Engineering Commons^™

In Vitro Growth Of Osteoblasts On Poly Lactic-Co-Glycolic Acid Scaffolds Created Via Gas Foaming, Matthew James Thomas

Master's Theses

This study analyzed the feasibility of using gas foaming to create Poly Lactic-co-Glycolic Acid (PLGA) scaffolds for use as a substrate in bone tissue engineering and set out to determine whether the presence of osteoblasts on these scaffolds enhanced their material stiffness. The process of bone formation involves osteoblasts depositing extracellular matrix and calcifying this matrix with calcium phosphate crystals (Hasegawa et al., 2017) and pits between 30-40μm in diameter on tissue engineering scaffold surfaces have been shown to best promote osteogenic activity in the presence of bone-forming cells (Halai et al., 2014).The scaffolds were determined to contain pits within …

Early Term Effects Of Rhbmp-2 On Pedicle Screw Fixation In A Sheep Model: Histomorphometric And Biomechanical Analyses, Jeffrey M. Toth, Mei Wang, Chetan Patel, Akshi Arora

Biomedical Engineering Faculty Research and Publications

Background: The effects of recombinant human bone morphogenetic protein-2 (rhBMP-2) on pedicle screw pullout force and its potential to improve spinal fixation have not previously been investigated. rhBMP-2 on an absorbable collagen sponge (ACS) carrier was delivered in and around cannulated and fenestrated pedicle screws in a sheep lumbar spine instability model. Two control groups (empty screw and ACS with buffer) were also evaluated. We hypothesized that rhBMP-2 could stimulate bone growth in and around the cannulated and fenestrated pedicle screws to improve early bone purchase.

Methods: Eight skeletally mature sheep underwent destabilizing laminectomies at L2–L3 and L4–L5 followed by …

Deformation Of A Ferrofluid Droplet In Simple Shear Flows Under Uniform Magnetic Fields, Md Rifat Hassan, Jie Zhang, Cheng Wang

Mechanical and Aerospace Engineering Faculty Research & Creative Works

We numerically investigate the deformation and orientation of a ferrofluid droplet in a simple shear flow under a uniform magnetic field. The numerical simulation is based on the finite element method and couples the magnetic and flow fields. A level set method is used to model the dynamic motion of the droplet interface. Systematic numerical simulations are used to assess the effects of the direction and the strength of the magnetic field. Focusing on low Reynolds number flows (Re ≲ 0.02), the numerical results indicate that at a small capillary number (Ca ≈ 0.02), the magnetic field dominates over the …

Temporal And Spatial Effects Of Shock Overpressure On Blood-Brain Barrier Permeability In Blast-Induced Traumatic Brain Injury, Matthew Joseph Kuriakose

Dissertations

Exposure to shock waves is the leading cause of traumatic brain injury (TBI) in military personnel and blast-induced TBI (bTBI) is considered the signature wound in recent conflicts in Iraq and Afghanistan. Many researchers attempt to replicate field-relevant shock waves in laboratory settings through the use of gas-driven shock tubes in order to investigate the generation and propagation of shock waves and also explore possible mechanisms of bTBI. Among several injury mechanisms of bTBI, damage to the blood-brain barrier (BBB) has been identified as a potential candidate and has been the focus of several clinical and experimental investigations aimed to …

Grant Funding Needs Parallel The Start-Up Venture: An Analogy For Translational Research Success, Brian W. Pogue

Dartmouth Scholarship

This editorial offers some ways to think about how best to position a research group for funding, by examining the parallels between what is needed for translational grants versus industry start-ups.

Cellulose-Derived Glycosaminoglycan Mimetic For Use In Cartilage Tissue Engineering Strategies, Roseline Dominic Menezes

Dissertations

Articular cartilage has limited healing and self-repair capability due to the absence of vasculature, lymphatic vessels, and nerves. Damage to articular cartilage becomes irreversible leading to formation of osteoarthritis that could severely degrade a person's quality of life. Approximately, 5-10% of cartilage tissue is made up of glycosaminoglycans (GAG), which sequester growth factors as well as provide structural integrity to the native cartilage tissue. Transforming growth factor-beta3 (TGF-β3) is an important growth factor for inducing chondrogenesis in mesenchymal stem cells (MSCs). Bioavailability of TGF-β3 plays a critical role in cartilage repair both in vitro and in vivo. This study evaluates …

Evaluating Nanoshells And A Potent Biladiene Photosensitizer For Dual Photothermal And Photodynamic Therapy Of Triple Negative Breast Cancer Cells., Rachel S. Riley, Rachel K O'Sullivan, Andrea M Potocny, Joel Rosenthal, Emily S Day

Henry M. Rowan College of Engineering Departmental Research

Light-activated therapies are ideal for treating cancer because they are non-invasive and highly specific to the area of light application. Photothermal therapy (PTT) and photodynamic therapy (PDT) are two types of light-activated therapies that show great promise for treating solid tumors. In PTT, nanoparticles embedded within tumors emit heat in response to laser light that induces cancer cell death. In PDT, photosensitizers introduced to the diseased tissue transfer the absorbed light energy to nearby ground state molecular oxygen to produce singlet oxygen, which is a potent reactive oxygen species (ROS) that is toxic to cancer cells. Although PTT and PDT …

Direct Quantification Of Deubiquitinating Enzyme Activity In Single Intact Cells, Nora Safabakhsh

LSU Doctoral Dissertations

Challenges in drug efficacy occur during the treatment of most types of cancer due to the heterogeneity of the tumor microenvironment. This has led to the development of personalized medicine. Due to the clinical success of the proteasome inhibitors Bortezomib and Carfilzomib in treatment of multiple myeloma, interest has shifted towards molecularly-targeted chemotherapeutics for ubiquitin-proteasome system (UPS). Deubiquitinating enzymes (DUBs) are an essential part of this pathway which have been found to promote Bortezomib resistance in multiple myeloma patients. Unfortunately, there is a lack of specific, high throughput biochemical assays to characterize DUB activity in patient samples before and after …

Method For The Destruction Of Endotoxin In Synthetic Spider Silk Proteins, Richard E. Decker, Thomas I. Harris, Dylan R. Memmott, Christopher J. Peterson, Randolph V. Lewis, Justin A. Jones

Biological Engineering Faculty Publications

Although synthetic spider silk has impressive potential as a biomaterial, endotoxin contamination of the spider silk proteins is a concern, regardless of the production method. The purpose of this research was to establish a standardized method to either remove or destroy the endotoxins present in synthetic spider silk proteins, such that the endotoxin level was consistently equal to or less than 0.25 EU/mL, the FDA limit for similar implant materials. Although dry heat is generally the preferred method for endotoxin destruction, heating the silk proteins to the necessary temperatures led to compromised mechanical properties in the resultant materials. In light …

Noninvasive Multi-Modality Studies Of Cardiac Electrophysiology, Mechanics, And Anatomical Substrate In Healthy Adults, Arrhythmogenic Cardiomyopathy, And Heart Failure, Christopher Andrews

McKelvey School of Engineering Graduate Student Theses & Dissertations

Heart disease is a leading cause of death and disability and is a major contributor to healthcare costs. Many forms of heart disease are caused by abnormalities in the electrical function of heart muscle cells or the cardiac conduction system. Electrocardiographic Imaging (ECGI) is a noninvasive modality for imaging cardiac electrophysiology. By combining recordings of the voltage distribution on the torso surface with anatomical images of the heart-torso geometry, ECGI reconstructs voltages on the epicardium. This thesis applies ECGI to novel studies of human heart function and disease and explores new combinations of ECGI with additional imaging modalities.

ECGI was …

In Vivo Vascular Imaging With Photoacoustic Microscopy, Hsun-Chia Hsu

McKelvey School of Engineering Graduate Student Theses & Dissertations

Photoacoustic (PA) tomography (PAT) has received extensive attention in the last decade for its capability to provide label-free structural and functional imaging in biological tissue with highly scalable spatial resolution and penetration depth. Compared to modern optical modalities, PAT offers speckle-free images and is more sensitive to optical absorption contrast (with 100% relative sensitivity). By implementing different regimes of optical wavelength, PAT can be used to image diverse light-absorbing biomolecules. For example, hemoglobin is of particular interest in the visible wavelength regime owing to its dominant absorption, and lipids and water are more commonly studied in the near-infrared regime.

In …

Radiological Pathological Correlations In Chronic Traumatic Encephalopathy, Mihika Gangolli

McKelvey School of Engineering Graduate Student Theses & Dissertations

Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disease that has been increasingly linked to traumatic brain injury. The neuropathology that distinguishes CTE from other tauopathies includes hyperphosphorylated tau (pTau) tangles and tau positive astrocytes irregularly distributed in cortical sulcal depths and clustered around perivascular foci. These features are clearly identified using immunohistochemistry, but are undetectable to current clinical imaging methods. Diffusion imaging has been proposed as a noninvasive method to detect the pathognomonic lesion of CTE in vivo because of its high sensitivity to microstructural alterations in tissue structure. While several diffusion imaging approaches, ranging from diffusion tensor imaging …

Controlling The Oxygen Microenvironment: The Role Of Hif-1Α In Early Tumor Progression, Sandra Lam

McKelvey School of Engineering Graduate Student Theses & Dissertations

Cancer drug efficacy has remained a critical obstacle for researchers as it has one of the lowest probabilities of success compared to other diseases. One method to help improve this success rate is to create better tumor models on which to perform the drug testing. With growing interesting in microphysiological systems, scientists can create more advanced in vitro models of human organ systems as well as diseased states. These “organ-on-a-chip” platforms aim to improve drug response prediction for both efficacy and toxicity. One underappreciated characteristic of many disease states is that they are often at a lower oxygen tension that …

Development And Evaluation Of Biocompatible Engineered Nanoparticles For Use In Ophthalmology, Bedia Begum Karakocak

McKelvey School of Engineering Graduate Student Theses & Dissertations

The synthesis and design of biocompatible nanoparticles for targeted drug delivery and bioimaging requires knowledge of both their potential toxicity and their transport. For both practical and ethical reasons, evaluating exposure via cell studies is a logical precursor to in vivo tests. As a step towards clinical trials, this work extensively investigated the toxicity of gold nanoparticles (Au NPs) and carbon dot (CD) nanoparticles as a prelude to their in vivo application, focusing specifically on ocular cells. As a further step, it also evaluated their whole-body transport in mice. The research pursued two approaches in assessing the toxicity of engineered …

Assessment And Diagnosis Of Human Ovarian And Colorectal Cancer Using Optical And Photoacoustic Imaging, Sreyankar Nandy

McKelvey School of Engineering Graduate Student Theses & Dissertations

Optical imaging modalities have the advantage of high resolution, label free, rapid, low cost imaging for both in vivo and ex vivo diagnosis of biological tissues. Optical scattering, which is the main contrast of optical coherence tomography (OCT), is related to elastic scattering components, mainly stromal collagen. Tissue elasticity has recently emerged as an important diagnostic parameter associated with tumor development and progression and is also related to the distribution of structural components such as tissue collagen. We have used an optical coherence tomography elastography (OCTE) system for characterizing the differences in the micro-mechanical properties of benign and malignant human …

Engineering Robust And Programmable Biological Systems, Tatenda Shopera

McKelvey School of Engineering Graduate Student Theses & Dissertations

The ability to engineer programmable biological systems using complex artificial gene networks has great potential to unlock important innovative solutions to many biotechnological challenges. While cells have been engineered to implement complex information processing algorithms and to produce food, materials, and pharmaceuticals, many innovative applications are yet to be realized due to our poor understanding of how robust, reliable, and predictable artificial gene circuits are built. In this work, we demonstrate that robust complex cellular behaviors (e.g., bistability and gene expression dynamics) can be achieved by engineering gene regulatory architecture and increasing the complexity of genetic networks. We further demonstrate …

Brain-Computer Interfaces Using Electrocorticography And Surface Stimulation, Jesse Wheeler

McKelvey School of Engineering Graduate Student Theses & Dissertations

The brain connects to, modulates, and receives information from every organ in the body. As such, brain-computer interfaces (BCIs) have vast potential for diagnostics, medical therapies, and even augmentation or enhancement of normal functions. BCIs provide a means to explore the furthest corners of what it means to think, to feel, and to act—to experience the world and to be who you are. This work focuses on the development of a chronic bi-directional BCI for sensorimotor restoration through the use of separable frequency bands for recording motor intent and providing sensory feedback via electrocortical stimulation. Epidural cortical surface electrodes are …

Hemodynamic Effects On Embryonic Arterial Growth And Matrix Remodeling, Maria Gabriela Espinosa

McKelvey School of Engineering Graduate Student Theses & Dissertations

Hemodynamic forces drive cardiovascular morphogenesis and remodeling in the developing embryo. Changes to the embryonic hemodynamic environment have been shown to induce a variety of congenital heart defects, but little attention has been given to vasculature-specific defects. Although vascular development has been widely studied in the context of genetics and molecular biology, this work investigates the impact of hemodynamic forces on arterial development and mechanics.

The dorsal aorta (DA) is the first intraembryonic vessel to form. Its passive mechanical properties are determined by the deposition of extracellular matrix (ECM) proteins, a hallmark of arterial maturation. We hypothesized that hemodynamic changes …

Forward Electrophysiological Modeling And Inverse Problem For Uterine Contractions During Pregnancy, Mengxue Zhang

McKelvey School of Engineering Graduate Student Theses & Dissertations

Uterine contractile dysfunction during pregnancy is a significant healthcare challenge that imposes heavy medical and financial burdens on both human beings and society. In the U.S., about 12% of babies are born prematurely each year, which is a leading cause of neonatal mortality and increases the possibility of having subsequent health problems. Post-term birth, in which a baby is born after 42 weeks of gestation, can cause risks for both the newborn and the mother. Currently, there is a limited understanding of how the uterus transitions from quiescence to excitation, which hampers our ability to detect labor and treat major …

Mathematical Models Of Innate Immune Cell Signaling Networks Using Protein Phosphorylation Patterns, Allison Anne Throm

McKelvey School of Engineering Graduate Student Theses & Dissertations

Immune dysregulation has been implicated in pediatric autoimmune disease

pathogenesis, but the underlying mechanisms still remain poorly understood. We explored

immune cell signaling dysregulation in two different pediatric autoimmune diseases:

polyarticular juvenile idiopathic arthritis (JIA), a disease characterized by pain, swelling, and

limited range of motion in five or more joints and juvenile dermatomyositis (JDM), a disease

characterized by pathognomonic skin rashes and proximal muscle weakness. Both polyarticular

JIA and JDM can be controlled with newer biologic medications, but a substantial fraction of

patients still experiences refractory disease courses. To explore potential immune cell signaling

dysregulation, mass cytometry was performed …

Multi-Beam Scan Analysis With A Clinical Linac For High Resolution Cherenkov-Excited Molecular Luminescence Imaging In Tissue., Mengyu Jeremy Jia, Peter Bruza, Lesley A. Jarvis, David J. Gladstone, Brian W. Pogue

Dartmouth Scholarship

Cherenkov-excited luminescence scanned imaging (CELSI) is achieved with external beam radiotherapy to map out molecular luminescence intensity or lifetime in tissue. Just as in fluorescence microscopy, the choice of excitation geometry can affect the imaging time, spatial resolution and contrast recovered. In this study, the use of spatially patterned illumination was systematically studied comparing scan shapes, starting with line scan and block patterns and increasing from single beams to multiple parallel beams and then to clinically used treatment plans for radiation therapy. The image recovery was improved by a spatial-temporal modulation-demodulation method, which used the ability to capture simultaneous images …

Efficacy Of Eluted Antibiotics In 3d Printed Orthopaedic Implants, Mohammed Mehdi Benmassaoud

Theses and Dissertations

Costs associated with musculoskeletal diseases in the United States account for 5.7 % of the Gross Domestic Product (GDP) [1]. As such, there is a need to pursue new ideas in orthopaedic implants that can decrease cost and improve patient care. In the recent years, 3D printing using Fused Deposition Modeling (FDM) or Stereolithography (SLA) has opened several exciting possibilities to create orthopaedic implants. Such implants can be engineered to release antibiotics in a controlled manner either by infusing the drug into the material during manufacturing or by using built-in design features such as micro-channels and reservoirs [2]. The use …

Bacteria Movement Near Surfaces, Shulin Wang, Adib Ahmadzadegan, Arezoo Ardekani

The Summer Undergraduate Research Fellowship (SURF) Symposium

Understanding the behaviors of bacteria near surfaces is crucial in many biological and ecological applications. This knowledge can be used to hinder undesired biofilm formation on medical instruments and wounds. On top of that, it could also provide further insights in biodegradation of dispersed oil. In this work, the behavior of Escherichia Coli near a surface was experimentally studied. We utilized an inverted microscope in the phase filed illumination mode and processed acquired images to track the motions of bacteria near surfaces with high accuracy and repeatability. Distribution of the cells when they reached a steady state shows that the …

Thin Film Cocaine Sensors, Datta Sheregar, Vick Hung, Jenna Walker, Orlando Hoilett, Jacqueline Linnes, Robert Nawrocki

The Summer Undergraduate Research Fellowship (SURF) Symposium

Over 7 million Americans suffer from a drug use disorder and up to 60% of individuals treated for addiction will ultimately relapse. We are developing ultra-thin film electrodes on a wearable substrate for a sensor that can detect minute amounts of cocaine in sweat droplets secreted from the skin. This will enable wearable drug monitoring for personalized rehabilitation treatment plans and improve long-term addiction recovery rates. The current research focuses on developing a thin-film sensor that can be applied directly to the skin. First a layer of PVP (poly4-vinylphenol) was prepared and then spun coated onto a piece of glass. …

Characterization And Quantification Of Fibrin Gel Mechanics With Fibroblast Invasion, Nicklaus Iavagnilio, Sarah Calve, Adrian Buganza-Tepole

The Summer Undergraduate Research Fellowship (SURF) Symposium

Cutaneous wounds undergo an intricate healing process stimulated by a variety of local mechanical and biological stimuli that lead to patterns of growth and remodeling. Despite significant research in dermal wound healing, pathological scarring is still common particularly in wounds closed under mechanical stress, or large wounds left to heal by secondary intention. The purpose of this study is to utilize previously established wound healing models using fibrin gels and fibroblasts to better understand the functional relationships of the biological processes of normal compared to abnormal wound healing. Increases in uni-axial strain and transforming growth factor beta-1 concentration have been …

Design Modifications For A Small, Affordable Low Intensity Focused Ultrasound Device, Sui Shen, Kelsey C. Bayer, Pedro P. Irazoqui

The Summer Undergraduate Research Fellowship (SURF) Symposium

Depression is a prevalent and serious medical illness, and while there are antidepressant drugs to mitigate depressive symptoms, 10 - 30% of patients either do not respond or develop a tolerance to these medications. Literature supports that there is an interrelation between the inflammatory response and treatment-resistant depression. A promising method to tackle depressive symptoms is to block the inflammatory signaling pathway with vagus nerve stimulation (VNS), reducing pro-inflammatory cytokine levels. Although electrical VNS devices exist, they are invasive, expensive, and have side effects including voice alteration, dyspnea, and cough. Low intensity focused ultrasound (LIFU) is a promising method that …

Rapid Sample Processing Of Foodborne Pathogens Using Cross-Flow Microfiltration, Casey Bomrad, Michael R. Ladisch, Linda Liu, Jessica Lynn Zuponcic, Eduardo Ximenes

The Summer Undergraduate Research Fellowship (SURF) Symposium

Foodborne illnesses are a prominent issue, causing 48 million illnesses annually. The Escherichia coli O157:H7 outbreak in romaine lettuce is a recent example. The source of the pathogen was contaminated irrigation water. The most common methods for detecting foodborne pathogens involve cultivation and enrichment of food samples. The enrichment steps are time-consuming, taking 24 to 72 hours to complete. Our study aims to accelerate irrigation water sample preparation for pathogenic microorganism fast detection through cross-flow microfiltration. This is accomplished by a device called a continuous cell concentration and recovery device (C3D). The C3D uses cross-flow microfiltration in a hollow fiber …

Developing Strategies To Toughen Bio-Inspired Adhesives, Narelli P. Narciso, Samuel Lee Huntington, Jonathan J. Wilker

The Summer Undergraduate Research Fellowship (SURF) Symposium

Mussels and other marine creatures adhere very well in underwater environments, having the ability to withstand the force of the sea. These animals have inspired synthetic biomimetic adhesives for wet systems, presenting potential for biomedical applications. However, most current commercial adhesives tend to be brittle, not resisting repetitive movements. This study assesses toughening strategies to improve the mussel-inspired adhesives’ ductility while maintaining its strength. The strategies included altering the polymer’s chemical structure by changing the percentage of polyethylene glycol (PEG) in the molecule and by adding fillers, such as calcium carbonate, silica and nacre - a calcium carbonate compound found …

Cost-Effective Paper-Based Diagnostic Using Split Proteins To Detect Yeast Infections, Zachary R. Berglund, Kevin V. Solomon, Mohit S. Verma, Moiz Rasheed, Zachary Hartley, Kevin Fitzgerald, Kok Zhi Lee, Janice Chan, Julianne Dejoie, Makayla Schacht, Alex Zavala

The Summer Undergraduate Research Fellowship (SURF) Symposium

The common yeast infection, vulvovaginal candidiasis, affects three out of four women throughout their lifetime and can be spread to their child in the form of oral candidiasis (thrush). This disease is caused by the fungal pathogen Candida albicans, which is also a major cause of systemic candidiasis, a rarer but deadly disease with up to a 49% lethality rate. Current widely-used diagnostic methods include cell cultures, pH tests, and antibody detection, to assist effective treatment. Despite availability of various diagnostic methods, there is no inexpensive, rapid, and accurate way to detect C. albicans infection. This project aims to …

Improving Biomanufacturing Production With Novel Elp-Based Transcriptional Regulators, Juya Jeon, Logan R. Readnour, Kevin V. Solomon

The Summer Undergraduate Research Fellowship (SURF) Symposium

Microbes can be used to produce valuable drugs, chemicals, and biofuels, but their potential has not been fully realized due to low production yields. To improve biomanufacturing processes and yield, we are developing novel, transcriptional regulators using biosynthesis technology in order to improve cellular health and overall production. Our regulator contains elastin-like polypeptides (ELPs), which make ideal sensors since they exhibit a sharp, inverse phase transition to indicators of cell health such as intracellular pH and ionic strength, and external stimuli such as temperature. We hypothesize that ELP can be fused to transcription factors to control expression of target genes. …