Engineering Commons^™

Feasibility Of Eeg Based Detection Of Ischemic Stroke: Studies In A Simple Computational Model, Charles F. Babbs

Weldon School of Biomedical Engineering Faculty Working Papers

Objective: To explore quantitatively, using streamlined mathematics, how transmembrane potential differences across cell bodies of individual cortical neurons could act to produce the skin surface potentials of the electroencephalogram (EEG), and how ischemic stroke might be detected using EEGs in prehospital settings. Methods: From fundamental principles of electrostatics, anatomy, and physiology, one can characterize the strength of apparent dipoles created during activation of the cell bodies of individual cortical neurons. The transient dipole strength in a cortical neuron depends upon the size and surface area of its cell body, its capacitance, and the difference in transmembrane electrical potentials appearing across …

An In Vitro Investigation Of Urothelial Cell Function In Response To Hypoxia And Pressure In Relation To Bladder Outlet Obstruction, Britney Hudson

All Dissertations

Bladder outlet obstruction (BOO) is a prevalent urological condition and can be characterized by the presence of lower urinary tract symptoms (LUTS), such as hesitancy, weak stream, and nocturia. The main cause of BOO is a partial blockage of the urethra, which results in elevated voiding pressure, high storage pressure, and tissue ischemia, which are thought to be the triggers of bladder inflammation and subsequent fibrosis. Often patients do not seek treatment until the conditions get severe. Thus, it would be ideal to have an early diagnostic tool to detect changes in the bladder due to BOO. Extracellular vesicles (EVs) …

4d Epr Oximetry Imaging For 4d Bioprinting And Tissue Engineering, Sajad Sarvari

Graduate Theses, Dissertations, and Problem Reports

Bioprinting, akin to 3D printing, employs cell-laden hydrogels such as GelMA (Gelatine Methacrylate) and Alginate instead of plastic or resin to create biological structures. The printing process followed by subsequent tissue maturation is known as 4D bioprinting, where the fourth dimension is time. Ensuring adequate and consistent oxygen, O2, supply within 3D bioprint volume over the entire maturation period process is crucial, as even transient hypoxia can impact cellular behavior and phenotypes. However, printing of fully developed vasculature remains an unresolved technical challenge. Several approaches to chemically (peroxides) or biologically (photosynthesis) generate oxygen during bioprint maturation have been proposed. However, …

Development Of An Angiogenic Tissue-On-A-Chip Microenvironment, Eric Stuehr

Master's Theses

Preclinical testing is necessary to investigate the safety and efficacy of novel therapeutics before moving to clinical trials, yet approximately 90% of these therapies fail once tested in humans. This has led to increased interest in developing robust preclinical models that accurately mimic the complex human in vivo physiology. Microfluidic devices that can introduce dynamic conditions to 3D cell/organoid cultures, also known as tissue-on-a-chip, have emerged as physiologically relevant in vitro preclinical models that can achieve high throughput screening of therapeutics. The research presented here aimed to develop an angiogenic environment within a novel microfluidic device to stimulate formation of …

Hypoxic Incubator Control System, Marina Zellers, Jennifer Rojas, Derek Tran

Biomedical Engineering

This paper describes the functionality of the current Hypoxic Incubator, a project started by BMED graduate students Simone Helfrich and Makenzie Jones, with the objective being to redesign the device to address potential areas of improvement. The hypoxic incubator has been designed to allow for the control of the O₂, CO₂, and N₂ levels such that researchers can grow and study cell culture in hypoxic conditions; however, its efficacy and efficiency are limited by the fact that it often overshoots the desired setpoints for O₂ and CO₂ in addition to being difficult to …

Investigation Of Dynamic Culture On Matrix-Derived Microcarriers As A Strategy To Modulate The Pro-Regenerative Phenotype Of Human Adipose-Derived Stromal Cells, Mckenna R. Tosh

Electronic Thesis and Dissertation Repository

Pre-conditioning of adipose-derived stromal cells (ASCs) by tuning the cellular microenvironment during expansion has the potential to modulate their pro-regenerative functionality. The current study investigated the effects of microcarrier composition (decellularized adipose tissue versus collagen), oxygen tension (2% versus ~20% O₂) and stirring rate (static, 20, 40 rpm) on human ASCs cultured within spinner flask bioreactors. Dynamic culturing under 20% O₂ resulted in more consistent cell growth on both microcarrier substrates, leading to increases in microcarrier contraction and stiffness. Culturing on the microcarriers modulated the hASC immunophenotype, with varying CD90 and CD26 expression levels observed under the …

Investigating Tgf-Β1 And Fibronectin Signaling In Low Oxygen Environments, Caitlin E. Williams

Theses and Dissertations

Breast cancer is the second leading cause of death in women, second to lung cancer. It’s one of the most well-known cancers, with almost 300,000 new cases estimated to be diagnosed in 2023. Breast cancer often begins in ductal epithelial cells, and these cells will typically undergo a cellular transformation process known as epithelial-mesenchymal transition (EMT) in early stages. Breast cancer becomes deadly when it reaches a metastatic stage. As a part of the metastatic process, transformed cells will conduct remodeling of the extracellular matrix (ECM) to allow for migration of an otherwise non-migratory cell type.

As dense tumors form, …

Integrative Physiology-Coupled Pilot-Centered Flight Simulation, Shawn C. Harrison

Electrical & Computer Engineering Theses & Dissertations

Maintaining the pilot’s physiological performance envelope within the limits of human capabilities may be crucial for avoiding hazardous physiological episodes in fighter aircraft that compromise safety. The main physiological episode of interest is impaired pilot respiration, better known as hypoxia caused by a high fraction of inspired oxygen (FiO₂) at high altitudes and variation in accelerative gravitational forces (g-forces). Integrated into fighter aircraft is an Onboard Oxygen Generating System (OBOGS) developed to mitigate the necessity of gaseous and liquid oxygen cannisters [1]. OBOGS act as a life support in hypoxic environments by providing oxygen-rich air, thereby oxygenating the …

Hypoxic Incubation Chamber, Simone Lisette Helfrich, Makenzie Nicole Jones

Master's Theses

This paper describes the design, manufacturing, and testing of a novel controllable hypoxic incubator with fully functional oxygen gas control and temperature control in a humid environment. On the current market, a majority of the few hypoxic incubators use pre-mixed gas that does not offer precise control over gas concentration. The objective for this project was to create a chamber that allows the user to set the O2 concentration to varying set points of % O2 while maintaining the chamber at a constant body temperature, CO2 level, humidity, and sterility. To start the project, multiple concepts were developed for the …

Determination Of Tissue-Level Changes In Tumors That Are Indicative Of Metastasis Using Optical Spectroscopy, Sanidhya D. Tripathi

Biomedical Engineering Undergraduate Honors Theses

Breast cancer, accounting for 12% of all new cancer cases, is one of the leading causes of death in women worldwide. Although patient survival has improved over the years, metastatic spread to other organ sites and not due to the primary tumor is the most common form of tumor recurrence, accounting for 90% deaths. Hypoxia is a common hallmark of solid tumors and is linked with metastasis, therapeutic resistance, and poor patient survival. Defined as a state of decreased oxygen availability, cells under hypoxia have an increased rate of genetic mutation, local invasion, and resistance to treatment such as radiation …

Investigating The Impact Of Hypoxia On Reactive Oxygen Species Generation Within Murine Breast Cancer Cells, Jared Mcpeake

Biomedical Engineering Undergraduate Honors Theses

When cancer metastasizes from a primary tumor site to secondary site through the bloodstream or lymph, the cancer becomes more difficult to treat. For this reason, it is vital to study what indicates the metastatic potential of a tumor. Current research has shown that cell lines with high metastatic potential display increased levels of metabolic adaptability over their nonmetastatic counterparts after undergoing hypoxic conditions. One method of assessing this adaptability is to measure the concentration of reactive oxygen species (ROS) produced by the cells while undergoing oxidative stress. In highly adaptable metastatic cells, an increase of ROS buildup within the …

Reciprocal Regulation Of Transketolase-Like 1 And Hypoxia-Inducible Factor 1 Alpha In Metabolic Reprogramming And Growth Of Diffuse Midline Glioma, H3 K27m-Mutant, Christopher Andrew Waker

Browse all Theses and Dissertations

Diffuse midline glioma, K27M-mutant (DMG) are intractable brain tumors, primarily occurring in the pediatric and adolescent population. Patients have a median survival of less than one year after diagnosis. A lack of therapeutic targets has been a barrier to improvement in patient survival. Irradiation therapy improves symptoms while chemotherapy and surgical intervention, for the most part, have not yet demonstrated utility for treatment. DMG are characterized by a histone H3 mutation that results in the genome-wide loss of epigenetic-repressive marks on K27 and is associated with the misexpression of genes, like Cancer/Testis antigens. A member of this group, transketolase-like 1 …

Acute Oxygen-Sensing By The Carotid Bodies : The Thermal Microdomain Model, Ryan Joseph Rakoczy

Browse all Theses and Dissertations

The carotid bodies (CB) are peripheral chemoreceptors that detect changes in arterial oxygenation and, via afferent inputs to the brainstem, correct the pattern of breathing to restore blood gas homeostasis. Elucidating the “signal” that couples carotid body sensory type I cell (CBSC) hypoxic mitochondrial inhibition with potassium channel closure has proven to be an arduous task; to date, a multitude of oxygen-sensing chemotransduction mechanisms have been described and altercated (Varas, Wyatt & Buckler, 2007; Gao et al, 2017; Rakoczy & Wyatt, 2018). Herein, we provide preliminary evidence supporting a novel oxygen-sensing hypothesis suggesting CBSC hypoxic chemotransductive signaling may in part …

Multiphysics Computational Model Of Fluid Flow And Mass Transport In Aneurysm, Tanja Cupac

Electronic Theses and Dissertations

The abdominal aortic aneurysm is progressive, asymptomatic, and can eventually lead to rupture which is a catastrophic event leading to massive internal bleeding and possibly death. AAA cases have been characterized by the development of an intraluminal thrombus (ILT). The ILT correlates with the progression of hypoxia in the arterial wall. The extent that ILT presence reduces oxygen flux to the wall has not been quantified and there is rather a poor understanding of key parameters that can affect thrombus-mediated oxygen transport in AAA. The purpose of this study is to address this gap and to assess the effects of …

Investigation Of Acute Radiation-Induced Changes In Oxygenation In A Murine Breast Tumor Model, Alaa Abdelgawad

Biomedical Engineering Undergraduate Honors Theses

Around 50-60% of all cancer patients undergo radiation therapy. Although some patients show complete response with no recurrence, a significant proportion of the population still develop radiation resistance. It is important to identify tumor resistance at early stages of therapy in order to adjust treatment protocol and avoid extra exposure to radiation. Current methods to assess treatment response are only limited to anatomical measurements of tumor volume after therapy. Novel approaches that shed the light on any functional information during the course of radiotherapy could significantly improve our ability to identify patients who do not respond to radiation therapy. Diffuse …

Progressive Hypoxia-On-A-Chip: An In Vitro Oxygen Gradient Model For Capturing The Effects Of Hypoxia On Primary Hepatocytes In Health And Disease, Young Bok Abraham Kang, Jinsu Eo, Beyza Bulutoglu, Martin L. Yarmush, O. Berk Usta

Faculty Publications - Biomedical, Mechanical, and Civil Engineering

Oxygen is vital to the function of all tissues including the liver and lack of oxygen, that is, hypoxia can result in both acute and chronic injuries to the liver in vivo and ex vivo. Furthermore, a permanent oxygen gradient is naturally present along the liver sinusoid, which plays a role in the metabolic zonation and the pathophysiology of liver diseases. Accordingly, here, we introduce an in vitro microfluidic platform capable of actively creating a series of oxygen concentrations on a single continuous microtissue, ranging from normoxia to severe hypoxia. This range approximately captures both the physiologically relevant oxygen gradient …

Effect Of Hypoxia On Spontaneous Neural Activity In The Cortex Of Neonate Mouse Pups, Krithikka Ravi Ms

Dissertations and Theses

Hypoxia caused by inadequate oxygenation has profound effects on the normal functioning of the brain in mammals. Acute or chronic hypoxic insults occur in the brain depending on the duration of hypoxic exposure. Hypoxia is known to occur in the human womb and exerts adverse effects on the developing fetus. Most of the ongoing research on hypoxia is performed on rodent brain slice taken from various brain regions using intracellular recording. Extensive work has been carried out to understand the effects of chronic hypoxia on the developing nervous system, specifically during intrauterine development. However, effects of acute hypoxia occurring perinatally, …

Blood Transfusions In Preterm Infants: Changes On Perfusion Index And Intermittent Hypoxemia, Katrina T. Ibonia, Henrietta S. Bada, Philip M. Westgate, Enrique Gomez Pomar, Prasad Bhandary, Abhijit R. Patwardhan, Elie G. Abu Jawdeh

Pediatrics Faculty Publications

BACKGROUND

Red blood cell (RBC) transfusion decreases intermittent hypoxemia (IH) events beyond the first week of life. This benefit may be related to improved perfusion to the respiratory control network. Perfusion index (PI) is a perfusion measure provided by the pulse oximeter. We hypothesized that the benefit in IH after RBC transfusion is associated with an increase in PI. In addition, we assessed the value of PI and clinical measures in predicting the effect of RBC transfusion on IH.

STUDY DESIGN AND METHODS

We prospectively enrolled infants less than 30 weeks' gestation age. PI and oxygen saturation (SpO₂) …

Developing Droplet Based 3d Cell Culture Methods To Enable Investigations Of The Chemical Tumor Microenvironment, Jacqueline A. De Lora

Biomedical Sciences ETDs

Adaptation of cancer cells to changes in the biochemical microenvironment in an expanding tumor mass is a crucial aspect of malignant progression, tumor metabolism, and drug efficacy. In vitro, it is challenging to mimic the evolution of biochemical gradients and the cellular heterogeneity that characterizes cancer tissues found in vivo. It is well accepted that more realistic and controllable in vitro 3D model systems are required to improve the overall cancer research paradigm and thus improve on the translation of results, but multidisciplinary approaches are needed for these advances. This work develops such approaches and demonstrates that new droplet-based cell-encapsulation …

Stabilization Of Hypoxia Inducible Factor By Cobalt Chloride Can Alter Renal Transepithelial, Subhra Sankar Nag

ETD Archive

Kidney cyst expansion, stagnant fluid accumulation, and insufficient vascular supply can result in localized chronic ischemia-hypoxia in kidney cysts, as well as in normal renal epithelia adjacent to a cyst. We hypothesize that in normal epithelia near a cyst, the stabilization of Hypoxia Inducible Factor 1a (HIF1a), a major regulator of cellular response to hypoxia, can cause altered paracellular and transcellular transport, transforming a normal absorptive phenotype to a secretory and paracellularly leaky phenotype, leading to cyst expansion. Using 100 µmol/L cobalt chloride (CoCl2), HIF1a was stabilized in cellular nucleus of a mouse cortical collecting duct cell line (mCCD 1296 …

Fundamental Characterization Of Oxygen Nanobubbles, John Hamlin, Yi Wen, Joseph Irudayaraj

The Summer Undergraduate Research Fellowship (SURF) Symposium

A hypoxic environment is created by tumors’ incredible growth rate. Hypoxia provides radioresistance to the tumors, thus making radiation treatment less effective. The issue is that increasing the radiation leads to increased side effects in patients. Our goal for the oxygen-filled nanobubble is to deliver oxygen to the tumor to lessen radioresistance and make radiation treatment more efficient. However, we need preliminary research to understand and improve the nanobubbles before further research and implementation. To do this, we synthesized different batches of nanobubbles to optimize the production method and find the best container and temperature to store nanobubbles. We measured …

Effects Of Short Term Hypoxia-Preconditioning On Glial Phenotype Induction Of Human Mesenchymal Stem Cells, Zichen Qian, Qi Xing, Corey Fase, Kyle Jansen, Feng Zhao

Michigan Tech Publications

Development of successful clinical treatments for peripheral nerve injury is limited due to the complications behind neural physiology. Human mesenchymal stem cells (hMSCs) have the ability to directly promote tissue repair and protect cells at the injury site. Studies have shown that hMSCs can be transplanted to improve nerve regeneration. Hypoxic culture condition has been proven to maintain the stemness of hMSCs for later differentiation. In this study, we investigated the effects of low oxygen (O₂) (2% and 5% O₂) pre-treatment and initial seeding density (500, 1000, and 2000 cells/cm²) on glial protein expression …

Development Of Peritoneal Microbubble Oxygenation As An Extrapulmonary Treatment For Hypoxia, Nathan Legband

Department of Mechanical and Materials Engineering: Dissertations, Theses, and Student Research

Patients affected by a respiratory disease or injury experience a substantially impaired respiratory system and as a consequence are unable to obtain a sufficient amount of oxygen. Hypoxia can quickly result in developing permanent tissue damage or death. Currently, the medical methods of treating hypoxia are mechanical ventilation or extracorporeal membrane oxygenation. However, these treatments are ineffective in certain cases and possess significant additional risks including barotrauma, infection, hemorrhage, and thrombosis.

The extrapulmonary method of peritoneal oxygenation has been investigated by other research groups as a potential alternative to providing supplemental oxygen in hypoxic animals. In peritoneal oxygenation, the peritoneum, …

Oxygen Transport In Carotid And Stented Coronary Arteries, Eoin A. Murphy

Doctoral

Oxygen deficiency, known as hypoxia, in arterial walls has been linked to increased intimal hyperplasia, which is the main adverse biological process causing in-stent restenosis. Stent implantation can have significant effects on the oxygen transport into the arterial wall. Helical flow has been theorised to improve the local haemodynamics and the oxygen transport within stented arteries. In this study an advanced oxygen transport model was developed to assess different stent designs. This advanced oxygen transport model incorporates both the free and bound oxygen contained in blood and includes a shear-dependent dispersion coefficient for red blood cells. In two test cases …

Nanobubbles Provide Theranostic Relief To Cancer Hypoxia, Christopher M. Long, Pushpak N. Bhandari, Joseph Irudayaraj

The Summer Undergraduate Research Fellowship (SURF) Symposium

Hypoxia is a common motif among tumors, contributing to metastasis, angiogenesis, cellular epigenetic abnormality, and resistance to cancer therapy. Hypoxia also plays a pivotal role in oncological studies, where it can be used as a principal target for new anti-cancer therapeutic methods. Oxygen nanobubbles were designed in an effort to target the hypoxic tumor regions, thus interrupting the hypoxia-inducible factor-1α (HIF-1α) regulatory pathway and inhibiting tumor progression. At less than 100nm, oxygen nanobubbles act as a vehicle for site-specific oxygen delivery, while also serving as an ultrasound contrast agent for advanced imaging purposes. Through in vitro and in vivo studies, …

Oxygen Mass Transport In Stented Coronary Arteries, Eoin Murphy, Adrian S. Dunne, David Martin, Fergal Boyle

Articles

Oxygen deficiency, known as hypoxia, in arterial walls has been linked to increased intimal hyperplasia, which is the main adverse biological process causing in-stent restenosis. Stent implantation has significant effects on the oxygen transport into the arterial wall. Elucidating these effects is critical to optimizing future stent designs. In this study the most advanced oxygen transport model developed to date was assessed in two test cases and used to compare three coronary stent designs. Additionally, the predicted results from four simplified blood oxygen transport models are compared in the two test cases. The advanced model showed good agreement with experimental …

An Investigation Of The Relation Between Sleep Disordered Breathing And Cognitive Function, Nazaneen Mousavi

Bioengineering Theses

Obstructive sleep apnea (OSA) is one of the most prevalent sleep related breathing disorders, with an estimated amount 17% of affected adults in the U.S. Research has linked OSA to mood and cognitive disorders, including Alzheimer’s disease. Structural changes in the brain have also been found to be associated with OSA. Several studies have shown deterioration of cognition in OSA patients because of structural and physiological changes due to apnea. The purpose of this research is to study the correlational relationships between cognitive measures and 1) quantitative measures of sleep quality; 2) measures of sleep disordered breathing; and 3) hypoxia …

Expanding Applications Of The Nano Intravital Device As A Platform For Exploring Tumor Microenvironments, Michael Padgen

Legacy Theses & Dissertations (2009 - 2024)

The tumor microenvironment has been demonstrated to be a key determinant in the progression of cancer. Unfortunately, the mechanisms behind the different microenvironments (cytokine gradients, hypoxia, hypoglycemia, etc) have not been fully elucidated. Identifying these mechanisms can lead to targeted, individualized therapy to prevent metastasis. The Nano Intravital Device (NANIVID) is a microfabricated, implantable device designed to initiate specific microenvironments in vivo so that the time course of the effects can be observed. With both spatial and temporal control over the induced environments, the affected regions of the tumor can be compared to the rest of the tumor. The NANIVID …

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 …

Hypoxia Preconditioning Increases Survival And Decreases Expression Of Toll-Like Receptor 4 In Pulmonary Artery Endothelial Cells Exposed To Lipopolysaccharide, Irshad Ali, Rahul Nanchal, Fouad Husnain, Said H. Audi, G. Ganesh Konduri, John C. Densmore, Meetha Medhora, Elizabeth R. Jacobs

Biomedical Engineering Faculty Research and Publications

Pulmonary or systemic infections and hypoxemic respiratory failure are among the leading causes of admission to intensive care units, and these conditions frequently exist in sequence or in tandem. Inflammatory responses to infections are reproduced by lipopolysaccharide (LPS) engaging Toll-like receptor 4 (TLR4). Apoptosis is a hallmark of lung injury in sepsis. This study was conducted to determine whether preexposure to LPS or hypoxia modulated the survival of pulmonary artery endothelial cells (PAECs). We also investigated the role TLR4 receptor expression plays in apoptosis due to these conditions. Bovine PAECs were cultured in hypoxic or normoxic environments and treated with …