Browsing by Subject "biomechanics"
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Item Contribution of alpha3(IV)alpha4(IV)alpha5(IV) Collagen IV to the Mechanical Properties of the Glomerular Basement Membrane(2016-05) Gyoneva, LazarinaThe glomerular basement membrane (GBM) is a vital part of the blood-urine filtration barrier in the kidneys. In healthy GBMs, the main tension-resisting component is α3(IV)α4(IV)α5(IV) type IV collagen, but in some diseases it is replaced by other collagen IV isoforms. As a result, the GBM becomes leaky and disorganized, ultimately resulting in kidney failure. Our goal is to understanding the biomechanical aspects of the α3(IV)α4(IV)α5(IV) chains and how their absence could be responsible for (1) the initial injury to the GBM and (2) progression to kidney failure. A combination of experiments and computational models were designed for that purpose. A model basement membrane was used to compare experimentally the distensibility of tissues with the α3(IV)α4(IV)α5(IV) chains present and missing. The experiments showed basement membranes containing α3(IV)α4(IV)α5(IV) chains were less distensible. It has been postulated that the higher level of lateral cross-linking (supercoiling) in the α3(IV)α4(IV)α5(IV) networks contributes additional strength/stability to basement membranes. In a computational model of supercoiled networks, we found that supercoiling greatly increased the stiffness of collagen IV networks but only minimally decreased the permeability, which is well suited for the needs of the GBM. It is also known that the α3(IV)α4(IV)α5(IV) networks are more protected from enzymatic degradation, and we explored their significance in GBM remodeling. Our simulations showed that the more protected network was needed to prevent the system from entering a dangerous feedback cycle due to autoregulation mechanisms in the kidneys. Overall, the work adds to the evidence of biomechanical differences between the α3(IV)α4(IV)α5(IV) networks and other collagen IV networks, points to supercoiling as the main source of biomechanical differences, discusses the suitability of α3(IV)α4(IV)α5(IV) networks to meet the mechanics and permeability needs of the GBM, and explores the role of biomechanics and enzymatic digestion in GBM remodeling.Item Failure Mechanics of Nonlinear, Heterogeneous, Anisotropic Cardiovascular Tissues: Implications for Ascending Thoracic Aortic Aneurysms(2019-06) Korenczuk, Christopher E.Characterizing the mechanical response and failure mechanisms of cardiovascular tissues is critically important, as these tissues play a vital role in the native functioning of the body. In the case of pathological events, such as aortic aneurysms or myocardial infarctions, mechanical behavior can be altered due to adverse remodeling, and thus affect the integrity of the tissue. Ascending thoracic aortic aneurysms (ATAAs) occur when the aorta enlarges beyond its normal diameter, and dilation is typically accompanied by disorganization of the underlying aortic fibrous structure. Current diagnostic methods depend solely on measuring aneurysm diameter, neglecting considerations of mechanical strength, which results in an inefficient risk assessment. To better understand the failure mechanism of ATAAs, the work presented here used a combination of experimental testing and computational modeling to characterize failure in human ATAA tissue. Experimental testing showed that ATAA tissue exhibited significantly lower mechanical strength when compared to healthy porcine tissue in multiple loading configurations. Furthermore, experimental tests highlighted the large disparity between uniaxial and shear strength in ATAA tissue, where the tissue was substantially weaker in shear loading conditions. A custom multiscale finite-element model was then used to interrogate fiber failure more closely in both experimental loading conditions, and inflation of a patient-specific ATAA geometry. Modeling results showed that fibers between the lamellar layers of the aortic wall failed significantly more than fibers within the planar layers in shear loading conditions, as well as during inflation of the patient-specific geometry. Taken together, these results suggest that intramural shear could be an important contributor to the failure or dissection of ATAAs.Item Mechano-to-Neural Transduction of the Pacinian Corpuscle(2017-10) Quindlen, JuliaCutaneous mechanoreceptors are responsible for our ability to distinguish between different touch modalities and experience the physical world around us. Mechanoreceptors are innervated by afferent mechanosensitive neurons that transduce mechanical stimuli into action potentials and terminate in specialized end organs. The Pacinian corpuscle (PC) has been studied more than any of our other mechanoreceptors due to its large size and ease of identification during dissection. The PC, which is found primarily within the dermis of glabrous skin, responds to low-amplitude, high-frequency vibrations in the 20-1000 Hz range. The PC functions as a bandpass filter to vibrations, an effect attributed to the structural and mechanical complexity of its end organ. The PC contains a central mechanosensitive nerve fiber (neurite) that is encapsulated by alternating layers of flat, epithelial-type cells (lamellae) and fluid. The overarching goal of this thesis was to unify the anatomical and electrophysiological observations of the PC via a detailed mechanistic model of PC response to mechanical stimulation, requiring a multiphysics, multiscale approach. First, we developed a multiscale finite-element mechanical model to simulate the equilibrium response of the PC to indentation while accounting for the layered, anisotropic structure of the PC and its deep location within the skin. Next, we developed a three-stage finite-element model of the PC’s mechanical and neural responses to a vibratory input that accounted for the lamellar mechanics and neurite electrochemistry. This mechano-neural model was able to simulate the PC’s band-pass filtration of vibratory stimuli and rapid adaptation to sustained mechanical stimuli. We then used this model to evaluate the relationship between the PC’s material and geometric parameters and its response to vibration and developed dimensionless expressions for the relationship between these parameters and peak frequency or bandwidth. We then embedded multiple mechano-neural PC models within a finite-element model of human skin to simulate the mechanical and neural behavior of a PC cluster in vivo. We then performed a literature search to compile the structural parameters of PCs from various species and used our mechano-neural model to simulate the frequency response across species. Finally, we isolated PCs from human cadaveric hands and performed micropipette aspiration experiments to determine an apparent Young’s modulus of the PC. The computational and experimental work performed in this thesis contribute to the understanding of the fundamental behavior of mechanoreceptors, which is a necessary first step towards the development of haptic feedback-enabled devices.Item Studies of Ablation Complications During the Treatment of Atrial Fibrillation(2015-09) Quallich, StephenThe complication rates during transcatheter cardiac ablation procedures remain concerning. The transseptal puncture procedure, the relative navigation of catheters to difficult anatomies, and the application of ablation modalities to ensure transmural lesions are all primary areas where therapeutic complications may arise. In my thesis projects, our work targeted these three areas while also specifically considering a means to reduce such complications. Specifically, iatrogenic atrial septal defect formation was investigated by assessing the biomechanical changes of the atrial septum that may occur during transseptal punctures and the further injury the septum may incur during subsequent catheter manipulations. Furthermore, the contact forces required to perforate the atria were characterized in order to determine the boundary force conditions associated with both catheter navigation and ablation energy application. In addition, the biophysical changes manifested during and following the application of ablation modalities, as well as, the parameters that facilitate the development of explosive steam pops were investigated. Finally, the cryothermal tolerances of cardiac tissues were identified to aid in reducing collateral injury and to optimize dose delivery. The insights gained from these translational studies will help define various parameters and boundary conditions that should improve both the safeties and efficacies of clinical cardiac ablation procedures. In addition to characterizing these factors, the direct visualization of such complications provides invaluable insights to engineers as well as clinicians.