The bladder wall consists primarily of detrusor smooth muscle. Tension-sensitive nerves in the bladder wall are responsible for providing bladder fullness information that is interpreted as urgency. Bladder wall tension, and therefore nerve output, is a function of bladder volume, shape and material properties. Studies have shown that the bladder wall exhibits acutely regulated detrusor compliance. In addition, bladder shape throughout filling depends on intra-abdominal forces and material properties of the bladder wall, such as regulated detrusor compliance. This thesis focused on modeling the potential influence of acute changes in bladder compliance, shape and bladder wall tension during filling. Laplace’s Law was used to demonstrate how wall tension can vary significantly with geometry in a vessel with uniform internal pressure and constant volume. A finite deformation model of the bladder was previously used to show that wall tension can increase significantly during filling with relatively little pressure change. In this thesis, published experimental data were used to determine ranges for regulated detrusor compliance, and the finite deformation model was expanded to illustrate the potential effects of regulated ix detrusor compliance on filling pressure and wall tension. Also, a geometric model was used to demonstrate that constraining a perfectly spherical bladder to fill as an oblate sphere increases wall tension, and therefore should increase nerve output, for a given volume. In addition, a spheroidal model consisting of three orthogonal circular rings was developed to predict the increase in pressure and wall tension associated with deforming a spherical bladder into an oblate spheroid. Together, these models demonstrate that defects in regulated detrusor compliance and/or acute or chronic changes in bladder shape due to changes in compliance or intra-abdominal forces could contribute to changes in wall tension for a given volume that could lead to urgency.

Tissue engineering has the potential of becoming an effective approach for the replacement of articular cartilage. However, the problems of small tissue size and inadequate mechanical properties of the tissue have yet to be overcome. Mechanical stimulation of cartilaginous tissues is one method of accelerating chondrocyte proliferation and ECM synthesis. While the effects of compression and shear have been well studied, the effects of tension have received little attention. Based on the findings of previous mechanical stimulation studies and photographic evidence of tension acting in native articular cartilage in its physiological environment, it was hypothesized that intermittent applications of tensile strain can be used to stimulate cellular proliferation and ECM synthesis and thereby improve the size and mechanical properties of cartilaginous tissues. A loading fixture was constructed to apply biaxial tensile strains (BTS) to cartilaginous tissues grown in vitro. The optimal conditions for stimulating proliferation and ECM synthesis were found to be static tension (as opposed to dynamic tension), 3.8% radial and 2.1% circumferential strain magnitude for a 30 minute duration. Tissues subjected to BTS stimulation for 4 weeks at a frequency of once every 2-3 days had increased thickness, wet weight, and proteoglycan content, but had little effect on tissue mechanical properties. Tissues stimulated at a frequency of once per day over the same period had a negligible effect. A subsequent experiment confirmed that the effects of BTS stimulation on proliferation and ECM synthesis were dependent on load frequency, as well as culture media pH. The experimental results of this thesis suggest that the physical stretching of chondrocytes may have had more of an impact on stimulating proliferation and ECM synthesis than induced interstitial fluid flow. Chondrocytes also require a period of preconditioning before the stimulated effects occur, but too high of a loading frequency can cause possible desensitization and/or a catabolic response. Overall, the experiments were successful in identifying the stimulatory potential of tensile strains. However, further improvements must be made to the long-term effects on tissue mechanical properties before tension can be used as an effective stimulus to produce better quality in engineered cartilaginous tissues. / Thesis (Master, Mechanical and Materials Engineering) -- Queen's University, 2009-03-05 18:06:46.925

Human lung undergoes respiration-induced deformation due to sequential inhalation and exhalation. Accurate determination of lung deformation is crucial for tumor localization and targeted radiotherapy in patients with lung cancer. Numerical modeling of human lung dynamics based on underlying physics and physiology enables simulation and virtual visualization of lung deformation. Dynamical modeling is numerically complicated by the lack of information on lung elastic behavior, structural heterogeneity as well as boundary constrains. This study integrates physics-based modeling and image-based data acquisition to develop the patient-specific biomechanical model and consequently establish the first consistent Young's modulus (YM) of human lung. This dissertation has four major components: (i) develop biomechanical model for computation of the flow and deformation characteristics that can utilize subject-specific, spatially-dependent lung material property; (ii) develop a fusion algorithm to integrate deformation results from a deformable image registration (DIR) and physics-based modeling using the theory of Tikhonov regularization; (iii) utilize fusion algorithm to establish unique and consistent patient specific Young's modulus and; (iv) validate biomechanical model utilizing established patient-specific elastic property with imaging data. The simulation is performed on three dimensional lung geometry reconstructed from four-dimensional computed tomography (4DCT) dataset of human subjects. The heterogeneous Young's modulus is estimated from a linear elastic deformation model with the same lung geometry and 4D lung DIR. The biomechanical model adequately predicts the spatio-temporal lung deformation, consistent with data obtained from imaging. The accuracy of the numerical solution is enhanced through fusion with the imaging data beyond the classical comparison of the two sets of data. Finally, the fused displacement results are used to establish unique and consistent patient-specific elastic property of the lung.

Cardiovascular disease continues to be a leading cause of death in the United States, and a source of financial strain on the healthcare system. This prompts the need for new methods of low-cost, noninvasive technologies for cardiac monitoring to improve patient health and reduce healthcare costs. While the first and second heart sounds are common references that are listened to during auscultation of heart, seismocardiography (SCG) is a technology that detects chest sound vibrations with an accelerometer and may offer more information beyond the audible heart sounds. There is currently limited information regarding both the relationship between audible heart sounds and SCG, as well as the low-frequency (<20 >Hz) characteristics of heart sounds. The intent of this thesis is to investigate the relationship between audible heart sounds and SCG, with the goal of understanding the clinical utility of SCG. This was done using both audible and subaudible frequencies. Comparisons indicate the SCG signal carries a greater amount of low-frequency content than audible heart sounds, which warrants further study to determine how SCG can be best harnessed for cardiac monitoring.

Motion of organs and tissues causes X-ray localization error during radiation therapy. Therefore, physical phantoms utilizing materials with tissue-equivalent mechanical and radiological properties are desired to simulate organ motion for radiotherapy optimization. However, it is still a challenge to develop such materials. Alginate hydrogels have similar properties to extra cellular matrix, which make them promising for use as tissue-equivalent materials. In this study, alginate hydrogels and hydrogel foams with desired mechanical and radiological properties were synthesized through in-situ release of Ca2+. The concentration, Ca2+:-COOH molar ratio, and air volume ratio were controlled to obtain hydrogels and hydrogel foams tailored to specific mechanical and radiological properties. Both macroscopic and microscopic morphologies of the materials were characterized. The change in molecular bonding in the hydrogels was characterized through FTIR. Tensional and compressive behaviors of the hydrogel material were investigated. Radiological properties were estimated theoretically and validated through CT scanning experiments. Ultimately, the synthesis-structure-property relationship was established to guide future developments. This study has elucidated the development of future tissue-equivalent materials which could be applied for optimization of radiation dosage and quality control during radiotherapy. The second component of this dissertation is the development of a novel metal matrix composite consisting of nanosilver/silver nanoparticles through an electroplating process. The composite offers excellent mechanical properties, high electrical conductivities, and scalability to meet desired industrial needs such as conductive coating in extreme environments. Specifically, metal matrix composites were prepared to obtain nanosilver/silver nanoparticle composites on a copper substrate. Nanosilver particles were introduced through an electroplating process to enhance the mechanical and conductive properties. The electroplating current and time were controlled to obtain composites with desired mechanical and conductive properties. The morphologies, mechanical properties, and electrical conductivity were determined. The influence of electroplating process parameters on the mechanical and conductive behaviors was investigated. This study has contributed to understanding the electroplating process-structure-property relation of metal matrix composites with improved mechanical properties and electrical conductivity.

Valve function is commonly assessed by effective orifice area (EOA) estimates using equations derived from conservation of mass and energy. Errors have been found with the method due to difficulties in determining the valve’s coefficient of discharge (Cd). The Cd, a factor that corrects the EOA for losses in the valvular wake region, has been shown previously to vary with the Reynolds number and valve geometry. In this study, a Cardio-Vascular Duplicator (CVD) is used to determine the Cd for three types of mitral valves, operating in modes ranging from normal to severely stenotic. Since orifice area methods do not account for regurgitant flow, the energy index (EI) method is derived and used in experiments with an aortic valve. Results show that the EI method is more powerful than the EOA because a single quantitative parameter is attributed to each valve, taking into account regurgitant, leakage and pressure losses.

The skin is the largest organ in the human body. It is the first line of contact with the outside world, being subject to a harsh array of physical loads and environmental factors. In addition to this, the skin performs numerous physiological tasks such as thermo-regualtion, vitamin D synthesis and neurotransduction. The skin, as with all biological tissue, is subject to chronological ageing, whereby there is a general breakdown of tissue function and a decline in mechanical properties. In addition to this, skin undergoes extrinsic forms of ageing through exposure to external factors such as ultraviolet radiation, air pollution and cigarette smoking. Skin modelling is an area of biomechanics that, although medical in nature, has expanded into areas such as cosmetics, military, sports equipment and computer graphics. Skin can be approximated at the macroscopic continuum scale as an anisotropic, nearly-incompressible, viscoelastic and non-linear material whose material properties are highly dependent on the ageing process. Through the literature, several phenomenologically based models have been satisfactorily employed to capture the behaviour inherent to the skin, but despite the intrinsic link to age, to date no constitutive model for the UV-induced ageing/damage of skin has been developed that is both capable of capturing the material and structural effects, and is embedded in the rigorous framework of non-linear continuum mechanics. Such a mechanistic model is proposed here. The macroscopic response of the skin is due to microscopic components such as collagen, elastin and the surrounding ground substance and the interaction between them. An overview on the structure of the skin helps motivate the form of the continuum model and identifies which aspects of the skin need to be captured in order to replicate the macroscopic response. Furthermore, the ageing process is explored and a firm understanding of the influence of ageing on the substructures is established. Over time, elastin levels tend to decrease which results in a loss of skin elasticity. Collagen levels drop with age, but tend to flatten out which results in an overall increase in skin stiffness and loss of anisotropy. A worm-like chain constitutive model, arranged in an 8-chain configuration, is employed to capture the mechanical response of the skin. The use of such a micro-structurally-motivated model attempts to connect the underlying substructures (collagen, elastin and ground substance) present in the skin to the overall mechanical response. The constitutive model is implemented within a finite element scheme. Simple uniaxial tests are employed to ascertain the validity of the model, whereby skin samples are stretched to elicit the typical anisotropic locking response. A more complex loading condition is applied through bulge tests where a pressure is applied to an in vitro skin specimen. This more complex test is subsequently used to conduct a series of ageing numerical experiments to ascertain the response of the model to changes in material properties associated with ageing. A modified model is then proposed to capture the ageing response of the skin. The key microscopic biophysical processes that underpin ageing are identified, approximated and adapted sufficiently to be of use in the macroscopic continuum model. Aspects of open-system thermodynamics and mixture theory are adapted to the context of ageing in order to capture a continuous ageing response.

The endothelium composes the inner lining of blood vessels, the heart, and lymphatic vessels. Within the cardiovascular system, it is an extremely important structure, aiding in the regulation of blood pressure with the vascular tone, recruiting immune response, regulating the transfer of material in and out of the bloodstream, and the creation of new blood vessels through angiogenesis. The endothelium is composed entirely of endothelial cells. These cells lay in a flat squamous formation and are in direct contact with blood and aid in the regulation and transfer of material in and out of the bloodstream via active and passive transport. Passive transport is regulated with cell-cell junctions between the endothelial cells, otherwise known as intercellular junctions, is the topic of interest in our first study. One cell-cell junction, adherens junctions are connected to the cytoskeleton of actin filaments. These actin filaments play an important role in the cell's ability to generate force through the contraction of the actin-myosin complex creating tension in the filaments. Because of the direct link between these two structures, there is a belief that there is a connection between the permeability of the endothelium and the cellular forces produced by the actin cytoskeleton. Also, other cell-cell junctions, gap junctions, and tight junctions have shown that when disrupted endothelial permeability increases. These junctions' relation between function and cell mechanics is not as well-known. Our goal is to determine if disruption of these junctions causes a similar stress environment as disruption of adherens junctions with the use of traction force microscopy and monolayer stress microscopy. The endothelium also plays an important role in the process of wound-healing. We look the endothelial cells role in wound-healing process as part of our second study. When an injury occurs and there is damaged tissue with inadequate oxygenation endothelial cells migrate into the wound space and begin the process of angiogenesis forming new blood vessels to support other cells in the process of wound-healing and providing oxygen to repair tissue. This process is so important that diseases that impede it can cause chronic wounds. To improve wound-healing rates, magnetic therapies have been looked at to stimulate the wound area and promote wound-healing. It is believed that cells are receptive to electrical and magnetic stimulation due to their ion-based communication methods. Magnetic field studies have shown promise in animal models. But contradictory results between different wound types and animal models leads us to look into an in-vitro human model to test the therapies potential effectiveness. To get a better idea of how magnetic therapy may affect human patients, we use human endothelial cells in an in-vitro scratch test study under several strength magnetic fields to determine if the therapies show any promise. Another therapy that shows promise is electrical stimulation. Studies show that the migration of single endothelial cells can be controlled using a voltage potential in-vitro. And in-vivo studies show promise in improving wound-healing times with diabetic ulcerations. To see if this improvement is potentially due to a collective migration response from the endothelial cells a similar set of scratch test in-vitro studies were conducted to see if endothelial wound-healing times improved under electrical stimulation. To determine the effectiveness of magnetic and electrical stimulations effect on wound-healing we look at the wound closure rate and average cell velocity of wounds created in these in-vitro models. Electrical stimulation has also shown promise as a wound-healing therapy with improvements in wound-healing for diabetic ulcers. Because of this improved wound-healing response from this therapy, we wish to look to see if endothelial cells are responsible for the improved wound-healing response. For electrical stimulation, a similar set of scratch tests were performed under a low voltage gradient to determine if collective cell migration and endothelial wound-healing were affected by electrical stimulation.

Endothelial cells, which form the inner layer of the vasculature, constantly interact with their external microenvironment called the extracellular matrix (ECM) by exerting contractile cell-substrate stresses called tractions and cell-cell stresses called intercellular stresses. This cellular mechanosensing can become aberrant and act as a precursor for many vascular pathological and physiological processes such as cancer metastasis, atherosclerosis, cell differentiation, migration, and morphogenesis. Also, intracellular calcium signalling plays an important role in endothelial cell motility and in maintaining vascular tone. Alteration in ECM composition has been linked to several pathologies, in fact, a transition to a fibronectin-rich matrix from a type I collagen-rich and elastin-rich matrix in coronary artery disease, for example. However, the influence of ECM compositions and intracellular calcium levels on cell mechanics is not clearly understood. The first study will shed light on ECM composition and its influence on endothelial mechanical properties including traction, intercellular stresses, cell velocity, and various morphological parameters. The second study will enhance our knowledge on the role calcium signaling plays on cellular tractions. The final chapters will focus on the development and utilization of Machine Learning (ML) models for the predictions of tractions and intercellular stresses with morphological and pharmacological predictors, which to our knowledge is the first work in the field. The results yielded from this work will further our understanding of cellular mechanics at the mesoscale by: i) Identifying the role of specific ECM molecules in mechanical signaling, ii) Understanding the influence of transient calcium signaling on tractions, and iii) Providing a machine learning framework that can be used for the prediction of tractions and intercellular stresses as a dose dependent response to a drug that is known to influence cell mechanics. These findings will be beneficial to drug development studies and targeted drug therapy for treating various vascular-related pathologies.

During this research, the first prototype of the Workshare Upper Lower Limb (WULL) exoskeleton was developed. The goal of this exoskeleton is to create a kinetic couple between the upper and lower body. To achieve the goal, existing orthoses were modified and fitted to each other to create an ergonomic platform to attach all the force transmission elements. The force was transmitted from the upper to the lower limbs by a system of pulleys and Bowden cables. The pulleys were placed on the joints with a Boa ratchet to tension each of the lines. The Bowden cables were routed through the back to avoid any entanglement. To test the efficacy of the device, eight EMG sensors were placed on five participants to track the muscle activation during different exercises. Besides the EMGs multiple IMUs were placed on the participant to also track the motion of the joints. The validation of the device was done over twenty sessions that consisted of 4 exercises. Overall, the device showed that when kinematically connecting the upper and lower body, the lower limbs exert less effort. When looking at low dynamic motions, the device was able to assist the participant by reducing the work of the muscle by about 20%. When the device was used in a high dynamic scenario, the change was not so clear. In the current state, the device requires good coordination between the upper and lower limbs to fully take advantage of the system. With this device and the results shown, a foundation for these kinematic couplers has been set, and many variations of this device can be made.