Biomedical Engineering and Bioengineering Commons^™

Influence Of Extracellular Matrix Stiffness And Topography On Neuronal Cell Behavior And Neurite Outgrowth, Mohan Yasodharababu

Graduate Theses and Dissertations

The focus of regeneration therapy for traumatic brain injuries and Alzheimer's disease is on the promotion and growth of neuronal cells. In vitro research attempts to improve this by modifying the stiffness and topography of the extracellular matrix (ECM). However, the limitations of in vitro experiments make it difficult to control the individual factors influencing neuronal cell growth. A computational model can be used to decouple individual factors and study them individually to gain a better understanding of the mechanics between the neuronal cell and ECM, which will aid in the design of in vitro experimental studies.

This study develops …

Extracellular Matrix Nanoparticles Effects On The Lung In Vivo, Brittaney E. Ritchie

Theses and Dissertations

Acute respiratory distress syndrome (ARDS) is a life-threatening condition that causes diffuse alveolar damage and a loss of the extracellular matrix (ECM). This leads to pulmonary edema and lung function deterioration. Our lab has created decellularized porcine lung, electrosprayed ECM nanoparticles that have been previously shown to have pro-regenerative capabilities in vitro.

In this study, the ECM nanoparticle effects on young murine lungs were tested in vivo. An ECM nanoparticle suspension, previously used for the in vitro studies, was aerosolized intratracheally into the lungs using a microsprayer. 24 hours later, the lung mechanics, bronchoalveolar lavage fluid, and histology …

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. …

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 …

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 …

Biophysical Features Of The Extracellular Matrix Direct Breast Cancer Metastasis, Alyssa Schwartz

Doctoral Dissertations

Breast cancer is plagued by two key clinical challenges; drug resistance and metastasis. Most work to date probes these events on an extremely rigid plastic surface, which recapitulates few aspects of these processes in humans. A malignant cell first resides in breast tissue, then likely travels to the bone, brain, liver, or lung, each of which has a distinct mechanical and biochemical profile. Cells transmit mechanical forces into intracellular tension and biochemical signaling events, and here we hypothesize that this mechanotransduction influences drug response, growth, and migration. To probe the impact of extracellular matrix on drug resistance, we defined a …

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 …

Biomaterials Approaches For Utilizing The Regenerative Potential Of The Peripheral Nerve Injury Microenvironment, Melissa Renee Wrobel

Wayne State University Dissertations

Clinically available treatments are insufficient to achieve full functional recovery in large (>3cm) peripheral nerve injuries (PNI). The objectives in this thesis were 1) to study often overlooked elements of intrinsic PNI repair including release of inhibitory CSPGs and post-injury responses of inflammatory macrophages and dedifferentiated Schwann cells; 2) to create biomaterial scaf-folds featuring topographical and adhesive cues to enhance neurite outgrowth; and 3) to test the ability of those cues to direct macrophages and Schwann cells towards a pro-regenerative phe-notype. It is hypothesized that recapitulating the positive and negative cues of the PNI microenvi-ronment can better improve regeneration. …

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 …

Development And Characterization Of Lung Derived Extracellular Matrix Hydrogels, Robert A. Pouliot

Theses and Dissertations

Chronic obstructive pulmonary disease (COPD) including emphysema is a devastating condition, increasing in prevalence in the US and worldwide. There remains no cure for COPD, rather only symptomatic treatments. Due to unique challenges of the lung, translation of therapies for acute lung injury to target chronic lung diseases like COPD has not been successful. We have been investigating lung derived extracellular matrix (ECM) hydrogels as a novel approach for delivery of cellular therapies to the pulmonary system.

During the course of this work we have developed and characterized a lug derived ECM hydrogel that exhibits “injectability,” allowing cells or dugs …

Creation Of A 3d Construct To Aid Cell Migration And Promote Cell Capture, Joseph Michael Sanders

Legacy Theses & Dissertations (2009 - 2024)

Most cancer-related deaths are attributed to metastasis. The tumor microenvironment is a complex environment which is not fully understood. The Nano Intravital Device (NANIVID) is a versatile, biocompatible device that allows for the manipulation of the tumor microenvironment in vitro and in vivo, providing a platform to study various aspects of tumor progression. The purpose of this study is to modify the NANIVID to resemble the tumor microenvironment in order to allow for a seamless transition from the in vivo environment into the engineered environment within the NANIVID. This engineered microenvironment will promote cell migration and cell capture. It has …

Development Of A Novel Device For The Perfusion Driven Decellularization Of Skeletal Muscle, Benjamin Kasukonis

Graduate Theses and Dissertations

Decellularization of skeletal muscle is a process that removes cellular components of skeletal muscle tissue while leaving behind the intact extracellular matrix (ECM). Skeletal muscle ECM is currently being studied as a biologic scaffold for repairing volumetric muscle loss (VML) because the removal of cells greatly reduces the antigenicity of the donor tissue. Decellularization usually relies on passive diffusion of detergents, surfactants and/or osmotic solutions to strip cells from the ECM. However, passive diffusion alone is usually not sufficient for complete removal of cells from the interior of large pieces of skeletal muscle using detergents, such as sodium dodecyl sulfate …

Mammary Epithelial Cells Cultured Onto Non-Woven Nanofiber Electrospun Silk-Based Biomaterials To Engineer Breast Tissue Models, Yas Maghdouri-White

Theses and Dissertations

Breast cancer is one of the most common types of cancer affecting women in the world today. To better understand breast cancer initiation and progression modeling biological tissue under physiological conditions is essential. Indeed, breast cancer involves complex interactions between mammary epithelial cells and the stroma, both extracellular matrix (ECM) and cells including adipocytes (fat tissue) and fibroblasts (connective tissue). Therefore, the engineering of in vitro three-dimensional (3D) systems of breast tissues allows a deeper understanding of the complex cell-cell and cell-ECM interactions involved during breast tissue development and cancer initiation and progression. Furthermore, such 3D systems may provide a …

Tissue Engineering Cellularized Silk-Based Ligament Analogues, Scott Sell

Theses and Dissertations

The resurgence, and eventual rise to prominence in the field of tissue engineering, that electrospinning has experienced over the last decade speaks to the simplicity and adaptability of the process. Electrospinning has been used for the fabrication of tissue engineering scaffolds intended for use in nearly every part of the human body: blood vessel, cartilage, bone, skin, nerve, connective tissue, etc. Diverse as the aforementioned tissues are in both form and function, electrospinning has found a niche in the repair of each due to its capacity to consistently create non-woven structures of fibers ranging from nano-to-micron size in diameter. These …