Biomechanics Commons^™

Quantitative Approaches To Unravel The Mechanobiology Of Cortical Folding, Ramin Balouchzadeh

McKelvey School of Engineering Graduate Student Theses & Dissertations

Quantitative Approaches to Unravel the Mechanobiology of Cortical Folding by Ramin Balouchzadeh Doctor of Philosophy in Mechanical Engineering Washington University in St. Louis, 2024 Professor Philip V. Bayly, Chair Professor Kara E. Garcia, Co-Chair Brain development is a highly complex process driven by mechanical forces and material properties that shape the cerebral cortex’s characteristic gyri and sulci. Abnormalities in this folding pro?cess are associated with neurodevelopmental disorders such as autism and schizophrenia. Despite significant advancements, the underlying mechanical principles governing brain morphogenesis remain incompletely understood. This body of work investigates three key aspects of brain de?velopment: stress-dependent growth, evolving tissue …

Bone-Ivd Crosstalk And The Role Of Rage Signaling In An Ivd Injury Model, Remy Walk

McKelvey School of Engineering Graduate Student Theses & Dissertations

Low back pain (LBP) is the number one musculoskeletal cause of disability with a lifetime prevalence of up to 85%. The causes of LBP are multifactorial with potential contributions from factors such as tissue injury and degeneration as well as social economic and psychological factors. Intervertebral disc (IVD) degeneration is associated with 26-40% of LBP cases and in a 2015 meta-analysis, it was estimated that a total 403 million people suffer from symptomatic IVD degeneration. IVD degeneration is characterized by loss of hydration in the nucleus pulposus (NP), damage accumulation in the annulus fibrosus (AF) and calcification of the cartilaginous …

Bone-Ivd Crosstalk And The Role Of Rage Signaling In An Ivd Injury Model, Remy Walk

McKelvey School of Engineering Graduate Student Theses & Dissertations

Low back pain (LBP) is the number one musculoskeletal cause of disability with a lifetime prevalence of up to 85%. The causes of LBP are multifactorial with potential contributions from factors such as tissue injury and degeneration as well as social economic and psychological factors. Intervertebral disc (IVD) degeneration is associated with 26-40% of LBP cases and in a 2015 meta-analysis, it was estimated that a total 403 million people suffer from symptomatic IVD degeneration. IVD degeneration is characterized by loss of hydration in the nucleus pulposus (NP), damage accumulation in the annulus fibrosus (AF) and calcification of the cartilaginous …

Modeling, Analysis, And Simulation To Reveal The Mechanisms Of Ciliary Beating, Louis Woodhams

McKelvey School of Engineering Graduate Student Theses & Dissertations

Cilia are microscopic cellular appendages that help us breathe by clearing our airways, maintain the health of our central nervous system by circulating cerebrospinal fluid, and allow us to reproduce by transporting eggs and propelling sperm cells. Cilia even determine the asymmetry of our internal organs during embryonic development. However, the mechanisms underlying ciliary beating are not fully understood. Questions remain as to how arrays of the motor protein dynein generate the propulsive waveforms observed in cilia and how structural elements within the cilium and its connection to the cell deform during beating. In the current work, mathematical modeling, analysis, …

Defining The Role Of Elastic Fibers In Tendon Mechanics, Jeremy D. Eekhoff

McKelvey School of Engineering Graduate Student Theses & Dissertations

Tendons serve as a linking component of the musculoskeletal system by transferring forces between muscle and bone. As such, the structural proteins of the tendon extracellular matrix are of vital importance for the tissue to function properly and maintain its mechanical integrity. Collagen is the principal constituent of tendon and makes up its aligned hierarchical organization. Other structural proteins, such as elastin, are in comparison understudied and not well understood in relation to tendon function. Elastin, the main component of elastic fibers, has unique mechanical properties including high extensibility, fatigue resistance, and elasticity; these properties are important for elastin-rich tissues …

Shear Wave Propagation Speeds And Estimation Of Mechanical Properties In Soft, Fibrous, Nonlinear Anisotropic Materials, Zuoxian Hou

McKelvey School of Engineering Graduate Student Theses & Dissertations

The mechanical properties of brain tissue may reflect or influence growth, remodeling, development, aging, and disease. However, brain tissue, especially white matter, is structurally anisotropic and has nonlinear strain-stress relationships, so common methods are not very useful to describe the mechanical properties of brain tissue. Magnetic resonance elastography (MRE), based on the MRI imaging technique, can be used for measuring tissue mechanical properties non-invasively. Therefore, the mathematical model that describes the relation between wave speed and tissue mechanical properties will essentially influence the accuracy of the prediction. The objective of this dissertation is to investigate the relationship between shear wave …

Synthetic Gene Circuits For Self-Regulating And Temporal Delivery Of Anti-Inflammatory Biologic Drugs In Engineered Tissues, Lara Pferdehirt

McKelvey School of Engineering Graduate Student Theses & Dissertations

The recent advances in the fields of synthetic biology and genome engineering open up new possibilities for creating cell-based therapies. We combined these tools to target repair of articular cartilage, a tissue that lacks a natural ability to regenerate, in the presence of arthritic diseases. To this end, we developed cell-based therapies that harness disease pathways and the unique properties of articular cartilage for prescribed, localized, and controlled delivery of biologics, creating the next generation of cell therapies and new classes of synthetic circuits. We created tissue engineered cartilage from murine induced pluripotent stem cells that had the ability to …

Subject-Specific Musculoskeletal Modeling Of Hip Dysplasia Biomechanics, Ke Song

McKelvey School of Engineering Graduate Student Theses & Dissertations

Developmental dysplasia of the hip (DDH) is characterized by abnormal bony anatomy, causes pain and functional limitations, and is a prominent risk factor for premature hip osteoarthritis. Although the pathology of DDH is believed to be mechanically-induced, little is known about how DDH anatomy alters hip biomechanics during activities of daily living, partly due to the difficulties with measuring hip muscle and joint forces. Musculoskeletal models (MSMs) are useful for dynamic simulations of joint mechanics, but the reliability of MSMs for DDH research is limited by an accurate model representation of the unique hip anatomy. To address such challenges, this …

Structural And Tissue-Level Adaptations Of Lumbar Intervertebral Discs In Humans With Inducible Low Back Pain Symptoms, Christian Isaiah Weber

McKelvey School of Engineering Graduate Student Theses & Dissertations

Low back pain (LBP) is a devastating musculoskeletal ailment that impacts majority of the global population. Up to 95% of cases are considered nonspecific where the origin is unclear. Although there is a diagnosis with these cases, there lacks specificity that would help individuals with treatment and pain management. Imaging techniques such as magnetic resonance imaging (MRI) are primarily utilized in the diagnosis of LBP as it illuminates internal structures of the spine. One important structure clearly identified with MRI is the intervertebral disc (IVD) that is susceptible to injury and disease. Further, diagnostic imaging is performed lying down where …

Development And Application Of New Methods For Magnetic Resonance Elastography Of The Brain, Charlotte Anne Guertler

McKelvey School of Engineering Graduate Student Theses & Dissertations

Accurate mechanical properties of the intact, living brain are essential for modeling traumatic brain injury (TBI). However, the properties of brain tissue in vivo have traditionally been measured in ex vivo samples. Magnetic resonance elastography (MRE) can be used to measure motion and estimate material properties of soft tissues in vivo, but MRE typically assumes tissue isotropy and homogeneity. The objective of this thesis is to improve MRE of soft tissue, like the brain, by developing and evaluating methods for in vivo estimation of heterogeneous, anisotropic properties. This was achieved through pursuit of the following aims: (1) quantifying the differences …

Improved Orthopaedic Repairs Through Mechanically Optimized, Adhesive Biomaterials, Stephen Wheeler Linderman

McKelvey School of Engineering Graduate Student Theses & Dissertations

Despite countless surgical advances over the last several decades refining surgical approaches, repair techniques, and tools to treat tendon and tendon-to-bone injuries, we are still left with repair solutions that rely on fairly crude underlying mechanical principles. Musculoskeletal soft tissues have evolved to transfer high loads by optimizing stress distribution profiles across the tissue at each length scale. However, instead of mimicking these natural load transfer mechanisms, conventional suture approaches are limited by high load transfer across only a small number of anchor points within tissue. This leads to stress concentrations at anchor points that often cause repair failure as …

Its Skin Is My Skin, Bryan Page

Graduate School of Art Theses

This text examines the complexity of attempting to empathize with bodies that are vastly othered from my own. This broad yet nuanced subject crosses epistemological boundaries and complicates the dualities between both the mind and body, and between the corporeal and the virtual. My desire to better understand the conditions of another’s experience originates from a painful traumatic loss which caused me to feel isolated and incomplete. In response to this suffering, I long to emotionally connect with other beings and create artwork that attempts to bridge the qualia of individual experience.

I am interested in the capacity (or lack …

Accurate Determination And Application Of Local Strain For Studying Tissues With Gradients In Mechanical Properties, John Boyle

McKelvey School of Engineering Graduate Student Theses & Dissertations

Determination of the mechanical behavior of materials requires an understanding of deformation during loading. While this is traditionally accomplished in engineering by examining a force displacement curve for a whole sample, these techniques implicitly ignore local geometric complexities and local material inhomogeneities commonly found in biologic tissues. Techniques such as normalized cross correlation have been classically applied to address this issue and resolve deformation at the local level; however, these techniques have proven unreliable when deformations become large, if the sample undergoes a rotation, and/or if strain fields become incompatible (e.g. at or near failure).

Presented here is a toolbox …

Mechanics Of The Developing Brain: From Smooth-Walled Tube To The Folded Cortex, Kara Ellspermann Garcia

McKelvey School of Engineering Graduate Student Theses & Dissertations

Over the course of human development, the brain undergoes dramatic physical changes to achieve its final, convoluted shape. However, the forces underlying every cinch, bulge, and fold remain poorly understood. This doctoral research focuses on the mechanical processes responsible for early (embryonic) and late (preterm) brain development.

First, we examine early brain development in the chicken embryo, which is similar to human at these stages. Research has primarily focused on molecular signals to describe morphogenesis, but mechanical analysis can also provide important insights. Using a combination of experiments and finite element modeling, we find that actomyosin contraction is responsible for …

Characterizing Anisotropy In Fibrous Soft Materials By Mr Elastography Of Slow And Fast Shear Waves, John Larson Schmidt

McKelvey School of Engineering Graduate Student Theses & Dissertations

The general objective of this work was to develop experimental methods based on magnetic resonance elastography (MRE) to characterize fibrous soft materials. Mathematical models of tissue biomechanics capable of predicting injury, such as traumatic brain injury (TBI), are of great interest and potential. However, the accuracy of predictions from such models depends on accuracy of the underlying material parameters. This dissertation describes work toward three aims. First, experimental methods were designed to characterize fibrous materials based on a transversely isotropic material model. Second, these methods are applied to characterize the anisotropic properties of white matter brain tissue ex vivo. Third, …

Mechanobiology Of Epithelial Clusters In Ecms Of Diverse Mechanical Properties, Samila Nasrollahi

McKelvey School of Engineering Graduate Student Theses & Dissertations

Cell clusters reside in complex extracellular matrices (ECMs) of varying mechanical properties. Epithelial cells sense and translate the mechanical cues presented by the surrounding ECM into biochemical signals through a process called ‘mechanotransduction’, which controls fundamental aspects of disease and development. During the course of metastasis, mechanical changes in the tumor microenvironment can lead to declustering of epithelial cells through a process called epithelial-to-mesenchymal transition (EMT). Throughout different steps of metastasis, escaped epithelial clusters encounter heterogeneous tissues of varying mechanical properties that ultimately influence their behavior in distant locations within the body. This dissertation investigates the mechanobiology of epithelial clusters …

New Tools For Viscoelastic Spectral Analysis, With Application To The Mechanics Of Cells And Collagen Across Hierarchies, Behzad Babaei

McKelvey School of Engineering Graduate Student Theses & Dissertations

Viscoelastic relaxation spectra are essential for predicting and interpreting the mechanical responses of materials and structures. For biological tissues, these spectra must usually be estimated from viscoelastic relaxation tests. Interpreting viscoelastic relaxation tests is challenging because the inverse problem is expensive computationally. We present here (1) an efficient algorithm and (2) a quasi-linear model that enable rapid identification of the viscoelastic relaxation spectra of both linear and nonlinear materials. We then apply these methods to develop fundamental insight into the mechanics of collagenous and fibrotic tissues.

The first algorithm, which we term the discrete spectral approach, is fast enough to …

Mechanics Of Early Retina And Lens Development In The Embryo, Alina Oltean

McKelvey School of Engineering Graduate Student Theses & Dissertations

Mechanical forces play an essential role in morphogenesis, the shaping of embryonic structures. This research focuses mainly on eye development, a problem that has been studied for decades using a variety of approaches. However, the mechanics of the early stages of eye formation remain incompletely understood.

The embryonic eyes begin as bilateral protrusions called optic vesicles (OVs) that grow outward from the anterior end of the brain tube. The optic vesicles contact and adhere to the overlying surface ectoderm (SE) via extracellular matrix (ECM). Then, both layers thicken in the region of contact to form the retinal and lens placodes, …