Engineering Commons^™

Decellularization Strategies Of Naturally Derived Biomaterials For Tissue Engineering Applications, Julia Elizabeth Hohn

Theses and Dissertations

In 2017, over 3.5 million peripheral vascular surgeries were performed worldwide with over 400,000 vascular repair or replacement surgeries being performed in the United States each year alone. As the number of vascular repair surgeries, including both coronary and peripheral bypass grafting procedures, continues to increase each year, these statistics indicate an urgent need for more effective and readily available replacement materials. Regenerative medicine and tissue engineering (TE) approaches, including the design, fabrication, and validation of suitable biomaterials in vitro that direct the repair and regeneration of damaged tissues, have been proposed to alleviate this problem. While advanced biomaterials have …

Impaired Metabolic Flexibility In A Mouse Model Of Leigh Syndrome, Richard Sterling Mccain Jr

Theses and Dissertations

Metabolic dysfunction burdens tissues with high energy demands, particularly the brain. Leigh syndrome is a mitochondrial encephalopathy stemming from genetic defects in the electron transport chain. Leigh syndrome patients develop lactic acidosis, ataxia, bilateral necrotizing lesions in the brainstem and basal ganglia, lesion microgliosis, and eventually death due to respiratory failure. The NADH dehydrogenase [ubiquinone] iron-sulfur protein 4 (NDUFS4) knockout mouse is an established model of Leigh syndrome due to impaired assembly of mitochondrial Complex I that develops motoric deficits and necrotizing lesions in the brainstem vestibular nuclei and olfactory bulb. In addition to the Complex I-derived bioenergetics defect, altered …

The Effect Of Low Dose Penicillin On Tumor Development In ApcMin/+ Mice, Kinsey Ann Sierra Meggett

Theses and Dissertations

Antibiotics have been our most effective weapon against bacterial infections since their discovery in the early 1900s. Their use has been critical in reducing mortality rate from infectious diseases. However, in the last few decades, the overuse of antibiotics, beginning at an early age and into adulthood, has become a growing concern globally. Penicillin is one of many extensively used antibiotics in early childhood that has been used to treat childhood infections. Recent studies showed that exposure to low dose penicillin can have adverse effects leading to chronic illness such as diabetes, allergies, inflammation, and susceptibility to obesity, with the …

Impact Of Acetylcholine On Internal Pathways To Basal Amygdala Pyramidal Neurons, Tyler Daniel Anderson-Sieg

Theses and Dissertations

The basolateral nuclear complex of the amygdala (BNC) – consisting of the lateral (LA), basolateral (BL), and basomedial nuclei (BM) – detects salient environmental stimuli (cue-detection) and motivates appropriate behavioral responses to their implied meaning (cue-guided behavior) via a precise pattern of internal circuitry. Glutamatergic signals representing environmental stimuli enter the LA and split into parallel streams that activate pyramidal neurons (PNs) in the anterior and posterior BL (BLa and BLp), which putatively mediate negative and positive emotions, respectively. The BL is the most densely innervated target of the cholinergic basal forebrain (CBF) and ACh transients (phasic ACh) in cortex …

A Novel Model To Study Adipose-Derived Stem Cell Differentiation, Austin N. Worden

Theses and Dissertations

The use of three-dimensional (3D) culture systems (hydrogels) and adipose-derived stem cells (ADSCs) in regenerative medicine to advance early-stage investigation and modeling of the mechanisms of diseases, treatments, targets, etc. has recently increased. ADSCs, specifically, are utilized due to their innate programming during embryogenesis and in adult tissues in addition to their ability to differentiate into mesodermal, endodermal, and ectodermal cell-specific lineages. Of importance is that these advancements do not involve a model specimen (i.e. mice or rats) and simulate the numerous conflicting signals a migrating cell is exposed to in vivo such as chemokines, extracellular matrix (ECM), growth factors, …

Nanoparticles For Targeted Drug Delivery To Cancer Stem Cells: A Review Of Recent Advances, Yavuz Nuri Ertas, Keyvan Abedu Dorcheh, Ali Akbari, Esmaiel Jabbari

Faculty Publications

Cancer stem cells (CSCs) are a subpopulation of cells that can initiate, self-renew, and sustain tumor growth. CSCs are responsible for tumor metastasis, recurrence, and drug resistance in cancer therapy. CSCs reside within a niche maintained by multiple unique factors in the microenvironment. These factors include hypoxia, excessive levels of angiogenesis, a change of mitochondrial activity from aerobic aspiration to aerobic glycolysis, an upregulated expression of CSC biomarkers and stem cell signaling, and an elevated synthesis of the cytochromes P450 family of enzymes responsible for drug clearance. Antibodies and ligands targeting the unique factors that maintain the niche are utilized …

Role Of Ahr Ligands In Immune Modulation To Suppress Inflammation Through The Regulation Of Microrna And Gut Microbiome, Osama Azeldeen Abdulla

Theses and Dissertations

The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor and an environmental sensor that is highly conserved evolutionarily. It was first discovered in the early 1970s for its ability to bind with high affinity to 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), an environmental pollutant and induce a xenobiotic-metabolizing enzyme known as aryl hydrocarbon hydroxylase (AHH). AhR was shown to regulate TCDD-mediated toxicity against a variety of tissues including the immune system. More recently, AhR has been characterized as key regulator of the immune system, specifically the differentiation of T cells. Also, several AhR ligands have been characterized in addition to TCDD such as …

17 Β-Estradiol And Phytoestrogens Attenuate Apoptotic Cell Death In Hiv-1 Tat Exposed Primary Cortical Cultures, Sheila Marie Adams

Theses and Dissertations

Despite the advent of highly active antiretroviral therapy (HAART), neurological disorders develop in most people infected with human immunodeficiency virus type 1 (HIV-1). The poor CNS delivery of anti-retrovirals allows continued virus production and renders neurons susceptible to the toxic effects of released viral proteins. The neurotoxic potential of HIV-1 viral protein Tat has been shown to include excitotoxicity, oxidative stress, and mitochondrial dysfunction leading to subsequent cell death. Thus, Tat is thought to have a key role in the pathogenesis of HIV-associated neurodegeneration. Estrogens are universally considered to be neuroprotective, as such; estrogens have positive implications in the treatment …

Expansion Microscopy: A New Approach To Microscopic Evaluation, Ashley Ferri

Theses and Dissertations

Optical microscopy resolution is limited by the wavelengths of light and the series of microscope lenses and other optical components used to create a magnified image of cell structures in a sample. Often the cell structures are smaller or closer together than the resolution limits of a light microscope. In 2015 the Boyden group at the Massachusetts Institute of Technology (MIT) created a sample preparation technique, expansion microscopy which involves embedding biological samples in a crosslinked, swellable, hydrogel polymer that allows for uniform physical separation of cell components so that they can subsequently be resolved by light microscopy. Using the …

Helicobacter’S Effects On Colitis/Colon Cancer And The Response To Indole 3-Carbinol, Rasha Raheem Abdulhamza Alkarkoushi

Theses and Dissertations

Enterohepatic Helicobacter (EHH) species are gram-negative bacteria, which are poorly studied. Several studies suggest that EHH species contribute to inflammatory bowel disease IBD in humans. IBD and colorectal cancer (CRC) has emerged as a public health challenge worldwide. Indole-3-carbinol (I3C) is one of the natural dietary indoles abundant in Brassica (cruciferous) vegetables. The aryl hydrocarbon receptor (AhR) plays an essential role as a regulator by controlling the balance between Tregs and Th17 cells. The activation of AhR by ligands derived from food or intestinal microbiota is an essential control mechanism in that balance. Moreover, many studies showed indoles achieving chemo-preventive …

Tissue-Specific Roles Of Transforming Growth Factor Beta Ligands In Cardiac Outflow Tract Malformations And Calcific Aortic Valve Disease, Nadia Al-Sammarraie

Theses and Dissertations

Congenital heart defects and adult calcific aortic valve disease are two of the leading causes of morbidity and mortality worldwide. To date, there is no medical cure and surgical intervention is the main option of treatment. The cardiac outflow tract is the major site for these abnormalities, which are triggered by genetic and/or environmental factors that alter development and/or homeostasis. Recently, significant roles of TGFβ signaling in development of cardiovascular disorders have become more evident in humans, however, the specific requirement of individual TGFβ ligands on the pathogenesis of OFT malformations and diseases remains elusive. In the present work, three …

Astrocyte Sensitivity To Dopamine In Culture And Ex Vivo, Ashley L. Galloway

Theses and Dissertations

Dopamine is critical for processing of reward and etiology of drug addiction. Astrocytes throughout the brain express dopamine receptors, but consequences of astrocytic dopamine receptor signaling are not well established. This thesis illustrates effects of dopamine on cultured astrocytes and astrocytes in brain slices (ex vivo). In striatal cultures, extracellular dopamine triggered changes in astrocytic Ca²⁺ signaling and rapid concentration-dependent stellation of astrocytic processes that was not a result of dopamine oxidation, but instead relied on both cAMP-dependent and cAMP-independent dopamine receptor signaling. To isolate possible mechanisms underlying these structural and functional changes, whole-genome RNA sequencing was …

Epigenetic And Purinergic Regulation Of Mast Cells Mediator Release, Zahraa Abdulmohsin Mohammed

Theses and Dissertations

Mast cells (MCs) are well known for their implications in allergic reactions. They are also known to have multiple functions in the innate and adaptive immune system. Their activation plays an essential role in many aspects of physiological and pathological conditions. Allergies are considered chronic conditions that affect more than 60 million people in the U.S. These diseases are driven by the activation of MCs in response to IgE-mediated antigen, rendering these cells as targets for the management of allergies and asthma. Therefore, this research considers the understanding of their activation and the regulation of their response to be an …

The Contribution Of Adipose Tissue From Ovariectomized Mice To Colon Cancer, Meredith Smith Carson

Theses and Dissertations

Obesity is considered a major public health concern worldwide due to the increased incidences of metabolic dysfunction and cancer risk. The obese state is, in part, attributable to the overconsumption of calorie-dense foods commonly seen in a standard Western diet, which aids in the progression of chronic, lowgrade inflammation. The role of estrogen varies depending on menopausal status, where estrogen deficiency coupled with increased visceral fat associated with post-menopause leads to increased secretions of pro-inflammatory adipokines and cytokines. However, the presence of estrogen in a premenopausal state has been shown to attenuate the pro-inflammatory response, which has been demonstrated when …

Effect Of Tcdd, An Environmental Contaminant, On Activation Of Ahr Leading To Induction Of Myeloid Derived Suppressor Cells (Mdscs) And The Ability Of Resveratrol, A Botanical, To Neutralize This Effect, Wurood Hantoosh Neamah

Theses and Dissertations

Aryl hydrocarbon receptor (AhR), is a ligand-activated transcription factor that integrates environmental, dietary, microbial and metabolic cues to control various cellular processes, such as the cell cycle, epithelial barrier function, cell migration and immune function. AhR was discovered as the receptor that binds with high affinity to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and leads to numerous of toxicological outcomes. In the current study, we discovered a critical role played by AhR, following activation by TCDD, in modulating a variety of immunological functions through regulation of epigenetic and microbial pathways. Our data demonstrated that AhR activation triggers MDSC mobilization from bone marrow to peritoneal …

Role Of Epigenetic, Molecular And Cellular Pathways In The Regulation Of Inflammation, William James Becker

Theses and Dissertations

Dysregulated inflammation is at the heart of countless human diseases. Graft rejection is the process by which an organ from an incompatible donor is rejected by the recipient whose immune cells attack the foreign tissue. Colitis is an inflammatory disorder caused by undue chronic inflammation in the colon and rectum that can progress to cancer. Colitis incidence is on the rise, especially in developing nations and Asia; and the list of patients who need organ transplants grow by the day. Therapies for both graft rejection and colitis are limited to immunosuppressive drugs that leaves patients vulnerable to infection, heart disease, …

Interdependent Mechanisms Of Stress Susceptibility, Julie Elaine Finnell

Theses and Dissertations

Social stress is a significant risk factor for the emergence of psychiatric disorders including depression and anxiety. While there are a number of commercially available therapeutic options for the treatment of these disorders, these treatments require weeks of continuous use to produce behavioral efficacy. It has also been suggested that these traditional therapies are only marginally effective in producing complete remission, suggesting that our understanding as it pertains to the mechanisms underlying stressinduced behavioral dysfunction is still in its infancy. In the last few years, inflammation has become a major focus in the field of stress and depression as clinical …

Three-Dimensional Plasma Cell Survival Microniche In Multiple Myeloma, Katrina A. Harmon

Theses and Dissertations

Multiple myeloma (MM) is an incurable malignancy characterized by the uncontrolled proliferation of long-lived plasma cells (PCs) in the bone marrow (BM), which constitute at least 10% of BM cellularity. Normally, long-lived plasma cells make up less than 1% of BM cells. Plasma cells become neoplastic when a clonal PC population produces a monoclonal immunoglobulin protein. A diagnosis of monoclonal gammopathy of undetermined significance (MGUS) is made when there is an increase in monoclonal PCs within the BM, but less than 10%, and the patient does not present with end-organ damage, which is associated with active MM. Though not considered …

Three-Dimensional Plasma Cell Survival Microniche In Multiple Myeloma, Katrina A. Harmon

Theses and Dissertations

Multiple myeloma (MM) is an incurable malignancy characterized by the uncontrolled proliferation of long-lived plasma cells (PCs) in the bone marrow (BM), which constitute at least 10% of BM cellularity. Normally, long-lived plasma cells make up less than 1% of BM cells. Plasma cells become neoplastic when a clonal PC population produces a monoclonal immunoglobulin protein. A diagnosis of monoclonal gammopathy of undetermined significance (MGUS) is made when there is an increase in monoclonal PCs within the BM, but less than 10%, and the patient does not present with end-organ damage, which is associated with active MM. Though not considered …

Biophysical Analyses Of Left Ventricular Remodeling Secondary To Myocardial Infarction And Left Ventricular Pressure Overload, William Manuel Torres

Theses and Dissertations

Left ventricular (LV) remodeling is nominally an adaptive process that restores biomechanical function following myocardial injury and/or sustained alterations in loading conditions. This remodeling can materialize as changes in myocardial geometry, composition, and mechanical properties. When these changes fail to restore LV biomechanical function, remodeling is termed maladaptive. It is generally accepted that maladaptive LV remodeling underlies the progression to heart failure in various forms of heart disease. The central hypothesis of this study is that we can leverage echocardiographic imaging techniques to non-invasively quantify changes in biomechanical function and mechanical properties in a serial manner throughout the progression towards …

Beneficial Effects Of Resveratrol Against Colitis And Colorectal Cancer Mediated By The Host Microbiome, Epigenome, And Immune Response, Haider Rasheed Daham Alrafas

Theses and Dissertations

Resveratrol, a natural polyphenol compound found in red wine, the skins of grapes, and other plant products, has been used as a traditional medicine for thousands of years throughout human history, but current research has revealed this natural component is capable of modulating a variety of immunological, microbial, and epigenetic mechanisms to improve overall health and well-being of hosts that consume it. Colitis, an inflammatory bowel disease characterized by chronic inflammation in the colon and rectum, which has been associated with colon cancer. This cancer incidence is rising in younger adults in the US. Thus, newer approaches to prevent colitis …

Role Of Mammary Microenvironment In Promoting Left-Right Differences In Tumor Progression, Metastasis, And Therapeutic Response, Huda Issa Atiya

Theses and Dissertations

Metastasis is the main cause of death in breast cancer patients; however, there are currently no treatments available to treat or prevent metastasis. This is in part because regulators of metastasis are not yet fully understood. Over the past century researchers began to study metastasis regulators by different hypotheses, such as the seed and soil hypothesis which focuses on studying the role of cancer cells, the seeds, and the tissue microenvironment, the soil, in regulating metastasis. Although lots of studies have focused on the microenvironment of metastatic sites and their roles in regulating metastasis, limited studies have focused on the …

Enhancements In Alginate Microencapsulation Technology & Impacts On Cell Therapy Development, Marwa Belhaj

Theses and Dissertations

Biodegradable alginate microcapsules (MC) are recently becoming widely used in the biomedical field, and have shown effectiveness as a drug delivery system. Alginate has been used in microencapsulation due to its simple gelling process, biodegradability, excellent biocompatibility, and its stability under in-vivo conditions. Alginate polymer is a natural polysaccharide derived from brown seaweed and has the ability to polymerize rapidly in the presence of cations to form a porous matrix. In order to advance the previous system for efficient protein and peptide delivery, we further lyophilized the peptide-filled microcapsules and we were able to rehydrate, and test them for sustained …

Impact Of Physical Activity In The Prevention Of Colorectal Cancer, Sarah Ashley Barnes

Theses and Dissertations

This review evaluates the current understanding of research on the impact of physical activity in the prevention of colorectal cancer. Current biological mechanisms implicated in physical activity and colorectal cancer risk reduction are blood glucose regulation, insulin sensitivity, leptin and adiponectin profiles, inflammation as well as secreted protein acidic and rich in cysteine (SPARC), an exercise induced myokine. Recent literature indicates that 30-60 minutes of moderate to vigorous activity a day is effective against colorectal cancer development, and there is convincing evidence of aerobic exercise as differently beneficial in recruiting mechanisms identified as preventative against colorectal cancer. This article provides …

The Anti-Angiogenic Effects Of Sparstolonin B, Henry Rhodes Bateman

Theses and Dissertations

Sparstolonin B (SsnB) is a novel bioreactive compound isolated from Sparganium stoloniferum, an herb historically used in Traditional Chinese Medicine as an anti-tumor agent. SsnB has demonstrated anti-inflammatory properties, inhibiting Toll-like receptor mediated inflammation in isolated macrophages and in mice. Angiogenesis, the process of new capillary formation from existing blood vessels, is dysregulated in many pathological disorders, including atherosclerosis, diabetic retinopathy, and tumor growth. The goal of the project was to investigate the anti-angiogenic effects of SsnB.

The first part of the project utilized in vitro functional assays to study how SsnB affected endothelial cells. SsnB inhibited endothelial cell tube …

Development Of Proteomic Characterization And Speciation Techniques Utilizing Tryptic Peptides With Maldi-Tof Ms And Lc-Esi Ms-Ms, Jennifer Marie Kooken

Theses and Dissertations

The characterization of microbes which can be opportunists and pathogens (e.g., methicillin resistant Staphylococcus aureus (MRSA)) is important in understanding and potentially treating diseases caused by various bacterial species. Common genera found in the human skin micro-biome include Micrococcus and Staphylococcus, but there only a limited number of tests to differentiate these genera and/or species. My research reflects methods development from distinguishing one closely related genera from another and then expanded to species identification. Tryptic peptides were analyzed by MALDI TOF MS and the mass profiles compared with those of a reference strain in both genus and species identification. Aconitate …

Linking Obesity To Colorectal Cancer: Recent Insights Into Plausible Biological Mechanisms, Catherine Guffey

Theses and Dissertations

Obesity has emerged as a leading environmental risk factor for the development of CRC. However, the mechanisms underlying this relationship have not yet been fully explained. Recent literature has focused on 1) inflammatory processes, 2) adipokines, and 3) estrogen. Obesity-enhanced inflammation is largely orchestrated by increases in adipose tissue macrophages leading to the secretion of TNF-alpha, MCP-1, and IL-6, all of which are linked to CRC. Adiponectin is decreased with obesity and has been reported to be negatively associated with CRC, while leptin, which is increased, is positively associated with the disease. Estrogen has been shown to influence CRC, although …

Investigation Of Start Domain Proteins In Human Luteinized Cells And Cos-1 Cells, Bo Shi

Theses and Dissertations

After the luteinizing hormone surge of the menstrual cycle, the ovarian follicular granulosa and theca cells terminally differentiate to form the luteal cells of the corpus luteum. During this process known as luteinization, granulosa cells begin to synthesize large quantities of progesterone, a hormone essential for pregnancy. The rate limiting step for the de novo synthesis of pregnenolone (the precursor to progesterone) is the transport of cholesterol from the outer to the inner mitochondrial membrane, a process mediated by STARD1. STARD1 contains a C-terminal lipid binding domain holding one molecule of cholesterol, and an N-terminal domain targeting STARD1 to the …

Osteon-Mimetic Nanocomposite Materials For Bone Regeneration, Ozan Karaman

Theses and Dissertations

The limitations of large bone defect regeneration has brought the focus of Bone Tissue Engineering research on fabricating three-dimensional bone-mimetic grafts that could enhance osteogenesis and vascularization. Osteons composed of apatite-deposited aligned collagen nanofiber layers are the fundamental building blocks of cortical bone. In natural cortical bone, mineralization is mediated by extracellular matrix (ECM) proteins with amino acid sequences rich in glutamic acid. This dissertation is focused on the establishment of a novel biomimetic approach to engineer scaffolds for healing large bone defects.

In the first part, we investigated the effect of calcium phosphate (CaP) deposition on aligned surface-modified nanofibers …

Characterizing Hypoxia And Its Behavioral Effects In 3-Dimensional Cell Aggregates, Matthew Lorincz Skiles

Theses and Dissertations

Cell transplantation can be considered a regenerative therapy, an intervention which attempts to replace or restore the function of compromised tissue by harnessing innate properties of cells that cannot be replicated artificially. For such therapies to succeed, it will be necessary to understand and closely match the physiological conditions that govern cell behaviors in vivo. One important factor is low oxygen tension, termed hypoxia, which is often overlooked in vitro. Because oxygen insufficiency can lead to cell death, hypoxia has traditionally been viewed as a negative condition. However, hypoxia can also serve as a potent regulator of crucial cell behaviors …