Engineering Commons^™

Extracellular Matrix Nanoparticles Effects On The Lung In Vivo, Brittaney E. Ritchie

Theses and Dissertations

Acute respiratory distress syndrome (ARDS) is a life-threatening condition that causes diffuse alveolar damage and a loss of the extracellular matrix (ECM). This leads to pulmonary edema and lung function deterioration. Our lab has created decellularized porcine lung, electrosprayed ECM nanoparticles that have been previously shown to have pro-regenerative capabilities in vitro.

In this study, the ECM nanoparticle effects on young murine lungs were tested in vivo. An ECM nanoparticle suspension, previously used for the in vitro studies, was aerosolized intratracheally into the lungs using a microsprayer. 24 hours later, the lung mechanics, bronchoalveolar lavage fluid, and histology …

Development Of A Torque-Based Device For The Quantification Of Arm Rigidity In Patients With Parkinson’S Disease, Georgina O. Miller

Theses and Dissertations

Parkinsonian rigidity is caused by the inability of the muscles to relax and extend properly, due to reduced dopamine levels and often begins on one side of the body before spreading contralaterally. The current standard for determining joint rigidity in a clinical setting is a test completed by the clinician based on the feel of the relaxed wrist and elbow joints as they are passively flexed and extended and a series of ordinal rating scales, the Movement Disorder Society’s – Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), Hoehn and Yahr Scale (H&Y), and Parkinson’s Disease Questionnaire-39 (PDQ-39). These methods are used …

Higher Tensile Forces Across Cellular Junctions And An Intact Nuclear Linc Complex Is Required For Epithelial Function And Stability, Fnu Vani Narayanan

Theses and Dissertations

Recent advances in three-dimensional (3D) cell culture systems have provided key insights into the understanding of biochemical and physiological states of native tissue. A significant progress in the field of mechanobiology involves measuring cellular traction forces in a more native 3D environment. However, the effects of mechanical forces exerted across cellular junctions and the nuclear LINC complex, in an organized 3D system has not been investigated thus far. Epithelial cells spontaneously form acini (also known as cysts or spheroids) with a single, fluid-filled central lumen, when grown in 3D matrices. The size of the lumen is dependent on apical secretion …

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 …

The Effect Of Intermittent Theta Burst Stimulation On Biceps Corticomotor Excitability In Non-Impaired Individuals And Individuals With Tetraplegia, Blaize Majdic

Theses and Dissertations

Neuromodulation of the primary motor cortex (M1) in pair with physical therapy may be a promising method for improving motor outcomes after spinal cord injury (SCI). Increased excitability of the corticospinal motor pathways (i.e. corticomotor excitability) has shown to be associated with improved motor learning and skill acquisition. Intermittent theta burst stimulation (iTBS) is a form of non-invasive brain stimulation which can increase corticomotor excitability, as measured by an increase in the amplitude of motor evoked potentials (MEPs). However, the ability for iTBS to increase the corticomotor excitability of proximal muscles such as the biceps, and muscles affected by spinal …

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

Theses and Dissertations

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

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

Theses and Dissertations

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

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

Theses and Dissertations

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

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

Theses and Dissertations

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

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

Theses and Dissertations

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

Engineering The Alveolar Gas Exchange Barrier With Extracellular Matrix Coatings For Bioengineered Lungs, Bethany M. Young

Theses and Dissertations

Lower respiratory diseases are currently the third leading cause of death worldwide. For many end-stage patients with these diseases, there is no cure and a shortage of donor organs available for transplant. A promising solution is to design regenerative scaffolds or complete bioengineered lungs, using decellularized lung tissues as a template for regeneration. Recent advances in the field have made significant strides towards developing a transplantable lung. However, the current technology has not produced a functional lung for in vivo transplant due to immature gas exchange barriers. The mechanisms driving alveolar barrier maturation and role that extracellular matrix (ECM) plays …

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

Theses and Dissertations

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

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

Theses and Dissertations

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

The Role Of The Mechanical Environment On Cd117+ Endothelial Cell Angiogenesis, Patrick Link

Theses and Dissertations

Angiogenesis is a complex process coordinating cell migration, proliferation, and lumen formation. Changes to the microenvironment regulate angiogenesis through mechanotransduction and cytokine signals. In pulmonary hypertension, something in the process becomes abnormal, resulting in changes to the microenvironment and the formation of a glomerulus of dysfunctional capillaries, called a plexiform lesion. Endothelial cells, expressing CD117 (CD117+ EC clones) increase in the plexiform lesions of pulmonary hypertension, independent of pro-angiogenic VEGF signaling. We hypothesize that the mechanical environment and the macromolecular composition of the extracellular matrix, both, contribute to the aberrant angiogenesis. When we changed the mechanical environment, we changed the …

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

Theses and Dissertations

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

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

Theses and Dissertations

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

Automatic Image Processing And Conversion To Tactile Graphics, Tyler Ferro

Theses and Dissertations

Graphical information has become a critical method for portraying information for education, work and personal tasks and decisions. Unfortunately there are currently limited means of providing this information to individuals who are blind or visually impaired: alternate text is frequently missing, and accessible tactile diagrams tend to be time consuming to make and require expertise in order for them to be interpretable (which may be costly to the user and/or impossible to get). The aim of this project is to provide an accessible system to automatically generate tactile graphics for those who need to interpret information contained in visual images. …

Improving Realtime 3-D Tracking Of High Dose Rate Radiation Source Using A Flat Panel Detector, Leo Uchechukwu Udeji

Theses and Dissertations

Previous research ¹ on this subject tracked the presumed exact path the HDR source would follow in real-time, during breast brachytherapy treatments in other to ensure accurate dose delivery and effectively confirm actual source position. As a continuation, this research has three objectives. Firstly, we will extract information from patient DICOM file which will be used to perform evaluations, then we will establish communication between our C program and the new Varex Paxscan flat panel detector (FPD). Finally, we will try to embed our C codes into a MATLAB graphical user interface (GUI) This research will attempt to improve the …

Nuclear Rupture In Progeria Expressing Cells, Kranthidhar Bathula

Theses and Dissertations

Cells regularly take on various types of force in the body. They have structures that are able to mediate, transfer and respond to the forces. A mutation in force regulating proteins such as lamin in the nucleus or the KASH domain which connects the nucleus to the cytoskeleton of the cell can cause catastrophic events to occur. The aims of this study were to better understand the response of the nucleus when structural proteins are mutated or are not present while under force. Progeria, a rare disease where an additional farnesyl group is attached to lamin was used in this …

Fibronectin Mechanics And Signaling In Tgf-Β1-Induced Epithelial To Mesenchymal Transition, Lauren Griggs

Theses and Dissertations

Epithelial to Mesenchymal Transition (EMT) is a dynamic process by which a distinct change in the phenotype and function of epithelial cells render them as mesenchymal cells. Characteristics of mesenchymal cells include the ability to invade, increased migratory kinetics and heightened resistance to apoptosis. Therefore, there is a strong need to fully understand the mechanism for the induction of EMT in pathological conditions such as carcinoma progression. Recent advances highlight two pivotal contributors, soluble growth factor (gf) signals, and mechanical signals, in the process. However, to date, no clear mechanism exists linking the two in epithelial transdifferentiation. Transforming Growth Factor-β1 …

Development Of Novel Models To Study Deep Brain Effects Of Cortical Transcranial Magnetic Stimulation, Farheen Syeda

Theses and Dissertations

Neurological disorders require varying types and degrees of treatments depending on the symptoms and underlying causes of the disease. Patients suffering from medication-refractory symptoms often undergo further treatment in the form of brain stimulation, e.g. electroconvulsive therapy (ECT), transcranial direct current stimulation (tDCS), deep brain stimulation (DBS), or transcranial magnetic stimulation (TMS). These treatments are popular and have been shown to relieve various symptoms for patients with neurological conditions. However, the underlying effects of the stimulation, and subsequently the causes of symptom-relief, are not very well understood. In particular, TMS is a non-invasive brain stimulation therapy which uses time-varying magnetic …

Reducing Uncertainty In Head And Neck Radiotherapy With Plastic Robotics, Mark R. Ostyn

Theses and Dissertations

One of the greatest challenges in achieving accurate positioning in head and neck radiotherapy is that the anatomy at and above the cervical spine does not act as a single, mechanically rigid body. Current immobilization techniques contain residual uncertainties that are especially present in the lower neck that cannot be reduced by setting up to any single landmark. The work presented describes the development of a radiotherapy friendly mostly-plastic 6D robotic platform for positioning independent landmarks, (i.e., allowing remote, independent positioning of the skull relative to landmarks in the thorax), including analysis of kinematics, stress, radiographic compatibility, trajectory planning, physical …

Engineering Surface Properties To Modulate Inflammation And Stem Cell Recruitment Through Macrophage Activation, Kelly M. Hotchkiss

Theses and Dissertations

Biomaterials are becoming the most commonly used therapeutic method for treatment of lost or damaged tissue in the body. Metallic materials are chosen for high strength orthopaedic and dental applications. Titanium (Ti) implants are highly successful in young, healthy patients with the ability to fully integrate to surrounding tissue. However the main population requiring these corrective treatments will not be healthy or young, therefore further research into material modifications have been started to improve outcomes in compromised patients. The body’s immune system will generate a response to any implanted material, and control the final outcome. Among the first and most …

Decellularized Matrices Effect On The Adaptive Immune Response, Kegan Sowers

Theses and Dissertations

Decellularized extracellular matrices have been a growing area of interest in the biomedical engineering fields of tissue engineering and regenerative medicine.As these materials move toward clinical applications, the immune response to these materials will be a driving force toward their success in clinical approaches. Fully digested decellularized matrix constructs derived from porcine liver, muscle and lung were created to test the adaptive immune response. Hydrogel characterization ensured that the materials had relatively similar stiffness levels to reduce variability, and in vitro studies were conducted. Each individual construct as well as a gelatin control were plated with a co-culture of macrophages …

Exogenous Fniii 12-14 Regulates Tgf-Β1-Induced Markers, Hilmi M. Humeid

Theses and Dissertations

The extracellular matrix protein Fibronectin (FN) plays an important role in cell contractility, differentiation, growth, adhesion, and migration. The 12th -14th Type III repeats of FN (FNIII 12-14), also referred to as the Heparin-II domain, comprise a highly promiscuous growth factor (GF) binding region. This binding domain aids in cellular signaling initiated from the ECM. Additionally, FN has the ability to assemble into fibrils under certain conditions, mostly observed during cell contractile processes such as those that initiate due to upregulation of Transforming Growth Factor Beta 1 (TGF-β1) [1], [2]. Previous work from our lab has shown that self-assembly of …

Investigation Of Polymeric Composites For Controlled Drug Release, Hsi-Wei Yeh

Theses and Dissertations

The Electrospray (ES) technique is a promising particle generation method for drug delivery due to its capabilities of producing monodisperse PLGA composite particles with unique configurations and high drug encapsulation efficiency. In the dissertation work, the coaxial dual capillary ES was used to generate drug-loaded core-shell PLGA particles to study the effects of particle filling materials, drug loading locations and particle shell thicknesses on the resultant in vitro release behaviors of the hydrophilic and/ or hydrophobic model drugs. Through release profile characterization of drug-loaded PLGA particles (particle size: 400 nm and 1 μm), it was confirmed that the co-encapsulation of …

Nanomedicine Drug Delivery Across Mucous Membranes, Michael G. Lancina Iii

Theses and Dissertations

NANOMEDECINE DRUG DELIVERY ACROSS MUCOUS MEMBRANES

By Michael G. Lancina III

A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy at Virginia Commonwealth University.

Virginia Commonwealth Univeristy, 2017.

Major Director: Dr. Hu Yang, Associate Professor, Chemical and Life Science Engineering

Control over the distribution of therapeutic compounds is a complex and somewhat overlooked field of pharmaceutical research. When swallowing a pill or receiving an injection, it is commonly assumed that drug will spread throughout the body in a more or less uniform concentration and find its way to wherever it is needed. In …

Modified Pamam Dendrimers In Tunable Drug-Delivery Systems: A Sustained-Release Dendrimer Hydrogel For Anti-Glaucoma Drugs And Surface-Engineered Macrophages As Nanoparticle Carriers For Targeted Anti-Cancer Therapy, Christopher A. Holden

Theses and Dissertations

Two specific drug-delivery applications were sought in this work using polyamidoamine (PAMAM) dendrimers. One drug-delivery system used a novel dendrimer hydrogel (DH) for sustained delivery of anti-glaucoma drugs. In this work, PAMAM G3.0 dendrimers were covalently bonded with poly(ethylene glycol) (PEG­₁₂₀₀₀) molecules which were subsequently acrylated, resulting in photocurable DH conjugates. For pharmacological studies, DH were loaded with a solution of intraocular pressure lowering drugs, brimonidine and timolol maleate, and were characterized for in vitro release and ex vivo transport and uptake. DH formulations were shown to increase the loading of drug molecules, increase transcorneal drug delivery, and …

Development And Validation Of A Novel Resonant Energy Transfer (Fret) Biosensor To Measure Tensile Forces At The Linc Complex In Live Cells, Paul Arsenovic

Theses and Dissertations

There is a large body of evidence supporting the theory that cell physiology largely depends on the mechanical properties of its surroundings or micro-environment. More recently studies have shown that changes to intra-cellular mechanical properties can also have a meaningful impact on cell function and in some cases lead to the progression of ailments or disease. For example, small changes to the protein sequence of a structural nuclear envelope protein called lamin-A is known to cause a variety of neurological and musculoskeletal diseases referred to as laminopathies. Currently, there is little incite into how these mutations lead to disease progression …

Altering A Runner’S Foot Strike Using A Modified Elliptical Trainer, Daniel Shull

Theses and Dissertations

One possible solution to common running related injuries is to transition runners from a rearfoot strike during initial contact to a midfoot strike. Natural rearfoot strike runners were studied to see if a modified elliptical trainer could be used to alter their running pattern to that of a midfoot strike runner. Their results were compared to subjects who ran on a non-modified elliptical trainer. After training on the modified elliptical trainer, subjects demonstrated a decrease in foot angle at initial contact when attempting to run with a midfoot strike. Training did not affect all kinetic metrics or stride frequency. However, …