Biomedical Engineering and Bioengineering Commons^™

Thermoresponsive Nanogels Based On Different Polymeric Moieties For Biomedical Applications, Sobhan Ghaeini-Hesaroeiye, Hossein Razmi Bagtash, Soheil Boddohi, Ebrahim Vasheghani-Farahani, Esmaiel Jabbari

Faculty Publications

Nanogels, or nanostructured hydrogels, are one of the most interesting materials in biomedical engineering. Nanogels are widely used in medical applications, such as in cancer therapy, targeted delivery of proteins, genes and DNAs, and scaffolds in tissue regeneration. One salient feature of nanogels is their tunable responsiveness to external stimuli. In this review, thermosensitive nanogels are discussed, with a focus on moieties in their chemical structure which are responsible for thermosensitivity. These thermosensitive moieties can be classified into four groups, namely, polymers bearing amide groups, ether groups, vinyl ether groups and hydrophilic polymers bearing hydrophobic groups. These novel thermoresponsive nanogels …

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

Theses and Dissertations

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

Using Human Granulosa Cells To Select The Most Competent Embryos For Uterine Transfer In In Vitro Fertilization Cycles, Richard John Kordus

Theses and Dissertations

Infertility is a worldwide epidemic often treated with in vitro fertilization. The success of in vitro fertilization is directly dependent upon the quality of oocytes produced during the controlled stimulation of the patient’s ovaries. There is a need for improved methods to allow embryologists to select the most viable embryos with the highest probability of leading to live births since in vitro fertilization success is far from optimal.

Oocyte and subsequent embryo quality are intimately influenced by the granulosa cells which surround the oocyte during follicular maturation. The oocytes require proper signaling and energy production form the surrounding granulosa cells …

The Role Of Acute And Chronic Neuroinflammation In Depression: Uncovering The Relationship Between Histamine And Serotonin Transmission, Melinda Hersey

Theses and Dissertations

Depression is the leading cause of disability worldwide. Disorders of the brain, including depression, are notoriously difficult to treat because the basic pathology underlying behavioral outcomes remains undefined. Robust chemical biomarkers of these diseases have not been identified, nor are there reliable methods to measure brain chemicals. Depression is associated with chemical and inflammatory changes in the brain that are predicted to contribute to the pathology. By studying the serotonin and histamine systems we aim to better define the neurochemical basis of depression. Serotonin has long been hypothesized to play a role in depression since selective serotonin reuptake inhibitors (SSRIs) …

Effect Of Cannabinoid Treatment On Immune Cell Functions During Acute Lung Injury, Amira Kamil Mohammed

Theses and Dissertations

Staphylococcal enterotoxin B (SEB) is a highly potent CDC select agent that can trigger acute lung injury (ALI) via robust T cell proliferation and differentiation, and massive cytokine and chemokine release. Δ9-Tetrahydrocannabinol (THC) is a psychoactive ingredient found in Cannabis sativa. In the current study, we investigated the effects of treatment with THC on SEB-induced acute lung injury. To this end, acute lung injury was induced by a dual dose of SEB in C3H/HeJ mice, which were then treated with vehicle or THC. THC-treatment led to survival of all the SEB-administered mice when compared to vehicle-treated. This corroborated with THC-induced …

Nitric Oxide Expression With Age And Diet In The Arterial Wall Of Apoe Knockout Mice, Kara Cooper

Theses and Dissertations

Background: Hypertension is a dangerous condition that precedes many cardiovascular events including myocardial infarction, stroke, transient cerebral ischemic attack and symptomatic aortoiliac occlusive disease. While it is universally accepted that arteries stiffen with age, the physiological reason for this is debated. In a previous study, by Dr. Shana Roach Watson it was shown that collagen fibers re-orient themselves in a circumferential direction, resulting in increased arterial stiffness. The study hypothesized that this collagen remodeling could be a result of decreased nitric oxide production.

Methods: This study measured nitric oxide in two different ways, indirectly via Immunoperoxidase staining for eNOS and …

Advanced Geometric Analyses In Vascular Disease And Interventions, Dara Ahmadi Azar

Theses and Dissertations

The central function of the vascular system is the transportation and distribution of blood throughout the body. Occurrence of various forms of vascular disease, in which this central function is compromised, is associated with high mortality and morbidity rates. Vascular disease is an active and multifactorial process causing changes in local hemodynamics and blood vessel wall mechanics. The work presented here aims to advance the current knowledge on the role of local geometrical parameters in vascular disease and endovascular intervention modalities. In our first set of studies, we develop a computational framework to understand the role of aortic geometry in …

The Use Of Natural Anthraquinone Emodin As A Primary And Complementary Therapeutic In The Treatment Of Colorectal Cancer, Alexander-Jacques Theodore Sougiannis

Theses and Dissertations

5 Fluorouracil (5FU) chemotherapy is widely used in the treatment of colorectal cancer (CRC), and has been the first-choice chemotherapy drug for CRC for many years. However, nearly 10% of patients receiving chemotherapy die during the first 30 days of treatment. Further, it is estimated that 70% of surviving patients will develop non-specific toxicities as a result of chemotherapy treatment. We characterize these toxicities in an animal model of chemotherapy treatment and show that perturbations in the gut microbiome might be exacerbate the prolonged effects of chemotherapy. A compound that could attenuate the multiple non-selective toxicities associated with chemotherapy could …

Microwave-Assisted And One-Step Synthesis Of Peg Passivated Fluorescent Carbon Dots From Gelatin As An Efficient Nanocarrier For Methotrexate Delivery, Nasser Arsalani, Parinaz Nezhad-Mokhtari, Esmaiel Jabbari

Faculty Publications

A green and simple process for preparing the polyethylene glycol passivated fluorescent carbon dots (CDs-PEG) have been studied by a microwave pyrolysis method, using gelatin and PEG as starting materials. This method is very effective for development of carbon-based quantum dots from gelatin with high quantum yield (QY). The synthesized CDs-PEG were found to emit blue photoluminescence (PL) with a maximum QY of 34%. At the following research, we investigated the effect of the presence of PEG on PL intensity, and the result showed that CDs-PEG becomes stronger PL properties than pure CDs from gelatin. The synthesized CDs-PEG were characterized …

Adipose Tissue Engineering: A Therapeutic Strategy For The Treatment Of Obesity And Glucose Intolerance, Michael A. Hendley

Theses and Dissertations

Despite available treatment options, the number of people afflicted by type 2 diabetes has steadily risen for decades. Nearly 90% of the diabetic population also suffers from obesity and the link between the two diseases is undeniable. Characterized by rapid expansion of the adipose tissue and improper lipid storage, the mishandling of lipids by adipose tissue promotes the diabetic state. Excess lipids, unable to be properly stored, build up in peripheral tissues promoting insulin resistance and type 2 diabetes. Therapeutic strategies designed to address adipose tissue lipid handling could represent a promising treatment strategy for obesity associated type 2 diabetes. …

Experimental Methods And Techniques For Improved Biomechanical Characterization Of Diverse Murine Aortopathies, Brooks Alexander Lane

Theses and Dissertations

Aortopathies constitute a broad class of diseases affecting the aorta – the largest artery responsible for distributing oxygenated blood to the systemic circulation. Specifically, aortic aneurysms (AAs) are described as a focal dilation of the vascular wall exceeding 50% of the normal vessel diameter. Ultimately AAs may stabilize, dissect, or rupture, with the latter virtually ensuring mortality. Currently clinicians consider prophylactic intervention based on size and growth-rate criteria that have been estimated from large-cohort statistical analyses. These criteria, however, fail to address the underlying mechanisms. Furthermore, 13% of small-to-mid sized AAs have been found to rupture prior to meeting these …

Experimental Study Of Free-Solution Separation Under Pulsed Electrophoresis In Microchip, Xin Liu

Theses and Dissertations

Microchip electrophoresis (MCE) is a promising analytical tool started more than two decades. With the characteristics of short analysis time, trace level sample, high- throughput and easily integration, lots of efforts have been done with the transportation of the applications from capillary to microfabricated devices. However, with the complex designs on microchip rather than a single straight capillary channel, the strategies and approaches have to be figured out under the challenges of sample introduction, the improvement of separation conditions and the detection, for instance.

In miniaturized microchip, the separation channel is reduced to several centimeters or less, fast and quality …

Three-Dimensional Collagen Tubes For In Vitro Modeling, Rebecca Jones

Theses and Dissertations

Collagen type I represents a novel material for three-dimensional in vitro models. While two-dimensional models are typically inadequate for recreating the complex processes of the body, collagen provides a three-dimensional basis with a variety of applications, including remodeling of vascular cells under tension and vascular stenosis. Smooth muscle cells reorganize and reconstruct their environment differently under conditions of tensions, such as with sutures, or under conditions without applied external tension. Vascular stenosis, the abnormal narrowing of blood vessels, arises from defective developmental processes or atherosclerosis-related adult pathologies. Stenosis triggers a series of adaptive cellular responses that induces adverse remodeling, which …

Analysis Of Cellular Interactions Within A Collagen Hydrogel, Austin N. Worden

Theses and Dissertations

Evidence has arisen over the past several years that use of a three- dimensional (3D) culture system provides a distinct advantage over two- dimensional (2D) systems when cellular interactions are examined in a more natural environment. Changes in morphology, speed, and directionality of cells tested in both planar and 3D matrices have all demonstrated that using 3D system is advantageous. The changes to the cellular migration patterns were shown to be dependent on several variables within the surrounding substrate including cellular content, physical environment, and the matrix chemical milieu. We have taken advantage of using collagen hydrogels as a 3D …

An Anatomical Basis Of The Differential Cholinergic Modulation Of Valence-Specific Pyramidal Neurons In The Basolateral Amygdala, Nguyen Vu

Theses and Dissertations

Emotion is a crucial component of the decision-making process. The amygdala, known as the “orchestrator” of the emotion circuit, associates emotional valence with incoming sensory stimuli and thus contributes to decision- making. Within the basolateral nucleus of the amygdala (BLA), spatially segregated and genetically distinct pyramidal neurons (PNs) have been identified based on their correspondence to distinct behavioral stimuli. These PNs project to several brain regions mediating different aspects of the emotional spectrum.

For example, BLA PNs projecting to prelimbic (PL) and infralimbic (IL) cortex are involved in fear acquisition and fear extinction, respectively. However, the mechanism by which these …

Role Of P-Glycoprotein In Alzheimer’S Disease For Enhanced Brain Elimination Of Amyloid-Β, Hope Holt

Theses and Dissertations

Alzheimer’s disease (AD), the most common form of neurodegenerative disorder, is characterized by deposition of amyloid-β (Aβ) plaques in the brain. Aβ monomer undergoes nucleation to form oligomers, then soluble aggregates, then fibrils which make up the plaques. Aβ oligomer species are believed to be the most neurotoxic aggregate species. Currently under investigation is a mechanism for Aβ removal from the brain, across the blood-brain barrier (BBB). P-glycoprotein (P-gp) is a membrane-bound efflux protein located on the apical, or blood, side of the BBB, which transports a wide variety of substrates. Further complicating this potential clearance mechanism is the reduction …

Rage Expression And Inflammation In Alzheimer’S Disease: In Vitro Model Development And Investigation Of A Potential Peptoid Inhibitor, Lauren Michell Wolf

Theses and Dissertations

Despite the increasing prevalence of Alzheimer’s disease (AD), efforts to establish a definitive treatment or cure have met with little success. Many previous therapeutic strategies for AD have focused on the aggregation and accumulation of amyloid-b (Ab) in the brain, concentrating on its small intermediate aggregates as the primary targets to ameliorate neurotoxicity and damage. This approach has yielded little progress, and more recent discussions have shifted to strategies geared toward a multifaceted pathology, with chronic neuroinflammation emerging as an important factor in the disease etiology and progression.

The receptor for advanced glycation end-products, or RAGE, is …

Obstacles To Translating The Promise Of Nanoparticles Into Viable Amyloid Disease Therapeutics, N. P. Van Der Munnik, M. A. Moss, M. J. Uline

Faculty Publications

Nanoparticles (NPs) constitute a powerful therapeutic platform with exciting prospects as potential inhibitors of amyloid-β (Aβ) aggregation, a process associated with Alzheimer's disease (AD). Researchers have synthesized and tested a large collection of NPs with disparate sizes, shapes, electrostatic properties and surface ligands that evoke a variety of responses on Aβ aggregation. In spite of a decade of research on the NP-Aβ system and many promising experimental results, NPs have failed to progress to any level of clinical trials for AD. A theoretical framework with which to approach this physical system is presented featuring two simple metrics, (1) the extent …

Quantifying Mg 2+ Binding To Ssdna Oligomers: A Self-Consistent Field Theory Study At Varying Ionic Strengths And Grafting Densities, Merina Jahan, Mark J. Uline

Faculty Publications

The performance of aptamer-based biosensors is crucially impacted by their interactions with physiological metal ions, which can alter their structures and chemical properties. Therefore, elucidating the nature of these interactions carries the utmost importance in the robust design of highly efficient biosensors. We investigated Mg ²⁺ binding to varying sequences of polymers to capture the effects of ionic strength and grafting density on ion binding and molecular reorganization of the polymer layer. The polymers are modeled as ssDNA aptamers using a self-consistent field theory, which accounts for non-covalent ion binding by integrating experimentally-derived binding constants. Our model captures the typical …

Identification Of The Mechanisms Through Which Botanicals Attenuate Pathogenesis Of Human Diseases, Esraah Alharris

Theses and Dissertations

Plant products have been used for a long time in treatment of diseases. In fact, more than half of approved medicines are derived from plants or other natural products. Even though the synthetic drugs are effective in treating many human diseases, there is no cure against several clinical disorders. Moreover, a significant number of diseases can be prevented thereby causing less burden on societal healthcare costs as well as promoting healthy lifestyles. Thus, botanicals offer a unique opportunity to explore novel compounds to prevent and treat various clinical disorders as well as understand their mode of action so that new …

Turning Up Antitumor Immunity Against Breast Cancer, Johnie Hodge

Theses and Dissertations

Breast cancer is the most common cancer in women worldwide, and is the second leading cause of cancer-related death in spite of significant advances in treatment and emphasis on early diagnosis. While treatment of localized disease is often successful, metastatic breast cancer, especially of the triple negative molecular subtype, carries a much poorer prognosis. The significant role of the immune system in the progression from localized to metastatic disease is becoming more and more appreciated. Tumor escape from immune surveillance and immune suppression in the tumor microenvironment have become therapeutic targets in addition to the traditional goals of directly killing …

Optimization Of Microfluidic Chip Fabrication Via Femtosecond Laser Ablation, Kenneth Aycock

Senior Theses

Microfluidic devices have become staple tools in biomedical research and have a promising future as low cost, point-of-care (POC) diagnostic devices. Despite the advancements in microfluidic device technology, the manipulation and fabrication of these systems can be tedious and expensive. Repeatable techniques in which computer-aided designs are translated into microfluidic systems in a matter of minutes are highly desirable both for researchers and manufacturers. Laser ablation of tape substrates has shown promise in producing cost-effective, rapidly manipulable devices, but the work done thus far has utilized continuous wave lasers that perform suboptimally due to the relatively short wavelengths used and …

Osteon Mimetic Scaffolding, Janay Clytus

Senior Theses

The purpose of this research is to provide an alternative to naturally derived bone grafts. There is a gap in the supply of donors and the demand of bone tissue. Artificial scaffold creation can work as an implant and decrease the shortage of bone grafts and increase the range of injuries that can be repaired. Current research focuses on optimizing mechanical properties such as porosity, improving vascularization using cells, and generating osteoconductivity. For osteodifferentiation, mesenchymal stem cells (MSCs) can differentiate into mesodermal lineages such as chondrocytes, osteoblasts, adipocytes, and tenocytes by supplementing cultures with lineage-specific soluble factors (Marchetti). Co-culturing ECFCs …

Integration Of A Sensory Driven Model For Hand Grasp Function In 3d Printed Prostheses, Austin T. Hetherington

Senior Theses

My Honors Thesis was completed through the Biomedical Engineering senior design project I worked on. Our project took a mechanically operated 3D printed prosthetic hand and automated the process by which it makes a grasp. The purpose of this project was to provide an affordable, automatic prosthetic hand to those either capable and incapable of wrist flexion. The current 3D printed prosthetic models require users to bend their wrist to initiate a simple grasp. However, our design took an alternative approach by using an EMG sensor placed on the ventral side of the forearm to record muscle activity, which, upon …

Increasing Drug Delivery Efficacy Of Drug-Coated Balloons, Alexander Galan, Eric Bidinger, Franco Godoy, Shrusti Patel

Senior Theses

Peripheral artery disease (PAD), the narrowing of peripheral arteries located in areas such as the arms and legs, is a common disease that affects 12% to 20% of people over 65. Numerous therapies have been developed to treat PAD, the most recent technology being drug-coated balloons. Drug-coated balloons release drugs, such as Paclitaxel (PTX), into the arterial wall during balloon angioplasty to locally treat PAD. Current levels of drug transfer from the balloon to the vascular endothelium are at a low 10%-18%. Our Biomedical Engineering Senior Design project aims to increase drug delivery of drug-coated balloons by manipulating the clinically-controllable …

Development Of Rule-Based Recognition Systems For Continuous Monitorization Of Pulse Oximetry, Brian Delehanty

Senior Theses

Pulse Oximeters provide a convenient, non-invasive method to quickly gather information about a patient's pulse rate (PR) and arterial blood oxygen saturation (SpO₂). Many pulse oximeters lack alert systems that notify caregivers if a patient's readings go outside the healthy range, and pulse oximeters that have these mechanisms are significantly more expensive. This project set out to write a program using LabVIEW that collects pulse oximeter data via Bluetooth and generates an alert when readings persist in the abnormal range for more than fifteen seconds. Due to privacy laws that allow pulse oximeter manufacturers to not disclose the …

Mechanical And Geometrical Determinants Of Wall Stress In Abdominal Aortic Aneurysms: A Computational Study, Dara Azar, Donya Ohadi, Alexander Rachev, John F. Eberth, Mark J. Uline, Tarek Shazly

Faculty Publications

An aortic aneurysm (AA) is a focal dilatation of the aortic wall. Occurrence of AA rupture is an all too common event that is associated with high levels of patient morbidity and mortality. The decision to surgically intervene prior to AA rupture is made with recognition of significant procedural risks, and is primarily based on the maximal diameter and/or growth rate of the AA. Despite established thresholds for intervention, rupture occurs in a notable subset of patients exhibiting sub-critical maximal diameters and/or growth rates. Therefore, a pressing need remains to identify better predictors of rupture risk and ultimately integrate their …

Regulation Of Pituitary Progenitor Differentiation By Β-Catenin, Julie Leann Youngblood

Theses and Dissertations

The pituitary gland is a critical organ that is necessary for many physiological processes, including growth, reproduction, and stress response. These vital processes are regulated through the secretion of pituitary hormones from specialized cell types. Pituitary hormone-producing cells arise from a common pool of pituitary progenitors in the developing Rathke’s pouch, and mutations that disrupt the formation and differentiation of pituitary progenitors often result in hypopituitarism, pituitary adenomas, or craniopharyngiomas. Thus, it is necessary to determine the mechanisms of pituitary development in order to understand the ways in which these congenital defects and tumors develop and disrupt pituitary function. Canonical …

The Visual Ecology Of Speyeria Mormonia, Natalie Sanchez Gonzalez

Theses and Dissertations

Variations in environmental factors such as temperature, precipitation, and day length during larval development are known to affect morphological traits in butterflies related to their visual ecology, including eye size and wing color. These vision-related traits are important for the ability of diurnal butterfly species to detect mates, especially at long distances. Thus, changes in environmental conditions may result in phenotypic modifications to butterflies which may alter their visual ecology and subsequently, their reproductive fitness. To study the interaction of phenotypic plasticity and visual ecology in the Mormon Fritillary, Speyeria mormonia, I set up a natural-laboratory experiment at the Rocky …

Association Between Mechanics And Biology In Vascular Graft Remodeling, David Andrew Prim

Theses and Dissertations

Coronary artery bypass grafting (CABG) restores myocardial perfusion in patients with severe coronary artery disease by utilizing autografts – usually at least one of the internal thoracic artery (ITA), radial artery (RA), and great saphenous vein (GSV) – to bypass stenosed regions of coronary arteries. While decades of research and clinical improvements have made CABG an indispensable procedure, tens of thousands of grafts fail each year, which is due, at least in part, to an inability of the source vessels to adapt to the altered stimuli of the coronary circulation. In this dissertation, we first quantify and compare the mechanical …