Biomedical Engineering and Bioengineering Commons^™

Enhancement Of Electrospun Nanofiber Properties Via Automated Track Post-Draw Processing, David Anthony Brennan

Theses and Dissertations

Electrospinning is an alternative manufacturing method, capable of producing fibers with nanoscale diameters from a wide range of different polymers in a process which is relatively simple and inexpensive in comparison to other forms of nanofiber production. This has made electrospinning the subject a great deal of research as a method of producing nanofibers for various high-performance applications. However, electrospun nanofiber tensile strength is weak in comparison to conventional fibers of the same material, preventing widespread use and marketization. This disparity in mechanical strength is attributed to poor polymer chain alignment in individual fibers, caused by the absence of a …

Establishing A Mechanistic Link Between Disturbed Flow And Aneurysm Formation In A 3d Cerebral Bifurcation Model, Nesrine Bouhrira

Theses and Dissertations

The effect of disturbed flow profiles on the endothelium have been studied extensively in systemic vasculature, but less is known about the response of the blood-brain barrier (BBB) to these flow regimes. Here we investigate the effect of steady and pulsatile disturbed flow on the integrity of the BBB using a three-dimensional, perfusable bifurcation model consisting of a co-culture of endothelial cells with mural and glial cells. Experimental flow patterns predicted by computational fluid dynamics mimic in vivo flow regimes, specifically the presence of a recirculation zone immediately downstream of the bifurcation reveal periodic changes in the instantaneous shear stress …

Scalable Fabrication Of Post-Drawn Bio-Based And Petroleum-Based Nanofibers With Tunable Fiber Alignment, Morphology, And Mechanical Properties Via An Automated Track Approach, Dave Jao

Theses and Dissertations

We propose to expand nanomanufacturing capabilities and develop processing methods to produce advanced nanofiber materials with enhanced macromolecular and functional properties. Over the past decade, there has been a tremendous increase in the demand for polymeric nanofibers, which are promising candidates for a wide range of technological applications, including tissue engineering, protective clothing, filtration/absorption materials, and sensors/electronic devices, batteries/energy harvest, and fiber-reinforced composites [1]. However, the accessibility of nanofiber materials is limited because it is impossible to produce polymer nanofibers using conventional techniques. Typically, conventional polymer fibers are manufactured by mechanical extrusion with a secondary post-drawing step that stretches the …

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 …

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 …

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 …

Regulation Of Osseous Healing By Macrophage-Derived Wnt Ligands, Jefferson Overlin Abaricia

Theses and Dissertations

Osseous healing is regulated by various classes of cells and signaling mechanisms. Of these, Wnt signaling has long been known to be critically important in directing the differentiation of mesenchymal stem cells (MSCs) into osteoblasts during bone healing. However, the source of these Wnt ligands is not known. Recently, a body of literature has arisen finding both beneficial and detrimental effects of macrophage-derived Wnt ligands on the regeneration of other tissues (liver, kidney, heart, and intestine), often by regulating inflammatory activation and stem cell behavior. As macrophages have been well-characterized as orchestrators of healing, their use of Wnt signaling to …

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 …

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 …

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 …

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) …

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 …

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) …

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 …

Therapeutic Modalities For Preventing Osteoarthritis Following Trauma To The Knee, Kayla M. Scott

Theses and Dissertations

Over 32.5 million adults in the United States and 300 million worldwide have osteoarthritis (OA). To date, there are no disease-modifying therapeutics, only strategies to slow OA progression through pain management, regenerative medicine approaches, and ultimately joint replacement.

On a microscale, a phenotypic shift of the normally quiescent articular chondrocytes leads to aberrant expression of pro-inflammatory and catabolic pathways, which are hypothesized to contribute to OA progression. Of note, interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and WNT/β-catenin signaling are key players disrupting cartilage homeostasis and driving inflammatory pathway activation. These pathways become dysregulated and form a positive feedback loop, increasing …

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, …

Nanoscale Material Interaction With Multicellular 3d Cancer Culture, Emilie Darrigues

Theses and Dissertations

Pancreatic ductal adenocarcinoma (PDAC) is the most common form of pancreatic cancer, it is difficult to diagnose, often recurs, has high resistance to chemotherapies, and can be marked by advanced metastatic stages. There is an urgent need to fill the knowledge on nanoparticle penetration, diffusion, and cellular interaction in the context of adaptive PDAC tumor microenvironment to allow the development of new imaging and therapeutic supports. Traditionally, cancer-treating nanoparticles have been engineered and tested on 2D cell cultures, but several studies indicate that this in vitro model does not mimic tumor features closely enough. In contrast, 3D culture models offer …

3d Printed Microporous Collagen Constructs Using The Freeze-Fresh Methodology, Thais Sousa Senzano

Theses and Dissertations

Scaffold microporosity is known to play a critical role in governing cellular response including cell migration, proliferation, and tissue-specific differentiation. While fabrication approaches such as solvent leaching and freeze-casting are commonly used for the generation of microporous biomaterial scaffolds, these methods provide little control over scaffold geometry and creation of complex tissue structures. Extrusion-based 3D printing, an additive manufacturing method, is a highly versatile layer-by-layer printing approach that allows for the fabrication of easily customizable 3D scaffolds with complex architecture using a vast selection of polymeric bioinks. These 3D printed constructs are porous at the macroscale, but achieving microporosity (i.e., < 100 μm) in printed constructs is challenging due to the sub-optimal resolution of the extrusion-based printing method. A recent study using alginate inks introduced a new fabrication technique termed Freeze-FRESH(FF)that combines extrusion printing and freeze-casting approaches to generate 3D constructs with hierarchical microporosity. However, the porosity of the resultant alginate constructs was comparable despite changing the freezing temperature. In the current study, the FF method was modified to print collagen constructs with greater control of microporous architecture. Highly concentrated collagen type I ink was used to 3D print collagen constructs using the freeform reversible embedding of suspended hydrogels (FRESH)approach. Modification of the FF technique entailed melting of the FRESH bath post printing via incubation at 37 °C followed by freezing and lyophilization to allow for collagen gelation and better heat transport during the freezing process. The effect of freezing temperature on micropore size, swelling degree, degradation, and mechanical properties of printed constructs was assessed. Finite element (FE) models were generated to predict the mechanical properties of microporous scaffolds. In addition, the effect of microporosity on Saos-2 cell morphology, proliferation, infiltration, and ALP activity was evaluated. Results from the study showed that freezing temperature effectively modulated micropore size and that constructs with larger micropore size were more stable. Microporosity had no effect on swelling ratio yet caused a decrease in mechanical properties of collagen constructs; FE models confirmed experimental results. Cell metabolic activity and infiltration was enhanced in microporous constructs with larger pore size, yet there was no effect on cell morphology, and ALP activity. In conclusion, the modified FF technique can be effectively used to fabricate hierarchically porous 3D collagen constructs.

Improving Long-Term Vascular Graft Viability Using Peritoneal Pre-Implantation And Epsin-Mimetic Peptides, Mahyar Sameti

Theses and Dissertations

The primary goal of this project was to produce and develop a tissue-engineered small-diameter vascular graft which can replace the arteries and function well for long-term grafting. Implanting an electrospun tubular conduit into the peritoneal cavity to recruit autologous cells prior to grafting the conduit into the artery is a method to achieve this goal. Incorporating an epsin-mimetic peptide on the conduit prior to grafting is another proposed method to reach the goal. This will be accomplished through four complementary studies: (1) determining the effect of a pouch in peritoneal pre-implantation and reducing the potential peritoneal adhesion formation;(2) determining the …

A Comparative Study Of Cannabinoids & Cb1 Receptor Gi Signaling, Haley Kristen Andersen

Theses and Dissertations

The legalization of medical marijuana has highlighted cannabinoids as a potential, opioid-free therapeutic option for pain management; however, the rise in illicit synthetic cannabinoid-induced toxicity has demonstrated the need to outline cannabinoid molecular signaling. The cannabinoid-type 1 (CB1) receptor is an endogenous G protein-gated receptor (GPCR), well-expressed in the central nervous system (CNS) associated with modulating neuronal activity. Cannabinoid agonists bind to the CB1 receptor resulting in the inhibitory G protein (Gi) complex to dissociate into two subunits, Gβγi and Gαi. The Gαi subunit inhibits adenylyl cyclase, leading to a decrease in cyclic adenosine monophosphate (cAMP). The Gβγi subunit activates …

Bioprinted In Vitro Model Of Human Glioblastoma, Rachel Lauren Schwartz

Theses and Dissertations

Glioblastoma multiform (GBM) is one of the most aggressive forms of primary brain tumors. GBM is fast progressing and resistant to treatment, resulting in a low survival rate. Conventional 2-dimensional tissue culture models cannot fully replicate the complexities of cancer lesions that contain multiple cell types and structures (e.g. vessels composed of endothelial cells, cancer cells, normal cells, etc.) as well as an intricate scaffold of proteins comprising the extracellular matrix (ECM). In addition, animal models cannot translate into the clinical disease in patients. Thus, this study has developed a bioprintable organ-on-a-chip (OOAC) model that mimics the important ECM factors …

Novel Material For Advanced Tissue Regeneration, Karrer Mahdi Kadum Alghazali

Theses and Dissertations

Nerve tissue damage or failure can occur for various reasons, including infection, disease, aging, and trauma. The tissue microenvironment (extracellular matrix-ECM) plays a key role in regulating the self-renewal and recovery of damaged tissue. ECM-cell interactions govern cell migration and physiology, with biochemical and biophysical boundaries being the main factors that control ECM-cell interaction. Optimizing these boundaries for the recovering tissue will create a healthy microenvironment to support and enhance the recovery rate (1, 2). We have developed a novel, multidimensional nanocomposite system that incorporates gold nanorods (AuNRs) (aspect ratio of around 3) as an artificial ECM for cell adhesion, …

Development Of A Graphical User Interface For Ecg Signals Classification Using Statistical Features Analysis, Mousa Hammad S Aldosari

Theses and Dissertations

Cardiac diseases are the most common cause of mortality in the world. The detection of cardiac arrhythmias is not a straightforward process, since minor variations in the electrocardiogram (ECG) signals cannot be easily identified manually. Therefore, automatic detection and classification of cardiac arrhythmia would shorten the diagnostic time and accelerate medical intervention resulting in reducing the mortality rate. In this thesis, I have developed a simple and low-cost computer-aided diagnostic system using MATLAB-based Graphical User Interface (GUI) to facilitate fast operation and access to the data along with the overall accuracy of the system. The acquired ECG signals are processed …

Mechanical And Material Properties Of Nitinol And Its Application To Stents, Ariana Solis Eichler

Theses and Dissertations

Nitinol is a functional material with superelastic and shape memory properties derived from its unique molecular structure. The purpose of this thesis is to explore how the material and mechanical properties of self-expanding Nitinol stents affects the forces applied to arterial walls during stent deployment compared to the traditional balloon-expanding stainless steel stents, in addition to contrasting thin and thick-walled pressure vessel mathematical models. Nitinol’s mechanical properties can be optimized for stent applications by tailoring its processing procedures. Nitinol stents demonstrated a reduced circumferential hoop stress on the vessel wall and greater factor of safety with respect to vessel rupture …

An Experimental And Computational Mechanical Analysis Of Bone Anchors And Substrate Interface, Samantha May Schultz

Theses and Dissertations

Screw loosening is a common concern in orthopedic surgery. Therefore, this study is a computational and experimental evaluation of bone substrate and cortical screw interface. An axial load test was performed in an Instron with titanium alloy screws with 2.7 mm, 3.5 mm, and 4.5mm diameter orthopedic cortical screws inserted into SawBone with densities varying from 10 to 50 pounds per cubic foot (PCF), incrementing in sets of 10 PCF. SawBone was chosen in place of human bone because it has been shown to emulate the same mechanical properties (1). Twelve samples were prepared for each screw size and substrate …

Cis-Resveratrol Upregulates Tyrosyl-Trna Synthetase And Inhibits The Proliferation Of Select Breast Cancer Cell Lines, Marion Cone Hope Iii

Theses and Dissertations

Breast cancer is one of the most commonly occurring cancers in women. 70% of breast cancer patients express ERα and are treated with tamoxifen (Tam), a drug that is used to directly target ERα. However, 20-30% of cancer patients develop a resistance to Tam. This resistance leads to a worse prognosis and other treatments such as DNA damaging drugs or radiation to eliminate these cells. Resveratrol (RSV) is a polyphenolic- compound found in plants such as grapes and hellebore and is known to evoke anti-cancer effects. While natural resveratrol exists as a mixture of both cis- and trans- isomers, so …

Synthesis And Characterization Of Novel Silicone Hydrogel Biomaterials With Advanced Properties For Ocular Drug Delivery, Liana D. Wuchte

Theses and Dissertations

There is a need for next generation silicone hydrogel biomaterials with greater compositional flexibility and tailorable material properties for advanced manufacturing and new applications for ocular drug delivery. Poly(DMS-R11-co-TRIS-co-DMA-co-PEG200DMA-co-DEAEM-co-DADMAC) silicone hydrogel contact lenses were synthesized with macromolecular memory and showed 7-day in vitro release of latanoprost acid via a microfluidic platform with controlled release and improved drug payload capacity compared to control lenses. Six newly synthesized silicone macromers were then incorporated into contact lens formulations for the first time to produce a novel, improved platform. Various silicone macromer structures showed significantly improved solubility with TRIS and DMA with components ranging …

Novel Injectable Plga-Peg-Plga Self-Assembled Hydrogels For The Extended And Controlled Release Of Dna Nanocarriers To Prevent Secondary Cataracts, Laura L. Osorno

Theses and Dissertations

Cataracts are the second leading cause of blindness worldwide. There are over 20 million cataract surgeries each year, and these cases are expected to double within the next ten years. Over 40% of adults and nearly all children develop secondary cataracts, or posterior capsule opacification (PCO), following cataract surgery. Currently, Nd:YAG laser therapy is used to treat PCO; however, laser therapy is not available worldwide and treatment may have adverse effects on surrounding ocular tissues. Thus, there is a considerable unmet need for more efficacious and convenient treatments to prevent PCO.

Injectable, stimuli-responsive gels were designed using poly(lactic-co-glycolic acid)-b-poly(ethylene glycol)) …

Designing Silk Protein-Based Composite Materials With Tunable Heat Transfer And Magnetic Properties, Ye Xue

Theses and Dissertations

Renewable and biocompatible silk protein materials with desired physical properties show promising applications in biomedical field. In this work, a set of protein-based composites with desired thermal and magnetic properties, enhanced by the appropriate distribution of nanofillers in the protein matrix in both 2D-film and 1D-fiber forms was investigated. Results indicate that secondary structures of silk protein materials regenerated by a formic acid-calcium chloride method are different from those of their respective natural silk fibers. Intramolecular beta-sheet structures were found to dominate these silk films, causing these regenerated samples to be water-insoluble but more flexible than traditional silk films with …

Study And Characterization Of Conductive Elastomers For Biomedical Applications, Hadis Gharacheh

Theses and Dissertations

Health issues have always been one of humankind's biggest challenges. Over the last century, there has been significant and monumental progress in health and biomedical science, with the end goal of alleviating and eliminating illnesses and ailments. For developing biomedical devices, polymers and elastomers group among other types of biomaterials have been highlighted to be used due to high flexibility, stability, biocompatibility, and mechanical and rheological characteristics. In this work, the characterization of acrylated poly glycerol_sebacate (PGSA) polymer conjugated with bio ionic liquid (BIL) was investigated. Results showed high biocompatibility, high printability with tunable mechanical, adhesive, and conductivity properties. For …