Theses and Dissertations from UMD
Permanent URI for this communityhttp://hdl.handle.net/1903/2
New submissions to the thesis/dissertation collections are added automatically as they are received from the Graduate School. Currently, the Graduate School deposits all theses and dissertations from a given semester after the official graduation date. This means that there may be up to a 4 month delay in the appearance of a give thesis/dissertation in DRUM
More information is available at Theses and Dissertations at University of Maryland Libraries.
Browse
54 results
Search Results
Item Gender Effects on Knee Loading and Prediction of Knee Loads Using Instrumented Insoles and Machine Learning(2024) Snyder, Samantha Jane; Miller, Ross H.; Shim, Jae Kun; Kinesiology; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Women are more likely to experience knee osteoarthritis as compared to men, but the underlying mechanisms behind this disparity are unclear. Greater knee loads, knee adduction moment, knee flexion moment, and medial joint contact force, are linked to severity and progression of knee osteoarthritis. However, it is unknown if greater knee loads in healthy, young women during activities of daily living (sit-to-stand, stand-to-sit, walking and running) can partially explain the higher prevalence of knee osteoarthritis rates in women. Although previous research showed no significant differences in peak knee adduction moment and knee flexion moment between men and women, differences in peak medial joint contact force are largely unexplored. Women also tend to take shorter steps and run slower than men. It is unknown if these differences may result in greater cumulative knee loading per unit distance traveled as compared to men. Furthermore, knee loading measurement is typically confined to a gait laboratory, yet the knee is subjected to large cyclical loads throughout daily life. The combination of machine learning techniques and wearable sensors has been shown to improve accessibility of biomechanical measurements without compromising accuracy. Therefore, the goal of this dissertation is to develop a framework for measuring these risk factors using machine learning and novel instrumented insoles, and to investigate differences in peak and cumulative per unit distance traveled knee loads between young, healthy men and women. In study 1 we developed instrumented insoles and examined insole reliability and validity. In study 2, we estimated knee loads for most activities with strong correlation coefficients and low to moderate mean absolute errors. In study 3, we found peak medial joint contact force was not significantly different across activities for men and women. Similarly, in study 4, we found no significant difference between men and women in knee loads per unit distance traveled during walking and running. These findings suggest biomechanical mechanisms alone cannot explain the disproportionate rate of knee osteoarthritis in women. However, in future research, the developed knee loading prediction models can help quantify daily knee loads and aid in reducing knee osteoarthritis risk in both men and women.Item Biomechanical regulation of T cells: The cytoskeleton at the nexus of force and function(2024) Pathni, Aashli; Upadhyaya, Arpita; Molecular and Cell Biology; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)The adaptive immune response is a sophisticated and multi-pronged defense mechanism that provides specific and long-lasting protection against infections and cancer. Central to this response are T lymphocytes - immune cells that orchestrate the immune response and directly eliminate infected or malignant cells. T cell function is intricately linked to their cytoskeleton, a dynamic network of protein filaments, consisting of actin, microtubules, and intermediate filaments, which provides structure, facilitates movement, and regulates intracellular transport. While the biochemical aspects of T cell function have been well-studied, recent advances have highlighted how mechanical forces influence T cell behaviors such as activation, migration, and effector functions—all processes driven by dynamic cytoskeletal remodeling. However, the mechanisms by which cytoskeletal dynamics, forces and mechanical stimuli drive T cell function remain poorly understood. This dissertation investigates this interplay, focusing on cytotoxic T lymphocytes (CTLs), a subtype of T cells that directly kill infected or cancerous cells. To launch a killing response, naïve CD8+ T cells must be activated by antigen-presenting cells (APCs) in lymph nodes, following which they proliferate and differentiate into an effector CTL population. CTLs eliminate targets via a specialized interface called the immunological synapse (IS), where they release lytic granules containing cytotoxic molecules and exert cytoskeletal forces to induce target cell death. A key event in IS formation is polarization of the centrosome, or the microtubule-organizing center, facilitating directional release of lytic granules. We first examined how biochemical signals provided by APCs modulate the cellular cytoskeleton. APCs provide not only antigenic stimulation, but also co-stimulatory signals required for full activation. Inflammatory cytokines such as interleukin-12 (IL-12) act as a third signal, enhancing CTL proliferation and cytotoxicity. Our findings demonstrate that CTLs activated in the presence of IL-12 exhibit enhanced IS formation, altered actin dynamics and microtubule growth, and generate greater mechanical forces, thus highlighting how activation signals can shape T cell mechanics, dynamics and function. Next, we investigated how the mechanical properties of target cells influence CTL function. Employing a biomimetic hydrogel system that mimics the stiffness of target cells, we demonstrate that substrate stiffness modulates multiple aspects of CTL responses. CTLs interacting with stiffer substrates exhibit enhanced spreading, accelerated actin ring formation, increased contractile forces, and more efficient centrosome polarization. Mechanical cues also influence lytic granule release and the nuclear translocation of mechanosensitive transcription factors. This work underscores the importance of mechanical cues in regulating immune responses. Given that coordinated cytoskeletal interactions are crucial for T cells to effectively respond to environmental cues, we further examined this crosstalk with a focus on intermediate filaments, the third, often understudied component of the cytoskeleton. Our characterization of the vimentin intermediate filament network reveals an expansive structure complementary to and dependent on other cytoskeletal components. We study the dynamics and organization of the vimentin network and find a close association of this network with the centrosome. Our results suggest a structural role for vimentin in supporting IS formation. Throughout this work, we use advanced imaging techniques and analysis approaches to probe various facets of T cell function. By bridging immunology, cell biology, and biophysics, this research contributes to our understanding of how physical forces shape immune responses.Item ROLE OF TRPV4 MECHANOSENSING REGULATING MACROPHAGE FUNCTIONS IN INFLAMMATORY DISEASES(2024) Dutta, Bidisha; Rahaman, Shaik O; Nutrition; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Macrophages are the most versatile cells of the hematopoietic system with roles in homeostasis, host-tissue development, innate immune response and tissue repair. Although the inflammatory activation and maintenance signals are tightly regulated, an imbalance in them results in unchecked inflammation resulting in cellular and tissue damage. Macrophages can affect most if not all phases of inflammation owing to their ability to adopt distinct functional states, secrete cytokines and phagocytose pathogens and debris. Recent evidence suggests that beyond biochemical cues, mechanical forces, like changing matrix stiffness in the tissue microenvironment, can shape immune cell functions involved in inflammation. These cells convert mechanical stimuli to biochemical signals in a process called mechanotransduction, regulating a multitude of cellular functions. However, knowledge about the molecular mediators of mechanotransduction and their functions in macrophage phenotypic and functional change is largely missing, highlighting the need for studying mechanosensory molecules such as ion channels. The present study focuses on the role of a specific mechanosensitive ion channel, Transient Receptor Potential Vanilloid 4 (TRPV4), in the regulation of macrophage mediated inflammatory responses. Given its emerging role in inflammatory diseases like fibrosis, arthritis, foreign body response (FBR), TRPV4’s contribution to macrophage behavior in inflammation is of growing interest. Employing cellular imaging and molecular biology techniques such as Ca2+ influx assays, immunohistochemistry, immunoblotting, and single nuclei RNA sequencing we delineate mechanisms by which biomechanical stimuli-mediated activation of TRPV4 affects macrophage function. We elucidate TRPV4’s role in macrophage mechanotransduction, providing a mechanistic understanding of inflammatory disease pathophysiology which could lead to the development of potential therapeutics for disease intervention.Item ENHANCING BIOPRINTING STRATEGIES TOWARDS THE DEVELOPMENT OF BIOMIMETIC OSTEOCHONDRAL TISSUE ENGINEERING SCAFFOLDS(2023) Choe, Robert; Fisher, John P; Bioengineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Osteoarthritis is a highly prevalent rheumatic musculoskeletal disorder that affects approximately 900,000 Americans annually and is characterized by the progressive breakdown of the articular cartilage and remodeling of the subchondral bone in the synovial joint. During early-stage osteoarthritis, the articular cartilage begins to degrade, the synovial joint space narrows, and the subchondral bone undergoes rapid bone turnover, leading to insufficient bone mineralization and compromised matrix integrity. While decades of research have revealed that an intricate balance between the bone and cartilage layers influences biochemical and biomechanical changes experienced within the osteochondral unit, most osteochondral tissue engineering scaffolds have not achieved clinical viability. Tissue engineering (TE) strategies, such as 3D bioprinting (3DP), offer a new avenue to help develop novel osteochondral tissue engineering scaffolds to regenerate healthy and diseased osteochondral joints. In this project, our immediate goal is to expand the repertoire of osteochondral bioprinting strategies toward developing a biomimetic, 3D-printed osteochondral scaffold that can be implanted into acute focal cartilage defects during early-stage OA. We will explore the designs and fabrication strategies of various 3D-printed biomimetic osteochondral interface scaffolds with enhanced mechanics guided by computational simulations. Additionally, we will examine the potential of utilizing osteoblast- and osteoclast-lineage cell co-cultures to improve regenerative outcomes at the bone scaffold layer of osteochondral tissue engineering scaffolds. The long-term goal of this work is to aid in developing a biomimetic 3D printed osteochondral scaffold that has enhanced load-bearing properties and elevated regeneration potential to recreate the unique osteochondral architecture at each distinct tissue layer.Item LOWER LIMB ASYMMETRY AND LOADING IN INDIVIDUALS WITH UNILATERAL TRANSFEMORAL AMPUTATIONS WITH A LIFETIME OF OSSEOINTEGRATED PROSTHESIS USE(2023) Burnett, Jenna K; Shim, Jae Kun; Kinesiology; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Individuals with transfemoral amputation commonly develop chronic health problems due to decreased physical activity as a result of the missing musculature and tissue on the amputated side, and the poor imitation of the intact limb provided by the prosthesis. In addition, the indirect and semi-rigid connection of the socket to the body may increase interlimb asymmetries, as well as lead to pain and discomfort on the residual limb. Recent innovations have introduced a bone-anchored or osseointegrated (OI) implant which connects the prosthesis to the skeleton, and removes most of the socket related pain and discomfort complaints, as well as providing a rigid connection which may reduce the interlimb asymmetries. However, the direct bone and prosthesis connection may also introduce longitudinal bone health concerns due to the repetitive loads during walking. This dissertation investigated the effect of walking speed on the loads placed on the lower limbs of 11 individuals who use an OI prosthesis at 3 different anatomical levels, including the whole limb through interlimb ground reaction force, the joints through interlimb joint kinematics and kinetics, and finally the residual limb bone through implant input forces, finite element analysis of bone strain, and the probability of bone injury with a simulated lifetime of use.In study 1, the interlimb ground reaction force asymmetries were found to be moderate to large at all walking speeds, and to have a general increase as individuals walked faster, indicating there is an intact limb reliance strategy which may be used to compensate for the limitations of the amputated limb. Similarly, in study 2, the interlimb joint kinematics and kinetics were found to have moderate to large asymmetries at each joint level, with a general increase in asymmetry at faster walking, with this increase largely due to limitations within the prothesis. In study 3, the abutment force decreased in magnitude with walking speed, but the peak strain on the bone, and the probability of injury was greater for the preferred speed and fast speed walking when compared to slow speed walking. However, the overall probability of injury was low for all speeds, indicating the ability of the bone to repair and adapt with sustained loading likely provides effective protection over a lifetime of simulated OI prothesis use. The findings of this dissertation suggest that the more rigid connection afforded by the OI implant cannot fully remove the interlimb asymmetries which occur as a result of the poor imitation of the intact limb provided by the prosthesis and prosthesis components, but that there is minimal risk to the bone due to a lifetime of sustained walking with an OI prosthesis as a result the inherent ability of the bone to repair and adapt to variable loads over time. Therefore, while an OI prosthesis may not fully mitigate the interlimb asymmetries which occur as a result of the prosthesis limitations, individuals who use an OI prosthesis may feel confident that there is minimal longitudinal risk to the bone as a result of walking over their lifetime.Item MODELING THE MECHANICAL CONSEQUENCES OF PREGNANCY ON KNEE JOINT LOADING AND FUTURE KNEE HEALTH(2023) Bell, Elizabeth M; Miller, Ross H; Shim, Jae K; Kinesiology; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Clinical evidence suggests that experiencing pregnancy increases a woman’s risk of knee osteoarthritis, a painful and mobility limiting disease that results from cartilage deterioration. While understanding the underlying causes and the association with pregnancy is complex, the mechanical load on cartilage during walking appears to be important to the initiation and progression of the disease, especially if walking mechanics are abnormal. Pregnancy involves various changes in mechanical factors like mass, center of mass, and joint laxity which are known to progressively change walking mechanics throughout gestation. However, it is unknown if mechanical changes associated with pregnancy, which may be substantial in magnitude but may be limited in duration, can explain the osteoarthritis risk since osteoarthritis is diagnosed later in life. Given that women typically experience pregnancy early in their lifetime and will need healthy knees for decades after they become mothers, this research aimed to model the mechanical consequences of pregnancy on knee joint loading and knee joint health over the lifetime. Specifically, this dissertation sought to (i) determine how pregnancy influences variables like resultant knee joint kinetics, which more directly indicate the load on cartilage over a range of walking speeds (ii) estimate the impact of pregnancy on internal knee joint forces and tibiofemoral cartilage load during walking and (iii) evaluate the isolated effect of altered loading experienced during pregnancy on cartilage degeneration and the risk of knee osteoarthritis throughout a woman's lifetime. Results suggest that (i) 3D knee joint moments over a range of walking speeds are greater in pregnant vs. non-pregnant individuals and knee adduction moments are altered as pregnant women walk faster. Similarly, pregnant women experience greater total knee joint loading and greater medial knee joint loading which results in additional and altered peak strain on knee cartilage with greater walking speed. Finally, the elevated and altered compressive load experienced over one or more pregnancies resulted in a greater cartilage failure probability, with differential effects when women experience multiple pregnancies later in their lifetime. These findings support the notion that the mechanical factors associated with pregnancy significantly alter knee joint loading and mechanical changes may, in part, contribute to the known association between pregnancy and risk for knee osteoarthritis risk over a woman’s lifetime. Further, present-day American mothers who are conceiving at later stages of life compared to previous generations may be more susceptible to knee osteoarthritis. Future investigations are needed to explore effects postpartum and for populations beyond healthy, active pregnant women. Further research could also investigate if biomechanical adjustments could be used as potential interventions to lessen knee joint loading and potentially decrease the risk of knee osteoarthritis among this population.Item INSTRUMENTATION AND AUTOMATION FOR STIMULATED BRILLOUIN SPECTROSCOPY(2023) Frank, Eric; Scarcelli, Giuliano; Bioengineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)The use of Brillouin spectroscopy for noninvasive probing of the mechanical properties of biologically relevant materials shows great promise. Stimulated Brillouin scattering (SBS) spectroscopy has the potential to significantly improve measurement speed and resolution by amplifying the scattered signal resonantly. However, current SBS spectrometers have been limited by fundamental and practical constraints in detection parameters. Here, we develop and demonstrate a novel LabVIEW-automated SBS instrumentation scheme in which a number of instruments that otherwise operate independently are automatized and synchronized from a singular LabVIEW program with emphasis on the user interface. Additionally, localization theory, originating from fluorescence-based super resolution microscopy techniques, is applied to the acquisition of SBS spectra, and experimentally demonstrated using this instrumentation scheme, resulting in spectra being acquired an order of magnitude faster while maintaining performances in terms of signal to noise ratio (SNR) and measurement precision.Item Dynamics of Elastic Capsules in Cross-Junction and T-Junction Microfluidic Channels(2017) Mputu udipabu, Pompon; Dimitrakopoulos, Panagiotis; Chemical Engineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)In this dissertation, we investigate via numerical computations the dynamicsof elastic capsules (made from a thin strain-hardening elastic membrane) in two microfluidic channels of cross-junction and T-junction geometries. For the cross-junction microfluidic channel, we consider an initially spherical capsule with a size smaller than the cross-section of the square channels comprising the cross-junction, and investigate the effects of the capsule size, flow rate, and lateral flow rates on the transient dynamics and deformation of low-viscosity and equiviscous capsules. In addition, we also study the effects of viscosity ratio on the transient capsule dynamics and deformation. Our investigation shows that the intersecting lateral flows at the cross-junction act like a constriction. Larger capsules, higher flow rates and higher intersecting lateral flows result in stronger hydrodynamic forces that cause a significant capsule deformation, i.e., the capsule’s length increases while its height decreases significantly. The capsule obtains different dynamic shape transitions due to the asymmetric shape of the cross-junction. Larger capsules take more time to pass through the cross-junction owning to the higher flow blocking. As the viscosity ratio decreases, the capsule’s transient deformation increases and tail formation develops transiently, especially for low-viscosity capsules owing to the normal-stress effects of the surrounding fluid on the capsule’s interface. However, the viscosity ratio does not affect much the capsule velocity due to a weak inner circulation. Our findings suggest that the tail formation of low-viscosity capsule may promote membrane breaking and thus drug release of pharmaceutical capsules in the microcirculation. Furthermore, we investigate via numerical computations the motion of an elastic capsule (made from an elastic membrane obeying the strain-hardening Skalak law) flowing inside a microfluidic T-junction device. In particular, we consider the effects of the capsule size, flow rate, lateral flow rate, and fluid viscosity ratio on the motion of the capsule in the T-junction micro-channel. As the capsule’s initial lateral position increases, the capsule moves faster and reaches different final lateral positions. As the capsule size increases, the gap between the capsule’s surface and the channel wall decreases. This results in the development of stronger hydrodynamic forces and a decrease in the capsule velocity due to flow blocking. As the capsule size increases, there is a small lateral migration towards the micro-channel centerline, which is the low-shear region of the T-junction micro-channel. This migration is in agreement with experimental and numerical studies on non-inertial lateral migration of vesicles in bounded Poiseuille flow by Coupier et al. [13] who showed that the combined effects of the walls and of the curvature of the velocity profile induce a lateral migration toward the centerline of the channel. As the capillary number Ca increases, the stronger hydrodynamic forces cause the capsule to extend along the flow direction (i.e., the capsule’s length Lx increases as the capsule enters the T-junctions and decreases as the capsule exits the T-junction). There is a small lateral migration away from the micro-channel centerline as the flow rate Ca increases. The capsule lateral position zc, main-flow velocity Ux and migration velocity Uz are practically not affected by the fluids viscosity ratio λ. As the channel’s lateral flow rate increases, the capsule migrates downwards towards the bottom of the device. Our findings on the lateral migration in the T-junction micro-channel suggest that there is a great potential for designing a T-junction microfluidic device that can be used to manipulate artificial and biological capsules.Item Quantitative Motion Analysis of the Upper Limb: Establishment of Normative Kinematic Datasets and Systematic Comparison of Motion Analysis Systems(2022) Wang, Sophie Linyi; Kontson, Kimberly L; White, Ian; Bioengineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Upper limb prosthetic devices with advanced capabilities are currently in development. With these advancements brings to light the importance of objectively and quantitatively measuring effectiveness and benefit of these devices. Recently, the application of motion capture (i.e., digital tracking of upper body movements in space) to performance-based outcome measures has gained traction as a possible tool for human movement assessment that could facilitate optimal device selection, track rehabilitative progress, and inform device regulation and review. While motion capture shows promise, the clinical, regulatory, and industry communities would benefit from access to large clinical and normative datasets from different motion capture systems and a better understanding of advantages and limitations of different motion capture approaches. The first objective of this dissertation is to establish kinematic datasets of normative and upper-limb prosthesis user motion. The normative kinematic distributions of many performance-based outcome measures are not established, and it is difficult to determine departures from normative patterns without relevant clinical expertise. In Specific Aim 1, normative and clinically relevant datasets were created using a gold standard motion capture system to record participants performing standardized tasks from outcome measures. Without kinematic data, it is also difficult to identify informative kinematic features and tasks that exhibit characteristic differences from normative motion. The second objective is to identify salient kinematic characteristics associated with departures from normative motion. In Specific Aim 2, an unsupervised K-means machine learning algorithm was applied to the previously collected data to determine motions and tasks that distinguish between normative and prosthesis user movement. The third objective is to compare three commonly used motion capture systems that vary in motion tracking mechanisms. The most informative tasks and kinematic characteristics previously identified will be used to evaluate the detection of these differences for several motion capture systems with varying tracking methods in Specific Aim 3.Item High Resolution Mapping of Intracellular Mechanical Properties during Key Stages of Cancer Progression(2022) Nikolic, Milos; Scarcelli, Giuliano; Tanner, Kandice; Biophysics (BIPH); Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)The mechanical phenotype of the living cell is critical for survival following deformations due to confinement and fluid flow. Furthermore, in recent years mechanical interaction between cells and the cellular environment has been implicated as one of the key regulators of cancer progression and malignant transformation. Due to the need to better understand the mechanical properties of invasive cells and how the mechanical phenotype plays a role in cancer progression, several microrheology techniques have been applied to study cell mechanics in a range of in vitro environments. However, many of these techniques have been limited either to studying cells in only one type of environment (e.g. 2D), with limited resolution, or with invasive probes. To begin to address this question, in this dissertation we aim to quantify the mechanical state of cells in a broader range of different contexts and geometries. To do this we use Brillouin microscopy, a non-contact, label free, non-invasive technique which enables us to probe the mechanical response of cells in a wide range of complex microenvironments. Here we introduce an improved Brillouin microscope with improved signal and acquisition speed which enables us to perform biological studies at the single cell level. Using the improved Brillouin microscopy, we find that individual cells can be softer as function of the invasive potential, but that cells are able to dynamically change their mechanical properties across many different contexts. We validate our results using complementary microrheology methods such as atomic force microscopy and broadband optical tweezer microrheology. We directly observe changes in cell mechanics in key processes relevant for metastatic migration, as well as a function of external and internal parameters like morphology, ECM properties, intracellular factors, and cell-cell cooperativity during multicellular tissue organization. These results support the paradigm that the mechanical state of a cell is a dynamic parameter that varies as a consequence of the microenvironmental and functional context, in addition to the observable changes in cell’s mechanical properties due to malignant transformation.