Biological Engineering Commons^™

Fluorescence-Based Quantification Of Hepatic Ldl Uptake And Donor Hepatocyte Engraftment Using Atto 700–Labeled Ldl, Victor Agustin Cortes Flores

All Theses

Familial hypercholesterolemia (FH) is an inherited disorder characterized by elevated low-density lipoprotein cholesterol (LDL-C) that increases the risk of premature atherosclerotic cardiovascular disease. In severe FH, including low-density lipoprotein receptor (LDLR), hepatic LDL clearance is profoundly impaired and many lipid lowering treatment strategies have limited effectiveness. Current advances in ex vivo CRISPR–Cas9 hepatocyte gene editing in vivo and ex vivo approaches for treatment of FH are under development.

However, a central barrier to translation is the ability to quantitatively measure the percentage of healthy gen edited hepatocytes in the liver while simultaneously assessing functional hepatic LDL handling. This thesis establishes …

Multiscale 3d Whole Joint Cellular And Molecular Mapping Reveals Disease-Specific Neurovascular Plasticity Underlying The Structure-Pain Relationship, Peng Chen, Jiaxin Chai, Abirami Soundararajan, R. Glenn Hepfer, Benjamin Kheyfets, Jiaxin Hu, Ishraq Alshanqiti, Swarnalakshmi Raman, Ikue Tosa, Jun Tae Huh, Matthew Yee, Brooke J. Damon, Shangping Wang, Yu Shin Kim, Man-Kyo Chung, Mildred C. Embree, Janice S. Lee, Tong Ye, Hai Yao

Publications

Understanding musculoskeletal joints from a 3D multiscale perspective, from molecular to anatomical levels, is essential for resolving the confounding relationships between structure and pain, elucidating mechanisms regulating joint health and diseases, and developing new treatment strategies. Here, a musculoskeletal joint immunostaining and clearing (MUSIC) method specifically developed to overcome key challenges of immunostaining and optical clearing of intact joints are introduced. Coupled with large-field light sheet microscopy, this approach achieves 3D high-resolution, microscale neurovascular mapping within the context of whole-joint anatomy without the need for image coregistration across various joints, including temporomandibular joints, knees, and spines, and multiple species, including …

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

All Dissertations

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

All Dissertations

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 …

1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine (Mptp)-Treated Adult Zebrafish As A Model For Parkinson’S Disease, Emmeline Bagwell

All Theses

The use of adult zebrafish, Danio rerio, as a model for human neurodegenerative diseases has proven valuable in pharmaceutical development and genetic disease research due to their high genetic homology to humans, cost-effective husbandry, and quick life cycle breeding times. Despite their promise, most zebrafish research has focused on embryonic stage organisms, primarily due to the ease of direct handling protocols and rapid progression through developmental stages. Recognizing the limitations of early-stage organisms in modeling adult diseases, recent efforts have shifted the applicability of zebrafish models, particularly for Parkinson's Disease, due to the nature of the disease impacting patients 55 …

Engineering Next-Generation Cardiovascular Therapies, Ryan Walker Barrs

All Dissertations

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

All Dissertations

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

All Dissertations

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 …

Photodynamic Therapy To Treat Triple Negative Breast Cancer In Vitro, Hunter S. Warren

All Theses

Triple negative breast cancer (TNBC) is the most resilient form of breast cancer, being one of the leading causes of death for women and making up 7% of all cancer deaths. Photodynamic therapy (PDT) offers a minimally invasive solution to TNBC as a passive-targeting treatment that reduces the need for other well established yet harsh treatments that can be taxing on the patient. PDT involves the use of a high-energy red light on the area of a tumor injected with photosensitizers (PS) that generate reactive oxygen species (ROS) in the tumor, triggering cell death. The PS tetra(hydroxyphenyl)chlorin (m-THPC) was used …

Laser Inscribed Graphene Aptasensor For Detection Of Apple Stem Pitting Virus, Yifan Tang

All Theses

Apple stem pitting virus (ASPV) is a latent RNA virus that could cause significant loss to apple production; early-stage field diagnosis could reduce the economic loss caused by ASPV infection. Biosensor is a promising user-friendly detection tool that could transduce biological or chemical interactions into electric signals. Among various types of biosensors, aptasensor, which use aptamers as recognition elements show potential as a high throughput, in-field test. The goal of this thesis is to develop an electrochemical aptasensor testing system for ASPV detection. The quality control study of laser inscribed graphene (LIG) based working electrode of the biosensor was conducted …

Insect Antennae As Bioinspirational Superstrong Fiber-Based Microfluidics, Griffin J. Donley

All Theses

Nature is frequently turned to for inspiration for the creation of new materials. Insect antennae are hollow, blood-filled fibers with complex shape, and are cantilevered at the head. The antenna is muscle-free, but the insect can controllably flex, twist, and maneuver it laterally. To explain this behavior, a comparative study of structural and tensile properties of the antennae of Periplaneta americana (American cockroach), Manduca sexta (Carolina hawkmoth), and Vanessa cardui (painted lady butterfly) was performed. These antennae demonstrate a range of distinguishable tensile properties, responding either as brittle fibers (Manduca sexta) or strain-adaptive fibers that stiffen when stretched (Vanessa cardui …

Toward Sustainable Urban Food Production: Integrating Hydroponic Cultivation With Wastewater Reuse, Amanda Tan

All Theses

The growing crisis of freshwater scarcity together with the increasing global food demand directs attention to the need for alternative water sources for agriculture. The research presented here engages this need by carrying out indoor cultivation of food crops in Nutrient Film Technique (NFT) hydroponic systems using residential wastewater. Randomized single factor experimental designs were used to investigate the physiochemical and microbiological makeup of the hydroponic nutrient solution throughout the cultivation cycle and their relationship with different plant development parameters.

For agricultural wastewater reuse to be of low risk to human health there must be some advancement in pathogen monitoring …

Nonlinear Optical Microscopy Assessment Of Tissue Structure And Chondrocyte Viability Of Articular Cartilage, Michael Le

All Theses

Articular cartilage functions to protect the ends of bones by providing a surface that can withstand compressive forces and minimize friction during movement. Collagen fibers form the organizational backbone of the extracellular matrix (ECM) in cartilage. Proteoglycans within the ECM function to retain water and provide the tissue with the swelling pressure needed to withstand compressional forces. Chondrocytes, the only type of cell found in articular cartilage, produces these collagen fibers and proteoglycans to maintain the tissue structure and function. Significant injuries to articular cartilage can damage the chondrocytes and disrupt their ability to maintain homeostasis in the tissue. Therefore, …

A Comparison Of Methods To Measure Crop Water Use In South Carolina, Andrew C. Ewing

All Theses

The objective of this thesis was to compare cost-effective methods of measuring crop water use, known as evapotranspiration (ET), in South Carolina’s humid climate. The methods analyzed were the surface renewal method (SR), the Eddy Covariance method (EC), large in-field weighing lysimeters, a newly developed pressure differential device (PDD), a Class A Evaporation pan, and the Penman-Monteith equation. In the first chapter, ET measurements obtained by SR were compared to ET measured by EC and weighing lysimeters. For reference, EC and SR track the energy budget to estimate ET, while the weighing lysimeters used in this study are box-like containers …

Endothelialization Using Protein Substrates And Hydrogels For Aortic Valve Applications, Elizabeth A. Fontaine

All Theses

Aortic valve disease is currently the leading cause of cardiovascular morbidity in the United States.1 In 2003, approximately 290,000 patients required heart valve replacement and that number is estimated to continue to rise as the average age of the population continues to increase.2 However, the current valve replacement options have multiple limitations. Tissue engineering hopes to address these shortcomings by providing a viable valve that more closely mimics the native valve, structurally and functionally.3 An ideal valve replacement should contain endothelial and interstitial cells, with the ability to remodel the extra-cellular matrix. While tissue-engineered heart valves are not uncommon in …