density along particle pathlines. This method had previously been applied only to simple analytical flow fields. The application of the method to CFD generated fluid velocity fields was shown to be possible, and the results obtained using the Full Lagrangian approach were compared to those from a traditional Lagrangian approach. It was found that better quality solutions could be obtained with the use of far fewer particle pathlines. An analysis of the manner in which the Full Lagrangian approach deals with particles whose paths cross each other (and the resulting discontinuity in particle density) was also undertaken, and this illustrates the sophistication of the method. The second part of the thesis comprises an experimental and theoretical study of the deposition of small particles in turbulent flows by thermophoresis. Thermophoresis is the phenomenon whereby small particles suspended in a gas in which there exists a temperature gradient experience a force in the direction opposite from that of the temperature gradient. Previous researchers have attempted to impose a radial temperature difference in pipe flow experiments, but have not yet succeeded in attaining a constant thermophoretic force along the length of the pipe. This limits the accuracy and usefulness of the data for the validation of theoretical expressions for the thermophoretic fluxes. An experimental rig has been designed to achieve a constant thermophoretic force. This was done by using an annular geometry with a cold inner wall and hot outer wall. The particle size was varied and the deposition flux was measured for turbulent flow with three temperature differences. The deposition fluxes for small particles were found to be independent of dimensionless particle size, with each increase in temperature difference resulting in an increase in magnitude of the flux. Evidence of a thermophoresis-turbulence coupling was found for intermediate-sized particles, and large particles were not influenced by thermophoresis. A theory of particle deposition, developed for the case of turbulent pipe flow, was modified to study flow in a turbulent annulus, so that theoretical expressions for the thermophoretic fluxes could be included and compared with the experimental results. Agreement with experimental data was quite good, but some deficiencies in a widely used theoretical expression for the thermophoretic flux were exposed. An alternative expression was used, which gave much better agreement with the experimental data, and the mechanisms behind the thermophoresis-turbulence coupling were also investigated. The validation of this expression for the thermophoretic force will allow its inclusion in numerical studies of particle deposition in more complex geometries.

Tissue engineering offers a paradigm shift in the treatment of back pain. Engineered intervertebral discs could replace degenerated tissue and overcome the limitations of current treatments that disrupt the biomechanics of the spine. New materials, which exhibit sophisticated mechanical responses, are needed to provide templates for tissue regeneration. These behaviours include time-dependent deformation---facilitating shock absorption and nutrient transfer---and strong material anisotropy and tensile-compressive nonlinearities---providing flexibility in controlled directions. In this work, frameworks for the design of materials with controllable structure-property relationships are developed. The time-dependent mechanical properties of composites of agar, alginate and gelatin hydrogels are investigated. It is shown that the time-dependent responses of the composites can be tuned over a wide range. It is then demonstrated that materials mimicking the fibre-reinforced nature of natural tissues can be developed by infiltrating thick electrospun fibre networks with alginate. These fibre-reinforced hydrogels have tensile and compressive properties that can be separately altered. To better understand the mechanical behaviour of these hydrogel-based materials, improved methods for characterising poroelastic and poroviscoelastic time-dependent material properties using indentation are developed. It is shown that poroviscoelastic relaxation is the product of separate poroelastic and viscoelastic relaxation responses. The techniques developed here provide a methodology to rapidly characterise the properties of time-dependent materials and to create materials with complex structure-property relationships similar to those found in natural tissues; they present a framework for biomimetic materials design. The work in this thesis can be used to inform the design of clinically relevant tissue engineering treatments and help the quarter of a million people each year who undergo spinal surgery to reduce back pain.