Biomedical Engineering and Bioengineering Commons^™

Evolutionary Conservation And Times Of Action Of Heterochronic Genes, Maria Ivanova

Theses and Dissertations

The heterochronic pathway of C. elegans is the most well-characterized system to date for controlling the sequence and timing of developmental events. However, we still have critical unanswered questions to address. First, little is known about the evolution of the heterochronic pathway, and of developmental timing in general. To determine if the roles of major heterochronic genes are conserved, I made mutants in orthologs of these genes in C. briggsae, using CRISPR/Cas9. My studies revealed a significant drift in the roles of some of the genes, although all of them are still involved in the developmental timing regulation, and several …

Deciphering The Firing Patterns Of Hippocampal Neurons During Sharp-Wave Ripples, Kourosh Maboudi Ashmankamachali

Theses and Dissertations

The hippocampus is essential for learning and memory. Neurons in the rat hippocampus selectively fire when the animal is at specific locations - place fields - within an environment. Place fields corresponding to such place cells tile the entire environment, forming a stable spatial map supporting navigation and planning. Remarkably, the same place cells reactivate together outside of their place fields and in coincidence with sharp-wave ripples (SWRs) - dominant electrical field oscillations (150-250 Hz) in the hippocampus. These offline SWR events frequently occur during quiet wake periods in the middle of exploration and the follow-up slow-wave sleep and are …

Behavioral And Histological Inflammatory Analysis Of A Single, Mild Traumatic Brain Injury And Repeated Subconcussive Brain Injury Using A Rodent Model., Anna Marie Clay

Theses and Dissertations

Subconcussive (SC) impacts have become a growing concern within the neuroscience community regarding the immediate and long-lasting effects of sports-related injuries. While a single low-level impact, i.e., a subconcussion, may not cause cerebral perturbations, it has been increasingly recognized that repeated SC exposure can induce deleterious effects. Therefore, determining the lower limits of systematic perturbation resulting from multiple SC impacts is of critical importance in expanding our understanding of cerebral vulnerability and recovery. Currently, there is a lack of correlation between a mild traumatic brain injury (mTBI) and repeated SC impacts with respect to injury biomechanics. Moreover, the cumulative threshold …

Biomimetic Strategies To Control Therapeutic Release From Novel Dna Nanoparticles, Robert J. Mosley

Theses and Dissertations

The inherent chemical, mechanical, and structural properties of nucleic acids make them ideal candidates for the formulation of tunable, personalized drug nanocarriers. However, none so far have exploited these properties for the controlled release of therapeutic drugs. In this dissertation, a biomimetic approach to controlling drug release is exhibited by specifically manipulating the architecture of novel, DNA nanoparticles to take advantage of drug binding mechanisms of action. Rationally designed DNA strands were immobilized on gold surfaces via a terminal thiol modification. Immobilized monomers can be manipulated to form distinct monolayer architectures including flat, folded, coiled, or stretched structures. Increasing the …

Electromechanical Fatigue Properties Of Dielectric Elastomer Stretch Sensors Under Orthopaedic Loading Conditions, Andrea Karen Persons

Theses and Dissertations

Fatigue testing of stretch sensors often focuses on high amplitude, low-cycle fatigue (LCF) behavior; however, when used for orthopaedic, athletic, or ergonomic assessments, stretch sensors are subjected to low amplitude, high-cycle fatigue (HCF) conditions. As an added layer of complexity, the fatigue testing of stretch sensors is not only focused on the life of the material comprising the sensor, but also on the reliability of the signal produced during the extension and relaxation of the sensor. Research into the development of a smart sock that can be used to measure the range of motion (ROM) of the ankle joint during …

Full-Body Biomechanical Characterization Of Children With Hypermobile Ehlers-Danlos Syndrome During Gait And Activities Of Daily Living, Anahita Alahmoradiqashqai

Theses and Dissertations

Hypermobile Ehlers-Danlos syndrome (hEDS) is an inherited connective tissue disorder, often under-diagnosed, and presenting with frequent chronic pain and severe musculoskeletal symptoms that can drastically reduce the quality of life during one’s life span. While there are limited quantitative approaches in the literature on adult movements, the biomechanics of movements during activities of daily living (ADLs) in children have not been investigated comprehensively. Therefore, the primary purpose of this dissertation was to characterize the biomechanics of the musculoskeletal system and investigate the biomechanics of hEDS by quantifying joint dynamics and muscle activations during ADLs and gait in the pediatric population. …

Theta Burst Brain Stimulation In Painful Diabetic Neuropathy Patients: Investigating Neural Mechanisms, Bhushan Thakkar

Theses and Dissertations

Chronic pain (CP) is a significant contributor to disability and disease burden globally. In 2019, approximately 50.2 million adults (20.4% of the US population) experienced chronic pain, contributing to $560-635 billion in direct medical costs. In addition, the worldwide prevalence of diabetes mellitus has reached epidemic proportions and is set to increase to 629 million by 2045. Almost 50% of patients with diabetes present with diabetic neuropathy (DN), and one in five patients with diabetes presents with painful DN (pDN) which is the most common cause of neuropathic pain (NP) in the US. Symptomatic treatment is the mainstay of management …

Effects Of Seat And Axle Position On Pain, Pathology, And Independence In Pediatric Manual Wheelchair Users With Spinal Cord Injury, Hannah Frank

Theses and Dissertations

Manual wheelchair (MWC) users with spinal cord injury (SCI) rely heavily on their upperextremities to complete daily occupations. Due to repetitive shoulder use during wheelchair mobility and propulsion, MWC users are at greater risk of shoulder pain and shoulder pathology, and thus decreased independence, and lower quality of life. The relative fit of the wheelchair and its parameters are critical and can further impact the user’s propulsion biomechanics. Parameters such as seat angle and axle position may put the user in detrimental shoulder positions for longer periods of time, impacting health outcomes even more. Although the effects of wheelchair setup …

Evaluating Neuromuscular Function Of The Biceps Brachii After Spinal Cord Injury: Assessment Of Voluntary Activation And Motor Evoked Potential Input-Output Curves Using Transcranial Magnetic Stimulation, Thibault Roumengous

Theses and Dissertations

Activation of upper limb muscles is important for independent living after cervical spinal cord injury (SCI) that results in tetraplegia. An emerging, non-invasive approach to address post-SCI muscle weakness is modulation of the nervous system. A long-term goal is to develop neuromodulation techniques to reinnervate (i.e. resupply nerve to) muscle fiber and thereby increase muscle function in individuals with tetraplegia. Towards this goal, developing monitoring techniques to quantify neuromuscular function is needed to better direct neurorehabilitation. Assessment of voluntary activation (VA) is a promising approach because the location of the stimulus can be applied cortically using transcranial magnetic stimulation (TMS) …

Nebulizer-Based Systems To Improve Pharmaceutical Aerosol Delivery To The Lungs, Benjamin M. Spence

Theses and Dissertations

Combining vibrating mesh nebulizers with additional new technologies leads to substantial improvements in pharmaceutical aerosol delivery to the lungs across therapeutic administration methods. In this dissertation, streamlined components, aerosol administration synchronization, and/or Excipient Enhanced Growth (EEG) technologies were utilized to develop and test several novel devices and aerosol delivery systems. The first focus of this work was to improve the poor delivery efficiency, e.g., 3.6% of nominal dose (Dugernier et al. 2017), of aerosolized medication administration to adult human subjects concurrent with high flow nasal cannula (HFNC) therapy, a form of continuous-flow non-invasive ventilation (NIV). The developed Low-Volume Mixer-Heater (LVMH) …

A Mechanism Behind The Mechanotransduction Of Surface Characteristics In Osteoblasts, Otto J. Juhl Iv

Theses and Dissertations

Biomaterials for use in bone regeneration and healing range from metal and metal alloy implants to hydrogel-based solutions. These materials can be optimized to increase bone healing and integration by improving the mechanical and biological properties. Regardless of the material itself, the cell-substrate interaction is key to the success of the biomaterial once implanted. Substrate surface characteristics such as roughness, wettability, and particle density are well-known contributors to a substrate’s overall osteogenic potential, and therefore the substrate's overall success. Unfortunately, it is still unknown how these substrate surface characteristics are transduced into intracellular signals by cells, preventing specific tailoring of …

Nature-Inspired Material Strategies Towards Functional Devices, Sayantan Pradhan

Theses and Dissertations

Naturally sourced, renewable biomaterials possess outstanding advantages for a multitude of biomedical applications owing to their biodegradability, biocompatibility, and excellent mechanical properties. Of interest in this dissertation are silk (protein) and chitin (polysaccharide) biopolymers for the fabrication of functional biodevices. One of the major challenges restricting these materials beyond their traditional usage as passive substrate materials is the ability to combine them with high-resolution fabrication techniques. Initial research work is directed towards the fabrication of micropatterned, flexible 2D substrates of silk fibroin and chitin using bench-top photolithographic techniques. Research is focused on imparting electrochemical properties to silk proteins using conducting …

Deterministic Model Of The Voltage Dependent Anion Channel (Vdac) Kinetics, Viren Shah

Theses and Dissertations

The voltage-dependent anion channel (VDAC) is a voltage gated channel residing on the outer mitochondrial membrane (OMM) that facilitates the flow of metabolites between the cytosol and mitochondria. The channel is regulated through conformational changes driven by electrostatic effects along with numerous regulatory mechanisms. The aim of this study is to mechanistically model kinetics of substrate flow through VDAC and incorporate them into existing mechanistic computational models of mitochondrial function. The resulting model is used in two ways: 1) to establish mitochondrial bioenergetics (conductance, permeability, and current/flux) under physiological conditions, and 2) to conduct perturbations simulating the effect of altered …

Quantitative Optical Imaging Of Metabolic And Structural Biomarkers In Rodent Injury Models, Shima Mehrvar

Theses and Dissertations

The assessment of organ metabolic function using optical imaging techniques is an overgrowing field of disease diagnosis. The broad research objective of my PhD thesis is to detect quantitative biomarkers by developing and applying optical imaging and image processing tools to animal models of human diseases. To achieve this goal, I have designed and implemented an optical imaging instrument called in vivo fluorescence imager to study wound healing progress. I have also developed a 3-dimensional (3D) vascular segmentation technique that uses intrinsic fluorescence images of whole organs.

Intrinsic fluorophores (autofluorescence signals) provide information about the status of cellular bioenergetics in …

The Impact Of Aging And Mechanical Injury On Alveolar Epithelial And Macrophage Responses In Acute Lung Injury And Inflammation, Michael S. Valentine

Theses and Dissertations

Patients with severe lung pathologies, such as Acute Respiratory Distress Syndrome (ARDS), often require mechanical ventilation as a clinical intervention; however, this procedure frequently exacerbates the original pulmonary issue and produces an exaggerated inflammatory response that potentially leads to sepsis, multisystem organ failure, and mortality. This acute lung injury (ALI) condition has been termed Ventilator-Induced Lung Injury (VILI). Alveolar overdistension, cyclic atelectasis, and biotrauma are the primary injury mechanisms in VILI that lead to the loss of alveolar barrier integrity and pulmonary inflammation. Stress and strains during mechanical ventilation are believed to initiate alveolar epithelial mechanotransduction signaling mechanisms that contribute …

Higher Tensile Forces Across Cellular Junctions And An Intact Nuclear Linc Complex Is Required For Epithelial Function And Stability, Fnu Vani Narayanan

Theses and Dissertations

Recent advances in three-dimensional (3D) cell culture systems have provided key insights into the understanding of biochemical and physiological states of native tissue. A significant progress in the field of mechanobiology involves measuring cellular traction forces in a more native 3D environment. However, the effects of mechanical forces exerted across cellular junctions and the nuclear LINC complex, in an organized 3D system has not been investigated thus far. Epithelial cells spontaneously form acini (also known as cysts or spheroids) with a single, fluid-filled central lumen, when grown in 3D matrices. The size of the lumen is dependent on apical secretion …

Quantitative Evaluation Of Geared Manual Wheelchair Mobility In Individuals With Spinal Cord Injury: An Integrative Approach, Omid Jahanian

Theses and Dissertations

The purpose of this dissertation is to quantify the effects of using geared wheelchair wheels on upper extremity biomechanics and energy expenditure during functional mobility tasks in individuals with spinal cord injury (SCI). The effects of using geared wheels on hand-rim biomechanics, glenohumeral joint dynamics, and shoulder muscle activity were investigated during manual wheelchair propulsion over tiled and carpeted level-floors and up a ramp in low gear (1.5:1) and standard gear (1:1) conditions. The results for the hand-rim biomechanics indicated that regardless of the terrain, using the geared wheels in the low gear condition significantly decreased the propulsion speed, stroke …

Eralpha Isoforms Modulate The Tumorigenicity Of 24r,25(Oh)2d3 In Estrogen-Responsive Cancer, Anjali Verma

Theses and Dissertations

Over 200,000 cases of breast cancer are diagnosed every year. Nearly 20% of these patients supplement their diets with some form of vitamin D. This high frequency of vitamin D supplement use may be due in part to research suggesting that cancer patients with higher serum vitamin D₃ levels have better prognoses than patients with low serum vitamin D_3. However, double-blind clinical trials on the efficacy of vitamin D₃ supplementation in breast cancer have been inconclusive. A recent meta-analysis showed evidence of reduced cancer recurrence in patients taking vitamin D₃ supplements who had ‘estrogen receptor positive’ …

The Role Of The Mechanical Environment On Cd117+ Endothelial Cell Angiogenesis, Patrick Link

Theses and Dissertations

Angiogenesis is a complex process coordinating cell migration, proliferation, and lumen formation. Changes to the microenvironment regulate angiogenesis through mechanotransduction and cytokine signals. In pulmonary hypertension, something in the process becomes abnormal, resulting in changes to the microenvironment and the formation of a glomerulus of dysfunctional capillaries, called a plexiform lesion. Endothelial cells, expressing CD117 (CD117+ EC clones) increase in the plexiform lesions of pulmonary hypertension, independent of pro-angiogenic VEGF signaling. We hypothesize that the mechanical environment and the macromolecular composition of the extracellular matrix, both, contribute to the aberrant angiogenesis. When we changed the mechanical environment, we changed the …

The Role Of Kras In Mechanosensing In Non-Small Cell Lung Cancer, Krista M. Powell

Theses and Dissertations

Lung cancer is the number one cause of cancer related death worldwide, with more than 1.6 million fatalities each year. Non-small cell lung cancer (NSCLC) accounts for 80-85% of all lung cancers, with KRAS being one of the most prevalent oncogenic driver mutations. Therapeutic approaches for KRAS-mutated NSCLC have been extensively explored due to the US National Cancer Institute RAS Initiative, but methods of directly targeting KRAS or downstream effectors, such as MEK, still have poor results. Previous reports have shown that KRAS-mutated NSCLC activate distinct receptor tyrosine kinases (RTKs) depending on the epithelial or mesenchymal state. Epithelial-to-mesenchymal transition (EMT) …

A Discrete-Event Simulation Approach For Modeling Human Body Glucose Metabolism, Buket Aydas

Theses and Dissertations

This dissertation describes CarbMetSim (Carbohydrate Metabolism Simulator), a discrete-event simulator that tracks the blood glucose level of a person in response to a timed sequence of diet and exercise activities. CarbMetSim implements broader aspects of carbohydrate metabolism in human beings with the objective of capturing the average impact of various diet/exercise activities on the blood glucose level. Key organs (stomach, intestine, portal vein, liver, kidney, muscles, adipose tissue, brain and heart) are implemented to the extent necessary to capture their impact on the production and consumption of glucose. Key metabolic pathways (glucose oxidation, glycolysis and gluconeogenesis) are accounted for by …

Engineering Surface Properties To Modulate Inflammation And Stem Cell Recruitment Through Macrophage Activation, Kelly M. Hotchkiss

Theses and Dissertations

Biomaterials are becoming the most commonly used therapeutic method for treatment of lost or damaged tissue in the body. Metallic materials are chosen for high strength orthopaedic and dental applications. Titanium (Ti) implants are highly successful in young, healthy patients with the ability to fully integrate to surrounding tissue. However the main population requiring these corrective treatments will not be healthy or young, therefore further research into material modifications have been started to improve outcomes in compromised patients. The body’s immune system will generate a response to any implanted material, and control the final outcome. Among the first and most …

Exogenous Fniii 12-14 Regulates Tgf-Β1-Induced Markers, Hilmi M. Humeid

Theses and Dissertations

The extracellular matrix protein Fibronectin (FN) plays an important role in cell contractility, differentiation, growth, adhesion, and migration. The 12th -14th Type III repeats of FN (FNIII 12-14), also referred to as the Heparin-II domain, comprise a highly promiscuous growth factor (GF) binding region. This binding domain aids in cellular signaling initiated from the ECM. Additionally, FN has the ability to assemble into fibrils under certain conditions, mostly observed during cell contractile processes such as those that initiate due to upregulation of Transforming Growth Factor Beta 1 (TGF-β1) [1], [2]. Previous work from our lab has shown that self-assembly of …

An Array Of Circular Dielectrophoresis Traps To Separate And Charaterize Individual Microparticles From Population, Hwangjae Lee

Theses and Dissertations

Dielectrophoretic traps have been broadly studied in light of their many advantages of high controllability, ease of operation, and high efficiency. In the previous studies, however, it was challenging to count captured particles or required work to capture particles. In the thesis, an array of circular dielectrophoresis (DEP) traps was developed and tested to manipulate population of microparticles in single particle level. The circular DEP traps enable more precise control of the force field than conventionally used interdigitated electrodes due to its omnidirectional and symmetric properties. The location of the captured microparticle inside the trap was confirmed by both of …

Fabrication Of Flexible, Biofunctional Architectures From Silk Proteins, Ramendra K. Pal

Theses and Dissertations

Advances in the biomedical field require functional materials and processes that can lead to devices that are biocompatible, and biodegradable while maintaining high performance and mechanical conformability. In this context, a current shift in focus is towards natural polymers as not only the structural but also functional components of such devices. This poses material-specific functionalization and fabrication related questions in the design and fabrication of such systems. Silk protein biopolymers from the silkworm show tremendous promise in this regard due to intrinsic properties: mechanical performance, optical transparency, biocompatibility, biodegradability, processability, and the ability to entrap and stabilize biomolecules. The unique …

Modulating The Innate Immune Response To Electrospun Scaffolds And Polymer Degradative Byproducts, Daniel Abebayehu

Theses and Dissertations

Implanted biomaterials often induce inflammation that frequently leads to the foreign body response, fibrosis, and the failure of the implant. Thus, it is important to evaluate how cells interact with materials to promote a more regenerative response. It is critical to determine how to modulate the response of tissue resident innate immune cells, as they are among the first cells to interact with implanted materials. Among tissue resident innate immune cells are mast cells, which are inflammatory sentinels that degranulate and orchestrate the fate of other cell populations, such as monocytes/macrophages and lymphocytes. Mast cells have also been reported to …

The Role Of E-Cadherin Force In The Maintenance Of Homeostasis In Epithelial Acini, Fnu Vani Narayanan

Theses and Dissertations

Numerous three-dimensional model systems have emerged for emulating the biochemical and physiological states of native tissue. Yet little is known about the effects of mechanical forces on cell behavior in the context of an organized tissue structure in three-dimensional cell-culture. Epithelial cells cultured in a three-dimensional environment comprised of extracellular matrix proteins form spheroids of polarized cells. Cellular responses to mechanical cues, generated from dynamic interactions with the extracellular matrix and neighboring cells, are known to influence cellular behavior to a great extent. Previous studies have shown that tumorigenic progression has been frequently linked to the down regulation of E-cadherin, …

Scattering Correction Methods Of Infrared Spectra Using Graphics Processing Units, Asher Imtiaz

Theses and Dissertations

Fourier transform infrared (FTIR) microspectroscopy has been used for many years as a technique that provides distinctive structure-specific infrared spectra for a wide range of materials (e.g., biological (tissues, cells, bacteria, viruses), polymers, energy related, composites, minerals). The mid-infrared radiation can strongly scatter from distinct particles, with diameters ranging between 2-20 micrometer. Transmission measurements of samples (approximately 100 micrometers x 100 micrometers x 10 micrometers) with distinct particles. will be dominated by this scattering (Mie scattering). The scattering distorts the measured spectra, and the absorption spectra appear different from pure absorbance spectra. This thesis presents development and implementation of two …

Multi-Platform Arabinoxylan Scaffolds As Potential Wound Dressing Materials, Donald C. Aduba Jr

Theses and Dissertations

Biopolymers are becoming more attractive as advanced wound dressings because of their naturally derived origin, abundance, low cost and high compatibility with the wound environment. Arabinoxylan (AX) is a class of polysaccharide polymers derived from cereal grains that are primarily used in food products and cosmetic additives. Its application as a wound dressing material has yet to be realized. In this two-pronged project, arabinoxylan ferulate (AXF) was fabricated into electrospun fibers and gel foams to be evaluated as platforms for wound dressing materials. In the first study, AXF was electrospun with varying amounts of gelatin. In the second study, AXF …

Ex Vivo Dna Cloning, Adam B. Fisher

Theses and Dissertations

Genetic engineering of microbes has developed rapidly along with our ability to synthesize DNA de novo. Yet, even with decreasing DNA synthesis costs there remains a need for inexpensive, rapid and reliable methods for assembling synthetic DNA into larger constructs or combinatorial libraries. While technological advances have resulted in powerful techniques for in vitro and in vivo assembly of DNA, each suffers inherent disadvantages. Here, an ex vivo DNA cloning suite using crude cellular lysates derived from E. coli is demonstrated to amplify and assemble DNA containing small sequence homologies. Further, the advantages of an ex vivo approach are …