Molecular, Cellular, and Tissue Engineering Commons^™

In Vitro Microfluidics System For Mechanobiologic Investigations, Michael A. Daanen

Honors Theses

Mechanobiology is an emerging field that aims to study the relationships between mechanical forces and cellular behavior. Such mechanobiological relationships are especially critical in the cardiovascular system, where endothelial cells lining the vasculature align in response to fluid shear stresses from blood flow (Sinha, 2016). Implanted flow devices, diabetes, chronic hypertension, and various other diseases and pathophysiologies alter vessel geometries and flow dynamics. Such alterations impact fluid shear stress and endothelial cell behavior, leading to microcirculatory dysfunction, vessel leakage, and organ failure (Poredos, 2021; Papadaki, 1999; Leitschuh, 1987). To simulate dysfunctional endothelial cell behavior in vitro and evaluate novel therapeutic …

Sdf-1Α Mediates Primary Tumor Escape In Glioblastoma Through Activation Of Mesenchymal Transitions, Charles T. Froman-Glover

The Cardinal Edge

Glioblastoma (GBM), a highly aggressive primary brain tumor originating in glial cells, poses a significant challenge due to its rapid growth and invasive nature within healthy brain tissue.

Current treatments involve surgical resection, chemotherapy, and radiation. These treatments alone are not enough to cure this disease, and a better understanding of the mechanics of the tumor's micro-environment is imperative to furthering the field of cancer research. This research focuses on understanding the tumor microenvironment's impact, specifically investigating the role of stromal cell-derived factor 1 (SDF-1) mechanics on GBM aggressiveness. SDF-1 is known to facilitate disease progression by facilitating chemotaxis toward …

Environment And Response Of 3d-Encapsulated Mesenchymal Stem Cells To Mechanical Loading, Augustus Greenwood

McKelvey School of Engineering Graduate Student Theses & Dissertations

This thesis explores the micromechanical environment induced when cyclically compressing hydrogels via finite element modeling and experimentally on the impact of loading on mesenchymal stem cells (MSCs) when encapsulated withing 3D hydrogel matrices. Degenerative joint diseases, characterized by cartilage degradation, present significant challenges due to cartilage's limited self-repair capacity. Innovative approaches, including stem cell-based therapies and engineered biomaterials, have emerged as promising strategies for cartilage repair and regeneration. This work specifically investigates the calibration of a bioreactor, the uniformity of load response across the hydrogel constructs via finite element modeling (FEM), and the stress response of MSCs subjected to various …

Investigating The Regulation Of Epithelial-Mesenchymal Transition Through Fibronectin-Mediated Tgf-Β1 Mechanotransduction Using In Vitro Models Of Triple-Negative Breast Cancer, Michael M. Sofroniou

Theses and Dissertations

TGF-β1 is a potent regulator of epithelial-mesenchymal transtion (EMT), a cellular
transdifferentation process that promotes cellular motility and matrix remodeling, critical to tumorigenesis and metastasis. TGF-β1-induced EMT promotes the assembly of FN, which synergistically binds latent TGF-β1 to aid in its activation. The purpose of of this work is to further probe the effects of autocrine TGF-β1 signaling during EMT progression by utilizing CRISPR-Cas9 deletion of the TGFB1 gene in in vitro models of triple-negative breast cancer. The studies outlined in this work demonstrate that autocrine TGF-β1 maintains a baseline level of mesenchymal marker expression. It also functions to desensitize …

The Sexually Dimorphic Role Of Connexin 43 In Bone Remodeling And Disuse-Induced Bone Loss, Gabriel A. Hoppock

Theses and Dissertations

Bone loss is frequently experienced by individuals undergoing long-term disuse, such as prolonged bedrest, immobilization due to paralysis or injury, and conditions such as spaceflight. Under normal physiological conditions, bone remodeling is balanced by bone-forming osteoblasts and bone-resorbing osteoclasts, and the activity of osteoblasts and osteoclasts is orchestrated by osteocytes. Osteocytes are the most abundant cell type found in bone and ample evidence suggests they are bone’s main mechanosensory cell type. Therefore, understanding osteocyte biology and responses to mechanical signals, or lack thereof during unloading, may lead to new therapeutic targets to combat bone loss during disuse. Previous data has …

Design, Development, And Validation Of A Perfusion-Compression Bioreactor To Study Osteogenesis In Bone Explants, Alexis Victoria Graham

Theses and Dissertations

The current gold standard treatment for bone defects is autologous cancellous bone graft, which involves increased surgery time and donor site morbidity, and limited supply of bone and cells for regeneration. Bioreactors may aid in the generation of mechanically conditioned bone grafts with more cells compared to traditional grafts. However, the specific parameters of fluid flow and mechanical loading which contribute to osteogenesis and cell viability in bioreactors are not fully characterized. Here, a perfusion-compression bioreactor system was developed to study osteogenesis in porcine trabecular bone explants. Loading accuracy was over 88% across six bioreactors at a 0.1 s-1 strain …

A Magneto-Rheological Platform To Dynamically Control Afterload In Engineered Micro Heart Muscles, David Schuftan

McKelvey School of Engineering Graduate Student Theses & Dissertations

Cardiovascular disease is the leading cause of death is the United States, accounting for nearly 1 in 5 deaths. Many types of cardiovascular disease are linked to the mechanical forces placed on the heart. However, how these mechanical forces exactly affect the cellular biology of the heart is not well defined. In vitro models using cardiomyocytes derived from human induced pluripotent stem cells enable researchers to develop medium throughput systems to study cardiac mechanobiology at the cellular level. Previous models have been developed to enable the study of mechanical forces such as cardiac afterload. However, most of these models require …

A Single Cell Pair Mechanical Interrogation Platform To Study Cell–Cell Adhesion Mechanics, Amir Monemianesfahani

Department of Mechanical and Materials Engineering: Dissertations, Theses, and Student Research

Cell-cell adhesion complexes are macromolecular adhesive organelles that integrate cells into tissues. Perturbations of the cell-cell adhesion structure or relatedmechanotransduction pathways lead to pathological conditions such as skin and heart diseases, arthritis, and cancer. Mechanical stretching has been used to stimulate the mechanotransduction process originating from the cell-cell adhesion and cell-extracellular matrix (ECM) complexes. The current techniques, however, have limitations on their ability to measure the cell-cell adhesion force directly and quantitatively. These methods use a monolayer of cells, which makes it impossible to quantify the forces within a single cell-cell adhesion complex. Other methods using single cells or cell …

A Computational Framework To Model Mesenchymal Stem Cell Nucleus Mechanics Using Confocal Microscopy, Zeke Kennedy

Boise State University Theses and Dissertations

The mechanical properties of the cell nucleus are emerging as a key component in genetic transcription. It has been shown that the stiffness of the nucleus in part regulates the transcription of genes in response to external mechanical stimuli. The stiffness has been shown to change as a result of both disease and changes to the external environment. While the mechanical structure of the nucleus can be visually documented using a confocal microscope, it is currently impossible to test the stiffness of the nucleus without a mechanical testing apparatus such as an atomic force microscope. This is problematic in that …

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 …

Controlling Strain Energy Density In 3d Cellular Collagen Constructs During Complex Loads, Katherine Hollar

Boise State University Theses and Dissertations

Mechanical stimulation applied to damaged soft tissues, such as ligament, can promote tissue remodeling to accelerate healing. To help identify treatments that encourage ligament healing, bioreactors have been designed to subject 3D cellularized constructs to various loading conditions in order to determine the mechanical mechanisms that trigger cell-mediated repair. An innovative approach is to use a bioreactor to apply controlled states of biaxial stress to study the effects of strain energy density and distortion energy on cell activity. Tissue distortion has been linked to changes in the structure and function of ligament, yet the specific impact of distortion energy on …

Quantifying The Effects Of Hydrostatic Pressure On Fibroblast Growth Factor-2 Binding By The Human Endothelium, Taylor R. Mckenty

Theses and Dissertations--Biomedical Engineering

Fluid pressures regulate endothelial cell (EC) tubulogenic activity involving fibroblast growth factor 2 (FGF-2) and its receptor, FGF receptor 2 (FGFR2). Our lab has recently shown that sustained 20 mmHg hydrostatic pressure (HP) upregulates EC sprout formation in a FGF2-dependent fashion. This upregulation of sprout formation may be due to enhanced FGF-2 / FGFR2 interactions in the presence of 20 mmHg HP. We hypothesize that exposure of ECs to 20 mmHg sustained HP enhances FGF-2 binding kinetics. We used a custom hydrostatic pressure system, immunofluorescence, and FACS to quantify FGF-2 binding by ECs in the absence or presence of a …