Biomedical Engineering and Bioengineering Commons^™

Toward Precision Medicine With Nanopore Technology, Trang Andrea Vu

Theses and Dissertations

Currently, when patients are diagnosed with cancer, they often receive a treatment based on the type and stage of the tumor. However, different patients may respond to the same treatment differently, due to the variation in their genomic alteration profile. Thus, it is essential to understand the effect of genomic alterations on cancer drug efficiency and engineer devices to monitor these changes for therapeutic response prediction. Nanopore-based detection technology features devices containing a nanometer-scale pore embedded in a thin membrane that can be utilized for DNA sequencing, biosensing, and detection of biological or chemical modifications on single molecules. Overall, this …

Using Human Granulosa Cells To Select The Most Competent Embryos For Uterine Transfer In In Vitro Fertilization Cycles, Richard John Kordus

Theses and Dissertations

Infertility is a worldwide epidemic often treated with in vitro fertilization. The success of in vitro fertilization is directly dependent upon the quality of oocytes produced during the controlled stimulation of the patient’s ovaries. There is a need for improved methods to allow embryologists to select the most viable embryos with the highest probability of leading to live births since in vitro fertilization success is far from optimal.

Oocyte and subsequent embryo quality are intimately influenced by the granulosa cells which surround the oocyte during follicular maturation. The oocytes require proper signaling and energy production form the surrounding granulosa cells …

The Role Of Acute And Chronic Neuroinflammation In Depression: Uncovering The Relationship Between Histamine And Serotonin Transmission, Melinda Hersey

Theses and Dissertations

Depression is the leading cause of disability worldwide. Disorders of the brain, including depression, are notoriously difficult to treat because the basic pathology underlying behavioral outcomes remains undefined. Robust chemical biomarkers of these diseases have not been identified, nor are there reliable methods to measure brain chemicals. Depression is associated with chemical and inflammatory changes in the brain that are predicted to contribute to the pathology. By studying the serotonin and histamine systems we aim to better define the neurochemical basis of depression. Serotonin has long been hypothesized to play a role in depression since selective serotonin reuptake inhibitors (SSRIs) …

Effect Of Cannabinoid Treatment On Immune Cell Functions During Acute Lung Injury, Amira Kamil Mohammed

Theses and Dissertations

Staphylococcal enterotoxin B (SEB) is a highly potent CDC select agent that can trigger acute lung injury (ALI) via robust T cell proliferation and differentiation, and massive cytokine and chemokine release. Δ9-Tetrahydrocannabinol (THC) is a psychoactive ingredient found in Cannabis sativa. In the current study, we investigated the effects of treatment with THC on SEB-induced acute lung injury. To this end, acute lung injury was induced by a dual dose of SEB in C3H/HeJ mice, which were then treated with vehicle or THC. THC-treatment led to survival of all the SEB-administered mice when compared to vehicle-treated. This corroborated with THC-induced …

Nitric Oxide Expression With Age And Diet In The Arterial Wall Of Apoe Knockout Mice, Kara Cooper

Theses and Dissertations

Background: Hypertension is a dangerous condition that precedes many cardiovascular events including myocardial infarction, stroke, transient cerebral ischemic attack and symptomatic aortoiliac occlusive disease. While it is universally accepted that arteries stiffen with age, the physiological reason for this is debated. In a previous study, by Dr. Shana Roach Watson it was shown that collagen fibers re-orient themselves in a circumferential direction, resulting in increased arterial stiffness. The study hypothesized that this collagen remodeling could be a result of decreased nitric oxide production.

Methods: This study measured nitric oxide in two different ways, indirectly via Immunoperoxidase staining for eNOS and …

Advanced Geometric Analyses In Vascular Disease And Interventions, Dara Ahmadi Azar

Theses and Dissertations

The central function of the vascular system is the transportation and distribution of blood throughout the body. Occurrence of various forms of vascular disease, in which this central function is compromised, is associated with high mortality and morbidity rates. Vascular disease is an active and multifactorial process causing changes in local hemodynamics and blood vessel wall mechanics. The work presented here aims to advance the current knowledge on the role of local geometrical parameters in vascular disease and endovascular intervention modalities. In our first set of studies, we develop a computational framework to understand the role of aortic geometry in …

The Use Of Natural Anthraquinone Emodin As A Primary And Complementary Therapeutic In The Treatment Of Colorectal Cancer, Alexander-Jacques Theodore Sougiannis

Theses and Dissertations

5 Fluorouracil (5FU) chemotherapy is widely used in the treatment of colorectal cancer (CRC), and has been the first-choice chemotherapy drug for CRC for many years. However, nearly 10% of patients receiving chemotherapy die during the first 30 days of treatment. Further, it is estimated that 70% of surviving patients will develop non-specific toxicities as a result of chemotherapy treatment. We characterize these toxicities in an animal model of chemotherapy treatment and show that perturbations in the gut microbiome might be exacerbate the prolonged effects of chemotherapy. A compound that could attenuate the multiple non-selective toxicities associated with chemotherapy could …

Fetal Evoked Responses: Improved Attenuation Of Cardiac Interference And Verification By Magnetic Dipole Fitting, Neslihan Bisgin

Theses and Dissertations

Early detection of fetal neurological disorders is of significant importance however, accessing the fetal brain signal has been a challenging issue. With highly sensitive Superconducting Quantum Interference Device (SQUID) sensors, fetal magnetoencephalography (fMEG) can be recorded and there have been many studies on understanding fetal brain activity through fMEG. The major problem about fMEG data is its low signal to noise ratio. fMEG is extracted from the mixture of maternal heart, fetal heart, fetal brain, and other biological signals from mother and the fetus. Effective removal of interferences is crucial in detecting the low amplitude fetal neurological signals. The objective …

Low-Cost Solid State Nanopore Biosensing Technology Towards Early Disease Detection, Julian Bello

Theses and Dissertations

Solid-state nanopore based biosensors are cost effective, high-throughput engines for single molecule detection of biomolecules, which is useful for detecting epigenetic modifications on DNA; one of these being the potentially cancerous hypo, or hypermethylation of CpG islands. Despite its immense potential in the realm of disease diagnostics, nanopore detection as it stands faces various limitations that inhibit it from widespread commercial use. These include the complex method of solid-state nanopore fabrication, fast DNA translocations through the pore causing poor resolution, and poor signal to noise ratio. The following work aims to improve the efficacy of the solid-state nanopore biosensing platform …

Fabrication Of Vascularized Scaffolds For The Treatment Of Spinal Cord Injury, Paul P. Partyka

Theses and Dissertations

The overall goal of the research presented here is to evaluate the efficacy of transplanting scaffolds containing central nervous system vasculature to repair spinal cord injury. There are three major phases of this effort: development of a three-dimensional model of central nervous system vasculature, transplantation of a pre-vascularized scaffold and optimization of the biomaterial used to deliver vasculature to the injured spinal cord. This research has produced the first ever compliant, three-dimensional (3D) blood-brain barrier (BBB) vessel. In order to create vascularized scaffolds appropriate for transplantation into a rat model of spinal cord injury, techniques to fabricate and spatially pattern …

Bioadhesive Hydrogel Composite Cell Carrier For The Repair Of The Degenerated Intervertebral Disc, Thomas Richard Christiani

Theses and Dissertations

Lower back pain (LBP) affects the worldwide population and can be attributed to the degeneration of the intervertebral disc (IVD). The IVD is composed of a central nucleus pulposus (NP), a peripheral annulus fibrosus (AF), and adjacent cartilage endplates (CEPs). IVD degeneration is characterized by proteoglycan loss, tissue dehydration, and decreased hydrostatic pressure. In this work, the use of an injectable bioadhesive hydrogel composite for replacement of the degenerated NP was investigated.

Results indicate that the composite exhibits similar mechanical properties to the NP, adheres to AF tissue, and supports encapsulated mesenchymal stem cell (MSC) differentiation toward an NP-like phenotype …

Development Of A Single Use Device Intended To Wash Blood Clot Debris From A Stent Retriever In The Operating Room, Shane Diller

Theses and Dissertations

Ischemic stroke is a life-threatening condition that requires immediate surgical intervention to remove the blood clot that is lodged in the blood vessels of the brain. Mechanical thrombectomy, performed by an endovascular surgeon, involves inserting a stent retriever, which deploys distally and attempts to capture the clot when dragged backwards. A complication prevalent in 50% - 67% of cases is that the blood clot is only partially removed and clings to the mesh framework of the stent. The operating surgeon must either clean the debris from the stent retriever, to be reinserted or throw the stent retriever away and open …

The Effect Of Intermittent Theta Burst Stimulation On Biceps Corticomotor Excitability In Non-Impaired Individuals And Individuals With Tetraplegia, Blaize Majdic

Theses and Dissertations

Neuromodulation of the primary motor cortex (M1) in pair with physical therapy may be a promising method for improving motor outcomes after spinal cord injury (SCI). Increased excitability of the corticospinal motor pathways (i.e. corticomotor excitability) has shown to be associated with improved motor learning and skill acquisition. Intermittent theta burst stimulation (iTBS) is a form of non-invasive brain stimulation which can increase corticomotor excitability, as measured by an increase in the amplitude of motor evoked potentials (MEPs). However, the ability for iTBS to increase the corticomotor excitability of proximal muscles such as the biceps, and muscles affected by spinal …

Formulation And Validation Of Nanoparticle Controlled Delivery For Chemotherapeutic Drug Products, Shani L. Levit

Theses and Dissertations

Taxol, a formulation of paclitaxel (PTX), is one of the most widely used anticancer drugs, particularly for treating recurring ovarian carcinomas following surgery. Clinically, PTX is used in combination with other drugs such as lapatinib (LAP) to increase treatment efficacy. Delivering drug combinations with nanoparticles has the potential to improve chemotherapy outcomes. In this study, we use Flash NanoPrecipitation, a rapid, scalable process to encapsulate weakly hydrophobic drugs (logP in vitro. Encapsulating either PTX or LAP into nanoparticles increases drug potency. When PTX and LAP are co-loaded in the same nanoparticle, they have a synergistic effect that is greater than …

Development Of A Torque-Based Device For The Quantification Of Arm Rigidity In Patients With Parkinson’S Disease, Georgina O. Miller

Theses and Dissertations

Parkinsonian rigidity is caused by the inability of the muscles to relax and extend properly, due to reduced dopamine levels and often begins on one side of the body before spreading contralaterally. The current standard for determining joint rigidity in a clinical setting is a test completed by the clinician based on the feel of the relaxed wrist and elbow joints as they are passively flexed and extended and a series of ordinal rating scales, the Movement Disorder Society’s – Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), Hoehn and Yahr Scale (H&Y), and Parkinson’s Disease Questionnaire-39 (PDQ-39). These methods are used …

Dendrimer-Based Therapeutic Delivery Vehicle For The Treatment Of Ocular Diseases, Remy C. Cooper

Theses and Dissertations

The treatment of ocular diseases poses a significant challenge to drug delivery design, due to the eye’s complex anatomy, with a semi-permeable blood-ocular barrier and associated immune privilege. To address some of the delivery challenges, polycationic dendrimers are explored as vehicle for the treatment of posterior chamber disease. Dendrimers are a class of polymeric nanoparticles that are highly branched, multivalent and monodisperse, whose three-dimensional globular architecture has given them the nickname of “synthetic proteins”. Dendrimers are synthesized by reacting monomers in a step-wise fashion to produce generationally and radially increasing structures, with core, interior and surface chains that are highly …

Quantification And Modeling Of Bladder Biomechanics Mechanisms Linking Spontaneous Rhythmic Contractions And Dynamic Elasticity To Detrusor Overactivity, Zachary E. Cullingsworth

Theses and Dissertations

Overactive bladder (OAB) is a chronic condition affecting approximately 20% of adults in the United States. Detrusor overactivity (DO) is the presence of non-voiding contractions in the detrusor (bladder) muscle during filling and is present in some individuals with OAB. DO is currently identified visually during a urodynamics (UD) study involving pressure catheters and filling and voiding of the bladder to evaluate function. UD provides limited subtyping of DO, and an incomplete understanding of mechanisms contributing to OAB.

Aim 1 of this study was to develop objective tools to quantify, subgroup and better understand …

On-Demand Electrically Induced Decomposition Of Thin-Film Nitrocellulose Membranes For Wearable Or Implantable Biosensor Systems, Benjamin M. Horstmann

Theses and Dissertations

Implantable or subcutaneous biosensors used for continuous health monitoring have a limited functional lifetime requiring frequent replacement and therefore may be highly discomforting to the patient and become costly. One possible solution to this problem is use of biosensor arrays where each individual reserve sensor can be activated on-demand when the previous one becomes inoperative due to biofouling or enzyme degradation. Each reserve biosensor in the array is housed in an individual Polydimethylsiloxane (PDMS) well and is protected from exposure to bodily fluids such as interstitial fluid ( ISF) by a thin-film nitrocellulose membrane. Controlled activation is achieved by decomposing …

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 …

Extracellular Matrix Nanoparticles Effects On The Lung In Vivo, Brittaney E. Ritchie

Theses and Dissertations

Acute respiratory distress syndrome (ARDS) is a life-threatening condition that causes diffuse alveolar damage and a loss of the extracellular matrix (ECM). This leads to pulmonary edema and lung function deterioration. Our lab has created decellularized porcine lung, electrosprayed ECM nanoparticles that have been previously shown to have pro-regenerative capabilities in vitro.

In this study, the ECM nanoparticle effects on young murine lungs were tested in vivo. An ECM nanoparticle suspension, previously used for the in vitro studies, was aerosolized intratracheally into the lungs using a microsprayer. 24 hours later, the lung mechanics, bronchoalveolar lavage fluid, and histology …

Automatic Hip Analysis Suite, Nathan J. Veilleux

Theses and Dissertations

Image recognition and computer vision are becoming increasingly useful for diagnostic and surgical planning purposes. Analyses of patient morphology can be performed much more quickly and reliably with algorithmic assistance. Traditional measurements of the hip involve visual inspection of patient radiographs or hand calculation with software assistance. In the most extreme cases, estimates of bone orientation are made via palpation of a patient’s hip. There is the possibility for significant improvements in reliability if measurements can be made in the absence of human interpretation. As many of these techniques require CT scans as a prerequisite, all of the necessary information …

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 …

Development Of A Novel System For The Analysis Of The Cardiovascular And Autonomic Nervous Systems, Seyedmohsen Dehghanojamahalleh

Theses and Dissertations

Chapter 1 - An introduction to autonomic nervous system (ANS) and cardiovascular system (CVS): The performance of the ANS can be evaluated by quantizing the changes made by the autonomic nervous system. The most common parameters that are being used in autonomic nervous system assessment tests are blood pressure, heart rate, pressure pulse wave velocity, heart rate variability, and pulse waveform. In this dissertation, we designed and developed a system that assesses the activity of these two systems. Therefore, we represented four methods to 1- evaluate the dependence of neuro- and cardiovascular systems on sex, 2- non-invasively estimate the blood …

Adipose Tissue Engineering: A Therapeutic Strategy For The Treatment Of Obesity And Glucose Intolerance, Michael A. Hendley

Theses and Dissertations

Despite available treatment options, the number of people afflicted by type 2 diabetes has steadily risen for decades. Nearly 90% of the diabetic population also suffers from obesity and the link between the two diseases is undeniable. Characterized by rapid expansion of the adipose tissue and improper lipid storage, the mishandling of lipids by adipose tissue promotes the diabetic state. Excess lipids, unable to be properly stored, build up in peripheral tissues promoting insulin resistance and type 2 diabetes. Therapeutic strategies designed to address adipose tissue lipid handling could represent a promising treatment strategy for obesity associated type 2 diabetes. …

The Impact Of Patient-Specific Vascular Structure On Localized Cooling In The Human Heart, Nathan Paul Spangenberg

Theses and Dissertations

Acute Myocardial Infarction (AMI) is the leading cause of worldwide death and disability, and approximately 720,000 Americans will experience an AMI in 2018. Studies have shown that rapid hypothermia therapy (<35°C) before reperfusion in patients with AMI can reduce infarct size by 37%. Localized therapeutic hypothermia has proven the potential to cool heart tissue rapidly following AMI, 3°C in 5 minutes. Using Materialise Mimics digital imaging software and the finite volume method we analyzed temperature distributions in six patient-specific left main coronary artery (LMCA) models. A mock circulatory loop was used to determine the exiting temperatures of a standard 7 Fr catheter to feed into our model with flow rates ranging from 29.2 ml/min to 68.85 ml/min. Our work showed that therapeutic hypothermia (TH) temperatures were evident at the outlets of three out of all six heart models, which varied in each left anterior descending (LAD) and left circumflex (LCX) artery depending on flowrate. Results of this study indicate that biovariability in patient-specific vascular structures significantly impacts therapeutic hypothermia (TH) treatment methods. These results indicate that further research is needed to examine more accurate physiological effects, such as pulsatile flow and vessel wall thickness. Future models will be used to provide insight to guide more efficient TH device designs and operation parameters to optimize patient outcomes following AMI.

Initial Development Of A Prototype Sensor Testbed For Fetal Monitoring, Christian Beauvais

Theses and Dissertations

The objective of this research is to design and manufacture a device that exhibits some of the bio-physiological signals relevant to fetal health monitoring. Currently, limited options exist for testing the performance of monitoring devices such as the tocodynamometer (TOCO) and electrocardiograph (ECG) that measure the bio-physiological signals of a woman and her fetus. Sensor designers need ways of generating and acquiring signals that do not carry the ethical burden of human testing. The development of such a device, as considered in this work, may involve using muscle wire or an inflatable tube as prospective foundations for simulating uterine contraction. …

Experimental Methods And Techniques For Improved Biomechanical Characterization Of Diverse Murine Aortopathies, Brooks Alexander Lane

Theses and Dissertations

Aortopathies constitute a broad class of diseases affecting the aorta – the largest artery responsible for distributing oxygenated blood to the systemic circulation. Specifically, aortic aneurysms (AAs) are described as a focal dilation of the vascular wall exceeding 50% of the normal vessel diameter. Ultimately AAs may stabilize, dissect, or rupture, with the latter virtually ensuring mortality. Currently clinicians consider prophylactic intervention based on size and growth-rate criteria that have been estimated from large-cohort statistical analyses. These criteria, however, fail to address the underlying mechanisms. Furthermore, 13% of small-to-mid sized AAs have been found to rupture prior to meeting these …

Gene Expression Studies For Analyzing Effects Of Space Radiation In Tissues, Amatulshakoor Mohammed Farooqui

Theses and Dissertations

Human exploration beyond the earth's orbit poses many risks for the crew on these missions. One of the major health risks is exposure to space radiation environment beyond the earth’s magnetic field. The space environment exposes astronauts to high levels of ionizing radiation such as galactic cosmic rays. The radiations can have acute and delayed effects on the human body. The primary response to tissue injury is increased oxidative stress and inflammation. The overall objective of this study was to analyze the effects of ionizing radiation in heart tissue by quantifying its impact on the expression of genes that correlate …

Controlling Co Dose From Corm-Loaded Electrospun Scaffolds With Diffusion-Based Modeling And Experimental Assessment Of Endothelial Cell Response, Kenyatta S. Washington

Theses and Dissertations

Cardiovascular disease (CVD) accounts for one in every five deaths in the United States alone due to occlusion in small diameter (< 6 mm) vessels. The current treatment options includes bypass grafting; however, more than 30 percent of patients do not have viable saphenous veins for autologous grafting [1]. Therefore, tissue engineering is being considered as an alternative approach. The overall goals of this project were to develop a tissue engineered vascular graft with the incorporation of carbon monoxide releasing molecules (CORMs) and to determine the impacts of carbon monoxide (CO) on endothelial cells (ECs) with the goal of promoting a functional endothelium within the graft. This was accomplished through two complementary studies: investigating the impacts of CO-loaded electrospun scaffolds on ECs for cardiovascular applications and diffusion-based modeling of drug delivery of gasotransmitters from tissue engineered scaffolds. In the first study, we extended the maximum in vitro incubation time to permit better cellular attachment and proliferation with a newly-synthesized, more hydrophobic CORM (DK3) and established the impact of CORMs on EC viability and function (e.g. reactive oxygen species (ROS) products, and ROS levels). We further investigated toxicity and biocompatibility of a newly synthesized CORM (DK4) loaded within PCL thin films and nanoparticles. We concluded that the DK4 and other compounds are not toxic at doses ranging from 0 – 50 μg/mL to the ECs both within nanoparticles that can be internalized within cells. We also conducted an in vivo pilot study to determine graft biocompatibility and preliminary results showed that CORM implants maintain mechanical integrity, support blood flow, and do not show toxicity for up to six weeks. In the second study, we validated a computational model and analyzed the output of CO delivery to better understand and control local dose. For CO release, this model is necessary because of the limitations with real-time experimental analysis and the need to better understand the dose available to the cells. We demonstrated that the validated model can be used to predict drug availability to cells for a variety of scaffolds and drug molecules. Our simulated results suggest that only a fraction of the initial concentration of gasotransmitters released from fibers that enters the interstitial fluid in vivo, or culture media in vitro, will be available to cells. We also demonstrated that fiber orientation and fiber diameter are important for drug delivery, but fiber density provides even more important information. The more contact area within the fiber scaffolds is equivalent to experimental conditions with more cell attachment and spreading. These parameters are not only important for traditional tissue engineering, but also for drug delivery. Overall, these results demonstrate the feasibility of making a tissue engineered vascular graft with the incorporation of CORMs and validating he importance of computational modeling of diffusion-based transport of CO. Future work will involve performing surface modifications to enhance cell attachment and proliferation, using the developed computational model to better predict dose available to cells, and experimentally determining impact of CO dose on ECs.

Inverted Cone Convolutional Neural Network For Deboning Mris, Oliver John Palumbo

Theses and Dissertations

Data plenitude is the power but also the bottleneck for data-driven approaches, including neural networks. In particular, Convolutional Neural Networks (CNNs) require an abundant database of training images to achieve a desired high accuracy. Current techniques employed for boosting small datasets are data augmentation and synthetic data generation, which suffer from computational complexity and imprecision compared to original datasets. In this thesis, we intercalate prior knowledge based on the temporal relation between the images in the third dimension. Specifically, we compute the gradient of subsequent images in the dataset to remove extraneous information and highlight subtle variations between the images. …