Biomedical Engineering and Bioengineering Commons^™

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. …

Development Of Investment Casting Method For Production Of Metal Foams For Tissue Engineering, Justin Aaron Womack

Theses and Dissertations

Ideal biomaterials for bone tissue regeneration are bone-mimicking structures that present a fully interconnected porous structure, have similar mechanical properties to bone, and exhibits a specific biodegradation behavior that is at the same rate as adjoining cell growth. Metals have high wear resistance, ductility, impact strength, and strain energy absorption capacity compared to other materials, which makes them suitable candidates for tissue engineering scaffolds. Magnesium and zinc are of interest for bone tissue regeneration for their biocompatibility and mechanical properties close to human bone. A newly developed process, presented in this thesis, for the creation of porous magnesium and zinc …

Investigation Of Dielectrophoretic Microfluidic Trap System For Separation And Parallel Analysis Of Single Particles, Tae Joon Kwak

Theses and Dissertations

Separation and identification of single molecules and particles based on their chemical, biochemical and physical properties are critical in wide range of biomedical applications. Manipulating a single biomolecule requires sensitive approaches to avoid damage to the molecule. Recent progress in micro- and nano-technology enabled the development of various novel methods and devices to trap, separate, and characterize micro- and nano-particles. In this dissertation, a microfluidic particle trap system to electrically separate particles at the single particle level was developed through particle manipulation methods using dielectrophoresis. The research in this dissertation will explain the operation strategy and setup of the novel …

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.

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 …

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. …

Bioprinting Of 3d Perfusable Structures Using An Extrusion-Based System, Prabhuti Kharel

Theses and Dissertations

Bioprinting is a technique of creating 3D cell laden structures by accurately dispensing biomaterial to form complex synthetic tissue. Bioprinting is a process of additive manufacturing where the cell functionality and viability is preserved within the printed structure. Bioprinting is a promising alternative to produce physiologically relevant 3D structures that mimic the native tissue. However, fabrication of complex structures with vascularization has been a major challenge in bioprinting. To overcome this challenge sacrificial printing in combination with fugitive inks has been explored to create vascularize structures. The objective of this study is to fabricate hollow channels within the bioprinted structure …

Fabrication Of Enhanced Carbon Based Biocompatible And Biodegradable Microelectronic Materials Derived From Lignocellulosic Biomass, Harrison Thomas Hawkins

Theses and Dissertations

The development of materials capable of harmlessly being broken down and removed from the body is a crucial step towards the development of short-term application electronic biomedical implants. Once developed, these implants, known as bioresorbable electronics, will open a wide array of temporary applications in the field of biomedical implantable devices. Necessary to the operation of bioresorbable electronics within the body is a power source that is similarly biocompatible and biodegradable. To this end, enhanced carbon-based materials and a bio-ionic liquid were developed for the fabrication of a preliminary implantable and bioresorbable battery and tested for functional properties. Electrodes were …

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

Theses and Dissertations

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

Hrv - Ecg Generator: Software For Testing Heart Rate Variability Detection, Matthew Joseph Pogorelec

Theses and Dissertations

Heart rate variability (HRV) has been shown to serve as an effective diagnostic and prognostic tool in a variety of clinical applications, including for patients who have suffered from myocardial infarction, sepsis and liver cirrhosis. There currently exist a variety of devices and software to quantify HRV based on RR interval series collected from ECG data. However, as the uses for HRV expand, a greater variety of devices for different applications are being designed and developed. Thus, it is useful to have available a method for efficiently testing preliminary software. The HRV/ECG Generator software is designed to build both an …

Rage Expression And Inflammation In Alzheimer’S Disease: In Vitro Model Development And Investigation Of A Potential Peptoid Inhibitor, Lauren Michell Wolf

Theses and Dissertations

Despite the increasing prevalence of Alzheimer’s disease (AD), efforts to establish a definitive treatment or cure have met with little success. Many previous therapeutic strategies for AD have focused on the aggregation and accumulation of amyloid-b (Ab) in the brain, concentrating on its small intermediate aggregates as the primary targets to ameliorate neurotoxicity and damage. This approach has yielded little progress, and more recent discussions have shifted to strategies geared toward a multifaceted pathology, with chronic neuroinflammation emerging as an important factor in the disease etiology and progression.

The receptor for advanced glycation end-products, or RAGE, is …

Experimental Study Of Free-Solution Separation Under Pulsed Electrophoresis In Microchip, Xin Liu

Theses and Dissertations

Microchip electrophoresis (MCE) is a promising analytical tool started more than two decades. With the characteristics of short analysis time, trace level sample, high- throughput and easily integration, lots of efforts have been done with the transportation of the applications from capillary to microfabricated devices. However, with the complex designs on microchip rather than a single straight capillary channel, the strategies and approaches have to be figured out under the challenges of sample introduction, the improvement of separation conditions and the detection, for instance.

In miniaturized microchip, the separation channel is reduced to several centimeters or less, fast and quality …

Analysis Of Cellular Interactions Within A Collagen Hydrogel, Austin N. Worden

Theses and Dissertations

Evidence has arisen over the past several years that use of a three- dimensional (3D) culture system provides a distinct advantage over two- dimensional (2D) systems when cellular interactions are examined in a more natural environment. Changes in morphology, speed, and directionality of cells tested in both planar and 3D matrices have all demonstrated that using 3D system is advantageous. The changes to the cellular migration patterns were shown to be dependent on several variables within the surrounding substrate including cellular content, physical environment, and the matrix chemical milieu. We have taken advantage of using collagen hydrogels as a 3D …

An Anatomical Basis Of The Differential Cholinergic Modulation Of Valence-Specific Pyramidal Neurons In The Basolateral Amygdala, Nguyen Vu

Theses and Dissertations

Emotion is a crucial component of the decision-making process. The amygdala, known as the “orchestrator” of the emotion circuit, associates emotional valence with incoming sensory stimuli and thus contributes to decision- making. Within the basolateral nucleus of the amygdala (BLA), spatially segregated and genetically distinct pyramidal neurons (PNs) have been identified based on their correspondence to distinct behavioral stimuli. These PNs project to several brain regions mediating different aspects of the emotional spectrum.

For example, BLA PNs projecting to prelimbic (PL) and infralimbic (IL) cortex are involved in fear acquisition and fear extinction, respectively. However, the mechanism by which these …

Role Of P-Glycoprotein In Alzheimer’S Disease For Enhanced Brain Elimination Of Amyloid-Β, Hope Holt

Theses and Dissertations

Alzheimer’s disease (AD), the most common form of neurodegenerative disorder, is characterized by deposition of amyloid-β (Aβ) plaques in the brain. Aβ monomer undergoes nucleation to form oligomers, then soluble aggregates, then fibrils which make up the plaques. Aβ oligomer species are believed to be the most neurotoxic aggregate species. Currently under investigation is a mechanism for Aβ removal from the brain, across the blood-brain barrier (BBB). P-glycoprotein (P-gp) is a membrane-bound efflux protein located on the apical, or blood, side of the BBB, which transports a wide variety of substrates. Further complicating this potential clearance mechanism is the reduction …

Three-Dimensional Collagen Tubes For In Vitro Modeling, Rebecca Jones

Theses and Dissertations

Collagen type I represents a novel material for three-dimensional in vitro models. While two-dimensional models are typically inadequate for recreating the complex processes of the body, collagen provides a three-dimensional basis with a variety of applications, including remodeling of vascular cells under tension and vascular stenosis. Smooth muscle cells reorganize and reconstruct their environment differently under conditions of tensions, such as with sutures, or under conditions without applied external tension. Vascular stenosis, the abnormal narrowing of blood vessels, arises from defective developmental processes or atherosclerosis-related adult pathologies. Stenosis triggers a series of adaptive cellular responses that induces adverse remodeling, which …

Analysis Of The Effect Of Corrosion On The Surface Chemistry Of Mild Steel Exposed To Biofuel, Timothy D. Plourde

Theses and Dissertations

The use of biofuels in society is steadily becoming more prevalent. Through this proliferation a concern regarding the role of the fungus Byssochlamys nivea in microbially induced corrosion has surfaced. Through the use of X-ray Photoelectron Spectroscopy (XPS) and Scanning Electron Microscope (SEM) technology, this thesis focused on attempting to determine what effect, if any, Byssochlamys nivea has on the corrosion of mild steel. For this analysis, samples were placed in environments that simulated the conditions of fuel tanks containing the biofuel B20, water, and spores of Byssochlamys nivea for varying lengths of time. However, due to a variety of …

Designing Biomimetic Implant Surfaces To Promote Osseointegration Under Osteoporotic Conditions By Revitalizing Mechanisms Coupling Bone Resorption To Formation, Ethan M. Lotz

Theses and Dissertations

In cases of compromised bone remodeling like osteoporosis, insufficient osseointegration occurs and results in implant failure. Implant retention relies on proper secondary fixation, which is developed during bone remodeling. This process is disrupted in metastatic bone diseases like osteoporosis. Osteoporosis is characterized low bone mass and bone strength resulting from either accelerated osteoclast-mediated bone resorption or impaired osteoblast-mediated bone formation. These two processes are not independent phenomena. In fact, osteoporosis can be viewed as a breakdown of the cellular communication connecting bone resorption to bone formation. Because bone remodeling occurs at temporally generated specific anatomical sites and at different times, …

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

Theses and Dissertations

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

Design And Testing Of An Agonist-Antagonist Position-Impedance Controlled Myoelectric Prosthesis, Christopher Aymonin

Theses and Dissertations

Intuitive prosthetic control is limited by the inability to easily convey intention and perceive physical requirements of the task. Rather than providing haptic feedback and allowing users to consciously control every component of manipulation, relegating some aspects of control to the device may simplify operation. This study focuses on the development and testing of a control scheme able to identify object stiffness and regulate impedance. The system includes an algorithm to detect the apparent stiffness of an object, a proportional nonlinear EMG control algorithm for interpreting a user’s desired grasp aperture, and an antagonistically acting impedance controller. Performance of a …

Development Of An Eye Movement Based Predictive Model For Discrimination Of Parkinson's Disease From Other Parkinsonisms And Controls, Mary Anisa Kannan

Theses and Dissertations

Purpose: Due to the neurological aspects of Parkinson’s Disease (PD) and the sensitivity of eye movements to neurological issues, eye tracking has the potential to be an objective biomarker with higher accuracy in diagnosis than current clinical standards. Currently when PD is diagnosed clinically, there is an accuracy of 74% when diagnosed by a general practitioner and 82% when diagnosed by a movement disorder specialist. This study was designed to: 1. Assess eye movements as a potential biomarker for Parkinson’s Disease. 2. Determine if eye movements can distinguish between Parkinson’s Disease and commonly confounded movement disorders with parkinsonian symptoms. 3. …

A Computational Assessment Of Lisfranc Injuries And Their Surgical Repairs, Michael Perez

Theses and Dissertations

While Lisfranc injuries in the mid foot are less common than other ankle and mid foot injuries, they pose challenges in both properly identifying them and treating them. When Lisfranc injuries are ligamentous and do not include obvious fractures, they are very challenging for clinicians to identify unless weight bearing radiographs are used. The result is that 20%-40% of Lisfranc injuries are missed in the initial evaluation. Even when injuries are correctly identified the outcomes of surgical procedures remain poor. Existing literature has compared the different surgical procedures but has not had a standard approach or procedures across studies. This …

Assessment Of Access Methods For Mobile Maps For Individuals Who Are Blind Or Visually Impaired, David Parker

Theses and Dissertations

When people go to a mall, museums, or other such locations they tend to rely on maps to find their way around. However, for people who are blind or visually impaired (BVI) maps are not easily accessible and they depend on other means, such as a guide, to get around. Research has only just begun to investigate providing maps for people who are BVI on touch screen devices. Many different types of feedback have been used: audio (sound), tactile (touch), audio-tactile, and multitouch. Some research has been conducted on the benefit of using multiple fingers (multitouch) and has found conflicting …

Cell Type And Substrate Dependence Of Fibronectin Properties And Mechanotransduction, Navpreet S. Saini

Theses and Dissertations

Fibronectin is an important protein that is able to bind to other fibronectin molecules and to cell surface receptors. In doing so, the interactions fibronectin can perform is important for the processes of cell migration and tissue formation. Understanding the properties of fibronectin and fibril assembly is useful for areas such as wound healing, where fibronectin molecules are assembled to protect the tissue and to perform other tasks. Because of these reasons, it is important to understand how fibronectin is assembled and how its properties affect the fibril assembly, which in return affects the way the cell matrix operates. Previously …

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

Theses and Dissertations

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

Mechanochemical Regulation Of Epithelial Tissue Remodeling: A Multiscale Computational Model Of The Epithelial-Mesenchymal Transition Program, Lewis Scott

Theses and Dissertations

Epithelial-mesenchymal transition (EMT) regulates the cellular processes of migration, growth, and proliferation - as well as the collective cellular process of tissue remodeling - in response to mechanical and chemical stimuli in the cellular microenvironment. Cells of the epithelium form cell-cell junctions with adjacent cells to function as a barrier between the body and its environment. By distributing localized stress throughout the tissue, this mechanical coupling between cells maintains tensional homeostasis in epithelial tissue structures and provides positional information for regulating cellular processes. Whereas in vitro and in vivo models fail to capture the complex interconnectedness of EMT-associated signaling networks, …