Biomedical Engineering and Bioengineering Commons^™

Automatic Analysis Of Surface Electromyography Of Reflexes For Central Nervous System Inhibition During Pregnancy, Neda Parvin

Theses and Dissertations

Eclampsia is a life-threatening neurological complication (seizures or coma) of pregnancy, and represents progression of pre-eclampsia (high blood pressure and protein in the urine isolated to pregnancy). Even though the exact mechanism of pre-eclampsia and its neurological manifestations have yet to be definitively established, it is known that there is a loss of inhibitory impulses between the cerebral cortex and the spinal cord resulting in exaggerated reflexes. In this work, we establish normative measures for deep tendon reflexes (DTR) during pregnancy. We quantified the surface electromyogram (EMG) at the knee and ankle of DTRs in 279 subjects. The signals were …

Far-Field Optical Microscopy Based On Stimulated Emission Depletion, Yunxia Wang

Theses and Dissertations

Conventional lens-based (far-field) fluorescence microscopy is a widely used imaging technique with spatial resolution up to 150–350 nm. However, this technology cannot discern very small structural features, because the spatial resolution is limited by diffraction to about half of the wavelength of light (λ/2，λ is the wavelength of light). Hence, most of the developments in microscopy aim at improving resolution. In the past decades, stimulated emission depletion (STED) microscopy has been developed to bypass the diffraction limit for the application in biological imaging with resolution approaching the nanoscale. The basic principle of STED microscopy is to employ a doughnut-shape laser …

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 …

Atherosclerotic Plaque Adhesion Strength And Its Role In Plaque Rupture, Bilal Merei

Theses and Dissertations

Cardiovascular diseases are disorders affecting the blood vessels and the heart. According to the World Health Organization, cardiovascular diseases are one of the leading causes of death worldwide. They are responsible for over 17.1 million deaths per year worldwide, representing 31.5% of deaths 1, 2. Atherosclerosis, a chronic inflammatory disorder affecting large arteries, is the underlying cause of many cardiovascular diseases. Plaque rupture is a serious complication of advanced atherosclerosis, often leading to life-threatening clinical consequences such as myocardial infarction (heart attack) or stroke. 75% of newly developed myocardial infarction cases are caused by atherosclerotic plaque rupture. It affects approximately …

Advancing Automated Methods For Microrna Profiling, Kia N. Zellars

Theses and Dissertations

The widespread influence of miRNAs in many biological processes and characteristic changes in expression profiles make them potential biomarkers for a range of diseases. With recent discoveries highlighting the enrichment of particular circulating miRNAs in plasma under pathological conditions, there has been a push for technological advances in miRNA profiling studies as a diagnostic tool. A standardized, automated, high-throughput method for miRNA isolation from human plasma samples was developed in this study. Samples were subject to full miRNome profiling utilizing RT-qPCR. These unique findings demonstrate that developing a distinct miRNA biomarker profile for heart failure patients is feasible and holds …

Eye Movement Control: An Index For Athleticism, Brittany L. Oshea

Theses and Dissertations

Athletic potential is one of the most complex human traits. An elite athlete is produced from a complex interaction of an innumerable number of traits exhibited by the athlete. However, it’s not clear whether these traits are innate, allowing the athlete to excel, or, alternatively, are a consequence of practice. To be successful, athletes rely heavily on sensory information from the visual and vestibular systems. This study investigated the relationship eye movement control has with innate athleticism by comparing the saccadic and Vestibulo-Ocular Reflex (VOR) responses of former, no longer practicing, elite athletes against their age and gender matched counterparts …

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 …

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 …

Fabrication Of Flexible, Biofunctional Architectures From Silk Proteins, Ramendra K. Pal

Theses and Dissertations

Advances in the biomedical field require functional materials and processes that can lead to devices that are biocompatible, and biodegradable while maintaining high performance and mechanical conformability. In this context, a current shift in focus is towards natural polymers as not only the structural but also functional components of such devices. This poses material-specific functionalization and fabrication related questions in the design and fabrication of such systems. Silk protein biopolymers from the silkworm show tremendous promise in this regard due to intrinsic properties: mechanical performance, optical transparency, biocompatibility, biodegradability, processability, and the ability to entrap and stabilize biomolecules. The unique …

The Effect Of Vibrotactile Feedback On Remote Manual Task Performance, Matthew S. Standard

Theses and Dissertations

Vibrotactile feedback offers a unique opportunity to augment or reconstruct impaired tactile sensations, whether that be in the form of enhancing prosthetics or specialized protective clothing. Important information about temperature and object slippage serve to endanger the human operator or equipment. This thesis presents three experiments which investigate amplitude modulated vibrotactile signals as a scalar dimension of roughness, the effect those signals and their locations (finger pad, forearm, bicep) have on the performance of two tasks: the sensing of temperatures simulated by vibrotactile signals and gripping an object of simulated surface texture. The results show task performance increase when the …

Modulating The Innate Immune Response To Electrospun Scaffolds And Polymer Degradative Byproducts, Daniel Abebayehu

Theses and Dissertations

Implanted biomaterials often induce inflammation that frequently leads to the foreign body response, fibrosis, and the failure of the implant. Thus, it is important to evaluate how cells interact with materials to promote a more regenerative response. It is critical to determine how to modulate the response of tissue resident innate immune cells, as they are among the first cells to interact with implanted materials. Among tissue resident innate immune cells are mast cells, which are inflammatory sentinels that degranulate and orchestrate the fate of other cell populations, such as monocytes/macrophages and lymphocytes. Mast cells have also been reported to …

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, …

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 …

Development Of An Electrospun And 3d Printed Cellular Delivery Device For Dermal Wound Healing, Ryan M. Clohessy

Theses and Dissertations

The goal of this research was to develop a system of individualized medicine that could be applied to dermal wounds serving as a wound dressing and synthetic extracellular matrix while delivering stem cells to the wound bed. First, fabrication parameters for electrospinning polymer fibers were determined. This involved evaluating fiber morphology with respect to polymer selection and solution concentration. Next, construct fabrication was examined to produce an integrated void space, or cargo area, suitable to maintain stem cells. In vitro studies to ensure stem cell viability and phenotype were conducted, and results supported the notion that cells could be administered …

Electrospraying Extracellular Matrix To Form Nanoparticles, Patrick Link

Theses and Dissertations

Chronic Obstructive Pulmonary Disease (COPD) is a leading cause of death worldwide. Alveolar wall destruction is a significant contributor to COPD. Inflammatory macrophages are a major source of the Extracellular Matrix (ECM) proteolysis. ECM breakdown causes air to get trapped in the alveoli, obstructing airflow. One step in curing COPD may be to convert inflammatory to pro-regenerative macrophages. Recently, decellularized ECM scaffolds have shown the ability to induce a pro-regenerative phenotype.

Yet these scaffolds are incapable for reaching the alveolar region of the lungs. To reach the alveolar region particles need a diameter of 1-5 μm or smaller than 300 …

Knee Joint Internal Forces During Squat Jump Exercise, Ricardo Moreno

Theses and Dissertations

The purpose of this research is to investigate muscular ligament and joint contact forces produced during squat jump exercise. An inverse dynamics, two dimensional, leg model is used to describe the motion in the sagittal plane. The lower extremity model includes two bones, tibia and femur, tibio-femoral ligaments, and muscles such as quadriceps, hamstrings, and gastrocnemius. The ligaments are anatomically modeled as nonlinear strings, but the femoral condyle is modeled as a circle and the tibial plateau as a straight line. Experimental squat jump exercises are conducted to obtain the ground reaction forces, the angular accelerations, and centroid linear acceleration …

Non-Invasive Real Time, Accurate And Affordable Monitoring Of Hemoglobin And Vital Parameters For Icu Patients, Harsh S. Modi

Theses and Dissertations

The measurement of hemoglobin concentration (Hb), oxygen consumption (mL and %), and partial pressure of oxygen inside the lungs are vital parameters in early prediction of respiratory diseases such as sepsis, septic shock, acute respiratory distress syndrome (ARDS) etc. The availability of these parameters in real time can play a crucial role in management of modes and parameters of the ventilators. The real time monitoring of patient’s vital signals in intensive care units can reduce the number of blood tests, time and cost spent inside the intensive care units. The medical conditions such as blood loss from surgery or an …

Developing The Three Dimensional Tumor Model For Melanoma Drug Screening, Guochang Ye

Theses and Dissertations

Two-dimensional (2D) Tissue Culture Treated Plastic (TCTP) is widely used for cancer drug screening and has dominated the field for a long time. Compared with traditional two dimensional cell culture, a three dimensional tumor model may able to provide more reliable experimental results related to drug screening and discovery. With the development of nanoparticle chemotherapies, there is a need for ways to better investigate and characterize the effect of the 3D tumor environment. Cerium oxide nanoparticles, Nanoceria, is one of the potential solutions being explored for treating melanoma in the future in combination with conventional chemotherapies. This is attributed to …

Design And Development Of A Physiological Stress Monitoring/Alert System Using A Wristband, Ritesh Varma Pathapati Thyagaraju

Theses and Dissertations

The design and development of wearable physiological systems for stress monitoring have gathered a lot of attention during the past few years. These systems have undergone much-needed development to tackle long-term effects such as a headache, depression, insomnia, high blood pressure, confusion, inability to make correct choices, etc. Accurately measuring physiological signals that are helpful to detect stress in its early stages using wearable technology have long been a goal in the healthcare industry. Current commercial products such as Fitbit and Empatica only monitor either the heart rate (Fitbit) or electrodermal activity in real time (Empatica) but these devices have …

Multiscale Mechanics Of Bone: Examining The Influence Of Genetic Alterations, Brendyn James Miller

Theses and Dissertations

This MSc thesis investigates how genetic alterations involved in the synthesis of proteins or in the regulation of tissue remodeling affects the composition, structure and mechanics of bone at the multiscale levels. This was accomplished by performing two mouse model studies. In the first study, bone properties of TIMP-3 knock-out (Timp-3⁻ˊ⁻) mice were examined by performing mechanical testing, µCT analysis, and FTIR analysis. Results demonstrated that the mechanical integrity of the Timp-3⁻ˊ⁻ bone was compromised. Decreased values for the yield and ultimate load, stress capacity, and fracture toughness were observed in both the TIMP-3 deficient bones. These reductions in the …

Assessment Of The Correlation Between Memory Span Test Result And Attention Using A Wireless Eeg System, Yu Yu

Theses and Dissertations

The process to encode, retain and retrieve information is known as memory. Ever since models for short-term memory and working memory systems were proposed, the function and importance of the short-term memory and working memory systems have been explored by a number of studies which in part have examined factors which may affect memory capacity. Although there are many undetermined factors which may affect the result of these two different memory span test, recent studies have suggested a link between human mental condition and memory capacity. These studies show that the results of simple memory span tests are improved when …

Rapid Generation Of 3d Microchannels Using A Multiphoton Laser System In Blended Hydrogels To Serve As Templates For Microvascular Generation, Stephanie Renée Burtch

Theses and Dissertations

Lack of scaffold microvascularization is one of the biggest problems facing graft survival and success within current tissue engineering applications. Fortunately, techniques aiming to form microchannels within three-dimensional scaffolds have shown promise in providing templates for tube-like cell formations. Unfortunately, many current patterning approaches are limited in the types of materials the technique can be applied to and lack the ability to form capillary-sized (<10 microns in diameter) networks. In this study, a multiphoton laser was used to create channels down to the micron level within an optically-clear hydrogel scaffold. Different percentages of poly (ethylene glycol) diacryate (PEGDA) and collagen were used to create different blends of hydrogels at 0%, 1%, 2%, and 3% collagen/PEGDA (w/w). Mechanical and transmittance testing were performed on all blends in order to determine which had optimal mechanical strength and optical clarity for laser subtractive printing. Swelling and degradation were measured to confirm the scaffolds served the tissue engineering requirement of eventual degradation. All gels with PEGDA incorporation showed an increase in mechanical stability and transparency when compared to pure collagen gels. Hydrogel blends showed resistance to degradation in phosphate-buffered saline, but appeared to exhibit collagen degradation in collagenase, although no statistical significance was seen. Cell viability tests within the hydrogels showed viability in cell-seeded hydrogels when compared to dead controls, although cells lacked some markers of healthy cells, such as spreading. In conclusion, results show that hydrogel blends provide a good matrix for subtractive optical micropatterning approaches, although other types of hydrogels may improve cell spreading and other cell responses.

Enabling Studies To Optimize Biomaterials For The Treatment Of Myocardial Infarction, Eva Adriana Romito

Theses and Dissertations

The canonical mechanism of wound healing is disrupted following a myocardial infarction (MI), manifesting as an unregulated response that negatively impacts left ventricular (LV) function. This mechanism, termed post-MI remodeling, culminates in an outcome that favors progression to a systolic heart failure state and death for the patient. Therapeutic approaches following the occurrence of a MI are designed to modulate the natural remodeling process and mitigate the loss of cardiac function. The mechanics and structure of the healing infarct have been the focus of numerous pre-clinical and clinical investigations, leading to the impending clinical introduction of material injections as a …

A Mechanical Approach To The Characterization Of Material Failure Of Atherosclerotic Lesions, Lindsey A. Davis

Theses and Dissertations

Failure of atherosclerotic plaques can lead to potentially life threatening clinical events such as myocardial infarction (MI), stroke, or transient ischemic attack (TIA). The most frequently described plaque failure mechanism is tensile rupture of the fibrous cap; however, often during angioplasty another plaque failure mechanism occurs in which the atherosclerotic plaque separates from the internal elastic lamina (IEL). This study aims assess the material strength of atherosclerotic lesions using mechanical concepts.

To assess likelihood of plaque dissection at the vessel wall, adhesion strength was assessed in both mouse and human specimens using plaque delamination experiments. Measuring plaque adhesion in transgenic …

The Role Of E-Cadherin Force In The Maintenance Of Homeostasis In Epithelial Acini, Fnu Vani Narayanan

Theses and Dissertations

Numerous three-dimensional model systems have emerged for emulating the biochemical and physiological states of native tissue. Yet little is known about the effects of mechanical forces on cell behavior in the context of an organized tissue structure in three-dimensional cell-culture. Epithelial cells cultured in a three-dimensional environment comprised of extracellular matrix proteins form spheroids of polarized cells. Cellular responses to mechanical cues, generated from dynamic interactions with the extracellular matrix and neighboring cells, are known to influence cellular behavior to a great extent. Previous studies have shown that tumorigenic progression has been frequently linked to the down regulation of E-cadherin, …

A Theoretical Study Of Polymer Based Drug Delivery Systems, Ebtisam Abdullatif Aldaais

Theses and Dissertations

Polymer nanostructured materials for drug delivery applications have witnessed tremendous progress in recent years due to their vast potential. One-end-grafted polymers can form grafted micelles with specific mechanical properties. Biological conditions can alter these properties resulting in the protection or release of drugs. Charged surfactants can also form micelles in an aqueous solution, which can also be manipulated through special conditions. On the micellar surface, self-organized polyelectrolytes can be stimulated to extend their attached ligands and thus increase the probability of binding to targeted receptors. This thesis focuses on modeling polymer-based drug delivery systems by studying the physical interactions between …

In Vitro Visualization Of Pediatric Sized Mechanical Heart Valve Performance Using Aortic Root Model In Mock Circulatory Loop, Sarah Lederer

Theses and Dissertations

Congenital heart valve disease is one of the most common abnormalities in children, with common valve defects being aortic stenosis, mitral stenosis, and valvular regurgitation. Although adult sized mechanical heart valve (MHV) replacements are widely studied and utilized, there are currently no FDA approved prosthetic heart valves available for the pediatric population. This is due to a variety of reasons such as a limited patient pool for clinical trials, limited valve sizes, and complex health histories in children. Much like adult sized mechanical heart valves, potential complications with pediatric heart valve replacements include thrombosis, blood damage due to high shear …

Efficiency Evaluation Of A Magnetically Driven Multiple Disk Centrifugal Blood Pump, Kayla H. Moody

Theses and Dissertations

Heart failure is expected to ail over 8 million people in America by 2030 leaving many in need of cardiac replacement. To accommodate this large volume of people, ventricular assist devices (VADs) are necessary to provide mechanical circulatory support. Current VADs exhibit issues such as thrombosis and hemolysis caused by large local pressure drops and turbulent flow within the pump. Multiple disk centrifugal pumps (MDCPs) use shearing and centrifugal forces to produce laminar flow patterns and eliminate large pressure drops within the pump which greatly reduce risks that are in current VADs. The MDCP has a shaft drive system (SDS) …

In-House Fabrication Of Multi-Sized Polystyrene Microcarriers For Neural Stem Cell Expansion, Jessica Forrester

Theses and Dissertations

The clinical demand for neural stem cells drives the need for a reproducible method used to generate a large quantity of well-characterized cells to support regenerative therapies. Microcarriers are currently being used as a scaffold for stem cell culture to aid in this expansion process because they provide a larger surface area while also requiring fewer cell passages compared to monolayer culture. The main objective of this project was to investigate how human neural stem cell attachment, proliferation, and multipotency would respond to three-dimensional (3D) culture using peptide-coated microcarriers of varying diameters. In this study, multi-sized polystyrene microcarriers were fabricated …

Effects Of Antidepressants On Human Mesenchymal Stem Cell Differentiation On Clinically Relevant Titanium Surfaces, Nancy B. Ayad

Theses and Dissertations

Selective Serotonin Reuptake Inhibitors (SSRIs) are the most frequently prescribed class of drugs worldwide and are implemented in the treatment of depression and other psychiatric disorders. SSRIs relieve depressive symptoms by modulating levels of the neurotransmitter serotonin in the brain. SSRIs block the function of the serotonin transporter, thereby increasing concentrations of extracellular serotonin. However, serotonin levels in the neurons of the brain only account for 5% while the remaining 95% is present outside the brain. Serotonin receptors and transporter are located on bone resident cells (mesenchymal stem cells (MSCs)), osteoblasts and osteoclasts, and serotonergic activity is believed to affect …