Biomedical Engineering and Bioengineering Commons^™

A Comprehensive Reengineering Of The Hospital Emergency Triage System, Nicholas D. Boltin

Theses and Dissertations

Hospital emergency triage and specifically Mass Casualty Incidents (MCIs) are of major concern with regard to treatment and patient outcomes. Traditional emergency department triage models are oversimplified and often lead to over/under triaging of patients. Furthermore, triage models do not account for the full spectrum of different types of MCIs which often results in misclassification. In this thesis, we begin by looking at traditional triage models currently being used in hospital systems and identify several shortcomings of using these models within the context of a chemical related MCI. I will then move to describe a new approach to creating a …

Changes Of Dispersal Ability In An Isolated Population, Connor Bacon

Theses and Dissertations

Dispersal is a core mechanism in the maintenance of metapopulations. It maintains genetic diversity by connecting subpopulations and generates new populations to replace those that die out. However, as populations become more isolated, as occurs in habitat fragmentation, dispersal becomes more difficult. This should lead to selective pressure against dispersive individuals, causing a reduction in dispersal traits. Over time, this can lead to variation in dispersal traits among populations. We examine this idea using an extreme case of isolation in Euphydryas gillettii, a population that has remained completely isolated for forty years. By comparing this population to a baseline established …

Modulation Of Amyloid-Β Aggregation Via Small Molecules And Glycine Zipper Alterations, Steven Zebulon Vance

Theses and Dissertations

Alzheimer’s disease (AD) is the most common form of neurodegenerative disease. Nationally, AD is the 6th leading cause of death and the only top 10 killer of Americans that cannot be slowed, cured, or prevented. AD is characterized by the deposition of extracellular plaques of aggregated amyloid-β protein (Aβ). Aβ originates from the amyloid precursor protein (APP), a transmembrane protein that is cleaved to form a short and inert protein fragment called Aβ. However, Aβ undergoes a nucleation process wherein aggregates from soluble oligomers to insoluble fibrils are formed. While uncertainty remains as to the exact mechanism, studies have associated …

Screening Of Novel Active Salicylic Acid Analogs And Identification Of A Bacterial Effector Targeting Key Proteins Involved In Salicylic Acid-Mediated Defense, Ian Palmer

Theses and Dissertations

The master regulator of salicylic acid (SA)-mediated plant defense, NPR1 (NONEXPRESSER OF PR GENES 1), and its paralogs NPR3 and NPR4 act as SA receptors. After the perception of a pathogen, plant cells produce SA in the chloroplast. In the presence of SA, NPR1 protein is reduced from oligomers to monomers, and translocated into the nucleus. There, NPR1 binds to TGA and WRKY transcription factors to induce expression of plant defense genes. EDS1 and PBS3 are two key proteins involved in SA biosynthesis. Previous research has shown that several plant pathogens produce SA hydroxylases. These pathogen-produced hydroxylases act to degrade …

Matrix Stiffness Modulates Mesenchymal Stem Cell Sensitivity To Geometric Asymmetry Signals, Maria Eugenia Piroli

Theses and Dissertations

Human stem cells hold significant potential for the treatment of various diseases. However, their use as a therapy is hampered by the limited understanding of the mechanisms by which stem cells respond to environmental stimuli. Efforts to understand extracellular biophysical cues have demonstrated the critical roles of geometric and mechanical signals in determining the fate of stem cells. The goal of this study was to explore the interplay between cell polarity and matrix stiffness in stem cell lineage specification. We hypothesize that confining cells to asymmetric extracellular matrix (ECM) islands will impart polarity at a single-cell level and result in …

Plants As Biofactories To Produce Mammalian Tumor Suppressor Micrornas, John Lachlan Macarthur

Theses and Dissertations

MicroRNAs (miRNAs) are small noncoding single stranded RNAs that are considered master regulators of gene expression. They are also an emerging class of therapeutic agents with significant potential for the prevention and treatment of many diseases, including cancer. Many different forms of cancer are associated with loss or reduced accumulation of one or more miRNAs that function as tumor suppressors. In animal models, restoration of missing tumor suppressor miRNAs prevents the initiation, progression and/or spread of the disease. However, the current absence of an efficient method for delivery of therapeutic miRNAs is a critical barrier to their use. The research …

Evaluation And Modeling Of The Different Material Properties Of The Captive And Wild Diets Of Carnivores, Jill Den Outer, Bethany Janos, Elizabeth Mccourt, William Molair

Senior Theses

Specific to captive BFFs, the most significant changes in cranial morphology are related to an increase in zygomatic arch width. The zygomatic arch region is the area along which the masseter muscle (a critical muscle of mastication for carnivores) is stretched3 . Mechanical stability of muscular tissues has been shown to be closely related to the structural integrity of the surrounding bones. In mice, mechanical unloading of the hind legs has been shown to induce muscular atrophy, which led to increased porosity and fragmentation in the femur and tibia4. As less force is required for a captive ferret to fully …

Far-Field Optical Microscopy Based On Stimulated Emission Depletion, Yunxia Wang

Theses and Dissertations

Conventional lens-based (far-field) fluorescence microscopy is a widely used imaging technique with spatial resolution up to 150–350 nm. However, this technology cannot discern very small structural features, because the spatial resolution is limited by diffraction to about half of the wavelength of light (λ/2，λ is the wavelength of light). Hence, most of the developments in microscopy aim at improving resolution. In the past decades, stimulated emission depletion (STED) microscopy has been developed to bypass the diffraction limit for the application in biological imaging with resolution approaching the nanoscale. The basic principle of STED microscopy is to employ a doughnut-shape laser …

Atherosclerotic Plaque Adhesion Strength And Its Role In Plaque Rupture, Bilal Merei

Theses and Dissertations

Cardiovascular diseases are disorders affecting the blood vessels and the heart. According to the World Health Organization, cardiovascular diseases are one of the leading causes of death worldwide. They are responsible for over 17.1 million deaths per year worldwide, representing 31.5% of deaths 1, 2. Atherosclerosis, a chronic inflammatory disorder affecting large arteries, is the underlying cause of many cardiovascular diseases. Plaque rupture is a serious complication of advanced atherosclerosis, often leading to life-threatening clinical consequences such as myocardial infarction (heart attack) or stroke. 75% of newly developed myocardial infarction cases are caused by atherosclerotic plaque rupture. It affects approximately …

Advancing Automated Methods For Microrna Profiling, Kia N. Zellars

Theses and Dissertations

The widespread influence of miRNAs in many biological processes and characteristic changes in expression profiles make them potential biomarkers for a range of diseases. With recent discoveries highlighting the enrichment of particular circulating miRNAs in plasma under pathological conditions, there has been a push for technological advances in miRNA profiling studies as a diagnostic tool. A standardized, automated, high-throughput method for miRNA isolation from human plasma samples was developed in this study. Samples were subject to full miRNome profiling utilizing RT-qPCR. These unique findings demonstrate that developing a distinct miRNA biomarker profile for heart failure patients is feasible and holds …

Enabling Studies To Optimize Biomaterials For The Treatment Of Myocardial Infarction, Eva Adriana Romito

Theses and Dissertations

The canonical mechanism of wound healing is disrupted following a myocardial infarction (MI), manifesting as an unregulated response that negatively impacts left ventricular (LV) function. This mechanism, termed post-MI remodeling, culminates in an outcome that favors progression to a systolic heart failure state and death for the patient. Therapeutic approaches following the occurrence of a MI are designed to modulate the natural remodeling process and mitigate the loss of cardiac function. The mechanics and structure of the healing infarct have been the focus of numerous pre-clinical and clinical investigations, leading to the impending clinical introduction of material injections as a …

Orthopedic Drill System With Screw Length Measurement And Heat Sink System, Hunter Wilcox Rafoth, John Patrick Metz

Senior Theses

Most orthopedic drills currently on the market are rudimentary tools that serve only one purpose: to drill holes through bone. Biosphinx envisions a more versatile orthopedic drill that could serve multiple purposes in the operating room. This report outlines Biosphinx’s solution to design a new orthopedic drill system that would include several key features to improve bone screw length measurement, increase patient safety, and reduce time spent in the operating room.

Next Generation Electrode, Joseph Daniel Bivona, Samuel Scott Dacus, Mary Harrell, James Frederick Weber Pike

Senior Theses

This senior thesis involves the results of a biomedical engineering senior design project where the group worked with Rhythmlink International LLC. The project involved the improvement of the manufacturing process of the Invisa Electrode, a CT compatible electrode sold and manufactured by Rhythmlink. The design of the electrode pin was altered to have a hollow center, where the lead wire can be inserted and heat welded, eliminating two key components of the original design and reducing production time and cost. The type of plastic used in the electrodes was also altered to be a 40% carbon loaded conductive plastic.

A Mechanical Approach To The Characterization Of Material Failure Of Atherosclerotic Lesions, Lindsey A. Davis

Theses and Dissertations

Failure of atherosclerotic plaques can lead to potentially life threatening clinical events such as myocardial infarction (MI), stroke, or transient ischemic attack (TIA). The most frequently described plaque failure mechanism is tensile rupture of the fibrous cap; however, often during angioplasty another plaque failure mechanism occurs in which the atherosclerotic plaque separates from the internal elastic lamina (IEL). This study aims assess the material strength of atherosclerotic lesions using mechanical concepts.

To assess likelihood of plaque dissection at the vessel wall, adhesion strength was assessed in both mouse and human specimens using plaque delamination experiments. Measuring plaque adhesion in transgenic …

A Theoretical Study Of Polymer Based Drug Delivery Systems, Ebtisam Abdullatif Aldaais

Theses and Dissertations

Polymer nanostructured materials for drug delivery applications have witnessed tremendous progress in recent years due to their vast potential. One-end-grafted polymers can form grafted micelles with specific mechanical properties. Biological conditions can alter these properties resulting in the protection or release of drugs. Charged surfactants can also form micelles in an aqueous solution, which can also be manipulated through special conditions. On the micellar surface, self-organized polyelectrolytes can be stimulated to extend their attached ligands and thus increase the probability of binding to targeted receptors. This thesis focuses on modeling polymer-based drug delivery systems by studying the physical interactions between …

Therapeutic Potential Of Catechins And Derivatives For The Prevention Of Alzheimer’S Disease, Shelby Elaine Chastain

Theses and Dissertations

Alzheimer’s disease (AD) is a neurodegenerative condition that affects 1 in 9 people over the age of 65, an estimated 5.4 million Americans. It is the only disease among the top 10 that cannot be prevented, cured, or treated. Based on the lack of a viable therapeutic for the prevention or cure of AD, it is vital that therapeutic research for AD continues. AD is characterized by the deposition of extracellular neuritic plaques comprised of insoluble amyloid-β (Aβ) fibrils. These plaques are formed from the amyloidogenic aggregation of Aβ monomer, generated from the cleavage of the amyloid precursor protein (APP) …

Automated Image Analysis And Spatial Computational Modeling Of Nf-Kb In Cerebrovascular Endothelial Cells, Kasey Catalfomo

Theses and Dissertations

Cerebrovascular endothelial cells play a key part in the inflammatory response of the blood-brain barrier in pathological conditions such as Alzheimer’s disease. Specifically, the NF-κB signaling pathway plays a central role. Better understanding of the factors in inflammatory disease progression can lead to more effective treatments for such devastating illnesses like Alzheimer’s, asthma, arthritis, cancer, diabetes and many more inflammatory diseases. The proposed approach analyzes spatial NF-κB distribution contained in multispectral stacked micrograph images of cerebrovascular endothelial cells indexed based on dose of the activating protein and the length of activation. Image analysis code identifies the location of nuclear boundaries …

Effects Of Cell Adhesion Peptides, Ph, And Matrix Shape On Maintenance Of Breast Cancer Stem Cells In An Engineered Hydrogel Matrix, Leily Daneshian

Theses and Dissertations

Metastasis, resistance to chemo- and radiotherapy, and eventual relapse has been attributed to a tumor subpopulation known as cancer stem cells (CSCs). CSCs are regulated in their tumor microenvironment by various factors. Synthetic hydrogels can be used to investigate the effects of individual environmental factors on CSCs by providing inert 3D matrices. In this thesis, poly ethylene glycol diacrylate (PEGDA) hydrogel with 5kpa modulus has been used as a culture system to study the effect of; I) integrin and heparin binding peptides, 2) pH, and 3) the shape of the microenvironment on breast CSCs maintenance and tumorsphere formation in PEGDA. …

New Design Of Nasogastric Decompression Tube That Incorporates A Self-Cleaning Brushing Mechanism, Nichole Abla, Lindsay Rucker, Paige Schroder

Senior Theses

Many hospitalized patients require the removal of secretions that accumulate in the stomach and must be removed by a nasogastric tube, which unfortunately clogs often. This project outlines the redesign of the nasogastric tube that will ideally prevent nasogastric tube clogging by incorporating a brush mechanism and a contracting tip mechanism, to act as preventative measures against clogging.

Design And Development Of A Ventilation Chamber For Testing Efficacy Of Tracheal Stents, Caroline N. Horton

Theses and Dissertations

Tracheobronchial malacia results in a weakening of the tracheal walls, leading to increased difficulty breathing. Stents are used to reopen the lumen of the trachea, however, current models are not personalized to each patient, leading to migration, inflammation, and breakage of the stents. In order to successfully test novel stent designs, a ventilation chamber is needed to recreate the breathing conditions of the body.

The following describes the iterative development of a ventilation chamber, which allows inflation and deflation of lungs via negative pressure ventilation, as representative of an actual body undergoing respiration. Previous work shows that lungs are not …

Material Considerations For Development Of 3d Printed Bronchial And Tracheal Stents, Nidah M. Hussain

Theses and Dissertations

Tracheobronchial malacia is a commonly under-diagnosed condition that results in difficulty breathing. The use of a tracheobronchial stent is the best course of treatment for patients whose quality of life has deteriorated due to malacia; unfortunately stents need replacing after issues with inflammation, migration, or eventual stent-breakdown resulting in fistula formation.

The purpose of this thesis is to use three-dimensional (3D) printing technology to improve on existing stents through designing and printing a bioresorbable/biodegradable tracheobronchial stent that can treat tracheobronchial malacia. This was undertaken by testing three biologically favorable materials, type I collagen, polycaprolactone (PCL), and thermoplastic polyurethane (TPU), with …

Experimental And Theoretical Studies Of Native And Engineered Vascular Tissue Mechanics, Boran Zhou

Theses and Dissertations

Background: Implantation of vascular grafts provides a means to restore blood flow in compromised regions of the circulatory system, and thus is used to treat a wide range of cardiovascular diseases. Despite significant advancements in autologous grafting strategies as well as the engineering of synthetic alternatives, mechanical, structural, and compositional incongruities between the graft and the host artery remain as contributing factors to graft failure. The typical failure modality manifests as proximal anastomotic intimal hyperplasia, which places restrictions on the host vessel size currently treated with grafting strategies (> 5 mm internal diameter). In order to improve long-term clinical outcomes, …

A Three-Dimensional In Vitromodel Of Atherogenesis, Pin Hsuan Chang

Theses and Dissertations

Atherosclerosis is the narrowing of arteries caused by accumulation of cholesterol, calcium and other cellular debris in the inner arterial wall. While extensive studies have been focusing on the inflammatory mechanisms of the disease, pathological and experimental evidence has shown that regions of disturbed flow are susceptible to the atherogenesis. To further understand the relationship between hemodynamics and atherogenesis, this research aims to generate a dynamic, 3D in vitro model of atherogenesis. This will allow for the investigation of specific cellular and molecular mechanisms of plaque formation that will pave the way for new therapies for the disease. A novel …

Developing A Bioreactor For Biaxial Mechanical Testing And Conditioning Of Vascular Tissue, Steve Marcous

Theses and Dissertations

Cardiovascular diseases are known to be one of the major causes of death around the world. One of the major causes of cardiovascular disease is arterial malfunction. Arteries malfunction when they experience chronic perturbations in their local environment above normal levels. Hence, we developed a bioreactor system in order to study the effect of chronic changes in the arterial global parameters (axial force, luminal pressure, and flow rate) on the behavior of local parameters (circumferential stress, axial stress, and flow induced shear stress). The bioreactor system was designed to (i) perform biaxial mechanical testing, (ii) incorporate, for the first time, …

Uncertainty Quantification Driven Predictive Multi-Scale Model For Synthesis Of Mycotoxins, Sourav Banerjee, Gabriel A. Terejanu, Anindya Chanda

Faculty Publications

Many toxic molds synthesize and release an array of poisons, termed mycotoxins that have an enormous impact on human health, agriculture and economy [1]. These molds contaminate our buildings, indoor air and crops, cause life threatening human and animal diseases and reduce agricultural output [2]. In order to design appropriate approaches to minimize the detrimental effects of these fungi, it is essential to develop diagnostic methodologies that can rapidly and accurately determine based on fungal strains and their growth patterns, the extent of mycotoxin mediated damage caused to the environment.Here we developed a novel multi-scale predictive mathematical model that could …

Modulation Of Leukocyte Infiltration And Phenotype In Microporous Tissue Engineering Scaffolds Via Vector Induced Il-10 Expression, R. Michael Gower, Ryan M. Boehler, Samira M. Azarin, Christine F. Ricci, Joshua N. Leonard, Lonnie D. Shea

Faculty Publications

Biomaterial scaffolds are central to many tissue engineering strategies as they create a space for tissue growth and provide a support for cell adhesion and migration. However, biomaterial implantation results in unavoidable injury resulting in an inflammatory response, which can impair integration with the host and tissue regeneration. Toward the goal of reducing inflammation, we investigated the hypothesis that a lentiviral gene therapy-based approach to localized and sustained IL-10 expression at a scaffold could modulate the number, relative proportions, and cytokine production of infiltrating leukocyte populations. Flow cytometry was used to quantify infiltration of six leukocyte populations for 21 days …

Identifying Performance Criteria Of Fully Bioresorbable Scaffolds For Endovascular Applications, Jahid Ferdous

Theses and Dissertations

Background: Bioresorbable scaffolds (BRS) have revolutionized percutaneous coronary intervention in clinical cardiovascular medicine. As opposed to permanent alternatives such as metallic stents, BRS have an inherent potential to reduce the occurrence of untoward events such as vessel re-narrowing or thrombosis by virtue of undergoing complete and controlled resorption post- implantation. While BRS platforms demonstrate a clear potential to mitigate risk stemming from incomplete vessel healing, they introduce a new set of considerations to clinical safety and efficacy. Foremost among these issues is the fate of and biological response to material by-products that evolve throughout the scaffold degradation and erosion processes, …

Isolation Of Natural Nrf2 Activators From American Ginseng, Akrm Abdalrahman

Theses and Dissertations

Nuclear factor erythroid-2 related factor 2 (Nrf2), a major transcription factor of the endogenous antioxidant defense system, has been proposed as a potential therapeutic target for the treatment of various diseases. However, a small molecule-driven Nrf2 signaling therapeutic approach remains to be established. Herein, we report one such possibility discovered by the bioassay-based fractionation of American ginseng. Since crude extract of American ginseng was found to suppress the expression of inducible nitric oxide synthase (iNOS) in lipopolysaccharide (LPS)-inflamed macrophages via activating Nrf2, we further fractioned the crude extract using solvents including hexane, dichloromethane, ethyl acetate, butanol, and water, and found …

Discovery And Characterization Of Multi-Target Directed Ligands As Inhibitors Of Amyloid-Β Aggregation And Regulators Of Alzheimer's Disease, Jui-Heng Tseng

Theses and Dissertations

Alzheimer's disease (AD) is the most common neurodegenerative disease in the world. As the disease advances, symptoms include confusion, language skill breakdown, and long term memory loss - and culminate in death. Existing therapies for AD provide symptomatic benefits but cannot halt or slow the disease pathogenesis.

Increasing evidence reveals the multi-factorial nature of AD. Numerous factors, including amyloid-β (Aβ) aggregation, calcium homeostasis dysregulation, and oxidative stress, contribute to disease development and interplay with each other. Therefore, multi-target directed ligands (MTDLs) may present an effective AD treatment. Among all factors, Aβ aggregation is suggested to play the most crucial role. …

Novel Conditioning Protocols Focusing On Oxygen Manipulation To Enhance Stem Cell Transplantation, Brandon William Hanna

Theses and Dissertations

Musculoskeletal tissue engineering involves the creation of multiple tissue types that interact together to form a particular function related to motion and maintaining the body's frame. In order to create a fully functional musculoskeletal system, a concrete method for the creation of the different tissue types must first be completed. Of the different tissue components related to the function of a musculoskeletal system, these studies deal with preconditioning circumstances of stem cells that will differentiate into cartilage and bone. These studies also deal with methods for the creation of functional bone and cartilage to be combined for the creation of …