Glioblastoma multiforme (GBM) is an aggressive Grade IV astrocytoma with a poor survival rate. This is largely due to the GBM tumor cells migrating away from the primary tumor site along white matter tracts and blood vessels leading to secondary tumor sites. It is unknown whether the microenvironment nanotopography influences the biomechanical properties of the tumor cells. Although these tumor cells have an innate propensity to migrate, we believe that the nanotopography changes the biomechanical properties to enhance the migratory phenotype. To study this, we used an in vitro polycaprolactone aligned nanofiber film that mimics the nanotopography of the white matter tracts and blood vessels to investigate the mechanical properties of the GBM tumor cells. Our data demonstrate that the cytoskeletal stiffness, traction force, and focal adhesion area are inherently lower in invasive GBM tumor cells compared to healthy astrocytes. Moreover, the tumor cytoskeletal stiffness was significantly reduced when cultured on the aligned nanofiber films compared to smooth and randomly aligned nanofibers films. Analysis of gene expression also showed that tumor cells cultured on the aligned nanotopography upregulated key migratory genes and downregulated key proliferative genes. In addition, cell cycle analysis exhibited a reduced proliferative state on aligned nanofibers, highlighting the dichotomy between proliferation and migration observed in GBM. Finally, focal adhesions of tumor cells were larger and more elliptical when grown on the aligned fibers, suggesting a more migratory state. Therefore, our data demonstrate that the invasive potential is elevated when the tumor cells are cultured on an aligned nanotopography. This in vitro model can further be used to identify the GBM tumor cells’ response in a mimetic in vivo tumor microenvironment and elucidate how the aligned nanotopography transduces into altered gene and protein expression, thus providing a mechanism to target to inhibit the enhanced migratory behavior observed in these cells.

The HydroBone is a variable stiffness load-bearing element, which utilizes jamming of granular media to achieve stiffness modulation, controlled by the application of positive pressure. Several compressive tests were conducted on the HydroBone in order to quantify the load-bearing capability of the system. It was determined that the stiffness of the HydroBone was a function of the internal pressure of the system. A controller was modeled based on this function to achieve automatic stiffness modulation of the HydroBone. An exoskeleton was designed based on the HydroBone and various actuators for the exoskeleton were considered. The HydroMuscle, a soft linear actuator was selected to provide knee actuation for the exoskeleton, based on several efficiency and force output test conducted. A knee brace was designed, capable of producing 15Nm of torque on the knee, actuated using Bowden cables coupled to the HydroMuscles.

Soft robots present the opportunity to extend the capabilities currently demonstrated within the field of robotics. By utilizing primarily soft materials in their construction, soft robots are inherently safe to operate around humans, can handle delicate tasks without advanced controls, and are robust to shocks and impacts during deployment. While proof-of-concept devices have been demonstrated successfully, there remains a need for widely applicable, reliable soft robotic components. This dissertation presents sensors to reliably measure the large deformations exhibited in soft robotic structures and responsive structures enabled by variable stiffness materials that can switch from flexible to stiff on-demand. By characterizing the sensors from the material level, through the manufacturing, to the completed functional device, the fabrication processes can be depended upon to produce sensors with predictable, reliable performance. The sensors were applied to various soft robotic systems through implementation on the surface of the structures to measure surface strains, and embedded in the body of the robot to measure body deformations. The sensory feedback was used to reconstruct the state of and to perform closed-loop control of the soft robot's position. Variable stiffness materials that switch from rigid to soft through application of heat were leveraged to create responsive structures that can be deformed or reconfigured on-demand. This capability is necessary for soft robots to exert load onto the external environment and enables a wider range of interactions with target objects. The work presented in this dissertation furthers the field of soft robotics by illustrating a path toward proven, reliable soft sensors for measuring large strains and variable stiffness materials to create responsive structures.

There are many aspects that have direct effects on total hip replacement performance (THR), such as material properties, applied loads, surgical approach, femur size and quality, prosthesis design, bone-implant interface etc. Bone mechanics and traditional implant materials cause a frequent problem for patients of total hip arthroplasty (THA): the bone becomes shielded from the loading. Bone structure follows what is called "Wolff's Law", meaning it has an adaptive structure, which alters its geometry when experiencing forces over its life (Goldstein, 1987); (Pearson & Lieberman, 2004). The improved femoral stems act weakly in transferring stress onto the remnant bone and bone tissue atrophies at the interface, which will result in loosening of the implant, pain and thus, revision surgery will need to take place to correct the issue ( Feldt, 2011). For the current study, an innovative hollow spherical structure is developed for femoral hip stems. The aim is to extract volume in the spherical shape from the stainless steel hip implant stems, in order to focus solely on correlating with titanium behaviour. Internal geometry for the femoral stem is optimised in order to transfer more stress onto the bone. Moreover, the approach involves extracting volume in the spherical shape from internal structure to reduce stress shieling. New novel implant is proposed that demonstrated reduction in stress shielding. A new structure has been developed in this study for biomedical applications, such as implants, with the aid of the rule of mixtures and finite element analysis was applied to various models with different complex internal structures. Firstly, the rule of mixtures was used as finite element could not handle the simulation due to the large number of elements created, and also helped developing the designs analysed in this study. Secondly, computational analysis was applied to simplified finite elements containing hollow spheres in their outer shell. Moreover, a compression test was applied to a solid sample and the experimental case. This approach was adopted to investigate the effects of a hollow structure near the side surface and the bone-implant interface. The same method was applied to samples containing uniformly distributed hollow spheres. In the both scenarios, the specimens were designed differently based on the sphere size, their distance from wall and that from each other. Finally, finite element was applied to actual implant samples containing hollow spheres. The sphered models have a smaller Young's modulus and strength than the solid stainless steel sample. The spheres in hollowed structures reduce the stress shielding and they transfer more stress onto the bone when compared to the solid stainless steel models. This approach also involves restructuring a hard material, such as stainless steel, to enhance osseointegration. The reduction of the Young's modulus and stress directly depends on the volume of the hollow spheres in the models; however, there is certain volume that can be extracted from solid.

Arterial stiffness is one of the major risk factors and markers of cardiovascular disease (CVD). An increase in the arterial stiffness is influenced by various factors such as age, lifestyle, genetics and the presence of other cardiovascular risks such as obesity and diabetes. Arterial stiffness is a consistent thread in this thesis. This thesis investigates the effects of exercise-based management programmes for CVD and risk factors with a focus on carotid-radial applanation tonometry which is a specific non-invasive technique for measuring arterial stiffness. Erectile dysfunction is a marker of CVD and is associated with endothelial dysfunction that leads to arterial stiffness. The effects of centrebased, supervised and exercise-based cardiac rehabilitation (CR) programmes were studied on the changes in arterial stiffness, erectile dysfunction and quality of life of patients with CVD. Despite the effectiveness of CR programmes, there is poor attendance at these programmes and unsupervised home-based, IT (information technology)-supported programmes could improve patient participation and cost effectiveness. Moreover, earlier identification of risks and appropriate management can reduce the incidence of CVD. There are no such programmes for early stages of CVD in practice, especially in developing countries such as India. A 12-week, IT-supported home-based exercise programme in India, for patients with metabolic syndrome was developed and studied. In general, arterial stiffness was improved in both centre-based and home-based exercise programmes. There were acute increases in arterial stiffness following exercise in healthy Caucasians and South Asians as well as people with metabolic syndrome. Carotid-radial pulse wave analysis could be a simple and reliable prognostic tool in exercise based rehabilitation programmes.

Cancer cells traveling to distant tissues during metastasis must survive passing through the circulation. However, the influence of this fluid microenvironment on these cells is poorly understood. It was previously viewed that exposure to the hemodynamic shear forces within circulation was inhospitable to cancer cells, causing the cells to be destroyed. Recent evidence indicates that transformed cells are markedly more resistant to fluid shear stress when compared to non-transformed epithelial cells. Furthermore, these cells selectively adapt following exposure to fluid shear stresses and become more resistant to subsequent exposures to shear stress. The mechanisms behind this difference in phenotype and induced resistance are investigated. The elastic modulus, a measure of stiffness, may play a role in resistance and is shown to be altered upon exposure to fluid shear forces. Additionally, plasma membrane repair is a critical process in the resistance phenotype as cells sustain damage but are able to maintain viability. Cytoskeletal dynamics are also shown to play a role in resistance to fluid shear forces.

Garments are everywhere in today’s society and often presented on the body, although the absence of the body in design can have an integral impact on how they are perceived by an audience. An experimental material coating, aided garments to become sculptural by portraying the essence of the body. This essay argues that garments are challenged through their perception and purpose by the absence of the body, allowing the sculptures to develop a language in their own right. Through means of forming methods, absence of the body and materiality, garments are able to evolve to communicate an idea challenging one’s preconceived garment notions and broadening the spectrum of situational presentational methods.

Age-related increases in arterial stiffness are mediated in part by mitochondrial dysfunction. Sirtuin 3 (SIRT3) is a mitochondrial NAD+-dependent deacetylase that regulates mitochondrial function. SIRT3 deficiency contributes to physiological dysfunction in a variety of pathological conditions. Here, we tested the hypothesis that age-associated arterial stiffness, assessed by aortic pulse wave velocity (PWV), would be accompanied with decreased renal and aortic SIRT3 expression and activity due to decreased NAD+ levels. We further tested whether boosting NAD+ concentration with nicotinamide riboside (NR), a NAD+ precursor, for 6 months would reverse the effects of aging. Old (~26 mo, n = 9) C57BL/6 male mice had higher PWV vs. young (6 mo, n = 10) (448 ± 14 vs 382 ± 13, p < 0.005), which was associated with reduced arterial SIRT3 protein (0.365 ± 0.088 AU’s vs 1.000 ± 0.000); p < 0.05). Furthermore, SIRT3 deficient male mice demonstrated higher PWV compared to age-matched control mice (480 ± 21 n = 6 vs. 391 ±12 n = 7, p < 0.005). Aortic SIRT3 protein was negatively correlated with PWV (r=-0.7798, p < 0.005). Old mice also exhibited reduced kidney SIRT3 protein (0.73 ± 0.10 AU’s) compared to young controls (1.00 ± 0.00; p = 0.0192) and reduced NAD+ (918.6 ± 50.5 pmol/mg vs. young 1302.0 ± 56.6 pmol/mg, p = 0.0036). Old mice supplemented with NR had increased NAD+ concentration in kidney tissue (1303.0 ± 90.2 pmol/mg) however, had no effect on normalizing age-associated arterial stiffness (402 ± 18 old with NR vs 418 ± 15 old; p = 0.78). Here we show for that SIRT3 protein correlates with aortic stiffness and may be required for the maintenance of healthy arteries and for the first time that supplementation with NR, a commercially available supplement, ameliorates age-associated decreases in renal NAD+ demonstrating therapeutic potential in kidney disease.

Introduction: The purpose of this study was to determine the effect of spinal manipulation therapy (SMT) duration and amplitude on spinal stiffness. Methods: Simulated SMTs were performed at the L6 spinous process in twenty-two felines. SMTs ranging from 25 to 250 ms duration were performed. Groups 1 and 2 received maximal displacements of 1.0mm to 3.0mm. Groups 3 and 4 received maximal loads of 25% to 85% body weight. Local stiffness was quantified by applying an indentation to the vertebra. Results: Repeated SMTs caused minimal changes in stiffness. The interaction effect of duration X displacement in Groups 1 and 2, and the effect of duration in Group 3 were significant. Conclusion: Repeated SMTs cause minimal changes in stiffness thought to be due to a viscoelastic response. Some of the changes following select SMT conditions may be the result of an interaction effect between SMT duration and amplitude. No specific threshold condition was identified as causing a greater stiffness change. / Physical Therapy

This thesis presents two unique micro-motion parallel kinematic manipulators (PKM): a three degrees of freedom (3-DOF) micro-motion manipulator and a 3-DOF micro-motion manipulator with actuation redundancy. The 3-DOF micro-motion manipulator has three linear-motion driving units, and the 3-DOF micro-motion manipulator with redundancy has four of these units. For both designs, the linear motion driving units are identical, and both machines have a passive link in the center of the structure. The purpose of this passive link is to restrain the movement of the manipulator and to improve the stiffness of the structure. As a result, both structures support 3-DOF, including one translation on the Z-axis and two rotations around the X and Y axes. The manipulator with redundancy is designed to prevent singularity and to improve stiffness. In this thesis, the inverse kinematic, Jacobian matrix and stiffness analyses have been conducted, followed by the design optimization for structures. Finally, the FEA (Finite Element Analysis) and dynamic analysis have also been performed. There are many practical applications for micro-motion parallel manipulators. The typical applications include micro-machine assembly, biological cell operation, and microsurgery . / UOIT