Biomedical Engineering and Bioengineering Commons^™

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 …

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, …

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 …

Improving The Early Detection Of Cardiovascular Toxicity Secondary To Radiotherapy For Lung Cancer Via Patient-Specific Quantitative Magnetic Resonance Imaging, Alireza Omidi

Theses and Dissertations

Purpose: To assess the cardiopulmonary-induced dose variation on the left ventricle (LV) and evaluate the spatiotemporal evolution of cardiac/aortic function following radiotherapy (RT).

Methods: 8 lung cancer patients who were scheduled to receive RT were recruited for this study. Each patient underwent one 4D-CT at baseline. MRI scans including cine GRE, T1/T2, LGE, and 4D-flow were acquired at baseline, 3-months and 6-months post-RT to evaluate the cardiac/aortic function. Finally, image registration was used to assess the cardiopulmonary-induced dose variation on the LV.

Results: Mean RT-dose was minimum during inspiration and systole (at expiration). No significant differences were found in the …

Modeling Of Patient-Specific Periaortic Mechanics And Pulmonary Artery Hemodynamics Based On Phase-Contrast Magnetic Resonance Imaging Sequences., Johane H. Bracamonte

Theses and Dissertations

Inverse modeling in cardiovascular medicine is a collection of methodologies that can provide non-invasive patient-specific estimations of clinical risk factors using medical imaging as inputs. Its incorporation into clinical practice has the potential to improve diagnosis and treatment planning with low associated risks and costs.

Herein, three different phase contrast magnetic resonance imaging (MRI) modalities were implemented as input data, displacement encoding with stimulated echoes (DENSE MRI) applied, and time-resolved velocity encoding phase-contrast MRI, in 1D and 3D, applied to pulmonary artery (PA) hemodynamics.

A model to account for the effect of periaortic interactions due to static and dynamic structures …

Dna Condensation State Regulates Nuclear Lamina Strain And Cellular Adaptation To Physiological Forces, Brooke E. Danielsson

Theses and Dissertations

The nucleus is the largest and stiffest organelle and is exposed to mechanical forces transmitted through the cytoskeleton from outside the cell, as well as from forces generation within the cell. In recent years, the nucleus has been proposed to act as a cellular mechanosensor, with changes to nuclear shape and architecture playing an important role in how the cell responds to physiological forces. Aberrant forms of the nuclear envelope protein lamin A/C, as well as epigenetic modifications to chromatin, has been shown to modify nuclear stiffness and viscosity, therefore effecting nuclear mechanics and mechanotransduction. Altered nuclear mechanics is associated …

Universal Design In Bci: Deep Learning Approaches For Adaptive Speech Brain-Computer Interfaces, Srdjan Lesaja

Theses and Dissertations

In the last two decades, there have been many breakthrough advancements in non-invasive and invasive brain-computer interface (BCI) systems. However, the majority of BCI model designs still follow a paradigm whereby neural signals are preprocessed and task-related features extracted using static, and generally customized, data-independent designs. Such BCI designs commonly optimize narrow task performance over generalizability, adaptability, and robustness, which is not well suited to meeting individual user needs. If one day BCIs are to be capable of decoding our higher-order cognitive commands and conceptual maps, their designs will need to be adaptive architectures that will evolve and grow in …

Novel Microfabricated Systems To Elucidate The Role Of Anisotropic Stiffness In The Tumor Microenvironment, Jiten Narang

Theses and Dissertations

Cancer is the second leading cause of death in women and late stage (metastatic) cancers have abysmal survival rates compared to early stage regional cases (27% vs 86%). As a tumor grows, the surrounding extracellular matrix (ECM) is reorganized into a dense, collagen rich matrix. The new matrix of aligned collagen fibers provides unique mechanical cues such as anisotropic stiffness and contact guidance. Matrix turnover also constricts local vasculature and restricts delivery of key nutrients and signaling molecules to malignant cells to outside the tumor creating a chemotactic gradient from outside to inside. In this work, we developed a novel …

Innovative Techniques Of Neuromodulation And Neuromodeling Based On Focal Non-Invasive Transcranial Magnetic Stimulation For Neurological Disorders, Ivan C. Carmona-Tortolero

Theses and Dissertations

This dissertation aims to develop alternative technology that improves the current range of application of transcranial magnetic stimulation (TMS), on a scale that would permit defining specific non-invasive treatments for Parkinson’s disease and other neurological disorders. This is accomplished through three specific objectives. 1) The design of a neurostimulation system that increases the focality in TMS to regions of narrow target areas and variable depths in the brain cortex. 2) The assessment of the feasibility of novel high-frequency neuromodulation techniques that would allow increasing the focality in deeper areas beyond the cortical surface. 3) The development of a computational model …

Towards The Systematic Evaluation Of Variable Modes Of Mechanical Conditioning On The Compositional, Microstructural And Mechanical Properties Of Engineered Tissue Vascular Grafts., Sarah Saunders

Theses and Dissertations

Coronary artery bypass surgery (CABG) remains one of the most common cardiac surgical procedures performed worldwide, frequently involving multiple bypasses, and commonly employing the patient’s internal mammary artery, radial artery, or saphenous vein. CABG is often not possible because native vessels were already employed in previous interventions or are diseased themselves. Synthetic vascular grafts are currently integral tools of vascular surgery and have had relative success in large-caliber applications providing substantial benefit to aortic or iliac grafting; however, small diameter (< 6 mm) arterial grafts have not yet translated into clinical effectiveness due to thrombosis and anastomotic intimal hyperplasia. ETVGs present an exciting potential alternative in vascular grafting by offering a blood vessel substitute that could exhibit all the functional characteristics of native vasculature. In addition to relieving supply limitations associated with coronary artery bypass surgery ETVGs are especially ideal for pediatric patients with congenital heart disease who require grafts that grow as they do, eliminating the need for reoccurring invasive surgeries.

Though the role of biomechanics in regulating cellular behavior promoting non-thrombogenicity, vasoactivity, and ECM synthesis and maintenance is well …

Theta Burst Brain Stimulation In Painful Diabetic Neuropathy Patients: Investigating Neural Mechanisms, Bhushan Thakkar

Theses and Dissertations

Chronic pain (CP) is a significant contributor to disability and disease burden globally. In 2019, approximately 50.2 million adults (20.4% of the US population) experienced chronic pain, contributing to $560-635 billion in direct medical costs. In addition, the worldwide prevalence of diabetes mellitus has reached epidemic proportions and is set to increase to 629 million by 2045. Almost 50% of patients with diabetes present with diabetic neuropathy (DN), and one in five patients with diabetes presents with painful DN (pDN) which is the most common cause of neuropathic pain (NP) in the US. Symptomatic treatment is the mainstay of management …

Therapeutic Approaches For Respiratory Distress Syndrome, Franck J. Kamga Gninzeko

Theses and Dissertations

Respiratory distress syndrome (RDS) is characterized by shortness of breath and low oxygen levels. RDS affects the neonatal and adult populations. In the neonatal population, RDS can be classified as NRDS (Neonatal respiratory distress syndrome), while in adults, it is known as ARDS (acute respiratory distress syndrome). This dissertation examines a therapeutic approach to NRDS and a mechanistic approach to ARDS with in vivo and in vitro models of lung injury. NRDS is characterized by a deficiency or lack of surfactant. Surfactant is an essential compound composed of phospholipids and proteins to prevent the lungs from collapsing. There are several …

Effect Of Viscoelasticity On Cellular Morphology And Activity, Thomas J. Petet Jr

Theses and Dissertations

It has been well established that there is a link between substrate stiffness and cellular activities such as proliferation, migration, and differentiation. Less characterized is the link between the time-dependent viscosity of a substrate with those cellular activities. To explore this, PDMS substrates were created with predictably tunable stiffness and viscosity parameters. A simulated model was also developed in parallel to explore the potential effects of viscosity in a computationally predictive way. It was found that the inclusion of viscosity caused a major paradigm shift to a non-zero substrate equilibrium that was sensitive to increases in the substrate stiffness. Finally, …

Applied Machine Learning In Extrusion-Based Bioprinting, Shuyu Tian

Theses and Dissertations

Optimization of extrusion-based bioprinting (EBB) parameters have been systematically conducted through experimentation. However, the process is time and resource-intensive and not easily translatable across different laboratories. A machine learning (ML) approach to EBB parameter optimization can accelerate this process for laboratories across the field through training using data collected from published literature. In this work, regression-based and classification-based ML models were investigated for their abilities to predict printing outcomes of cell viability and filament diameter for cell-containing alginate and gelatin composite hydrogels. Regression-based models were investigated for their ability to predict suitable extrusion pressure given desired cell viability when keeping …

Effect Of Stimulus Waveform On Transcranial Magnetic Stimulation Metrics In Proximal And Distal Arm Muscles, Christopher Lynch

Theses and Dissertations

Objectives: The purpose of this study was to determine the effect of common transcranial magnetic stimulation (TMS) waveforms (monophasic and biphasic) on resting motor threshold (RMT), active motor threshold (AMT), and motor evoked potential (MEP) amplitudes in the biceps and first dorsal interosseous (FDI) because waveforms may affect motor targets differently. Additionally, we determined the test-retest reliability of TMS metrics for each stimulation type and muscle.

Methods: Ten individuals participated in two sessions of single-pulse TMS delivered to the motor cortex perpendicular to the central sulcus. MEPs were normalized to the maximum EMG signal during contraction and were recorded at …

Estimating Affective States In Virtual Reality Environments Using The Electroencephalogram, Meghan R. Kumar

Theses and Dissertations

Recent interest in high-performance virtual reality (VR) headsets has motivated research efforts to increase the user's sense of immersion via feedback of physiological measures. This work presents the use of electroencephalographic (EEG) measurements during observation of immersive VR videos to estimate the user's affective state. The EEG of 30 participants were recorded as each passively viewed a series of one minute immersive VR video clips and subjectively rated their level of valence, arousal, dominance, and liking. Correlates between EEG spectral bands and the subjective ratings were analyzed to identify statistically significant frequencies and electrode locations across participants. Model feasibility and …

Nebulizer-Based Systems To Improve Pharmaceutical Aerosol Delivery To The Lungs, Benjamin M. Spence

Theses and Dissertations

Combining vibrating mesh nebulizers with additional new technologies leads to substantial improvements in pharmaceutical aerosol delivery to the lungs across therapeutic administration methods. In this dissertation, streamlined components, aerosol administration synchronization, and/or Excipient Enhanced Growth (EEG) technologies were utilized to develop and test several novel devices and aerosol delivery systems. The first focus of this work was to improve the poor delivery efficiency, e.g., 3.6% of nominal dose (Dugernier et al. 2017), of aerosolized medication administration to adult human subjects concurrent with high flow nasal cannula (HFNC) therapy, a form of continuous-flow non-invasive ventilation (NIV). The developed Low-Volume Mixer-Heater (LVMH) …

Imaging Potential In Saturation Recovery Methods For Sarcoidosis Patients With Medical Devices, Samantha Zhao

Theses and Dissertations

Cardiovascular magnetic resonance (CMR) imaging is a preferred imaging methodology due to its lack of ionizing radiation and ability to detect myocardial inflammation and fibrosis using quantitative T1 mapping techniques. Cardiac sarcoidosis (CS) is characterized as the formation of granulomas in the myocardium. Current methods for detection include measuring non-cardiac specific C-reactive protein (CRP) levels, or PET imaging, which uses ionizing radiation, therefore CMR would make an ideal imaging option. However, many CS patients have implanted cardiac devices which can cause degradation in image. The modified Look-Locker inversion recovery (MOLLI) method is widely used in quantitative T1 mapping with high …

Intermittent Theta Burst Stimulation: Application To Spinal Cord Injury Rehabilitation And Computational Modeling, Neil Mittal

Theses and Dissertations

Loss of motor function from spinal cord injuries (SCI) results in loss of independence. Rehabilitation efforts are targeted to enhance the ability to perform activities of daily living (ADLs), but outcomes from physical therapy alone are often insufficient. Neuromodulation techniques that induce neuroplasticity may push the limits on recovery. Neuromodulation by intermittent theta burst transcranial magnetic stimulation (iTBS) induces neuroplasticity by increasing corticomotor excitability, though this has most frequently been studied with motor targets and on individuals not in need of rehabilitation. Increased corticomotor excitability is associated with motor learning. The response to iTBS, however, is highly variable and unpredictable, …

Evaluating Neuromuscular Function Of The Biceps Brachii After Spinal Cord Injury: Assessment Of Voluntary Activation And Motor Evoked Potential Input-Output Curves Using Transcranial Magnetic Stimulation, Thibault Roumengous

Theses and Dissertations

Activation of upper limb muscles is important for independent living after cervical spinal cord injury (SCI) that results in tetraplegia. An emerging, non-invasive approach to address post-SCI muscle weakness is modulation of the nervous system. A long-term goal is to develop neuromodulation techniques to reinnervate (i.e. resupply nerve to) muscle fiber and thereby increase muscle function in individuals with tetraplegia. Towards this goal, developing monitoring techniques to quantify neuromuscular function is needed to better direct neurorehabilitation. Assessment of voluntary activation (VA) is a promising approach because the location of the stimulus can be applied cortically using transcranial magnetic stimulation (TMS) …

A Mechanism Behind The Mechanotransduction Of Surface Characteristics In Osteoblasts, Otto J. Juhl Iv

Theses and Dissertations

Biomaterials for use in bone regeneration and healing range from metal and metal alloy implants to hydrogel-based solutions. These materials can be optimized to increase bone healing and integration by improving the mechanical and biological properties. Regardless of the material itself, the cell-substrate interaction is key to the success of the biomaterial once implanted. Substrate surface characteristics such as roughness, wettability, and particle density are well-known contributors to a substrate’s overall osteogenic potential, and therefore the substrate's overall success. Unfortunately, it is still unknown how these substrate surface characteristics are transduced into intracellular signals by cells, preventing specific tailoring of …

Improving Patient-Specific Assessments Of Regional Aortic Mechanics Via Quantitative Magnetic Resonance Imaging With Early Applications In Patients At Elevated Risk For Thoracic Aortopathy, Patrick A. Jones

Theses and Dissertations

Unstable aortic aneurysms and dissections are serious cardiovascular conditions associated with high mortality. The current gold standards for assessment of stability, however, rely on simple geometric measurements, like cross-sectional area or increased diameter between follow-up scans, and fail to incorporate information about underlying aortic mechanics. Displacement encoding with stimulated echoes (DENSE) magnetic resonance imaging (MRI) has been used previously to determine heterogeneous circumferential strain patterns in the aortas of healthy volunteers. Here, I introduce technical improvements to DENSE aortic analysis and early pilot application in patients at higher risk for the development of aortopathies. Modifications to the DENSE aortic postprocessing …

Nature-Inspired Material Strategies Towards Functional Devices, Sayantan Pradhan

Theses and Dissertations

Naturally sourced, renewable biomaterials possess outstanding advantages for a multitude of biomedical applications owing to their biodegradability, biocompatibility, and excellent mechanical properties. Of interest in this dissertation are silk (protein) and chitin (polysaccharide) biopolymers for the fabrication of functional biodevices. One of the major challenges restricting these materials beyond their traditional usage as passive substrate materials is the ability to combine them with high-resolution fabrication techniques. Initial research work is directed towards the fabrication of micropatterned, flexible 2D substrates of silk fibroin and chitin using bench-top photolithographic techniques. Research is focused on imparting electrochemical properties to silk proteins using conducting …

Rheological Analysis Of The Mechanical Properties Of Murine Lungs Over The Lifespan, Olajumoke Olufunke Harrison

Theses and Dissertations

To study the effects of aging in murine lungs, we characterized C57Bl6j mice from neonatal to 24-month-old mice. Samples were divided into two groups: Young Mice (YM) and Middle Age/Old Age Mice (MOM). The YM group included the neonatal and 6-10week. The MOM group included 7- and 22–24-month-old mice. Rheological testing was performed using a TA Instruments DHR-2 Rheometer to collect the mechanics of each mice sample. Utilizing a 20-mm parallel plate fixture, a gap of 0.8-1.0-mm, and a temperature setting of 25C, we conducted a frequency sweep. Samples were the decellularized over a four-day process then lyophilized for mass …

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 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 …

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 …

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 …

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 …