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Full-Text Articles in Biomedical Engineering and Bioengineering

Comparison Of In-Vitro 3d Human Embryoids With Current Models For Gastrulation, Jin Park Jan 2023

Comparison Of In-Vitro 3d Human Embryoids With Current Models For Gastrulation, Jin Park

McKelvey School of Engineering Theses & Dissertations

Gastrulation is an early morphogenetic process that is conserved across most metazoans and lays out the future body plan through the formation and shaping of the three germ layers: endoderm, mesoderm, and ectoderm. Despite its importance, not much is known about the events surrounding human gastrulation that occurs in utero due to ethical and technical limitations on studying human embryos. Therefore, many researchers have devised protocols for creating in vitro models of gastrulation using embryonic stem cells. Initially starting with mouse embryonic stem cells, the field of in vitro embryo models has advanced rapidly, with protocols using human embryonic stem …


Human Ipsc Tissue-Engineered Cartilage For Disease Modeling Of Skeletal Dysplasia-Causing Trpv4 Mutations, Amanda R. Dicks Aug 2021

Human Ipsc Tissue-Engineered Cartilage For Disease Modeling Of Skeletal Dysplasia-Causing Trpv4 Mutations, Amanda R. Dicks

McKelvey School of Engineering Theses & Dissertations

Cartilage is essential to joint development and function. However, there is a variety of cartilage diseases, ranging from developmental (e.g., skeletal dysplasias) to degenerative (e.g., arthritis), in which treatments and therapeutics are lacking. For example, specific point mutations in the ion channel transient receptor potential vanilloid 4 (TRPV4) prevent proper joint development, leading to mild brachyolmia and severe, neonatally lethal metatropic dysplasia. Tissue-engineered cartilage offers an opportunity to elucidate the underlying mechanisms of these cartilage diseases for the development of treatments. Human induced pluripotent stem cells (hiPSCs) are an improved cell source option for cartilage tissue engineering given their minimal …


Synthetic Gene Circuits For Self-Regulating And Temporal Delivery Of Anti-Inflammatory Biologic Drugs In Engineered Tissues, Lara Pferdehirt May 2021

Synthetic Gene Circuits For Self-Regulating And Temporal Delivery Of Anti-Inflammatory Biologic Drugs In Engineered Tissues, Lara Pferdehirt

McKelvey School of Engineering Theses & Dissertations

The recent advances in the fields of synthetic biology and genome engineering open up new possibilities for creating cell-based therapies. We combined these tools to target repair of articular cartilage, a tissue that lacks a natural ability to regenerate, in the presence of arthritic diseases. To this end, we developed cell-based therapies that harness disease pathways and the unique properties of articular cartilage for prescribed, localized, and controlled delivery of biologics, creating the next generation of cell therapies and new classes of synthetic circuits. We created tissue engineered cartilage from murine induced pluripotent stem cells that had the ability to …


Differentiating Human Embryonic Stem Cells In Micropatterns To Study Cell Fate Specification And Morphogenetic Events During Gastrulation, Kyaw Thu Minn Jan 2021

Differentiating Human Embryonic Stem Cells In Micropatterns To Study Cell Fate Specification And Morphogenetic Events During Gastrulation, Kyaw Thu Minn

McKelvey School of Engineering Theses & Dissertations

During mammalian embryogenesis, the first major lineage segregation occurs when embryonic epiblast, and extraembryonic trophectoderm and hypoblast arise in the blastocyst. In the next fundamental and conserved phase of animal embryogenesis known as gastrulation, extraembryonic cells provide signals to epiblast to instruct embryonic patterning, and epiblast gives rise to germ layers ectoderm, mesoderm, and endoderm, that will establish all embryonic tissues. Proper specification and morphogenesis of germ layers during gastrulation is vital for correct embryonic development. Due to ethical and legal restrictions limiting human embryo studies, human gastrulation is poorly understood. Our knowledge of human gastrulation has largely been derived …


Mechanosensitive Epithelial Cell Scattering And Migration On Layered Matrices, Christopher Michael Walter Aug 2019

Mechanosensitive Epithelial Cell Scattering And Migration On Layered Matrices, Christopher Michael Walter

McKelvey School of Engineering Theses & Dissertations

Epithelial cells form multi-layered tissue scaffolding that makes up every organ in the body. Along with epithelial cells, the basement membrane (BM) and connective tissue are composed of various proteins that sculpt the organs and protect them from foreign macromolecules. Epithelial cells respond to various cues, both chemical and mechanical, from their surrounding matrices to aid in maintenance and repair of these layers through degradation and deposition of extracellular matrix (ECM) proteins. In cancer progression, epithelial cells lose their normal function of supporting tissue structure and instead adopt more aggressive behaviors through an epithelial-to-mesenchymal transition (EMT) of their cellular traits. …


Binding Affinity And Specificity Of Sh2 Domain Interactions In Receptor Tyrosine Kinase Signaling Networks, Tom Ronan Dec 2017

Binding Affinity And Specificity Of Sh2 Domain Interactions In Receptor Tyrosine Kinase Signaling Networks, Tom Ronan

McKelvey School of Engineering Theses & Dissertations

Receptor tyrosine kinase (RTK) signaling mechanisms play a central role in intracellular signaling and control development of multicellular organisms, cell growth, cell migration, and programmed cell death. Dysregulation of these signaling mechanisms results in defects of development and diseases such as cancer. Control of this network relies on the specificity and selectivity of Src Homology 2 (SH2) domain interactions with phosphorylated target peptides. In this work, we review and identify the limitations of current quantitative understanding of SH2 domain interactions, and identify severe limitations in accuracy and availability of SH2 domain interaction data. We propose a framework to address some …