Biomedical Engineering and Bioengineering Commons^™

Levofloxacin Incorporated Extracellular Matrix Nanoparticles For Pulmonary Cystic Fibrosis Infections, Raahi Patel

Theses and Dissertations

Cystic fibrosis (CF) is a progressive genetic disorder that affects around 40,000 people in the United States. CF is characterized by a mutation in the CFTR protein that causes dysregulated ion transport across epithelial cells, producing viscous mucus in the lung that increases bacterial invasion, causing persistent infections and subsequent inflammation. Pseudomonas aeruginosa and Staphylococcus aureus are two of the most common infections in CF patients that are resistant to antibiotics. One antibiotic approved to treat these infections is levofloxacin (LVX) that functions to inhibit bacterial replication, but can be further developed into tailorable particles. Nanoparticles are an emerging inhaled …

The Effects Of Various Nanoplastics On The Inflammatory Response In Primary Alveolar Epithelial Cells, Eunice J. Pak

Theses and Dissertations

As plastic pollution begins to multiply in the environment and the workplace, gradual degradation of these plastics creates an unseen threat to biological health: nanoplastics. These nanoplastics are common in day-to-day life, and have been found in various internal organs of the human body. The biological and health effects of these nanoplastics are still widely unknown, and only recently has research focused on the impacts of these particles on human health at the cellular level.

In this thesis, poly(methyl methacrylate) and three forms of polystyrene (carboxyl-modified, amine-modified, and neutral surface charge) have been tested on submerged primary C57BL/6 mouse alveolar …

The Effect Of 17Β Estradiol On Local Production Of Active Vitamin D3 Metabolites In Laryngeal Squamous Cell Carcinoma, Tillat Batool

Theses and Dissertations

Laryngeal squamous cell carcinoma (LSCC) has garnered attention as a sex-hormone-dependent cancer with notable responsiveness to 17β-estradiol (E₂), in which it’s tumorigenesis can be mediated through estrogen receptors (ER). The ESR1 gene encodes for the classical full-length ERα66, as well as splice variants ERα36 and ERα46. Previous studies have shown that an active vitamin D₃metabolite, 24R,25(OH)₂D_3. has pro-tumorigenic or anti-tumorigenic responses in LSCC cells with different ER profiles, and that the tumor cells have the capability of localized production of vitamin D metabolites at the cellular level when treated with 25(OH)D₃-d6 …

Multi-Magnetic Material Transcranial Magnetic Stimulation Coils Development And Electric Field Measurement & Modeling Using Machine Learning, Mohannad Tashli

Theses and Dissertations

Transcranial Magnetic Stimulation (TMS) is a safe, effective, and non-invasive therapy for treating several psychiatric and neurological disorders. TMS is Food and Drug Administration (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 …

Muscle-Nerve Signaling And Its Role In Myogenesis, Synaptogenesis, And Regeneration, James T. Redden

Theses and Dissertations

Despite only comprising 0.1% of the myofiber surface area, a healthy motor endplate is densely packed with acetylcholine receptors (AChRs) responsible for mediating activity between the connected motor neuron and skeletal muscle via the neurotransmitter, acetylcholine. Loss of the endplate, known as fragmentation, is caused by car crashes, deep lacerations, and other traumatic injuries to the innervating nerve or direct injuries to the limb muscle(s) with intramuscular denervation as a common comorbidity. In both cases, endplate fragmentation begins within a week of injury proceeding muscle atrophy causing decreased mobility, paralysis, and quality of life. Endplate fragmentation of intact muscle fibers …

T Cell Polarization Regulates The Inflammatory Response And Tissue Regeneration At The Peri-Implant Interface, Derek Avery

Theses and Dissertations

Unresolved healing and localized chronic inflammation are common occurrences after biomaterial implantation, resulting in unfavorable clinical outcomes such as implant failure or fibrous encapsulation. T cells are adaptive immune cells found in lymph nodes, thymus, spleen, bone marrow, and around biomaterials, significantly impacting the degree of inflammation and wound healing. T cells are vital for inflammatory cytokine production and modulation of innate immune cells, including neutrophils and macrophages. T cells can be differentiated into two primary subsets, CD4⁺ and CD8⁺ T cells, playing distinctive roles in various pathologies and disease states. While T cells have been characterized well …

The Regulation Of Laryngeal Cancer Cell Phenotype And Proliferation By 24r,25-Dihydroxyvitamin D3 Is Correlated With Erα Isoform Expression, Cydney Dennis

Theses and Dissertations

Laryngeal cancer is the most common type of head and neck cancer and is associated with poor prognosis due to common delayed diagnoses. The sex disparities associated with laryngeal cancer are constantly growing, as the risk of malignancy in males is continually increasing compared to women. Due to the high chance of late-stage diagnosis requiring aggressive treatments, there is a high demand for less aggressive treatment options and early-stage diagnostic markers. The apparent sex disposition of the larynx, the correlation between sex hormones, and the risk of malignancy in aging men suggest that estrogen may play a role in laryngeal …

The Sexually Dimorphic Role Of Connexin 43 In Bone Remodeling And Disuse-Induced Bone Loss, Gabriel A. Hoppock

Theses and Dissertations

Bone loss is frequently experienced by individuals undergoing long-term disuse, such as prolonged bedrest, immobilization due to paralysis or injury, and conditions such as spaceflight. Under normal physiological conditions, bone remodeling is balanced by bone-forming osteoblasts and bone-resorbing osteoclasts, and the activity of osteoblasts and osteoclasts is orchestrated by osteocytes. Osteocytes are the most abundant cell type found in bone and ample evidence suggests they are bone’s main mechanosensory cell type. Therefore, understanding osteocyte biology and responses to mechanical signals, or lack thereof during unloading, may lead to new therapeutic targets to combat bone loss during disuse. Previous data has …

Borophene And Graphene For Non-Enzymatic Biosensor- Ab-Initio Study, Omar A. Ismail

Theses and Dissertations

Non-enzymatic glucose sensing holds promise to overcome limitations associated with glucose oxidase, such as oxygen dependence and short shelf life. This study explores the potential sensing capabilities of borophene and graphene through direct interaction with various compounds, including β-glucose, uric acid, ascorbic acid, fructose, and acetaminophen. Using Density Functional Theory (DFT), we calculated binding energies and the respective Density of States (DOS) for these adsorbates on both graphene and borophene surfaces. Preliminary results suggest that borophene might exhibit nearly twice the affinity for β-glucose compared to graphene. Moreover, the calculated Density of States reveals distinct distortions in the electronic states …

Fabrication And Characterization Of Flexible Microelectrode Arrays On Kapton Polyimide For Implantable Spinal Cord Stimulation Applications, Nabil Jamhour

Theses and Dissertations

Recent advances in spinal cord stimulation (SCS) technology have made a significant impact in the treatment of chronic pain which is a prevalent issue amongst 20% of the population in developed nations. A few medical device manufactures have developed SCS devices that have been studied in clinical environments and reported to be effective and safe for commercial use. However, the current SCS devices available are bulky, rigid, and still present infection, fibrosis, discomfort, pulse delivery challenges and other concerns for patients. In this study, flexible electrodes processed on Kapton® polyimide films by physical vapor and inkjet deposition are fabricated and …

Electroencephalography And Biomechanics Of The Basketball Throw, Phong Ky Phan

Theses and Dissertations

According to various studies, compared with novice athletes, experts exhibit superior integration of perceptual, cognitive, and motor skills. This superior ability has been associated with the focused and efficient organization of task-related neural networks. Specifically, skilled individuals demonstrate a spatially localized or relatively lower response in brain activity, characterized as ‘neural efficiency’, when performing within their domain of expertise. Previous works also suggested that elite basketball players can predict successful free throws more rapidly and accurately based on cues from body kinematics. These traits are the result of a prolonged training of specific motor skills and focused excitability of the …

Design, Development, And Validation Of A Perfusion-Compression Bioreactor To Study Osteogenesis In Bone Explants, Alexis Victoria Graham

Theses and Dissertations

The current gold standard treatment for bone defects is autologous cancellous bone graft, which involves increased surgery time and donor site morbidity, and limited supply of bone and cells for regeneration. Bioreactors may aid in the generation of mechanically conditioned bone grafts with more cells compared to traditional grafts. However, the specific parameters of fluid flow and mechanical loading which contribute to osteogenesis and cell viability in bioreactors are not fully characterized. Here, a perfusion-compression bioreactor system was developed to study osteogenesis in porcine trabecular bone explants. Loading accuracy was over 88% across six bioreactors at a 0.1 s-1 strain …

Study Of Surface And Groundwater Quality And Quantity At Watershed Scale In Mississippi, Dipesh Nepal

Theses and Dissertations

Hydrology and water quality are affected by land use and climate changes. Mississippi’s diverse agro–ecosystem comprises of a range of land use land cover (LULC) including agriculture, forest, wetlands, urban, and grasslands. The objectives of this study were to investigate the impacts of various factors such as Best Management Practices (BMPs), wetlands, LULC, and climate changes on water quality and quantity. The hydrologic and water quality responses to dynamic LULC input in Soil and Water Assessment Tool (SWAT) were evaluated. Results showed that agricultural and forest expansion were major drivers of hydrologic and water quality changes in Big Sunflower River …

Development Of An Automated Delivery System To Apply Copper Sulfate Crystals Using Precision Dry Fertilizer Application Technology, Kevin Charles Wise

Theses and Dissertations

The digenetic trematode, Bolbophorus damnificus, poses a substantial threat to catfish aquaculture, causing significant economic losses. Infestations lead to suppressed feed consumption, secondary bacterial infections and poor production performance. Survey data reveals widespread infestation in the in the southeastern United States. Current control strategies involve the application of a concentrated copper sulfate solution to reduce snail populations which serve as the first intermediate host of the trematode life cycle. This study aimed to improve treatment efficacy by developing a granular copper sulfate application system. A modified Gandy fertilizer applicator, equipped with a programmable control system, demonstrated accurate distribution of copper …

Process-Structure-Property Relationships Of Nanofibers For Biomedical Applications, Dipasree Bhowmick

Theses and Dissertations

This thesis explores the fabrication, characterization, and applications of nanofiber membranes utilizing Forcespinning® technology. Two distinct nanofiber systems were developed and evaluated, one focusing on pH-responsive Eudragit-baicalin loaded nanofibrous membranes for wound healing and the second one on thermo-responsive nanofiber-hydrogel (PNIPAAm) systems for biosensing applications, specifically dopamine detection. In the first project, nanofiber membranes loaded with Eudragit and baicalin demonstrated superior antibacterial properties against both gram-negative (E. coli) and gram-positive (B. meg) bacteria. Additionally, these membranes exhibited antioxidant properties and enhanced cell proliferation of 3TT cells, making them promising candidates for wound healing dressings. In the second project, a …

An Improved Saliency Map With Trustworthiness For Localizing Abnormalities In Medical Imaging, Nolan C. Skelly

Theses and Dissertations

Saliency maps are a widely used methodology to make deep learning models more interpretable. They provide post-hoc explanations through identification of the most pertinent areas of an input medical image. These techniques have been assessed based on 1) localization utility, 2) sensitivity to model weight randomization, 3) repeatability, and 4) reproducibility. Ten saliency map techniques will be tested, Grad, Smooth Grad, Integrated Gradients, Smooth Integrated Gradients, XRAI, Grad-CAM, Guided Backpropagation, Guided GradCAM, GradCAM++, and ScoreCAM. The neural networks used to predict and read medical information require a reliable solution to provide medical practitioners intelligible results. Using the information of two, …

Investigating The Effects Of Collagen Alignment And Tricalcium Phosphate Incorporation On Osteoblast Cell Response, Kathryn Elizabeth Bock

Theses and Dissertations

Every year, over 20 million people globally are affected by bone tissue loss due to disease or trauma. Bone tissue engineering (BTE) is touted as a promising approach to promote bone tissue repair and regeneration. In this realm, development of collagen-based scaffolds incorporated with a bioceramic is often attempted to generate tissue scaffolds that resemble the organic and inorganic composition of native bone. In addition, a variety of different collagen processing techniques have been employed to produce anisotropically aligned scaffolds that can provide the essential biochemical and structural cues to guide cell response. While there have been numerous studies on …

Development Of A Physics-Informed Neural Network For Prediction Of Blood Flow, Marcello Vittorio Mattei Di Eugenio

Theses and Dissertations

Abstract—Objective: We propose a new neural network architecture that accepts point clouds and outputs 3D velocity profiles for aneurysm geometries. Methods: We generated a synthetic aneurysm 3D flow dataset using CFD and used it to train our model architecture and compare it with other popular architectures like U-net and PointNet. We incorporate tools for improving model performance such as incorporating a distance function, a physics-informed loss to enforce the law of mass conservation, and the Huber loss to learn patterns across heterogeneous velocity components of multiple dimensions. Results: The tools implemented together with our architecture achieved the best performance on …

Deep Learning And Generative Ai Approaches For Automated Diagnosis And Personalized Treatment: Bridging Machine Learning, Medicine, And Biomechanics In Predicting Tissue Mechanics And Biomaterial Properties., Yasin Shokrollahi

Theses and Dissertations

Machine learning, particularly deep neural networks, has demonstrated significant potential in predicting high-dimensional tasks across various domains. This work encompasses a detailed review of Generative AI in healthcare and three studies integrating machine learning with finite element analysis for predicting biomechanical behaviors and properties. Initially, we provide a comprehensive overview of Generative AI applications in healthcare, focusing on Transformers and Denoising Diffusion models and suggesting potential research avenues to address existing challenges.

Subsequently, we addressed soccer-related ocular injuries by combining finite element analysis and machine learning to predict retinal mechanics following a soccer ball hit rapidly. The prediction errors are …

Evolutionary Conservation And Times Of Action Of Heterochronic Genes, Maria Ivanova

Theses and Dissertations

The heterochronic pathway of C. elegans is the most well-characterized system to date for controlling the sequence and timing of developmental events. However, we still have critical unanswered questions to address. First, little is known about the evolution of the heterochronic pathway, and of developmental timing in general. To determine if the roles of major heterochronic genes are conserved, I made mutants in orthologs of these genes in C. briggsae, using CRISPR/Cas9. My studies revealed a significant drift in the roles of some of the genes, although all of them are still involved in the developmental timing regulation, and several …

Leveraging Inflammatory Responses Toward Advancing Alzheimer’S Disease Treatments And Biomaterial Implantation, Mihyun Lim Waugh

Theses and Dissertations

Inflammation is a body’s physiological response to pathogens, foreign materials, or tissue injury. When immune system is triggered, activated leukocytes produce cytokines and chemokines that promote migration of neutrophils and macrophages to the inflammatory regions. At early stages of injury, acute inflammation occurs immediately to fight off the pathogens and restore tissues to homeostasis. However, if the inflammation-inducing stimulus is not removed and thus cells and tissues do not return to its homeostatic state, the prolonged inflammatory responses become a chronic condition. Recent studies have indicated that the receptor for advanced glycation end-products (RAGE), a key receptor of innate immune …

Advanced Processing Techniques For Electrospun Nanofibers: Investigating Annealing And Laser Zone-Drawing Effects On Material Characteristics, Matthew D. Flamini

Theses and Dissertations

Electrospun nanofibers hold potential for a wide range of commercial and scientific applications; however, their properties must be optimized through post-processing treatments to achieve optimal performance. This dissertation investigates the effects of annealing and laser zone-drawing on electrospun nanofiber properties. Annealing polycaprolactone nanofibers at 70°C results in the highest rate of crystallization and molecular alignment, impacting long-term stability and mechanical properties. A multivariate linear model incorporating crystallinity and molecular alignment predicts the material properties resulting from annealing under different conditions. Laser zone-drawing experiments reveal that polylactide fiber thinning under laser irradiation primarily occurs due to drawing rather than ablation. Steady-state …

The Effects Of Mechanical Strain On Vascular Calcification And The Canonical Wnt Pathway, Hannah E. Douglas

Theses and Dissertations

Cardiovascular disease is a significant health crisis, representing 32% of deaths worldwide in 2019. Vascular calcification (VC), a major contributor to cardiovascular disease, is a regulated biomineralization process whose exact mechanisms are unknown. Additionally, vascular smooth muscle cells (VSMCs) significantly contribute to VC by undergoing a phenotypic switch and differentiating into osteoblast-like cells. When factors like hypertension cause disturbed laminar flow in the body’s vasculature, the mechanical stress promotes the phenotypic switch and calcification of VSMCs via mechanotransduction. VC is also induced by the Wnt pathway, which is activated via mineral imbalance and mechanical stimulation. However, the exact mechanisms behind …

Nanoscale Modeling Of Membrane Systems Under Mechanical Deformation In Traumatic Brain Injury Using Molecular Dynamics, Anh Thi Ngoc Vo

Theses and Dissertations

Neuronal membrane disruption and mechanoporation are nanoscale damage mechanisms that critically affect brain cell viability during traumatic brain injury (TBI). These nanoscale cellular impairments are elusive in experiments and necessitate in silico approaches such as molecular dynamics (MD) simulations. Implementing MD, this research aims to investigate the effects of different key factors related to membrane deformation and damage, including force field resolutions, lipid compositions, and loading conditions.

To examine the impact of force field resolution, MD deformation simulations were conducted on 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylcholine (POPC) lipid bilayer membranes, using all-atom (AA), united-atom (UA), and coarse-grained Martini (CG-M) force fields. The mechanical responses …

Multi-Objective Design Optimization Of Two Configurations Of Ventricular Shunts For Hydrocephalus, Will Kirkpatrick

Theses and Dissertations

Hydrocephalus is developed when the flow of cerebrospinal fluid is obstructed in the ventricles and a pressure build-up is generated within the brain. Ventricular shunts are used to remove excess fluid from the brain, but these shunts have a common problem of failure due to the shunt being obstructed by the build-up of astrocytes. To address this, two sets of 27 designs of ventricular shunts were identified and analyzed with parameters that could potentially reduce obstruction risks. The performance of these designs was examined using fluid simulations on these two sets of 27 designs. One set explored close-tipped shunt designs, …

Chemical And Polymer Characterization Of The Potential Modes Of Degradation Of An Injectable Nucleus Pulposus Replacement Device, Antonio G. Abbondandolo

Theses and Dissertations

HYDRAFIL™ is a poly(vinyl alcohol)/poly(ethylene glycol)-based hydrogel nucleus pulposus replacement device that is injected in situ and has demonstrated efficacy in lowering the prevalence and pain associated with back. In this work, we developed a method to analyze HYDRAFIL™ polymer composition using (TGA) and characterized intermolecular bonding interactions within the hydrogel through (FTIR). To function as a permanent implant for nucleus pulposus replacement, HYDRAFIL™ must be stable when exposed to a multitude of degradation pathways, namely, thermal, chemical, and mechanical. We subjected HYDRAFIL™ to accelerated thermal and chemical degradation pathways and described compositional, physical and chemical property changes using a …

Understanding Vascular Calcification Through The Lens Of Canonical Wnt Signaling, Karlee Mcneel

Theses and Dissertations

Every 37 seconds, someone in the United States dies from cardiovascular disease. Vascular calcification is one of the underlying causes of these fatal events. Medial calcification develops following arteriosclerosis, or hardening of the arteries. Medial calcification is characterized by the deposition of hydroxyapatite in the medial layer of the arteries after normal vascular smooth muscle cells undergo a phenotypic switch to resemble osteoblast-like cells. It is hypothesized that this switch is caused by the wingless related (WNT)-Signaling pathway. The WNT-Signaling pathway, upon activation, causes the upregulation of osteogenic markers for the development of osteoblast-like cells. Current treatments alleviate consequences of …

Xeno-Free Biomimetic Ecm Model For Investigation Of Matrix Properties On Astrocyte Cell Response, Bayan Saleh

Theses and Dissertations

Astrocytes are crucial in preserving the structural and functional integrity of the central nervous system (CNS). They participate in several physiological processes, such as the uptake of neurotransmitters, control of extracellular ion concentration, and preservation of the blood-brain barrier. Recent research has raised the possibility that astrocytes are also involved in the onset and development of Alzheimer's disease (AD). While the precise mechanisms underlying the development and progression of AD are not fully understood, recent research has suggested that age-related changes in the brain extracellular matrix (ECM) properties may play a critical role in the progression of the disease. Investigating …

Characterizing Endothelial Damage During Ischemic Stroke Treatment With 3d Cerebrovascular Live Cellular And Finite Element Models, Ana Regina Martinez Dehesa

Theses and Dissertations

Stent retriever mechanical thrombectomy (SRMT) is part of the clinical standard-of-care for acute ischemic stroke (AIS) patients with large vessel occlusion (LVO). Endothelial injury (EI) is widely associated with SRMT. Studies report finding EI markers in over 50% of retrieved clots, suggesting the frequency of EI in MT patients is rather common. The mechanism of EI and its contribution to MT failure and clinical outcomes remain poorly understood because of a lack of techniques to observe EI and study it in vitro. This study aims to investigate the mechanisms of EI induced by SRMT, as well as the effect stent …

Development Of A Pediatric Heart Assist Device Monitoring System, Natalie Hill

Theses and Dissertations

Heart failure (HF) is one of the leading causes of deaths for adults worldwide, but has disproportionately significant effects on pediatric patients that are often overshadowed. Treatment options for pediatric patients with HF are extremely limited, resulting in increased mortality rates within hospitals. Patients often depend on ventricular assist device (VAD) support as a bridge to transplant. The Berlin Heart EXCOR is the only FDA approved device for pediatric use in the US. However, many hemodynamic and neurological complications continue to arise; for instance, up to 30% of EXCOR patients suffer from stroke. Currently, there is no effective way to …