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Inflammation

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An In Vitro Investigation Of Urothelial Cell Function In Response To Hypoxia And Pressure In Relation To Bladder Outlet Obstruction, Britney Hudson May 2024

An In Vitro Investigation Of Urothelial Cell Function In Response To Hypoxia And Pressure In Relation To Bladder Outlet Obstruction, Britney Hudson

All Dissertations

Bladder outlet obstruction (BOO) is a prevalent urological condition and can be characterized by the presence of lower urinary tract symptoms (LUTS), such as hesitancy, weak stream, and nocturia. The main cause of BOO is a partial blockage of the urethra, which results in elevated voiding pressure, high storage pressure, and tissue ischemia, which are thought to be the triggers of bladder inflammation and subsequent fibrosis. Often patients do not seek treatment until the conditions get severe. Thus, it would be ideal to have an early diagnostic tool to detect changes in the bladder due to BOO. Extracellular vesicles (EVs) …


Developing An Immunomodulatory Strategy Using Biophysical Cues To Modulate Macrophage Phenotype For Fracture Healing And Bone Regeneration, Harshini Suresh Kumar Jan 2024

Developing An Immunomodulatory Strategy Using Biophysical Cues To Modulate Macrophage Phenotype For Fracture Healing And Bone Regeneration, Harshini Suresh Kumar

Theses and Dissertations--Biomedical Engineering

Chronic inflammation is a major cause of the pathogenesis of musculoskeletal diseases such as fragility, fracture, and nonunion. Studies have shown that modulating the immune phenotype of macrophages from proinflammatory to pro-healing can heal recalcitrant bone defects. Current therapeutic strategies predominantly apply biochemical cues, which often lack target specificity, and controlling their release kinetics in vivo is challenging spatially and temporally. We have developed a magnetic iron-oxide nanocomplexes (MNC)-based therapy for resolving chronic inflammation in the context of promoting fracture healing. Here, we show that MNC internalized macrophages, when coupled with an external magnetic field, can exert an intracellular magnetic …


Editorial: Intervertebral Disc Degeneration And Osteoarthritis: Mechanisms Of Disease And Functional Repair., Graciosa Q Teixeira, Jana Riegger, Raquel M Gonçalves, Makarand V. Risbud Jul 2023

Editorial: Intervertebral Disc Degeneration And Osteoarthritis: Mechanisms Of Disease And Functional Repair., Graciosa Q Teixeira, Jana Riegger, Raquel M Gonçalves, Makarand V. Risbud

Department of Orthopaedic Surgery Faculty Papers

No abstract provided.


Extracellular-Vesicle-Based Therapeutics In Neuro-Ophthalmic Disorders, Hamed Massoumi, Sohil Amin, Mohammad Soleimani, Bita Momenaei, Mohammad Javad Ashraf, Victor H Guaiquil, Peiman Hematti, Mark I Rosenblatt, Ali R Djalilian, Elmira Jalilian May 2023

Extracellular-Vesicle-Based Therapeutics In Neuro-Ophthalmic Disorders, Hamed Massoumi, Sohil Amin, Mohammad Soleimani, Bita Momenaei, Mohammad Javad Ashraf, Victor H Guaiquil, Peiman Hematti, Mark I Rosenblatt, Ali R Djalilian, Elmira Jalilian

Wills Eye Hospital Papers

Extracellular vesicles (EVs) have been recognized as promising candidates for developing novel therapeutics for a wide range of pathologies, including ocular disorders, due to their ability to deliver a diverse array of bioactive molecules, including proteins, lipids, and nucleic acids, to recipient cells. Recent studies have shown that EVs derived from various cell types, including mesenchymal stromal cells (MSCs), retinal pigment epithelium cells, and endothelial cells, have therapeutic potential in ocular disorders, such as corneal injury and diabetic retinopathy. EVs exert their effects through various mechanisms, including promoting cell survival, reducing inflammation, and inducing tissue regeneration. Furthermore, EVs have shown …


Development Of A Multispectral Vis-Swir Imaging Modality For Cutaneous Water Assessment, Quinlan Mcgrath May 2023

Development Of A Multispectral Vis-Swir Imaging Modality For Cutaneous Water Assessment, Quinlan Mcgrath

McKelvey School of Engineering Theses & Dissertations

Inflammatory skin diseases are estimated to impact 20% of the global population and are the fourth leading cause of nonfatal disability worldwide. Diagnosis and management are predominantly based on clinician visual assessment of disease related changes in skin morphology. The qualitative nature of this method can result in misdiagnosis and underdiagnoses of treatable diseases. There persists systematic undertreatment of skin of color patients given the more subtle presentation of erythema against pigmented skin. There exists a clinical need for a quantitative and objective inflammation assessment tool that meets the needs of a diverse patient population. The accumulation of interstitial fluid …


Anti-Inflammatory And Anti-Thrombogenic Properties Of Arterial Elastic Laminae, Jeremy Goldman, Shu Q. Liu, Brandon J. Tefft Mar 2023

Anti-Inflammatory And Anti-Thrombogenic Properties Of Arterial Elastic Laminae, Jeremy Goldman, Shu Q. Liu, Brandon J. Tefft

Michigan Tech Publications

Elastic laminae, an elastin-based, layered extracellular matrix structure in the media of arteries, can inhibit leukocyte adhesion and vascular smooth muscle cell proliferation and migration, exhibiting anti-inflammatory and anti-thrombogenic properties. These properties prevent inflammatory and thrombogenic activities in the arterial media, constituting a mechanism for the maintenance of the structural integrity of the arterial wall in vascular disorders. The biological basis for these properties is the elastin-induced activation of inhibitory signaling pathways, involving the inhibitory cell receptor signal regulatory protein α (SIRPα) and Src homology 2 domain-containing protein tyrosine phosphatase 1 (SHP1). The activation of these molecules causes deactivation of …


Simulating The Effect Of Gut Microbiome On Cancer Cell Growth Using A Microfluidic Device, Ekansh Mittal, Grace Cupp, Youngbok (Abraham) Kang Jan 2023

Simulating The Effect Of Gut Microbiome On Cancer Cell Growth Using A Microfluidic Device, Ekansh Mittal, Grace Cupp, Youngbok (Abraham) Kang

Faculty Publications - Biomedical, Mechanical, and Civil Engineering

The imbalance in the gut microbiome plays a vital role in the progression of many diseases, including cancer, due to increased inflammation in the body. Since gut microbiome-induced inflammation can serve as a novel therapeutic strategy, there is an increasing need to identify novel approaches to investigate the effect of inflammation instigated by gut microbiome on cancer cells. However, there are limited biomimetic co-culture systems that allow testing of the causal relationship of the microbiome on cancer cells. Here we developed a microfluidic chip that can simulate the interaction of the gut microbiome and cancer cells to investigate the effects …


Impacts Of Diverse Inflammatory Stimuli On Neutrophil Behavior: Extracellular Vesicles, E-Cigarettes, And Nanoparticles, Hunter T. Snoderly Jan 2023

Impacts Of Diverse Inflammatory Stimuli On Neutrophil Behavior: Extracellular Vesicles, E-Cigarettes, And Nanoparticles, Hunter T. Snoderly

Graduate Theses, Dissertations, and Problem Reports

Neutrophils are the body’s front-line defenders against foreign insult and are key players in a variety of inflammatory conditions. This body of work examines the role of neutrophils in promoting pathology in three distinct inflammatory contexts. In the pro-inflammatory state provoked by breast cancer, neutrophils decondense their nuclei and release cytotoxic web-like structures known as neutrophil extracellular traps (NETs). NETs form most commonly via histone modifications facilitated by the enzyme PAD4. NETs are known to be a harbinger of disease progression and promote metastasis through capture of circulating tumor cells. It was hypothesized that breast tumors release small particles known …


Mesenchymal Stromal Cells And Alpha-1 Antitrypsin Have A Strong Synergy In Modulating Inflammation And Its Resolution, Li Han, Xinran Wu, Ou Wang, Xiao Luan, William Velander, Michael Aynardi, E. Scott Halstead, Anthony S. Bonavia, Rong Jin, Guohong Li, Yulong Li, Yong Wang, Cheng Dong, Yuguo Lei Jan 2023

Mesenchymal Stromal Cells And Alpha-1 Antitrypsin Have A Strong Synergy In Modulating Inflammation And Its Resolution, Li Han, Xinran Wu, Ou Wang, Xiao Luan, William Velander, Michael Aynardi, E. Scott Halstead, Anthony S. Bonavia, Rong Jin, Guohong Li, Yulong Li, Yong Wang, Cheng Dong, Yuguo Lei

Department of Chemical and Biomolecular Engineering: Faculty Publications

Rationale: Trauma, surgery, and infection can cause severe inflammation. Both dysregulated inflammation intensity and duration can lead to significant tissue injuries, organ dysfunction, mortality, and morbidity. Anti-inflammatory drugs such as steroids and immunosuppressants can dampen inflammation intensity, but they derail inflammation resolution, compromise normal immunity, and have significant adverse effects. The natural inflammation regulator mesenchymal stromal cells (MSCs) have high therapeutic potential because of their unique capabilities to mitigate inflammation intensity, enhance normal immunity, and accelerate inflammation resolution and tissue healing. Furthermore, clinical studies have shown that MSCs are safe and effective. However, they are not potent enough, alone, to …


Piglet Cardiopulmonary Bypass Induces Intestinal Dysbiosis And Barrier Dysfunction Associated With Systemic Inflammation, Jeffrey D. Salomon, Haowen Qiu, Dan Feng, Jacob Owens, Ludmila Khailova, Suzanne Osorio Lujan, John Iguidbashian, Yashpal S. Chhonker, Daryl J. Murry, Jean-Jack Riethoven, Merry L. Lindsey, Amar B. Singh, Jesse A. Davidson Nov 2022

Piglet Cardiopulmonary Bypass Induces Intestinal Dysbiosis And Barrier Dysfunction Associated With Systemic Inflammation, Jeffrey D. Salomon, Haowen Qiu, Dan Feng, Jacob Owens, Ludmila Khailova, Suzanne Osorio Lujan, John Iguidbashian, Yashpal S. Chhonker, Daryl J. Murry, Jean-Jack Riethoven, Merry L. Lindsey, Amar B. Singh, Jesse A. Davidson

Nebraska Center for Biotechnology: Faculty and Staff Publications

The intestinal microbiome is essential to human health and homeostasis, and is implicated in the pathophysiology of disease, including congenital heart disease and cardiac surgery. Improving the microbiome and reducing inflammatory metabolites may reduce systemic inflammation following cardiac surgery with cardiopulmonary bypass (CPB) to expedite recovery postoperatively. Limited research exists in this area and identifying animal models that can replicate changes in the human intestinal microbiome after CPB is necessary. We used a piglet model of CPB with two groups, CPB (n=5) and a control group with mechanical ventilation (n=7), to evaluate changes to the microbiome, …


Fabrication Of Polymeric Microparticles Loaded With Zoledronic Acid To Treat Osteoarthritis, Yohely Maria Espiritusanto Jul 2022

Fabrication Of Polymeric Microparticles Loaded With Zoledronic Acid To Treat Osteoarthritis, Yohely Maria Espiritusanto

Theses - ALL

Osteoarthritis (OA), a disease caused by wearing and tearing of articular cartilage, affectsover 32.5 million Americans. Synovial inflammation is now recognized as a major contributor to OA progression and pain. Activated synovial macrophages in an OA joint are believed to play a major role in low grade inflammation found in OA. Bisphosphonates such as zoledronic acid (ZA) are known to induce apoptosis specifically in macrophages and several of them are being evaluated as a disease-modifying osteoarthritis drug in clinical trials. However, ZA is rapidly cleared from the joint after systemic or localized direct injection into the joint. In this study …


Biomarkers Of Inflammation And Oxidative Stress In The Prediction And Management Of Acute Coronary Syndrome, Udaya Ralapanawa, Sivakanesan R Jan 2022

Biomarkers Of Inflammation And Oxidative Stress In The Prediction And Management Of Acute Coronary Syndrome, Udaya Ralapanawa, Sivakanesan R

Health Sciences

The assessment of patients presenting with chest pain or symptoms indicative of cardiac ischemia remains a diagnostic challenge. Many types of research have focused on the search for ideal biological markers for the rapid detection of cardiac cell injuries. Markers of inflammation and oxidative stress are the way forward. At present, the biomarker most widely used for diagnosing acute coronary syndrome is cardiac troponin though it has some limitations. Apart from cardiac troponin, several other biomarkers, especially inflammation and oxidative stress markers in acute coronary syndrome, have been investigated. However, most of them still require validation in further studies. As …


Defining The Innate Immune Responses For Sars-Cov-2-Human Macrophage Interactions, Mai M. Abdelmoaty, Pravin Yeapuri, Jatin Machhi, Katherine E. Olson, Farah Shahjin, Vikas Kumar, You Zhou, Jingjing Liang, Kabita Pandey, Arpan Acharya, Siddappa N. Byrareddy, R. Lee Mosley, Howard E. Gendelman Oct 2021

Defining The Innate Immune Responses For Sars-Cov-2-Human Macrophage Interactions, Mai M. Abdelmoaty, Pravin Yeapuri, Jatin Machhi, Katherine E. Olson, Farah Shahjin, Vikas Kumar, You Zhou, Jingjing Liang, Kabita Pandey, Arpan Acharya, Siddappa N. Byrareddy, R. Lee Mosley, Howard E. Gendelman

Nebraska Center for Biotechnology: Faculty and Staff Publications

Host innate immune response follows severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and it is the driver of the acute respiratory distress syndrome (ARDS) amongst other inflammatory end-organ morbidities. Such life-threatening coronavirus disease 2019 (COVID-19) is heralded by virus-induced activation of mononuclear phagocytes (MPs; monocytes, macrophages, and dendritic cells). MPs play substantial roles in aberrant immune secretory activities affecting profound systemic inflammation and end-organ malfunctions. All follow the presence of persistent viral components and virions without evidence of viral replication. To elucidate SARS-CoV- 2-MP interactions we investigated transcriptomic and proteomic profiles of human monocyte-derived macrophages. While expression of the …


Evaluating The Structural And Functional Consequences Of Traumatic Joint Injury And Their Relation To Nf-Κb In A Non-Invasive Model Of Post-Traumatic Osteoarthritis, Ian Matthew Berke Jan 2021

Evaluating The Structural And Functional Consequences Of Traumatic Joint Injury And Their Relation To Nf-Κb In A Non-Invasive Model Of Post-Traumatic Osteoarthritis, Ian Matthew Berke

McKelvey School of Engineering Theses & Dissertations

Post-traumatic osteoarthritis (PTOA) is a painful and debilitating disease of the synovial joint, characterized by degenerative changes to various joint tissues following traumatic joint injury. While several risk factors have been identified in the symptomatic progression of PTOA following injury, inflammation and NF-κB mediated changes are believed to significantly contribute to symptomatic joint dysfunction and pain. However, the temporal presentation of these pro-inflammatory signals following clinically relevant injury and their relationship to the development of symptomatic disease have not been thoroughly investigated. Therefore, there exists a critical need to better understand how these early inflammatory events following injury may contribute …


The Sars-Cov-2 Spike Protein Alters Barrier Function In 2d Static And 3d Microfluidic In-Vitro Models Of The Human Blood-Brain Barrier., Tetyana P Buzhdygan, Brandon J Deore, Abigail Baldwin-Leclair, Trent A Bullock, Hannah M Mcgary, Jana A Khan, Roshanak Razmpour, Jonathan F Hale, Peter Galie, Raghava Potula, Allison M Andrews, Servio H Ramirez Dec 2020

The Sars-Cov-2 Spike Protein Alters Barrier Function In 2d Static And 3d Microfluidic In-Vitro Models Of The Human Blood-Brain Barrier., Tetyana P Buzhdygan, Brandon J Deore, Abigail Baldwin-Leclair, Trent A Bullock, Hannah M Mcgary, Jana A Khan, Roshanak Razmpour, Jonathan F Hale, Peter Galie, Raghava Potula, Allison M Andrews, Servio H Ramirez

Henry M. Rowan College of Engineering Departmental Research

As researchers across the globe have focused their attention on understanding SARS-CoV-2, the picture that is emerging is that of a virus that has serious effects on the vasculature in multiple organ systems including the cerebral vasculature. Observed effects on the central nervous system include neurological symptoms (headache, nausea, dizziness), fatal microclot formation and in rare cases encephalitis. However, our understanding of how the virus causes these mild to severe neurological symptoms and how the cerebral vasculature is impacted remains unclear. Thus, the results presented in this report explored whether deleterious outcomes from the SARS-CoV-2 viral spike protein on primary …


The Role Of Gene Transcription And Inflammatory Cytokines In Bone Fracture Repair, Brandon Alan Coates May 2020

The Role Of Gene Transcription And Inflammatory Cytokines In Bone Fracture Repair, Brandon Alan Coates

McKelvey School of Engineering Theses & Dissertations

In most instances, the skeleton has a remarkable capacity for repair following injury. However, in 5 to 10% of patients, fractures fail to properly heal resulting in non-union. A need exists for a more comprehensive understanding of the complex biology of fracture repair, which involves the coordinated work of many cell types including osteoblasts, osteoclasts, and immune cells. Depending on the extent of injury, fractures will heal through either intramembranous bone formation, involving the direct formation of bone callus, or endochondral bone formation, featuring a cartilage intermediary prior to bone callus formation. Both processes begin with inflammation, which sets the …


Pilot Study Exploring The Effect Of Targeted Cox-2 Inhibition In Macrophages Responding To Neuronal Injury; Promoting Enhanced Axonal Regeneration, Alyssa Brauckmann May 2020

Pilot Study Exploring The Effect Of Targeted Cox-2 Inhibition In Macrophages Responding To Neuronal Injury; Promoting Enhanced Axonal Regeneration, Alyssa Brauckmann

Electronic Theses and Dissertations

Celecoxib nanoemulsion (CXB-NE) has been developed as a macrophage targeted analgesics by Dr. Janjic and her team at Duquesne University, (Janjic et al, 2018; Liu et al, 2020; Saleem et al, 2019b; Vasudeva et al, 2014). The CXB-NE nanoemulsion carrying a Nonsteroidal Anti-inflammatory (NSAID) inhibitor of COX-2 activity result in a reduction in PGE2 expression in macrophages. Using CXB-NE in rats that have peripheral nerve injury constricting the sciatic nerve relieves hypersensitivity, a pain-like behavior. The treatment also decreases inflammation associated with this chronic constriction injury (Janjic et al, 2018; Saleem et al, 2019b; Stevens et al, 2019). In this …


The Role Of Acute And Chronic Neuroinflammation In Depression: Uncovering The Relationship Between Histamine And Serotonin Transmission, Melinda Hersey Apr 2020

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) …


Electrochemical Detection Of Reactive Oxygen Species Via A Platinum Microelectrode Array, Victor M. Carriere Jr. Jan 2020

Electrochemical Detection Of Reactive Oxygen Species Via A Platinum Microelectrode Array, Victor M. Carriere Jr.

Master's Theses

Oxidative stress, an excess of endogenous or exogenous reactive oxygen species (ROS) in the body, is closely aligned with inflammatory responses. ROS such as hydrogen peroxide, superoxide, and radical hydroxyl ion serve essential functions in fighting infection, but chronic elevation of these species irreversibly damages cellular components. Given the central role of inflammation in a variety of diseases, including Alzheimer’s Disease, atherosclerosis, and rheumatoid arthritis, a low-cost, extracellular, non-invasive assay of ROS is needed.

This work reports the use of a platinum microelectrode array (Pt MEA)-based ceramic probe to detect time- and concentration-dependent variations in hydrogen peroxide (H2O2) production by …


The Impact Of Aging And Mechanical Injury On Alveolar Epithelial And Macrophage Responses In Acute Lung Injury And Inflammation, Michael S. Valentine Jan 2020

The Impact Of Aging And Mechanical Injury On Alveolar Epithelial And Macrophage Responses In Acute Lung Injury And Inflammation, Michael S. Valentine

Theses and Dissertations

Patients with severe lung pathologies, such as Acute Respiratory Distress Syndrome (ARDS), often require mechanical ventilation as a clinical intervention; however, this procedure frequently exacerbates the original pulmonary issue and produces an exaggerated inflammatory response that potentially leads to sepsis, multisystem organ failure, and mortality. This acute lung injury (ALI) condition has been termed Ventilator-Induced Lung Injury (VILI). Alveolar overdistension, cyclic atelectasis, and biotrauma are the primary injury mechanisms in VILI that lead to the loss of alveolar barrier integrity and pulmonary inflammation. Stress and strains during mechanical ventilation are believed to initiate alveolar epithelial mechanotransduction signaling mechanisms that contribute …


Scaffold Design Considerations For Soft Tissue Regeneration, Madeleine M. Di Gregorio Aug 2019

Scaffold Design Considerations For Soft Tissue Regeneration, Madeleine M. Di Gregorio

Electronic Thesis and Dissertation Repository

Tissue engineering has emerged as a promising strategy for the replacement of degenerating or damaged tissues in vivo. Also known as regenerative medicine, integral to this therapeutic strategy is biomimetic scaffolds and the biomaterial structural components used to form them. In this study, three different biomaterial scaffolds for tissue engineering applications were fabricated: three-dimensional reverse embedded collagen scaffolds, polymer fusion printed polycaprolactone (PCL) scaffolds, and electrospun gelatin scaffolds. Three-dimensional collagen and PCL scaffolds promoted human adipose-derived stem/stromal cell (ASC) spreading, proliferation, and fibronectin deposition in vitro. Secondly, this study investigated the efficacy of exogenous galectin-3 delivery as a …


Effect Of Physical Stimuli On Angiogenic Factor Expression In Retinal Pigment Epithelial Cells, Farhad Farjood May 2019

Effect Of Physical Stimuli On Angiogenic Factor Expression In Retinal Pigment Epithelial Cells, Farhad Farjood

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

Age-related macular degeneration (AMD) is a major cause of blindness in adults. Abnormal growth of blood vessels in the eye during the course of AMD causes damage to the retina, resulting in irreversible blindness. The goal of this research was to determine whether physical pressure on retinal cells can contribute to the increased blood vessel formation. To replicate the tears in the cell layers, a micropatterning method was used as a means of detaching cells from each other. Two new devices were also developed to mimic slow and fast increases in mechanical pressure on cell layers of the eye. After …


Volumetric Muscle Loss: The Role Of Physical Activity And Autologous Repair On Force Recovery And Signaling Pathways, Richard Perry May 2019

Volumetric Muscle Loss: The Role Of Physical Activity And Autologous Repair On Force Recovery And Signaling Pathways, Richard Perry

Graduate Theses and Dissertations

Volumetric muscle loss affects both military and civilian persons. The hallmark of this injury is incomplete muscle regeneration, excessive fibrosis, and chronic inflammatory signaling resulting in permanent functional loss. Since permanent functional loss drastically reduces quality of life, many studies have been conducted to improve force recovery. Current scientific literature considers a repair strategy of either devitalized scaffolds infused with growth factors or viable tissue plus activating factors to be the more promising interventions for optimal force recovery. PURPOSE The purpose of this study is to incorporate autologous repair and physical activity and observe the effects of muscle force recovery …


A Pilot Study Identifying Brain-Targeting Adaptive Immunity In Pediatric Extracorporeal Membrane Oxygenation Patients With Acquired Brain Injury, Sterling B. Ortega, Poornima Pandiyan, Jana Windsor, Vanessa O. Torres, Uma M. Selvaraj, Amy Lee, Michael Morriss, Fenghua Tian, Lakshmi Raman, Ann M. Stowe Mar 2019

A Pilot Study Identifying Brain-Targeting Adaptive Immunity In Pediatric Extracorporeal Membrane Oxygenation Patients With Acquired Brain Injury, Sterling B. Ortega, Poornima Pandiyan, Jana Windsor, Vanessa O. Torres, Uma M. Selvaraj, Amy Lee, Michael Morriss, Fenghua Tian, Lakshmi Raman, Ann M. Stowe

Neurology Faculty Publications

OBJECTIVES: Extracorporeal membrane oxygenation provides short-term cardiopulmonary life support, but is associated with peripheral innate inflammation, disruptions in cerebral autoregulation, and acquired brain injury. We tested the hypothesis that extracorporeal membrane oxygenation also induces CNS-directed adaptive immune responses which may exacerbate extracorporeal membrane oxygenation-associated brain injury.

DESIGN: A single center prospective observational study.

SETTING: Pediatric and cardiac ICUs at a single tertiary care, academic center.

PATIENTS: Twenty pediatric extracorporeal membrane oxygenation patients (0-14 yr; 13 females, 7 males) and five nonextracorporeal membrane oxygenation Pediatric Logistic Organ Dysfunction score matched patients.

INTERVENTIONS: None.

MEASUREMENTS AND MAIN RESULTS: Venous blood samples were …


Cardiac Regenerative Medicine: Insights From Healthy And Diseased Engineered Tissues, Pamela Grace Hitscherich Dec 2018

Cardiac Regenerative Medicine: Insights From Healthy And Diseased Engineered Tissues, Pamela Grace Hitscherich

Dissertations

Cardiovascular disease remains the leading cause of mortality in the United States. Current tissue engineering approaches have fallen short of promoting fully functional cardiovascular cells and the post-myocardial infarction microenvironment is still not well understood. These gaps in knowledge are addressed in this dissertation through the development of in vitro engineered cardiac tissues using electroactive materials to enhance the differentiation of pluripotent stem cell derived cardiomyocytes and through the development of in vitro myocardial inflammation models dedicated to understanding cardiomyocytes and macrophages interactions.

Specifically, piezoelectric poly (vinylidene fluoride-trifluoroethylene) (PVDF-TrFE) supports the attachment and survival of mouse embryonic stem cell derived …


Decellularized Matrices Effect On The Adaptive Immune Response, Kegan Sowers Jan 2018

Decellularized Matrices Effect On The Adaptive Immune Response, Kegan Sowers

Theses and Dissertations

Decellularized extracellular matrices have been a growing area of interest in the biomedical engineering fields of tissue engineering and regenerative medicine.As these materials move toward clinical applications, the immune response to these materials will be a driving force toward their success in clinical approaches. Fully digested decellularized matrix constructs derived from porcine liver, muscle and lung were created to test the adaptive immune response. Hydrogel characterization ensured that the materials had relatively similar stiffness levels to reduce variability, and in vitro studies were conducted. Each individual construct as well as a gelatin control were plated with a co-culture of macrophages …


Delivery Of Antioxidant And Anti-Inflammatory Agents For Tissue Engineered Vascular Grafts, Kenyatta S. Washington, Chris A. Bashur Sep 2017

Delivery Of Antioxidant And Anti-Inflammatory Agents For Tissue Engineered Vascular Grafts, Kenyatta S. Washington, Chris A. Bashur

Biomedical Engineering and Sciences Faculty Publications

The treatment of patients with severe coronary and peripheral artery disease represents a significant clinical need, especially for those patients that require a bypass graft and do not have viable veins for autologous grafting. Tissue engineering is being investigated to generate an alternative graft. While tissue engineering requires surgical intervention, the release of pharmacological agents is also an important part of many tissue engineering strategies. Delivery of these agents offers the potential to overcome the major concerns for graft patency and viability. These concerns are related to an extended inflammatory response and its impact on vascular cells such as endothelial …


Design And Validation Of Delivery Systems For Galectin-3 For Skin Healing Applications, Karrington A. Mcleod May 2017

Design And Validation Of Delivery Systems For Galectin-3 For Skin Healing Applications, Karrington A. Mcleod

Electronic Thesis and Dissertation Repository

Chronic wounds present a significant burden to patients, causing pain, impairing limb function, and often resulting in the need for amputation. Treatment of chronic dermal wounds is challenging, with current therapies showing limited efficacy in clinical trials. As galectin-3 has been implicated in several wound healing processes, its efficacy as a therapeutic in skin healing was investigated in this study. An electrospun gelatin scaffold loaded with galectin-3 was developed as a delivery system. The influence of human recombinant galectin-3 in skin healing, when delivered topically and using an electrospun scaffold, was then investigated in wild type and diabetic mice. Electrospun …


Human Igg1 Antibodies Suppress Angiogenesis In A Target-Independent Manner, Sasha Bogdanovich, Younghee Kim, Takeshi Mizutani, Reo Yasuma, Laura Tudisco, Valeria Cicatiello, Ana Bastos-Carvalho, Nagaraj Kerur, Yoshio Hirano, Judit Z. Baffi, Valeria Tarallo, Shengjian Li, Tetsuhiro Yasuma, Parthasarathy Arpitha, Benjamin James Fowler, Charles B. Wright, Ivana Apicella, Adelaide Greco, Arturo Brunetti, Menotti Ruvo, Annamaria Sandomenico, Miho Nozaki, Ryo Ijima, Hiroki Kaneko, Yuichiro Ogura, Hiroko Terasaki, Balamurali K. Ambati, Jeanette H. W. Leusen, Wallace Y. Langdon, Michael R. Clark, Bradley D. Gelfand, Jayakrishna Ambati Jan 2016

Human Igg1 Antibodies Suppress Angiogenesis In A Target-Independent Manner, Sasha Bogdanovich, Younghee Kim, Takeshi Mizutani, Reo Yasuma, Laura Tudisco, Valeria Cicatiello, Ana Bastos-Carvalho, Nagaraj Kerur, Yoshio Hirano, Judit Z. Baffi, Valeria Tarallo, Shengjian Li, Tetsuhiro Yasuma, Parthasarathy Arpitha, Benjamin James Fowler, Charles B. Wright, Ivana Apicella, Adelaide Greco, Arturo Brunetti, Menotti Ruvo, Annamaria Sandomenico, Miho Nozaki, Ryo Ijima, Hiroki Kaneko, Yuichiro Ogura, Hiroko Terasaki, Balamurali K. Ambati, Jeanette H. W. Leusen, Wallace Y. Langdon, Michael R. Clark, Bradley D. Gelfand, Jayakrishna Ambati

Ophthalmology and Visual Science Faculty Publications

Aberrant angiogenesis is implicated in diseases affecting nearly 10% of the world’s population. The most widely used anti-angiogenic drug is bevacizumab, a humanized IgG1 monoclonal antibody that targets human VEGFA. Although bevacizumab does not recognize mouse Vegfa, it inhibits angiogenesis in mice. Here we show bevacizumab suppressed angiogenesis in three mouse models not via Vegfa blockade but rather Fc-mediated signaling through FcγRI (CD64) and c-Cbl, impairing macrophage migration. Other approved humanized or human IgG1 antibodies without mouse targets (adalimumab, alemtuzumab, ofatumumab, omalizumab, palivizumab and tocilizumab), mouse IgG2a, and overexpression of human IgG1-Fc or mouse IgG2a-Fc, also inhibited angiogenesis in wild-type …


The Rheological Impact Of Cell Activation On The Flow Behavior Of Neutrophils, Nolan M. Horrall Jan 2016

The Rheological Impact Of Cell Activation On The Flow Behavior Of Neutrophils, Nolan M. Horrall

Theses and Dissertations--Biomedical Engineering

Previously, it was reported that the morphological changes (pseudopod projection) that circulating neutrophils adopt due to cell activation raises peripheral vascular resistance by disrupting microvascular rheology. Studies utilized murine muscle preparations to link neutrophil pseudopod formation to cell activation and a viscous impact on hemodynamic resistance. But because of the complexity associated with the organization of the vasculature and microvasculature in tissues, it was unclear whether the effects of neutrophil activation on hemodynamic resistance were associated with the macro-/micro- circulation. This research describes an in vitro analysis using viscometry and microvascular network mimics (microporous membranes) to assess the rheological impact …