Biomedical Engineering and Bioengineering Commons^™

Re-Engineering Cardio-Oncology Testing Using Biomimetic Heart Slice Cultures., Jessica Miller

Electronic Theses and Dissertations

28% of drug withdrawal from the market are due to unforeseen disruptions in cardiomyocyte contractility and electrophysiology. The most commonly used platforms for drug testing are in vivo animal models and in vitro cell culture models. While both have been of paramount importance for the discovery and detection of many cardiotoxicities and mechanisms of action, they lack the ability to model an intact human myocardium. This work aims to establish cardiac tissue slices, which are 300-micron thin tissue sections taken from the left ventricular myocardium, as an alternative platform for cardio-oncology studies, specifically cardiotoxicity testing. Additionally, this work aims to …

Fiber-Based Time-Correlated Single Photon Counting As A Method For Investigating Metabolism During Tetanic Contraction Of Skeletal Muscle, Kathryn Miller Priest

Graduate Theses and Dissertations

Nicotinamide adenine dinucleotide (NAD) is a cofactor that serves to shuttle electrons during metabolic processes such as glycolysis, the tricarboxylic acid cycle, and oxidative phosphorylation (OXPHOS) [1-5]. The reduced form of NAD, NADH, is autofluorescent, making it a measurable characteristic in the investigation of metabolic changes. The fluorescence lifetime of NADH is dependent on the state of protein binding, specifically free or bound NADH, allowing for detection of metabolic shifts between glycolysis (free NADH) and OXPHOS (bound NADH) [6-16]. Fiber-coupled time-correlated single photon counting (TCSPC) equipped with an implantable needle probe can be used to measure NADH lifetime in vivo …

Development And Validation Of A Three-Dimensional Optical Imaging System For Chest Wall Deformity Measurement, Nahom Kidane

Electrical & Computer Engineering Theses & Dissertations

Congenital chest wall deformities (CWD) are malformations of the thoracic cage that become more pronounced during early adolescence. Pectus excavatum (PE) is the most common CWD, characterized by an inward depression of the sternum and adjacent costal cartilage. A cross-sectional computed tomography (CT) image is mainly used to calculate the chest thoracic indices. Physicians use the indices to quantify PE deformity, prescribe surgical or non-surgical therapies, and evaluate treatment outcomes. However, the use of CT is increasingly causing physicians to be concerned about the radiation doses administered to young patients. Furthermore, radiographic indices are an unsafe and expensive method of …

Piglet Cardiopulmonary Bypass Induces Intestinal Dysbiosis And Barrier Dysfunction Associated With Systemic Inflammation, Jeffrey D. Salomon, Haowen Qiu, Dan Feng, Jacob Owens, Ludmila Khailova, Suzanne Osorio Lujan, John Iguidbashian, Yashpal S. Chhonker, Daryl J. Murry, Jean-Jack Riethoven, Merry L. Lindsey, Amar B. Singh, Jesse A. Davidson

Nebraska Center for Biotechnology: Faculty and Staff Publications

The intestinal microbiome is essential to human health and homeostasis, and is implicated in the pathophysiology of disease, including congenital heart disease and cardiac surgery. Improving the microbiome and reducing inflammatory metabolites may reduce systemic inflammation following cardiac surgery with cardiopulmonary bypass (CPB) to expedite recovery postoperatively. Limited research exists in this area and identifying animal models that can replicate changes in the human intestinal microbiome after CPB is necessary. We used a piglet model of CPB with two groups, CPB (n=5) and a control group with mechanical ventilation (n=7), to evaluate changes to the microbiome, …

Modification Of The Tumor Microenvironment Enhances Anti-Pd-1 Immunotherapy In Metastatic Melanoma, Guilan Shi, Megan Scott, Cathryn G. Mangiamele, Richard Heller

Bioelectrics Publications

Resistance to checkpoint-blockade treatments is a challenge in the clinic. Both primary and acquired resistance have become major obstacles, greatly limiting the long-lasting effects and wide application of blockade therapy. Many patients with metastatic melanoma eventually require further therapy. The absence of T-cell infiltration to the tumor site is a well-accepted contributor limiting immune checkpoint inhibitor efficacy. In this study, we combined intratumoral injection of plasmid IL-12 with electrotransfer and anti-PD-1 in metastatic B16F10 melanoma tumor model to increase tumor-infiltrating lymphocytes and improve therapeutic efficacy. We showed that effective anti-tumor responses required a subset of tumor-infiltrating CD8⁺ and CD4 …

Advances In 3d Culture Systems For Therapeutic Discovery And Development In Brain Cancer, Janith Wanigasekara, Patrick J. Cullen, Paula Bourke, Brijesh Tiwari, James F. Curtin

Articles

This review focuses on recent advances in 3D culture systems that promise more accurate therapeutic models of the glioblastoma multiforme (GBM) tumor microenvironment (TME), such as the unique anatomical, cellular, and molecular features evident in human GBM. The key components of a GBM TME are outlined, including microbiomes, vasculature, extracellular matrix (ECM), infiltrating parenchymal and peripheral immune cells and molecules, and chemical gradients. 3D culture systems are evaluated against 2D culture systems and in vivo animal models. The main 3D culture techniques available are compared, with an emphasis on identifying key gaps in knowledge for the development of suitable platforms …

Functionality Of The Gracilis Collateral Is Impaired Following Arteriogenesis And Cell Transplantation, Ada A. Tadeo

Biomedical Engineering

Peripheral Arterial Disease involves narrowed arteries, reducing blood flow to limbs. Increasing blood flow to those extremities is possible by redirecting the blood to flow through natural bypasses (i.e. collateral arteries), which can enlarge via arteriogenesis to maintain blood supply once the prominent arteries have become occluded. This study aims to investigate how arteriogenesis affects collateral function, if myoblast transplantation can stimulate collateral growth, and how that in turn may affect collateral function. Femoral artery ligation was performed to mimic the blockage that occurs in patients with ischemic diseases on lean mice and mice with diet induced obesity (DIO). A …

Synthesis Of Alginate/Hydroxyapatite Beads For Acetaminophen Delivery, Anesylvia Angan, Nonni Soraya Sambudi

Makara Journal of Science

Conventional drug delivery systems usually involve the intake of multiple drugs, which could amplify the risk of overdosing. Acetaminophen is a widely used pain relief substance that is prone to accidental overdosing. Hence, a controlled drug delivery system is needed to ensure its efficacy. A nanocomposite hydroxyapatite/alginate system that was used as a drug carrier for acetaminophen was synthesized through the sol-gel method, and the mechanism underlying its controlled drug delivery was investigated. Spherical nanocomposite bead samples were synthesized by incorporating 5 wt%, 10 wt%, and 15 wt% hydroxyapatite into mixtures containing alginate. The mixtures were then dropped into calcium …

Sensorimotor Content Of Multi-Unit Activity In The Paramedian Lobule Of The Cerebellum, Esma Cetinkaya

Dissertations

Based on Center for Disease Control and Prevention report 2016, around 39.5 million people in the United States suffer from motor disabilities. These disabilities are due to traumatic conditions like traumatic brain injury (TBI), neurological diseases such as amyotrophic lateral sclerosis (ALS), or congenital conditions. One of the approaches for restoring the lost motor function is to extract the volitional information from the central nervous system (CNS) and control a mechanical device that can replace the function of a paralyzed limb through systems called Brain-Computer Interfaces (BCI).

One of the major challenges being faced in BCIs and also in general …

Development And Evaluation Of A Hand Exoskeleton For Neurorehabilitation Post Stroke, Ashley Joyce Mont

Dissertations

Stroke affects approximately 800,000 people in the United States each year, and due to its chronic effects, it is one of the leading causes of disability. Many individuals with stroke suffer the loss of motor function in their paretic upper extremity, and longitudinal studies show that 30 — 66% of individuals with hemiplegia fail to regain arm function six months post stroke. After a stroke, the brain undergoes neuroplasticity which will promote recovery of function. Investigators and clinicians are trying to develop rehabilitation interventions that can be designed to promote neuroplasticity, enhancing the recovery outcomes of therapy.

For individuals with …

Decoding Human Movement Through Experiments And Simulation, Vishnu Deep Chandran

Dissertations

The ability to walk or move independently plays a decisive role in one's quality of life. This human ability requires complex coordination with several systems, such as the nervous, muscular, skeletal, and sensory organs, to execute movement tasks. Hence, any disorder of these systems from injury, disease, or aging severely affects the ability to walk or move independently. Disabilities that impair movement severely affect the quality of life. Therefore, studying the changes affecting human movement is necessary to improve the lives of individuals with impaired movement. Since human movement is complex and many systems interact in non-intuitive ways, the overarching …

Design Of Novel Metalloenzymes And Investigation Of Protein-Metal Interactions, Alona Kulesha

Dissertations - ALL

Metalloproteins are the proteins that utilize metals or metal complexes as cofactors and exhibit a wide range of functions from oxygen transport and regulation of transcription to hydroxylation of alkanes and water splitting, even though they employ a limited set of metals and metal-binding ligands. The investigation of metalloprotein amino acid sequence, structure and function relationships can uncover the principles behind natural metalloprotein design and opens the possibility of their implication as scaffolds for the design of novel catalysts and biomaterials. Protein engineering is a set of techniques that allows to install new functionalities into existing proteins or to design …

Analysis And Visualization Of Molecular Docking 2hi4 Protein, Innas Widiasti

Indonesian Journal of Medical Chemistry and Bioinformatics

The crystal structure of the human microsomal complex P450 1A2 with alpha-naphthoflavone, a cytochrome P450 (CYP) enzyme is particularly important, as it is abundant in the human liver and alters a more diverse xenobiotic array than any other group of metabolic enzymes. CYP1A2 is abundantly found in the liver and involved in the metabolism of about 10% of clinically used drugs metabolized by CYP enzymes. The current drug discovery and development mostly uses high-throughput screening (HTS). However, this regular method is time-consuming and costly. To address the issue, an advanced drug discovery and development method namely chemical compound database screening …

Cellular Bioenergetics: Experimental Evidence For Alcohol-Induced Adaptations, Liz Simon, Patricia E. Molina

School of Medicine Faculty Publications

At-risk alcohol use is associated with multisystemic effects and end-organ injury, and significantly contributes to global health burden. Several alcohol-mediated mechanisms have been identified, with bioenergetic maladaptation gaining credence as an underlying pathophysiological mechanism contributing to cellular injury. This evidence-based review focuses on the current knowledge of alcohol-induced bioenergetic adaptations in metabolically active tissues: liver, cardiac and skeletal muscle, pancreas, and brain. Alcohol metabolism itself significantly interferes with bioenergetic pathways in tissues, particularly the liver. Alcohol decreases states of respiration in the electron transport chain, and activity and expression of respiratory complexes, with a net effect to decrease ATP content. …

Role Of Ligand Architecture On Collective Cell Invasion, Amrit Bagchi

McKelvey School of Engineering Graduate Student Theses & Dissertations

Epithelial cell collectives utilize extra-cellular matrix (ECM) fibers to undergo collective migration critical in regeneration, repair and cancer metastasis. However, very little is known about the various factors which determine the ability of cellular collectives to utilize ECM fibers to undergo these critical processes in-vivo. First part of the dissertation focusses on understanding how cell collectives exploit specific properties, like stiffness and fiber length to undergo collective streaming. It is also unclear how cellular forces, cell-cell adhesion, and velocities are coordinated within streams. To independently tune stiffness and collagen fiber length, we developed new hydrogels and discovered invasion-like streaming of …

Understanding Control Of Metabolite Dynamics And Heterogeneity, Christopher John Hartline

McKelvey School of Engineering Graduate Student Theses & Dissertations

Microbes live in complex and continually changing environments. Rapid shifts in nutrient availability are a common challenge for microbes, and cause changes in intracellular metabolite levels. Microbial response to dynamic environments requires coordination of multiple levels of cellular machinery including gene expression and metabolite concentrations. This coordination is achieved through metabolic control systems, which sense metabolite concentrations and direct cellular activity in response. Several reoccurring control architectures are found throughout diverse metabolic systems, which suggests underlying evolutionary advantages for using these control systems to coordinate metabolism. One common, yet understudied, control architecture is the positive feedback metabolite uptake loop, which …

Machine Learning And Scalable Informatics Methods To Predict Disease Status From Multimodal Biomedical Data, Hossein Mohammadian Foroushani

McKelvey School of Engineering Graduate Student Theses & Dissertations

Biological understanding of complex diseases such as stroke and obesity is critical for the advancement of medicine. Further knowledge discovery can provide effective biomarkers to improve disease diagnosis and prognosis, identify driver mutations, predict individual genetic susceptibility for early prevention and effective disease management, and facilitate development of personalized drugs. Stroke is the second leading cause of death and long-term disability in the world. Thus, stroke management is a time-sensitive emergency. The initial hours after stroke onset map the trajectory of subsequent neurologic complications. Cerebral edema develops hours to days after acute ischemic stroke and may result in midline shift …

Ligand- And Strain-Specific Control Of Microbial Communities, Austin Grant Rottinghaus

McKelvey School of Engineering Graduate Student Theses & Dissertations

Microbes naturally coexist in complex, multi-strain communities that are valuable assets for their host. Commensal and probiotic microbes prevent pathogen colonization, reduce the frequency and severity of various ailments, provide essential nutrients, and offer various additional benefits. Understanding the dynamics of and tailoring microbial communities to provide additional beneficial functions is a primary focus of researchers in medicine and agriculture. To date, consortia have primarily been manipulated by supplementing the communities with microbes that were engineered in vitro or by introducing stimuli that alter the metabolism or composition of the community. This method has proven successful, with numerous microbes engineered …

Noninvasive Neuromodulation Via Ultrasonic Activation Of Endogenous And Exogenous Ion Channels, Yaoheng Yang

McKelvey School of Engineering Graduate Student Theses & Dissertations

Neuromodulation technology is key to understanding brain function and treating brain diseases. Conventional neuromodulation technologies, such as direct current stimulation, transcranial magnetic stimulation, and optogenetics, predominately rely on electromagnetic waves. However, the fundamental physical law  the tradeoff-relationship between penetration and spatial resolution, limits their transcranial penetration within the superficial cortex layer. To overcome this challenge, electrodes or optical fibers need to be surgically implanted into the brain to modulate specific brain regions. Different from electromagnetic waves, ultrasound, as a mechanical wave, can non-invasively penetrate through the intact skull to reach deep brain regions with millimeter spatial focus. Ultrasound has …

Development Of The Assessment Of Clinical Prediction Model Transportability (Apt) Checklist, Sean Chonghwan Yu

McKelvey School of Engineering Graduate Student Theses & Dissertations

Clinical Prediction Models (CPM) have long been used for Clinical Decision Support (CDS) initially based on simple clinical scoring systems, and increasingly based on complex machine learning models relying on large-scale Electronic Health Record (EHR) data. External implementation – or the application of CPMs on sites where it was not originally developed – is valuable as it reduces the need for redundant de novo CPM development, enables CPM usage by low resource organizations, facilitates external validation studies, and encourages collaborative development of CPMs. Further, adoption of externally developed CPMs has been facilitated by ongoing interoperability efforts in standards, policy, and …

Development Of Noninvasive Biomarkers For Cervical Spondylotic Myelopathy, Dinal Jayasekera

McKelvey School of Engineering Graduate Student Theses & Dissertations

Cervical spondylotic myelopathy (CSM) represents the most common cause of chronic spinal cord injury (SCI) in adults. Many patients with symptomatic CSM will experience a decline in neurological function and consequently undergo surgical decompression. Unfortunately, surgeons are unable to adequately counsel patients about the benefits of surgery because the natural history of disease and outcome after decompression vary widely among patients. This can hinder the decision-making capacity of patients and physicians. Therefore, we require additional tools to help guide therapy and counsel patients with CSM. Noninvasive biomarkers present valuable potential as predictors of a patient’s recovery in the long term. …

Intrinsic Cardiac Effects Of Severe Acute Respiratory Syndrome Coronavirus 2 In Coronavirus Disease 2019, Brittany Danielle Brumback

McKelvey School of Engineering Graduate Student Theses & Dissertations

Cardiac arrhythmias, particularly ventricular arrhythmias, can be life-threatening and caused by both congenital genetic mutations and acquired cardiac injury. My thesis work was originally focused on delineating the effects of genetic mutation-driven dysregulation of a protein called Hey2 in Brugada Syndrome, a complex disease characterized by a predisposition to dangerous arrhythmias originating in the right ventricular outflow tract. In response to the pandemic, my thesis work shifted toward understanding the mechanisms of cardiovascular injury in Coronavirus disease 2019 (COVID-19), which is associated with serious cardiovascular complications, including ventricular arrhythmias and sudden cardiac death as well as endothelial dysfunction and coagulopathies. …

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 …

Biodegradable Microneedle Patch For Delivery Of Meloxicam For Managing Pain In Cattle, David A. Castilla-Casadiego, Katherine A. Miranda-Munoz, Jesse L. Roberts, Anne D. Crowell, David Gonzalez-Nino, Dipankar Choudhury, Frank O. Aparicio-Solis, Shannon L. Servoss, Adrianne M. Rosales, Gary Prinz, Min Zou, Yuntao Zhang, Johann F. Coetzee, Lauren F. Greenlee, Jeremy Powell, Jorge Almodovar

Chemical Engineering Faculty Publications and Presentations

Microneedle patches are a promising source for transdermal diffusion of macromolecules and are designed to painlessly penetrate the skin. In this study, a biodegradable chitosan microneedle patch to deliver meloxicam for managing pain in cattle was tested. The potential of reuse of the polymeric solution to fabricate the patches, optimization of fabrication, morphological analysis of the microneedle patch and analysis of preservation of the chemical composition after sterilization were evaluated. In-vitro analysis consisted of studying in-vitro penetration mechanical properties, compression testing analysis of microneedle patch, and in-vitro drug release analysis. In-vivo studies were performed to analyze the dissolution capability of …

Effect Of Dorsal Quadrant Or Ventral Quadrant Spinal Cord Injury On Gait Features During Locomotion., Anya Nicole Trell

Electronic Theses and Dissertations

In the Unites States, approximately 1.5 million people currently have a spinal cord injury and suffer permanent sensory and motor loss due to the disruption of the spinal cord. Due to the significant morbidity, it is vital to understand the functional impact of disrupting neural descending pathways that modulate spinal neurons involved in intermuscular coordination critical for gait behaviors. Tasks that are more difficult require additional input from these neural pathways; therefore, fourteen feline subjects were familiarized with level overground locomotion and stair descent gait tasks. After collection of baseline kinematic data, the subjects received either a dorsal or ventral …

Engineering Of Ideal Systems For The Study And Direction Of Stem Cell Asymmetrical Division And Fate Determination, Martina Zamponi

Biomedical Engineering Theses & Dissertations

The cellular microenvironment varies significantly across tissues, and it is constituted by both resident cells and the macromolecules they are exposed to. Cues that the cells receive from the microenvironment, as well as the signaling transmitted to it, affect their physiology and behavior. This notion is valid in the context of stem cells, which are susceptible to biochemical and biomechanical signaling exchanged with the microenvironment, and which plays a fundamental role in establishing fate determination and cell differentiation events. The definition of the molecular mechanisms that drive stem cell asymmetrical division, and how these are modulated by microenvironmental signaling, is …

Utilization Of Finite Element Analysis Techniques For Adolescent Idiopathic Scoliosis Surgical Planning, Michael A. Polanco

Mechanical & Aerospace Engineering Theses & Dissertations

Adolescent Idiopathic Scoliosis, a three-dimensional deformity of the thoracolumbar spine, affects approximately 1-3% of patients ages 10-18. Surgical correction and treatment of the spinal column is a costly and high-risk task that is consistently complicated by factors such as patient-specific spinal deformities, curve flexibility, and surgeon experience. The following dissertation utilizes finite element analysis to develop a cost-effective, building-block approach by which surgical procedures and kinematic evaluations may be investigated. All studies conducted are based off a volumetric, thoracolumbar finite element (FE) model developed from computer-aided design (CAD) anatomy whose components are kinematically validated with in-vitro data. Spinal ligament stiffness …

Modeling The Impact And Accelerating The Process Of Transitioning To A Sustainable Healthy Diet Through Decision Support Systems, Prince Agyemang

Graduate Theses and Dissertations

Food production and consumption are essential in human existence, yet they are implicated in the high occurrences of preventable chronic diseases and environmental degradation. Although healthy food may not necessarily be sustainable and vice versa, there is an opportunity to make our food both healthy and sustainable. Attempts have been made to conceptualize how sustainable healthy food may be produced and consumed; however, available data suggest a rise in the prevalence of health-related and negative environmental consequences of our food supply. Thus, the transition from conceptual frameworks to implementing these concepts has not always been effective. This paper explores the …

Using Scratch Wound Assay To Study The Effect Of Soil Arsenic On Human Keratinocyte Cell Migration Due To Contact Exposure, Manas Warke, Laura De March, Srinivas Kannan, Madeline English, Rohan Sarkar, Rupali Datta, Smitha Rao

Michigan Tech Research Data

The scratch wound assay was performed on Human immortalized keratinocytes (HaCaT) cells to observe the effect on cell migration due to contact exposure to arsenic-contaminated Immokalee soil. The cell migration was observed through a microscope for 72 h. HaCaT cells were seeded in 48-well plate. On day 3, treatment media was added (n=8). The cells were treated with four concentrations of soil As (45, 225, 450, and 900 mg/kg) and two controls - Negative control (NC; Pure media) and control (C; 0 mg/kg soil As) for 72 h. A scratch was made using a pipette tip. The wound healing was …

Using Scratch Wound Assay To Study The Effect Of Soil Arsenic On Human Dermal Fibroblasts Cell Migration Due To Contact Exposure, Manas Warke, Laura De Marchi, Srinivas Kannan, Madeline English, Rohan Sarkar, Rupali Datta, Smitha Rao

Michigan Tech Research Data

The scratch wound assay was performed on Normal Human Primary Dermal Fibroblasts (HDFa) cells to observe the effect on cell migration due to contact exposure to arsenic-contaminated Immokalee soil. The cell migration was observed through a microscope for 72 h. HDFa cells were seeded in 48-well plate. On day 3, treatment media was added (n=8). The cells were treated with four concentrations of soil As (45, 225, 450, and 900 mg/kg) and two controls - Negative control (NC; Pure media) and control (C; 0 mg/kg soil As) for 72 h. A scratch was made using a pipette tip. The wound …