Engineering Commons^™

The Influence Of Cholesterol-Related Membrane Fluidity On The Shear Stress Control Of Neutrophil Adhesion And Its Implications In Hypercholesterolemia, Michael L. Akenhead

Theses and Dissertations--Biomedical Engineering

Hypercholesterolemia is a significant risk factor in the development of cardiovascular disease and is associated with chronic leukocyte adhesion in the microvasculature. While the underlying mechanisms behind this have yet to be determined, it may be possible that hypercholesterolemia impairs the fluid shear stress (FSS) inactivation of neutrophils through the rigidifying effect of cholesterol on membrane fluidity. FSS restricts surface expression of CD18 integrins through cathepsin B (ctsB) proteolysis, which minimizes neutrophil adhesivity. If hypercholesterolemia blocks FSS mechanotransduction, then the inhibition of CD18 cleavage may link pathologic blood cholesterol elevations with dysregulated neutrophil adhesion. We hypothesized that elevated cholesterol contributes …

Improving Nano-Drug Delivery By Using Near-Real Time Sensing And Feedback, Pratik Adhikari

Doctoral Dissertations

Personalized medicine, seen as the solution to address the variability among the individuals, is the movement which proposes customization of medical procedures based on the need of the patient during the stages of prevention, diagnosis, treatment, and follow up. As the technology in medicine expands and newer methods of diagnosis and treatment are introduced in the clinic, real time data from the procedures is critical to assess the performance at point of care. Real time feedback, through collection of data at point of care would help make informed clinical decisions, potentially improving the efficacy of the treatment. In this dissertation, …

Stimulus And Optode Placement Effects On Functional Near-Infrared Spectroscopy Of Visual Cortex, Nasser H. Kashou, Brenna M. Giacherio

Biomedical, Industrial & Human Factors Engineering Faculty Publications

Functional near-infrared spectroscopy has yet to be implemented as a stand-alone technique within an ophthalmology clinical setting, despite its promising advantages. The present study aims to further investigate reliability of visual cortical signals. This was achieved by: (1) assessing the effects of optode placements using the 10–20 International System of Electrode Placement consisting of 28 channels, (2) determining effects of stimulus size on response, and (3) evaluating response variability as a result of cap placement across three sessions. Ten participants with mean age 23.8 4.8 years (five male) and varying types of hair color and thickness were recruited. Visual stimuli …

Hand-Grasping And Finger Tapping Induced Similar Functional Near-Infrared Spectroscopy Cortical Responses, Nasser H. Kashou, Brenna M. Giacherio, Ramzi W. Nahhas, Sudarshan R. Jadcherla

Biomedical, Industrial & Human Factors Engineering Faculty Publications

Despite promising advantages such as low cost and portability of functional near-infrared spectroscopy (fNIRS), it has yet to be widely implemented outside of basic research. Specifically, fNIRS has yet to be proven as a standalone tool within a clinical setting. The objective of this study was to assess hemodynamic concentration changes at the primary and premotor motor cortices as a result of simple whole-hand grasping and sequential finger-opposition (tapping) tasks. These tasks were repeated over 3 days in a randomized manner. Ten healthy young adults (23.8 4.8 years) participated in the study. Quantitatively, no statistically significant differences were discovered between …

Finite Element Analysis Of Superior C3 Cervical Vertebra Endplate And Cancellous Core Under Static Loads, Isaac Mabe, Tarun Goswami

Biomedical, Industrial & Human Factors Engineering Faculty Publications

Subsidence is a type of failure associated with implanted cervical cages or artificial intervertebral discs. It is defined as a loss of postoperative disc height. Actuarial rates show a risk of subsidence at 16 weeks at 70.7 percent. This study examines the changes in the vertebral endplate morphology and the resulting effect on the stresses developed in the endplate and in the vertebral core. A three-dimensional linear elastic model was created from computed tomographic (CT) scans and material properties were assigned according to various studies. Particular care was taken in the superior endplate that was modeled according to experimental measurements. …

Analysis Of A Clinically Failed, Mechanically Intact, Hemi-Toe Implant, Swetha Varadharajan, Richard T. Laughlin, Tarun Goswami

Biomedical, Industrial & Human Factors Engineering Faculty Publications

In this case study a clinically failed, mechanically intact, hemi-toe device was investigated. The clinical indication of the failure constitutes radiolucent line indicating loosening of the implant and possible interactions among the bone-implant initiated by osteolysis may become a factor, producing pain, inflammatory reactions, deformity and discomfort. The patient file was not available to determine these parameters. The device was titanium coated, Cobalt Chromium alloy used for making hemi-toe. Degeneration of hemi implant was due to spalling of the coating from the surface, causing loosening of stem from bone. However, pre-removal X-ray films were not available to confirm. Mechanism by …

Low-Cost, Wireless Optical Oximeter For Monitoring Of Brain Function In High-Risk Pediatric Population, Zahra Meghjani

Browse all Theses and Dissertations

Nearly 4 million neonates die every year due to brain injuries, most caused by hypoxia. Neonatal ICU requires newborns with critical health conditions to be monitored continuously calling for the need of a non-invasive, compact and portable device. However, commercial devices are mostly bulky and/or expensive. The neonatal mortality is higher in under-developed countries, where such expensive and large devices are not affordable. Hence, my thesis focuses on building first generation compact, inexpensive, and wireless device that can monitor and provide feedback to clinicians during intervention. This approach is based on light absorption by oxy- and deoxy-hemoglobin chromophores. The total …

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) …

Development And Characterization Of Lung Derived Extracellular Matrix Hydrogels, Robert A. Pouliot

Theses and Dissertations

Chronic obstructive pulmonary disease (COPD) including emphysema is a devastating condition, increasing in prevalence in the US and worldwide. There remains no cure for COPD, rather only symptomatic treatments. Due to unique challenges of the lung, translation of therapies for acute lung injury to target chronic lung diseases like COPD has not been successful. We have been investigating lung derived extracellular matrix (ECM) hydrogels as a novel approach for delivery of cellular therapies to the pulmonary system.

During the course of this work we have developed and characterized a lug derived ECM hydrogel that exhibits “injectability,” allowing cells or dugs …

An Injectable Stem Cell Delivery System For Treatment Of Musculoskeletal Defects, Shirae Leslie

Theses and Dissertations

The goal of this research was to develop a system of injectable hydrogels to deliver stem cells to musculoskeletal defects, thereby allowing cells to remain at the treatment site and secrete soluble factors that will facilitate tissue regeneration. First, production parameters for encapsulating cells in microbeads were determined. This involved investigating the effects of osmolytes on alginate microbead properties, and the effects of alginate microbead cell density, alginate microbead density, and effects of osteogenic media on microencapsulated cells. Although cells remained viable in the microbeads, alginate does not readily degrade in vivo for six months. Therefore, a method to incorporate …

A Computational Study Of Curvature In The Outflow Graft Of A Continuous Flow Left Ventricular Assist Device, Laura Patterson

Theses and Dissertations

Left ventricular assist devices (LVADs) are an increasingly utilized therapy for end-stage heart failure. Thrombosis within the graft from the pump to the aorta has been documented, but is poorly researched. This study examines the effect of graft geometry, as measured by radius of curvature, bend angle, and diameter, on thrombogenic flow patterns within the graft for a range of flow conditions. It also examines the effect blood properties, including viscosity and density, on these flow patterns. The results indicated that radius of curvature had a powerful effect on thrombogenic flow patterns. Flowrate and bend angle were also influential. The …

Role Of E-Cadherin Force In The Spatial Regulation Of Cell Proliferation, Abhinav Mohan

Theses and Dissertations

Cell proliferation and contact inhibition play a major role in maintaining epithelial cell homeostasis. A hallmark of epithelial cells is strong cell-cell junctions. These junctions include E-Cadherin, a type of adherens junction that is critical for both barrier function and contact inhibition. Prior experiments by other groups have shown that adherens junctions are subject to mechanical tension. Externally applied forces (e.g. stretch) results in changes in E-Cadherin forces that coordinate proliferation. My current work tests the hypothesis that E-Cadherin forces mediate the spatial regulation of cell proliferation even in the absence of externally applied forces.

Effect Of Twisted Fiber Anisotropy In Cardiac Tissue On Ablation With Pulsed Electric Fields, Fei Xie, Christian W. Zemlin

Bioelectrics Publications

Background: Ablation of cardiac tissue with pulsed electric fields is a promising alternative to current thermal ablation methods, and it critically depends on the electric field distribution in the heart.

Methods: We developed a model that incorporates the twisted anisotropy of cardiac tissue and computed the electric field distribution in the tissue. We also performed experiments in rabbit ventricles to validate our model. We find that the model agrees well with the experimentally determined ablation volume if we assume that all tissue that is exposed to a field greater than 3 kV/cm is ablated. In our numerical analysis, we considered …

Cell Electrosensitization Exists Only In Certain Electroporation Buffers, Janja Dermol, Olga N. Pakhomova, Andrei G. Pakhomov, Damijan Miklavčič

Bioelectrics Publications

Electroporation-induced cell sensitization was described as the occurrence of a delayed hypersensitivity to electric pulses caused by pretreating cells with electric pulses. It was achieved by increasing the duration of the electroporation treatment at the same cumulative energy input. It could be exploited in electroporation-based treatments such as electrochemotherapy and tissue ablation with irreversible electroporation. The mechanisms responsible for cell sensitization, however, have not yet been identified. We investigated cell sensitization dynamics in five different electroporation buffers. We split a pulse train into two trains varying the delay between them and measured the propidium uptake by fluorescence microscopy. By fitting …

Cytosolic Dna Sensor Upregulation Accompanies Dna Electrotransfer In B16.F10 Melanoma Cells, Katarina Znidar, Masa Bosnjak, Maja Cemazar, Loree C. Heller

Bioelectrics Publications

In several preclinical tumor models, antitumor effects occur after intratumoral electroporation, also known as electrotransfer, of plasmid DNA devoid of a therapeutic gene. In mouse melanomas, these effects are preceded by significant elevation of several proinflammatory cytokines. These observations implicate the binding and activation of intracellular DNA-specific pattern recognition receptors or DNA sensors in response to DNA electrotransfer. In tumors, IFN β mRNA and protein levels significantly increased. The mRNAs of several DNA sensors were detected, and DAI, DDX60, and p204 tended to be upregulated. These effects were accompanied with reduced tumor growth and increased tumor necrosis. In B16. F10 …

Analysis Of Ca²⁺ Mobilization Of Nanosecond Pulses In Cells, Iurii Semenov

Bioelectrics Publications

Exposure to nanosecond electric pulses (nsEPs) evokes transient rise of cytosolic free Ca²⁺ concentration ([Ca²⁺]i) in the cells. We quantified the external Ca²⁺ uptake, intracellular Ca²⁺ release and uncover interplay of these processes for CHO-K1 cells upon exposure to single 60 ns pulse in the range of amplitudes from 0 to 30 kV/cm. NsEPs are distinguished by the ability to electroporate intracellular membranes. We studied how duration of nsEPs is related to efficiency of intracellular membranes electroporation comparing ability of single 300-, 60- and 10 ns pulses to recruit Ca²⁺ from endoplasmic reticulum (ER) in respect to the uptake of …

Activation Of Dna Pattern Recognition Receptors After Plasmid Electrotransfer In Melanoma Cells And Tumors, Loree Heller, Masa Bosnjak, Katarina Znidar, Maja Cemazar

Bioelectrics Publications

(First sentence) In vivo electroporation or electrotransfer, the application of controlled electric pulses, enhances delivery of plasmid DNA to a wide variety of healthy tissues as well as tumor types.

Computational Assessment Of Neural Probe And Brain Tissue Interface Under Transient Motion, Michael Polanco, Sebastian Bawab, Hangsoon Yoon

Mechanical & Aerospace Engineering Faculty Publications

The functional longevity of a neural probe is dependent upon its ability to minimize injury risk during the insertion and recording period in vivo, which could be related to motion-related strain between the probe and surrounding tissue. A series of finite element analyses was conducted to study the extent of the strain induced within the brain in an area around a neural probe. This study focuses on the transient behavior of neural probe and brain tissue interface with a viscoelastic model. Different stages of the interface from initial insertion of neural probe to full bonding of the probe by astro-glial …

Quantitative Assessment Of Brain Iron Content As A Function Of Age Using Magnetic Resonance Imaging, Kiarash Ghassaban

Wayne State University Theses

As the most abundant transition metal in the brain, iron is known to play a key role in a variety of functional and cellular processes. Recent in vivo and post-mortem studies have shown that the levels of iron deposition in the brain, particularly in deep gray matter nuclei, vary as a function of age. On the other hand, elevated iron has also been associated with some neurodegenerative diseases such as Multiple Sclerosis (MS) and Parkinson’s disease (PD) among others.

Magnetic Resonance Imaging (MRI) is a widely used non-invasive and non-ionizing imaging modality which is sensitive to magnetic properties of materials …

Animal Models Of Osteogenesis Imperfecta: Applications In Clinical Research, Tanya A. Enderli, Stephanie R. Burtch, Jara N. Templet, Alessandra Carriero

Biomedical Engineering and Sciences Faculty Publications

Osteogenesis imperfecta (OI), commonly known as brittle bone disease, is a genetic disease characterized by extreme bone fragility and consequent skeletal deformities. This connective tissue disorder is caused by mutations in the quality and quantity of the collagen that in turn affect the overall mechanical integrity of the bone, increasing its vulnerability to fracture. Animal models of the disease have played a critical role in the understanding of the pathology and causes of OI and in the investigation of a broad range of clinical therapies for the disease. Currently, at least 20 animal models have been officially recognized to represent …

Restriction And Characterization Of Human Breast Cancer Using A Three-Dimensional Embryonic Stem Cell Model, Bridget Mooney

Legacy Theses & Dissertations (2009 - 2024)

Human breast cancer is currently the highest diagnosed form of cancer and the second leading cause of cancer-related deaths in American women. Triple negative breast cancer is of the basal subtype and displays the worst prognosis owing to its highly metastatic properties. Current treatments focused on eradicating breast tumors in lieu of or following local therapy include chemotherapy, hormonal therapy, and targeted therapy. Hormonal therapy is not an option for triple negative breast cancer as it does not contain hormone receptors and there are currently no approved biological targeted therapies. Chemotherapy has proven unsuccessful because triple negative breast cancer is …

Investigation Of Enzymatically Synthesized Glycogen As A Novel Nanodendrimer For Therapeutic Delivery, Sarah Ann Engelberth

Legacy Theses & Dissertations (2009 - 2024)

The field of medicinal chemistry is ever expanding, designing and discovering new therapeutic strategies. Oftentimes, it is challenging for these therapeutics to undergo clinical translation due to ineffective administration or unwanted toxicity in vivo. As such, drug delivery vehicles are designed to overcome these hurdles, allowing for delivery to the site of action by improving biodistribution, protecting therapeutic cargo, and decreasing toxicity. The work presented here aims to investigate a naturally-derived carbohydrate nanodendrimer, enzymatically synthesized glycogen (ESG) for drug delivery. This nontoxic, highly-branched, glucose-based structure has interior void volumes to allow for cargo encapsulation as well as a large density …

Nanotechnology & Human Stem Cells : Applications In Cardiogenesis And Neurogenesis, Martin Lyubomirov Tomov

Legacy Theses & Dissertations (2009 - 2024)

Human stem cell research holds an unprecedented promise to revolutionize the way we approach medicine and healthcare in general, moving us from a position of mostly addressing the symptoms to a state where treatments can focus on removing the underlying causes of a condition. Stem cell research can shed light into normal developmental pathways, as we are beginning to replicate them in a petri dish and can also be used to model diseases and abnormal conditions. Direct applications can range from finding cures for single or multigene diseases to demonstrating that we can replace these genes with a normal copy. …

Use Of Lidar In The Design Of Grassed Waterways: Case Study In Agricultural Management In Oklahoma, Annette Sparks

Dissertations, Master's Theses and Master's Reports

Before the advent of Light Detection and Ranging (LiDAR) technology, farm-level infrastructure for sustainable agriculture was designed using topographic maps. LiDAR is a remote sensing method whereby reflected laser pulses are measured to generate high-resolution 3D images of the terrain. This report compares these two methods in the design of grassed waterways for flood drainage and evaluates how the quantitative difference between the two methods can affect the overall hydrologic design. The benefits of LiDAR are expected to be higher accuracy and precision in design, as well as greater reproducibility or consistency, regardless of the designer. To carry out this …

Enhanced Corrosion Protection And Biocompatibility Of A Plga-Silane Coating On Az31 Mg Alloy For Orthopaedic Applications, Sankalp Agarwal, Muhammad Morshed, Marie-Noelle Labour, David Hoey, Brendan Duffy, James Curtin, Swarna Jaiswal

Articles

This paper reports a multi-step procedure to fabricate a novel corrosion resistant and biocompatible PLGA-silane coating on the magnesium (Mg) alloy AZ31. The first step involves alkaline passivation followed by dip coating in a methyltriethoxysilane (MTES) and tetraethoxysilane (TEOS) mixture to produce a cross-linked siloxane coating. The second step is to impart an amine functionalization to the silane modified surface by using 3-aminopropyl-triethoxy silane (APTES) for promoting adhesion of the acid terminated poly-(lactic-co-glycolic) acid (PLGA) as a final coating step. Static contact angle measurements, Fourier transform infrared spectroscopy and scanning electron microscopy analysis confirmed the successful assembly of coatings on …

Role Of Micro-Ct In The Visualization, Measurement, And Quantification Of Bone Structure In Osteogenesis Imperfecta, Robert C. Molthen, John Jameson, Carolyne Albert, Peter Smith, Gerald F. Harris

Biomedical Engineering Faculty Research and Publications

No abstract provided.

Automated Image Analysis And Spatial Computational Modeling Of Nf-Kb In Cerebrovascular Endothelial Cells, Kasey Catalfomo

Theses and Dissertations

Cerebrovascular endothelial cells play a key part in the inflammatory response of the blood-brain barrier in pathological conditions such as Alzheimer’s disease. Specifically, the NF-κB signaling pathway plays a central role. Better understanding of the factors in inflammatory disease progression can lead to more effective treatments for such devastating illnesses like Alzheimer’s, asthma, arthritis, cancer, diabetes and many more inflammatory diseases. The proposed approach analyzes spatial NF-κB distribution contained in multispectral stacked micrograph images of cerebrovascular endothelial cells indexed based on dose of the activating protein and the length of activation. Image analysis code identifies the location of nuclear boundaries …

Enhancement Of Cancer Vaccine Efficacy Via Nanoparticle Or Molecular-Based Adjuvants, Myunggi An

Wayne State University Theses

Adjuvants are immunomodulators which enhance immune responses to vaccines. However, parenteral administration of unformulated adjuvants fails to reach lymph nodes (LNs), the anatomic organ where the primary functions of immune cells are orchestrated. The LN-targeting delivery plays the key roles in promoting immune activation and has the great potential to transform disease treatment. The main goal of this thesis is to develop efficient vaccine delivery systems to target therapeutics into draining lymph nodes (dLNs) for ensuring their immunostimulatory activity. We introduced therapeutic applications of activating TLR9 with synthetic CpG oligodeoxynucleotide (ODN) agonists in nanoparticle or molecular form to activate immune …

Toward Magnetic Resonance Only Treatment Planning: Distortion Mitigation And Image-Guided Radiation Therapy Validation, Ryan Glen Price

Wayne State University Dissertations

While MR-only treatment planning has shown promise, there are still several well-known challenges that are currently limiting widespread clinical implementation.

Firstly, MR images are affected by both patient-induced and system-level geometric distortions that can significantly degrade treatment planning accuracy. . In addition, the availability of comprehensive distortion analysis software is currently limited. Also while many groups have been working toward a synthetic CT solution, further study is needed on the implementation of synCTs as the reference datasets for linac-based image-guided radiation therapy (IGRT) to help determine their robustness in an MR-only workflow.

A 36×43×2 cm3 phantom with 255 known landmarks …

Modification Reactivity Analysis Of Human Replication Protein A In Biologically Important States, Ryan James Yoakum

Browse all Theses and Dissertations

Human Replication Protein A (RPA) is a heterotrimeric protein consisting of 70, 32, and 14 kDa subunits. RPA is the predominant single stranded DNA binding protein within the cell. It is involved in all forms of the DNA metabolic pathways, including but not limited to, replication, recombination, damage repair, as well as cell cycle and DNA check point signaling. RPA is phosphorylated (pRPA) during G1-S phase and is dephosphorylated during M phase. Further, RPA is hyperphosphorylated during DNA damage. Through the use of x-ray crystallography and nuclear magnetic resonance, researchers have proposed models and structures based on truncated portions of …