Biomedical Engineering and Bioengineering Commons^™

Development Of A Customizable Framework For Data Driven Hemodynamic Analysis With Applications In Neurovascular And Cardiovascular Scenarios, Rachel Mae Hillner

Theses and Dissertations

Cardiovascular disease, including but not limited to heart failure and aneurysms, remain a leading cause of death worldwide. Persons over the age of 40 experience upwards of a 20% chance of developing heart failure in their lifetime. With a decrease in viable donor hearts, the reliance on mechanical heart assist devices is on the rise. However, such devices are not without their complications. Specifically, for left heart failure, a common treat, the left ventricular assist device, is characterized by clotting, stroke, and low survival rates as a result. Many studies suggest that such unfavorable results are correlated to adverse hemodynamic …

A Reduced Order Model For Estimation Of Fractional Flow Reserve (Ffr) In Coronary Artery Disease: Assessing The Impact Of Side Branches, Arber Vila

Theses and Dissertations

Coronary Artery Disease (CAD) affects millions of people worldwide and remains a leading cause of morbidity and mortality. To effectively plan treatment and risk stratification, assessing CAD severity is of paramount importance. Fractional flow reserve (FFR) is a critical clinical parameter used to evaluate CAD severity, measured by the ratio of mean distal coronary pressure to mean aortic pressure during hyperemic conditions. Although non-invasive FFR estimation methods have gained popularity, computational fluid dynamics (CFD) is impractical for routine clinical use due to the time and resources required. To address this issue, a reduced order model is proposed that accurately captures …

Neurodevelopmental And Transient Impacts Of Brain Kynurenic Acid Elevation And Sleep-Wake Behavior, Katherine Rentschler

Theses and Dissertations

Sleep is vital for healthy cognition and mood. Sleep dysregulation is implicated in psychiatric disorders such as schizophrenia and bipolar disorder. Sex differences in sleep and arousal dysregulation are prominent in patients with psychotic disorders. Elevated levels of the neuroactive tryptophan metabolite, kynurenic acid (KYNA), have been found in cerebrospinal fluid and postmortem brain tissue samples from patients with psychotic disorders. KYNA is an astrocyte derived antagonist at N-methyl-D-aspartate (NMDA) glutamate receptors and α7 nicotinic acetylcholine (α7nACh) receptors. KYNA is synthesized in the brain from its biological precursor, kynurenine, via the enzyme kynurenine aminotransferase II (KAT II), a potential therapeutic …

Gluten Free Diet Ameliorates Si Enteropathy In Iga Deficient Mice, Ryan Albert William Ball

Theses and Dissertations

Secretory IgA is the most abundant antibody in the intestinal mucosal and functions as the first line of defense against pathogens and micro-organisms in the gut. Selective IgA deficiency is the most common form of antibody deficiency. Clinically, IgA deficient patients are largely asymptomatic, they are however at a higher risk of developing certain inflammatory conditions like Celiac disease; an SI-specific enteropathy triggered by exposure to dietary gluten. Interestingly, celiac patients are 10-15 times more likely to have an IgA deficiency. Recent studies have shown that IgA^-/- mice develop enteropathy specifically in the ileum. We confirmed this phenotype in …

Detecting Physiological Concentrations Of Alzheimer’S Associated Amyloid-Β Protein Utilizing A Cell-Based Response, Brittany Elizabeth Watson

Theses and Dissertations

Alzheimer’s disease (AD) is characterized symptoms of cognitive impairment resulting from blood-brain barrier (BBB) breakdown and neuronal cell death. AD is associated with aggregated amyloid-β (Aβ) plaques deposited around brain vasculature and within the brain. Changes in the brain occur up to 20 years before symptoms arise; however, there is currently no pre-symptomatic detection method available for AD. An intact BBB requires tight junction proteins (TJs) that render relatively high transendothelial electrical resistance (TEER). AD-associated breakdown of the BBB correlates with vascular Aβ deposition, suggesting that aggregated, pathological Aβ can modulate TEER. We explore leveraging this cellular response for early …

Efficient Scopeformer: Towards Scalable And Rich Feature Extraction For Intracranial Hemorrhage Detection Using Hybrid Convolution And Vision Transformer Networks, Yassine Barhoumi

Theses and Dissertations

The field of medical imaging has seen significant advancements through the use of artificial intelligence (AI) techniques. The success of deep learning models in this area has led to the need for further research. This study aims to explore the use of various deep learning algorithms and emerging modeling techniques to improve training paradigms in medical imaging. Convolutional neural networks (CNNs) are the go-to architecture for computer vision problems, but they have limitations in mapping long-term dependencies within images. To address these limitations, the study explores the use of techniques such as global average pooling and self-attention mechanisms. Additionally, the …

Prediction Of Persistent Post-Traumatic Headache With Long Short-Term Memory Networks, Todd C. Campo

Theses and Dissertations

Military members in combat situations are at a high risk for experiencing a Traumatic Brain Injury (TBI), often leaving them with Post-Traumatic Headache (PTH). There is currently a poor understanding of what factors predict if a patient will endure acute (short-term) PTH or Persistent PTH (PPTH). The Concussion Assessment, Research, and Education (CARE) Consortium dataset contains a variety of pre-and-post-injury concussion assessments taken by NCAA athletes and service academy cadets between 2014 and 2018. Participants in this study (n = 1769) suffered a TBI. Using this longitudinal data, three models were constructed: an LSTM model using the raw assessment scores, …

Formulation Of Encapsulated Nanoparticles Of Leek Extract As Antimicrobial And Anticancer Agent, Rawan Hassan Mohamed Elghanam

Theses and Dissertations

Leek extract (LEK) has broad therapeutic activity. However, plant extract use has many drawbacks, which could be resolved using nanocarriers. The purpose of this research work was to prepare chitosan nanoparticles (CS NPs) encapsulating LEK and investigate their antioxidant, antimicrobial, and anticancer activity. Gas chromatography-mass spectroscopy was used to determine the LEK components. The CS-LEK NPs were produced by tripolyphosphate (TPP) crosslinking with chitosan (CS) the ionic gelation methodology. The particle size was 331 nm, zeta potential (ZP) was 28.9 mv, polydispersity index (PDI) was 0.4, encapsulation efficiency (EE) was 65.6%, and loading capacity (LC) was 28.8 % of the …

An Epileptic Seizure Detection Method From Eeg Signals Based On A Classifier-Driven Feature Reduction Technique, Raymond N. Kamel

Theses and Dissertations

Epileptic seizure detection can improve the quality of life of epileptic patients, allow for more accurate medication, and minimize the risk of sudden unexpected death in epilepsy (SUDEP). This thesis work aims to develop a robust and stable algorithm for epileptic seizure detection through the classification of EEG signals. To achieve this aim, a methodology is proposed to develop a classifier that can differentiate between the healthy (normal), interictal, and ictal states of EEG signals, while maximizing the classification accuracy and minimizing the computational redundancy. The main pillar upon which this methodology is designed is using a problem-specific classifier-driven feature …

Electrochemical Sensors And Biosensors Of Biomarkers And Therapeutic Agents Detection, Mahmoud Abdelhakem

Theses and Dissertations

Electrochemical sensing is a pioneering tool amongst all other sensing techniques even though it had been started in the early 20th century. Due to their cost efficacy, accuracy, and real-time measurement, electrochemical sensing has been utilized in a vast of biomedical applications in therapeutic drug monitoring and biomarker detection. This thesis work concerned the monitoring of three therapeutic agents in spiked plasma, urine, dosage form, and interstitial skin fluid with high specificity and accuracy. Two of our sensing platforms utilized nanomaterials for sensing (sensors) of Cilostazol and Velpatasvir utilizing α-MnO2-V2O5 (metal oxide nanorods) and NH2- MIL-53 (Aluminum-based metal organic frameworks), …

Polyethyleneimine Shell Nucleic Acid Nanostructures From Gold Nanoparticle Template For Chemotherapeutic Drug Delivery, Brendan Guy Rucci

Theses and Dissertations

The next generation of anticancer agents will emerge from rationally designed nanostructured materials. This work involved the synthesis and characterization of novel hollow DNA-conjugated gold nanoparticles (DNA-AuNPs) for controlled drug delivery. Polyethyleneimine (PEI) was bound to citrate-capped AuNPs, forming polymer-shell nanoparticles. Dissolution of the gold core via iodine formed hollow core polymeric nanoparticles (HCPPs) and a high density of DNA (85 molecules/particle) containing daunorubicin was conjugated. Particles were spherical with an average diameter of 105.7±17.3 nm and zeta potential of 20.4±3.54 mV. We hypothesize the DNA backbone electrostatically condensed to the primary amines on the surface of the particle toroidally, …

A 3d Bioprinted Hydrogel Microfluidic Device For Screening Applications, Anant Bhusal

Theses and Dissertations

The microfluidic enabled the integration of engineered miniaturized tissue models for drug screening. Conventional polydimethylsiloxane or plastic-based devices require multiple fabrication steps, which are challenging. We developed a 3D bioprinting approach to create prototypes of hydrogel-based multi-material microfluidic devices integrated with microtissue models. The approach utilizes poly(ethylene glycol) diacrylate and gelatin-methacryloyl to create microfluidic chips using multi-material bioprinting capacity with a high resolution of 15µm on x-y and 50µm on the z-axis and post-printing viability of >90%. We demonstrated easy regulation of stiffness from 24±5 kPa to 1,180±9 kPa and burst pressure from 16±1kPa to 256±19 kPa in the chip …

Computational Modeling Of Temporal Eeg Responses To Cyclic Binary Visual Stimulus Patterns, Connor M. Delaney

Theses and Dissertations

The human visual system serves as the basis for many modern computer vision and machine learning approaches. While detailed biophysical models of certain aspects of the visual system exist, little work has been done to develop an end-to-end model from the visual stimulus to the signals generated at the visual cortex measured via the scalp electroencephalogram (EEG). The creation of such a model would not only provide a better understanding of the visual processing pathways but would also facilitate the design and evaluation of more robust visual stimuli for brain-computer interfaces (BCIs). A novel experiment was designed and conducted where …

Characterization And Decoding Of Speech Activity From Intracranial Signals, Pedram Zanganeh Soroush

Theses and Dissertations

Speech is the first and foremost means of human communication. Millions of people worldwide suffer from severe speech disorders due to neurological diseases such as amyotrophic lateral sclerosis (ALS), brain stem stroke, and severe paralysis. A speech neuroprosthesis that decodes speech directly from neural signals could dramatically improve life for these individuals. Recent studies have demonstrated that it is possible to decode and synthesize various aspects of acoustic speech directly from intracranial measurements of electrophysiological brain activity. For those who have completely lost the ability to speak, the objective is to synthesize acoustic speech directly from brain activity during imagined …

Advanced Modeling And Innovative Transcranial Magnetic Stimulation Coil Designs For The Treatment Of Neurological Disorders, Mohannad Tashli

Theses and Dissertations

Transcranial magnetic stimulation (TMS) is a safe, effective and non-invasive treatment for several mental and psychiatric disorders. TMS is an FDA approved treatment and is commonly applied to patients who do not respond to medications for the treatment of clinical depression, smoking cessation, obsessive-compulsive disorder and migraine. Recently, there has been an increase in the development of electromagnetic neuromodulation techniques targeted at enhancing the effectiveness of TMS devices for the treatment of mental diseases. In TMS stimulation, focality is an important factor which determines the specificity of the pulses induced in different brain tissues. The electromagnetic pulses must be confined …

The Wound Healing And Antibacterial Properties Of Mesenchymal Stromal Cell Extracellular Matrix Nanoparticles, Emily N. Wandling

Theses and Dissertations

Treatments for acute respiratory distress syndrome (ARDS) are still unavailable and the prevalence of the disease has only increased due to the Covid-19 pandemic. Mechanical ventilation regiments are still utilized to support declining lung function, but they also contribute to lung damage and increase the risk of bacterial infection. The anti-inflammatory and pro-regenerative abilities of mesenchymal stromal cells (MSCs) have shown to be a promising therapy for ARDS. We propose to utilize the regenerative effects of MSC secretome and the extracellular matrix (ECM) into a nanoparticle. Our mouse MSC (MMSC) ECM nanoparticles were characterized using size, zeta-potential, and mass spectrometry …

Quantifying Fibronectin Mechanical Properties Using Antibody-Mediated Optical Tweezing (Amot), Caleb Dalton

Theses and Dissertations

Despite decades of investigations into fibronectin (FN) fibrillogenesis, fibril mechanics remain unclear. One of the most important roles for FN fibrils is in the arena of cellular mechanotransduction. Numerous studies have demonstrated that cells sense and respond to the mechanical properties of their surroundings; since FN fibrils are a major constituent of the ECM that links cells to their surroundings, mechanotransduction cannot be fully understood without understanding the mechanical properties of FN fibrils. In this proposal, a novel biomechanical assay is developed to probe isolated FN fibrils and quantify their response to specific loading conditions. This will be accomplished by …

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, …

Development Of A Crosslinked Osteochondral Xenograft And A Collagen Stabilizing Intra-Articular Injection To Remediate Cartilage Focal Lesions To Prevent Osteoarthritis, Mark Lewis Mosher

Theses and Dissertations

Osteoarthritis is one of the most common causes of disability in adults in America. It is a progressive and degenerative disease where the articular cartilage is broken down and lost from the surfaces of bones causing chronic pain and swelling in the joints, and currently has no cure. The most commonly osteoarthritis starts from a focal lesion on the cartilage surface, which will expand on the surface and downwards through the thickness of the tissue. The current gold standard for correcting cartilage focal lesions is the osteochondral autograft/allograft transplantation (OAT), which replaces the defect with a fresh osteochondral graft. The …

Oxidized Fibrin Alginate Microbeads To Treat Vascular Calcification, Brittany Nichole Macha

Theses and Dissertations

Calcification is linked to a high prevalence of cardiovascular events and mortality due to arterial stiffness. Stiffening of the arteries in the case of medial calcification is due to hydroxyapatite mineral deposited in the artery thus leading to the loss of elastin. A possibility of removing this rogue mineral along the vessel walls could be the use of osteoclasts. Osteoclasts, a type of osteocyte, have the unique ability to absorb bone in the bone turnover process. It is proposed that in the future, osteoclasts be delivered to the site of mineralization through oxidized alginate-fibrin microbeads. Alginate hydrogels have proven great …

Investigating The Role Of Cryptochrome Activity In Arabidopsis Plant And Blue Light Exposure In Saos-2 Cell-Mediated Mineralization, Maria Nijr Albaqami

Theses and Dissertations

Cryptochromes (CRYs) are flavoproteins that absorb blue light and are associated with the perception of electromagnetic stimuli in a variety of organisms including animals and plants. When exposed to blue light, CRYs undergo flavin redox cycles and form radical pairs intermediates that are assumed to be magnetically sensitive as predicted by the radical-pair hypothesis. However, it is unknown if CRYs fulfill the criteria to act as biological magnetosensors. In the first aim, Arabidopsis thaliana seedlings were exposed to blue light and a time-dependent weak magnetic field at radiofrequency (RF) of 7 MHz as a diagnostic tool to test the radical-pair …

Importance Of Light Activation For Plant Cryptochrome And Antibacterial Drug Delivery Strategies, Merfat Ahmed Hammad

Theses and Dissertations

The goal of this project is to investigate the benefits of applying light in different systems. In the first part, the magnetoreception process that occurs in the light activated cryptochrome of Arabidopsis Thaliana was investigated. In the second part, photo-carbon monoxide releasing molecules (photo-CORMs) were investigated for their antibacterial effect to develop biomedical strategies. Overall, this has been achieved in three different studies. The first study investigated if the forward lightdriven reaction is involved in the magnetoreception process or not in cryptochrome (CRY). To accomplish this, the plant seedlings were tested for 90 minutes as follows: 5 minutes in the …

Bioactive Self-Forming Hydrogels For Biomedical Applications, Kirstene Arcuino Gultian Giddings

Theses and Dissertations

Hydrogels are soft biomaterials that feature a wide range of physical and biochemical properties. Although highly versatile, hydrogels typically require an exogeneous input (e.g., light, pH, temperature) to form, and this limits their use to conditions where a catalyst is present. The goal of this dissertation is to expand the use of catalyst-based hydrogels by developing hydrogels with independently tunable properties which gel in situ without external stimuli. This new class of hydrogels was developed by first modifying macromers with norbornene (Nor) or tetrazine (Tet) moieties. Macromers containing Nor or Tet remain liquid when dissolved, and upon mixing self-form into …

Investigation Of Flexible And Wearable Devices For The Analysis Of Biological Signals, Muhammad Usman

Theses and Dissertations

The application potential for flexible and wearable electronics in the field of healthcare has received great interest in recent years. Flexible and wearable devices based on soft, biocompatible materials can be comfortably attached to the human skin for continuous health monitoring. In this work, we present two novel wearable bioelectrical impedance analysis (BIA) systems for body composition measurement. First, we developed a wearable ring-based BIA system for body fat monitoring. The wearable ring contains flexible copper electrodes to interface with the human body. The device is tested on 40 healthy volunteers and the results demonstrate a high correlation with an …

Biomaterials With Diverse Physical & Chemical Signals For Tissue Engineering Applications, Mohammed Mehdi Benmassaoud

Theses and Dissertations

Cells within natural tissues are exposed to a myriad of biochemical and biophysical cues, and it is challenging to recapitulate these signals in vitro. The goal of this dissertation is to create materials with distinct biophysical and biochemical signals as platforms that induce controllable yet diverse cellular responses. To evaluate the effects of heterogeneous biophysical cues on cell behavior, cells were encapsulated in porous scaffold-hydrogel composites, and it was found that cellular metrics (morphology, matrix mechanosensing) varied within soft (hydrogel) and rigid (scaffold) composite regions. To create soft materials with spatially defined biochemical signals, hydrogels that can be subsequently photopatterned …

Investigating The Impact Of Endothelial Dysfunction And Aging On Vascular Remodeling Using Mouse Models, Liya Du

Theses and Dissertations

Endothelial dysfunction, characterized by a reduction in the bioavailability of nitric oxide (NO), is a major factor in the initiation and progression of atherosclerosis, an age-related chronic inflammatory process in the arterial wall and the leading cause of mortality and morbidity globally. A better understanding of alterations in vascular structure and function associated with endothelial dysfunction can facilitate the early detection of atherosclerosis and the development of potential pharmaceutical interventions. This study aims to clarify the impact of endothelial dysfunction in conjunction with aging on the microstructure of aortic extracellular matrix (ECM) and to elucidate the relationship between microstructural adaptation …

Histomechanical Compatibility Of Coronary Artery Bypass Grafts, Colton J. Kostelnik

Theses and Dissertations

Coronary artery disease is a localized form of atherosclerosis that can severely restrict blood flow to the heart often requiring a surgical intervention known as coronary artery bypass grafting (CABG) to reestablish perfusion to this essential circulation. To some extent, the selection of the autograft tissue is at the surgeon’s discretion with factors such as stenosis location and the existing tissue’s pathological state contributing to a choice that could be deterministic in surgical outcomes. Many post-operative complications and premature graft failures originate from graft-target tissue incompatibilities and altered blood flow patterns. We hypothesize that mechanical mismatching between the graft material …

Effects Of Cell-Cell Signaling On Mesenchymal Stem Cell Mechanosensing And Adaptation To Dynamic Material, Matthew E. Lowe

Theses and Dissertations

The goal of this research is to identify the role of engineered cell-cell signals on how cells sense material properties. Mesenchymal stem cells (MSCs) are adult cells whose behavior is regulated by matrix mechanosensing, which is characterized by stiffness-dependent changes in cell shape and the nuclear localization of mechano-transducer proteins including YAP (Yes-associated Protein). MSC area and nuclear YAP translocation increase with increasing stiffness, and although low levels of N-cadherin-based cell-cell signaling reduce this effect, two fundamental questions remain: (1) do engineered cell-cell signals at higher concentrations further reduce matrix mechanosensing, and (2) does N-cadherin signaling affect MSC adaptation to …

The Role Of Small Gtpases In Regulating Blood-Brain Barrier Mechanotransduction, Brandon Jude Deore

Theses and Dissertations

Fluid shear stress is an important mediator of vascular permeability, yet the molecular mechanisms underlying the effect of shear on the blood-brain barrier (BBB) have yet to be clarified in cerebral vasculature despite its importance for brain homeostasis.. Neurological symptoms including the formation of microclots, stroke, and other neurological pathologies associated with changes in cerebral blood flow are hallmarks of BBB dysfunction. The in vitro model used in this dissertation is compatible with real-time measurement of barrier function using a transendothelial electrical resistance as well as immunocytochemistry and dextran permeability assays. These experiments reveal that there is a threshold level …

Bioengineered Scaffolds To Induce Alignment And Promote Axon Regeneration Following Spinal Cord Injury, Kiet Anh Tran

Theses and Dissertations

Scaffolds delivered to injured spinal cords to stimulate axon connectivity often act as a bridge to stimulate regeneration at the injured area, but current approaches lack the permissiveness, topology and mechanics to mimic host tissue properties. This dissertation focuses on bioengineering scaffolds through the means of altering topology in injectables and tuning mechanics in 3D-printed constructs as potential therapies for spinal cord injury repair. A self-assembling peptide scaffold, RADA-16I, is used due to its established permissiveness to axon growth and ability to support vascularization. Immunohistochemistry assays verify that vascularized peptide scaffolds promote axon infiltration, attenuate inflammation and reduce astrogliosis. Furthermore, …