Biological Engineering Commons^™

Development Of Translational Microscale Systems To Interrogate How Biophysical And Biochemical Cues Alter The Phenotype Of Hormone Positive Breast Cancer, Braulio Ortega Quesada

All Dissertations

Cancer is a complicated disease and one in every three diagnoses are women with breast cancer. Recent research shows that the progression of cancer depends strongly on interactions with other non-cancerous cells and non-cellular components. Metastasis, the spread of cancer to other parts of the body, is a key step in cancer progression and makes treatment harder, leading to poor response to treatments culminating in death in ~90% of patients. This dissertation focused on creating a series of microdevices as novel pre-clinical models of breast cancer. Two different devices were fabricated to (1) study how exposing cancer cells to the …

Investigating The Role Of Cd44 In Her2+ Breast Cancer Cells During Cancer Cell Redirection, Holly Caroline Jordan Campbell

All Dissertations

Despite a rise in survival rates of breast cancer patients due to advances in modern medicine, breast cancer is the most common type of cancer in women and is the second leading cause of cancer death in the United States. Early detection and a more personalized treatment of breast cancer has slowly improved patient outcomes. Nevertheless, there are impediments to better patient outcomes due to the complexity of the disease physiology. Therefore, there is a demand for a comprehensive understanding of cancer development as well as a need to understand tumor progression for enhanced therapies for patients.

Previous in vivo …

The Role Of Kinases Signaling In Organogenesis, Fatemeh Nasehi

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Kinases are crucial regulators of organ development and differentiation. This thesis investi- gates the roles of TAK1, TGFbeta-Activate Kinase 1 (TAK1/Map3K7), and Akt3 kinases in skeletal, cardiac muscle, and cartilage. TAK1 is pivotal for the differentiation of various organ systems, including sinoatrial node and cartilage, and is responsible for phosphorylat- ing a diverse array of downstream kinases. We identified several novel proteins, including phospho-Akts, that are upregulated in response to TAK1 activation. We discovered severe Dilated Cardiomyopathy (DCM) and cartilage defects in Akt3 mutant mice. Although this mouse mutant has been studied for over two decades, we are the first …

Novel Nucleus Pulposus Biomaterial Development And Low Field Mri Assessment For Intervertebral Disc Degeneration, Mario Krussig

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Intervertebral disc degeneration (IVDD) is a prominent pathology in the modern world that causes debilitating pain for many patients. The onset of IVDD occurs in the nucleus pulposus (NP). NP biomaterials will play a vital role in mitigating the progression of IVDD. Within this work, we sought to synthesize a solubilized extracellular matrix (ECM)-based NP biomaterial. Utilizing pepsin or urea extraction, bovine NP ECM was successfully solubilized (SBNPs). SBNP formulations were characterized biochemically, evaluated for cytotoxicity, and down-selected for front-running formulations. Leading candidate SBNPs were incorporated into an alginate bead biomaterial model to determine the potential bioactivity with human adipose-derived …

Engineering Next-Generation Cardiovascular Therapies, Ryan Walker Barrs

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Cardiovascular diseases are the leading cause of death worldwide. Heart disease, in particular, accounted for 1 in every 5 deaths in the United States in 2021, representing a substantial public health burden that will require more effective treatment options to alleviate. Heart transplant surgery is currently the only option to completely restore cardiac function, but many patients die while waiting for a transplant due to a longstanding organ donor shortage. Thus, there is a dire need for accessible treatment options that can repair damaged hearts. Recent advances in tissue engineering and regenerative medicine have accelerated the development of therapies for …

Prevention And Reversal Of Elastin-Associated And Phosphate-Dependent Arterial Calcification Using Targeted Nanotherapeutics In Pre-Clinical Models, Fatema Tuj Zohora

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Vascular calcification can be life-threatening, involving calcium phosphate crystal deposits in the blood vessels. The calcification in the intimal layer of the arterial wall is usually associated with atherosclerotic plaque build-up that, in the advanced stage, harbors ‘dispersed’ and ‘spotty’ deposits of calcium phosphate crystals in the necrotic core of the plaque. In contrast, medial arterial calcification (MAC) can form independently of atherosclerosis and appears as ‘Railroad-like’ calcific deposits along degraded elastin lamellae in the medial layer of arteries. The mechanisms of such elastin-associated medial arterial calcification and potential therapies are the key concerns of this dissertation. MAC is common …

Investigating The Potential Of A Cell-Based Gene Editing Therapy For Inherited Metabolic Liver Disease, Ilayda Ates

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Inherited metabolic diseases (IMDs) affecting the liver are relatively rare but collectively have a prevalence of 1 in 800 live births. These diseases result from autosomal recessive single-gene mutations, leading to organ dysfunction and potentially fatal consequences if left untreated. One potential therapeutic strategy for IMDs of the liver involves using CRISPR-Cas9-induced loss of function mutations. However, translating this approach into the clinic is limited by the need for safe and effective CRISPR delivery methods. Adeno-associated viral vectors (AAVs), commonly used for CRISPR delivery, are associated with significant safety and efficacy concerns, including risks for immunogenicity, off-target mutagenesis, and genotoxicity …