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Articles 31 - 58 of 58
Full-Text Articles in Molecular, Cellular, and Tissue Engineering
Higher Tensile Forces Across Cellular Junctions And An Intact Nuclear Linc Complex Is Required For Epithelial Function And Stability, Fnu Vani Narayanan
Higher Tensile Forces Across Cellular Junctions And An Intact Nuclear Linc Complex Is Required For Epithelial Function And Stability, Fnu Vani Narayanan
Theses and Dissertations
Recent advances in three-dimensional (3D) cell culture systems have provided key insights into the understanding of biochemical and physiological states of native tissue. A significant progress in the field of mechanobiology involves measuring cellular traction forces in a more native 3D environment. However, the effects of mechanical forces exerted across cellular junctions and the nuclear LINC complex, in an organized 3D system has not been investigated thus far. Epithelial cells spontaneously form acini (also known as cysts or spheroids) with a single, fluid-filled central lumen, when grown in 3D matrices. The size of the lumen is dependent on apical secretion …
The Impact Of Aging And Mechanical Injury On Alveolar Epithelial And Macrophage Responses In Acute Lung Injury And Inflammation, Michael S. Valentine
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 …
Designing Biomimetic Implant Surfaces To Promote Osseointegration Under Osteoporotic Conditions By Revitalizing Mechanisms Coupling Bone Resorption To Formation, Ethan M. Lotz
Theses and Dissertations
In cases of compromised bone remodeling like osteoporosis, insufficient osseointegration occurs and results in implant failure. Implant retention relies on proper secondary fixation, which is developed during bone remodeling. This process is disrupted in metastatic bone diseases like osteoporosis. Osteoporosis is characterized low bone mass and bone strength resulting from either accelerated osteoclast-mediated bone resorption or impaired osteoblast-mediated bone formation. These two processes are not independent phenomena. In fact, osteoporosis can be viewed as a breakdown of the cellular communication connecting bone resorption to bone formation. Because bone remodeling occurs at temporally generated specific anatomical sites and at different times, …
Cell Type And Substrate Dependence Of Fibronectin Properties And Mechanotransduction, Navpreet S. Saini
Cell Type And Substrate Dependence Of Fibronectin Properties And Mechanotransduction, Navpreet S. Saini
Theses and Dissertations
Fibronectin is an important protein that is able to bind to other fibronectin molecules and to cell surface receptors. In doing so, the interactions fibronectin can perform is important for the processes of cell migration and tissue formation. Understanding the properties of fibronectin and fibril assembly is useful for areas such as wound healing, where fibronectin molecules are assembled to protect the tissue and to perform other tasks. Because of these reasons, it is important to understand how fibronectin is assembled and how its properties affect the fibril assembly, which in return affects the way the cell matrix operates. Previously …
The Role Of The Mechanical Environment On Cd117+ Endothelial Cell Angiogenesis, Patrick Link
The Role Of The Mechanical Environment On Cd117+ Endothelial Cell Angiogenesis, Patrick Link
Theses and Dissertations
Angiogenesis is a complex process coordinating cell migration, proliferation, and lumen formation. Changes to the microenvironment regulate angiogenesis through mechanotransduction and cytokine signals. In pulmonary hypertension, something in the process becomes abnormal, resulting in changes to the microenvironment and the formation of a glomerulus of dysfunctional capillaries, called a plexiform lesion. Endothelial cells, expressing CD117 (CD117+ EC clones) increase in the plexiform lesions of pulmonary hypertension, independent of pro-angiogenic VEGF signaling. We hypothesize that the mechanical environment and the macromolecular composition of the extracellular matrix, both, contribute to the aberrant angiogenesis. When we changed the mechanical environment, we changed the …
Engineering The Alveolar Gas Exchange Barrier With Extracellular Matrix Coatings For Bioengineered Lungs, Bethany M. Young
Engineering The Alveolar Gas Exchange Barrier With Extracellular Matrix Coatings For Bioengineered Lungs, Bethany M. Young
Theses and Dissertations
Lower respiratory diseases are currently the third leading cause of death worldwide. For many end-stage patients with these diseases, there is no cure and a shortage of donor organs available for transplant. A promising solution is to design regenerative scaffolds or complete bioengineered lungs, using decellularized lung tissues as a template for regeneration. Recent advances in the field have made significant strides towards developing a transplantable lung. However, the current technology has not produced a functional lung for in vivo transplant due to immature gas exchange barriers. The mechanisms driving alveolar barrier maturation and role that extracellular matrix (ECM) plays …
Eralpha Isoforms Modulate The Tumorigenicity Of 24r,25(Oh)2d3 In Estrogen-Responsive Cancer, Anjali Verma
Eralpha Isoforms Modulate The Tumorigenicity Of 24r,25(Oh)2d3 In Estrogen-Responsive Cancer, Anjali Verma
Theses and Dissertations
Over 200,000 cases of breast cancer are diagnosed every year. Nearly 20% of these patients supplement their diets with some form of vitamin D. This high frequency of vitamin D supplement use may be due in part to research suggesting that cancer patients with higher serum vitamin D3 levels have better prognoses than patients with low serum vitamin D3. However, double-blind clinical trials on the efficacy of vitamin D3 supplementation in breast cancer have been inconclusive. A recent meta-analysis showed evidence of reduced cancer recurrence in patients taking vitamin D3 supplements who had ‘estrogen receptor positive’ …
Mechanochemical Regulation Of Epithelial Tissue Remodeling: A Multiscale Computational Model Of The Epithelial-Mesenchymal Transition Program, Lewis Scott
Theses and Dissertations
Epithelial-mesenchymal transition (EMT) regulates the cellular processes of migration, growth, and proliferation - as well as the collective cellular process of tissue remodeling - in response to mechanical and chemical stimuli in the cellular microenvironment. Cells of the epithelium form cell-cell junctions with adjacent cells to function as a barrier between the body and its environment. By distributing localized stress throughout the tissue, this mechanical coupling between cells maintains tensional homeostasis in epithelial tissue structures and provides positional information for regulating cellular processes. Whereas in vitro and in vivo models fail to capture the complex interconnectedness of EMT-associated signaling networks, …
Exogenous Fniii 12-14 Regulates Tgf-Β1-Induced Markers, Hilmi M. Humeid
Exogenous Fniii 12-14 Regulates Tgf-Β1-Induced Markers, Hilmi M. Humeid
Theses and Dissertations
The extracellular matrix protein Fibronectin (FN) plays an important role in cell contractility, differentiation, growth, adhesion, and migration. The 12th -14th Type III repeats of FN (FNIII 12-14), also referred to as the Heparin-II domain, comprise a highly promiscuous growth factor (GF) binding region. This binding domain aids in cellular signaling initiated from the ECM. Additionally, FN has the ability to assemble into fibrils under certain conditions, mostly observed during cell contractile processes such as those that initiate due to upregulation of Transforming Growth Factor Beta 1 (TGF-β1) [1], [2]. Previous work from our lab has shown that self-assembly of …
Decellularized Matrices Effect On The Adaptive Immune Response, Kegan Sowers
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 …
Mechanical And Material Characterization Of Advanced Materials For Tissue Regeneration, Bailey Kylara Ricketts Jackson
Mechanical And Material Characterization Of Advanced Materials For Tissue Regeneration, Bailey Kylara Ricketts Jackson
Theses and Dissertations
In natural disasters and military deployment operations, injury to long bone can cause extensive damage and be difficult to treat and heal quickly. Explosive devices and trauma often produce long-bone (>2-cm length) wounds that are more complicated than common fractures. Due to the size and complexity of these injuries, they can be difficult to treat in a battlefield environment and take a long time to heal completely and properly. Even after the long healing period, these injuries often require rehabilitation to strengthen the muscles that have weakened in the wounded limb. For military applications especially, these effects can put …
Fibronectin Mechanics And Signaling In Tgf-Β1-Induced Epithelial To Mesenchymal Transition, Lauren Griggs
Fibronectin Mechanics And Signaling In Tgf-Β1-Induced Epithelial To Mesenchymal Transition, Lauren Griggs
Theses and Dissertations
Epithelial to Mesenchymal Transition (EMT) is a dynamic process by which a distinct change in the phenotype and function of epithelial cells render them as mesenchymal cells. Characteristics of mesenchymal cells include the ability to invade, increased migratory kinetics and heightened resistance to apoptosis. Therefore, there is a strong need to fully understand the mechanism for the induction of EMT in pathological conditions such as carcinoma progression. Recent advances highlight two pivotal contributors, soluble growth factor (gf) signals, and mechanical signals, in the process. However, to date, no clear mechanism exists linking the two in epithelial transdifferentiation. Transforming Growth Factor-β1 …
Nuclear Rupture In Progeria Expressing Cells, Kranthidhar Bathula
Nuclear Rupture In Progeria Expressing Cells, Kranthidhar Bathula
Theses and Dissertations
Cells regularly take on various types of force in the body. They have structures that are able to mediate, transfer and respond to the forces. A mutation in force regulating proteins such as lamin in the nucleus or the KASH domain which connects the nucleus to the cytoskeleton of the cell can cause catastrophic events to occur. The aims of this study were to better understand the response of the nucleus when structural proteins are mutated or are not present while under force. Progeria, a rare disease where an additional farnesyl group is attached to lamin was used in this …
Engineering Surface Properties To Modulate Inflammation And Stem Cell Recruitment Through Macrophage Activation, Kelly M. Hotchkiss
Engineering Surface Properties To Modulate Inflammation And Stem Cell Recruitment Through Macrophage Activation, Kelly M. Hotchkiss
Theses and Dissertations
Biomaterials are becoming the most commonly used therapeutic method for treatment of lost or damaged tissue in the body. Metallic materials are chosen for high strength orthopaedic and dental applications. Titanium (Ti) implants are highly successful in young, healthy patients with the ability to fully integrate to surrounding tissue. However the main population requiring these corrective treatments will not be healthy or young, therefore further research into material modifications have been started to improve outcomes in compromised patients. The body’s immune system will generate a response to any implanted material, and control the final outcome. Among the first and most …
Modulating The Innate Immune Response To Electrospun Scaffolds And Polymer Degradative Byproducts, Daniel Abebayehu
Modulating The Innate Immune Response To Electrospun Scaffolds And Polymer Degradative Byproducts, Daniel Abebayehu
Theses and Dissertations
Implanted biomaterials often induce inflammation that frequently leads to the foreign body response, fibrosis, and the failure of the implant. Thus, it is important to evaluate how cells interact with materials to promote a more regenerative response. It is critical to determine how to modulate the response of tissue resident innate immune cells, as they are among the first cells to interact with implanted materials. Among tissue resident innate immune cells are mast cells, which are inflammatory sentinels that degranulate and orchestrate the fate of other cell populations, such as monocytes/macrophages and lymphocytes. Mast cells have also been reported to …
Development Of An Electrospun And 3d Printed Cellular Delivery Device For Dermal Wound Healing, Ryan M. Clohessy
Development Of An Electrospun And 3d Printed Cellular Delivery Device For Dermal Wound Healing, Ryan M. Clohessy
Theses and Dissertations
The goal of this research was to develop a system of individualized medicine that could be applied to dermal wounds serving as a wound dressing and synthetic extracellular matrix while delivering stem cells to the wound bed. First, fabrication parameters for electrospinning polymer fibers were determined. This involved evaluating fiber morphology with respect to polymer selection and solution concentration. Next, construct fabrication was examined to produce an integrated void space, or cargo area, suitable to maintain stem cells. In vitro studies to ensure stem cell viability and phenotype were conducted, and results supported the notion that cells could be administered …
Development And Validation Of A Novel Resonant Energy Transfer (Fret) Biosensor To Measure Tensile Forces At The Linc Complex In Live Cells, Paul Arsenovic
Development And Validation Of A Novel Resonant Energy Transfer (Fret) Biosensor To Measure Tensile Forces At The Linc Complex In Live Cells, Paul Arsenovic
Theses and Dissertations
There is a large body of evidence supporting the theory that cell physiology largely depends on the mechanical properties of its surroundings or micro-environment. More recently studies have shown that changes to intra-cellular mechanical properties can also have a meaningful impact on cell function and in some cases lead to the progression of ailments or disease. For example, small changes to the protein sequence of a structural nuclear envelope protein called lamin-A is known to cause a variety of neurological and musculoskeletal diseases referred to as laminopathies. Currently, there is little incite into how these mutations lead to disease progression …
Role Of E-Cadherin Force In The Spatial Regulation Of Cell Proliferation, Abhinav Mohan
Role Of E-Cadherin Force In The Spatial Regulation Of Cell Proliferation, Abhinav Mohan
Theses and Dissertations
Cell proliferation and contact inhibition play a major role in maintaining epithelial cell homeostasis. A hallmark of epithelial cells is strong cell-cell junctions. These junctions include E-Cadherin, a type of adherens junction that is critical for both barrier function and contact inhibition. Prior experiments by other groups have shown that adherens junctions are subject to mechanical tension. Externally applied forces (e.g. stretch) results in changes in E-Cadherin forces that coordinate proliferation. My current work tests the hypothesis that E-Cadherin forces mediate the spatial regulation of cell proliferation even in the absence of externally applied forces.
The Role Of E-Cadherin Force In The Maintenance Of Homeostasis In Epithelial Acini, Fnu Vani Narayanan
The Role Of E-Cadherin Force In The Maintenance Of Homeostasis In Epithelial Acini, Fnu Vani Narayanan
Theses and Dissertations
Numerous three-dimensional model systems have emerged for emulating the biochemical and physiological states of native tissue. Yet little is known about the effects of mechanical forces on cell behavior in the context of an organized tissue structure in three-dimensional cell-culture. Epithelial cells cultured in a three-dimensional environment comprised of extracellular matrix proteins form spheroids of polarized cells. Cellular responses to mechanical cues, generated from dynamic interactions with the extracellular matrix and neighboring cells, are known to influence cellular behavior to a great extent. Previous studies have shown that tumorigenic progression has been frequently linked to the down regulation of E-cadherin, …
Novel Small Airway Model Using Electrospun Decellularized Lung Extracellular Matrix, Bethany M. Young
Novel Small Airway Model Using Electrospun Decellularized Lung Extracellular Matrix, Bethany M. Young
Theses and Dissertations
Chronic respiratory diseases affects many people worldwide with little known about the mechanisms diving the pathology, making it difficult to find a cure. Improving the understanding of smooth muscle and extracellular matrix (ECM) interaction is key to developing a remedy to this leading cause of death. With currently no relevant or controllable in vivo or in vitro model to investigate diseased and normal interactions of small airway components, the development of a physiologically relevant in vitro model with comparable cell attachment, signaling, and organization is necessary to develop new treatments for airway disease. The goal of this study is to …
Characterization Of Poly(Dimethylsiloxane) Blends And Fabrication Of Soft Micropillar Arrays For Force Detection, Thomas J. Petet Jr
Characterization Of Poly(Dimethylsiloxane) Blends And Fabrication Of Soft Micropillar Arrays For Force Detection, Thomas J. Petet Jr
Theses and Dissertations
Diseases involving fibrosis cause tens of thousands of deaths per year in the US alone. These diseases are characterized by a large amount of extracellular matrix, causing stiff abnormal tissues that may not function correctly. To take steps towards curing these diseases, a fundamental understanding of how cells interact with their substrate and how mechanical forces alter signaling pathways is vital. Studying the mechanobiology of cells and the interaction between a cell and its extracellular matrix can help explain the mechanisms behind stem cell differentiation, cell migration, and metastasis. Due to the correlation between force, extracellular matrix assembly, and substrate …
Primary Cilia Mechanotransduction And Microtubule Stability In Mechanically Stretched Lung Adenocarcinoma Cells, Monika Rassi Radhika
Primary Cilia Mechanotransduction And Microtubule Stability In Mechanically Stretched Lung Adenocarcinoma Cells, Monika Rassi Radhika
Theses and Dissertations
The objective of this study is to investigate the role of microtubule based organelle, the primary cilia in lung adenocarcinoma by i) Quantifying the presence of primary cilia in several Non Small Cell Lung Cancer (NSCLC) cell lines in response to mechanical stimuli, ii) Attempting to determine the role of primary cilia in cell migration, iii) Investigating the effects of Paclitaxel(Taxol) resistance in lung cancer cells, iv) Analyzing the response of lung cancer cells to Smoothened Inhibitors and v) Determining the effects of Transforming Growth Factor Beta-1(TGF-β1) induced Epithelial to Mesenchymal Transition(EMT) in lung cancer cells. To ascertain the effects …
Ex Vivo Dna Cloning, Adam B. Fisher
Ex Vivo Dna Cloning, Adam B. Fisher
Theses and Dissertations
Genetic engineering of microbes has developed rapidly along with our ability to synthesize DNA de novo. Yet, even with decreasing DNA synthesis costs there remains a need for inexpensive, rapid and reliable methods for assembling synthetic DNA into larger constructs or combinatorial libraries. While technological advances have resulted in powerful techniques for in vitro and in vivo assembly of DNA, each suffers inherent disadvantages. Here, an ex vivo DNA cloning suite using crude cellular lysates derived from E. coli is demonstrated to amplify and assemble DNA containing small sequence homologies. Further, the advantages of an ex vivo approach are …
Automating The Process Of Fabricating Uniform-Sized Cell Spheroids For Three-Dimensional Bioprinting, Ganesh Sosale
Automating The Process Of Fabricating Uniform-Sized Cell Spheroids For Three-Dimensional Bioprinting, Ganesh Sosale
Theses and Dissertations
Although researchers have been able to print small, simple, and avascular tissues, they have been unsuccessful in creating large, complex and vascularized organs. Printing large and complex three-dimensional tissues or organs involves utilizing a large quantity of cellular spheroids and layer-by-layer addition of spheroids. In this study, an in-house cell spheroid fabrication system was developed to produce cell spheroids with human liver cells (hepG2), human endothelial cells (hEC), human neural stem cells (hNSC), and induced pluripotent stem cells (iPSC). It offers the ability of fabricating uniform-sized spheroids repeatedly, which is essential when large and complex structures need to be produced. …
Analysis And Modeling Of The Roles Of Actin-Myosin Interactions In Bladder Smooth Muscle Biomechanics, Seyed Omid Komariza
Analysis And Modeling Of The Roles Of Actin-Myosin Interactions In Bladder Smooth Muscle Biomechanics, Seyed Omid Komariza
Theses and Dissertations
Muscle mechanical behavior potentially plays an important role in some of the most common bladder disorders. These include overactive bladder, which can involve involuntary contractions during bladder filling, and impaired contractility or underactive bladder, which may involve weak or incomplete contractions during voiding. Actin-myosin cross-bridges in detrusor smooth muscle (DSM) are responsible for contracting and emptying the bladder. The total tension produced by muscle is the sum of its preload and active tensions. Studies suggest that actin-myosin cross-links are involved in adjustable preload stiffness (APS), which is characterized by a preload tension curve that can be shifted along the length …
Tissue Engineering Scaffold Fabrication And Processing Techniques To Improve Cellular Infiltration, Casey Grey
Tissue Engineering Scaffold Fabrication And Processing Techniques To Improve Cellular Infiltration, Casey Grey
Theses and Dissertations
Electrospinning is a technique used to generate scaffolds composed of nano- to micron-sized fibers for use in tissue engineering. This technology possesses several key weaknesses that prevent it from adoption into the clinical treatment regime. One major weakness is the lack of porosity exhibited in most electrospun scaffolds, preventing cellular infiltration and thus hosts tissue integration. Another weakness seen in the field is the inability to physically cut electrospun scaffolds in the frontal plane for subsequent microscopic analysis (current electrospun scaffold analysis is limited to sectioning in the cross-sectional plane). Given this it becomes extremely difficult to associate spatial scaffold …
Synthetic Polymeric Carbohydrates Recognized Toxoplasma Gondii Tachyzoites And Induced Early Phagocytosis By Macrophages, Souzan Hussain Eassa
Synthetic Polymeric Carbohydrates Recognized Toxoplasma Gondii Tachyzoites And Induced Early Phagocytosis By Macrophages, Souzan Hussain Eassa
Theses and Dissertations
Toxoplasmosis is a parasitic disease caused by the intracellular protozoan Toxoplasma gondii your words (T. gondii your words) that affects most types of warm-blooded vertebrate cells. Up to one third of the humans population in the world is chronically infected by this parasite. Human and animals at risk for toxoplasmosis include fetuses, newborns, and immunologically impaired patients. To date, there is no vaccine available and no drug has a successful effective against chronic form of toxoplasmosis. Recent Toxoplasma your words diagnostic methods showed high false positive results and cannot detect the parasite in the early infection stage. Early diagnosis of …
Biomolecular Mechanisms And Functional Characterization Of Nanomaterials In Programmed Cancer Cell Death For Potential Applications In Medicine, Biomedical Sciences, And Bioengineering, Md. Zakir Hossain
Theses and Dissertations
Cancer bionanotechnology is an interdisciplinary area of research in applied biosciences, biomedical engineering, and nano-medicine. Currently, apoptotic cell death inducers and regulators are considered to have significant potential for cancer therapy. The ability to escape apoptosis is one of the key properties of human cancer. Pancreatic cancer that has the highest fatality rates of all cancers is prompt to evade apoptosis. Nanomaterials like Ni NWs have various novel properties that could be very useful in bio-medical applications at the molecular and cellular levels. The overall objective of this research was to investigate the antiproliferative and apoptogenic properties of Ni NWs …