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 …

Broadening The Application Range Of Cell-Free Protein Expression Systems, Matthew Becker

All Theses

Centralized protein manufacturing platforms make the delivery of needed therapies to places with limited infrastructure almost impossible. Cell-free protein expression systems, systems that utilize protein production machinery extracted from cells, offer these communities a viable protein expression platform that is robust and easily deliverable to the place of need. Much work in cell-free system engineering looks to increase the hardiness of cell-free system (CFS) components, like the extract and reaction buffer, needed to carry transcription and translation of gene therapeutic targets forward. Freeze- and air-drying of extract, reaction buffer, or both with certain additives, like sugar molecules, has been proposed …

Advancements Of A Breast Tissue Marker And Localization System, Azrin Jamison

All Theses

Breast cancer has become the most prominent cancer worldwide in women. Annual mammograms are encouraged for women of high risk to increase early detection allowing for lumpectomies rather than mastectomies to occur. Prior to a lumpectomy, a biopsy must be taken to determine if the tissue is cancerous, and a breast cancer biopsy marker (BBM) is left in the region of possible cancerous tissue. Wire localization has been the gold standard for localizing these BBMs. However, due to the reported patient discomfort and logistical inefficiencies faced by healthcare providers (HCP), non-wire localization solutions have been recently developed. This study aims …

Hand Movement Analysis For Surgical Suturing Skill Assessment, Amir Mehdi Shayan

All Theses

To enhance patient safety, surgical education is increasingly incorporating simulation for formative skills assessment and training. However, many standardized assessment tools rely on human raters for performance assessment, which is resource-intensive and subjective. Simulators that provide automated and objective metrics from sensor data can address this limitation. This thesis presents an instrumented bench suturing simulator, patterned after the Clock Face (CF) radial suturing model from the Fundamentals of Vascular Surgery (FVS), for automated and objective assessment of open suturing skills by particularly focusing on biomechanical analysis of hand movements. For this research, 97 participants (35 attending surgeons and fellows, 32 …

Development Of A Cost-Affordable Thin-Layer Chromatography Testing Kit For Falsified And Substandard Pharmaceuticals In Tanzania, Eleanor Hatcher

All Theses

A significant number of pharmaceuticals supplied to Tanzania are falsified or substandard. A majority of these inadequate pharmaceuticals are medications to treat life-threatening conditions. This problem not only causes mistrust in the healthcare system but also prolonged illness and potentially death for the patients. This calls for the need for the development of a cost-affordable testing kit for falsified and substandard pharmaceuticals in Tanzania. Thin-layer chromatography (TLC) was used as the testing method since it is inexpensive and requires a low skill level to complete. Malaria, human immunodeficiency virus, hypertension, tuberculosis, and diabetes are five of the most prevalent diseases …

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 …

Medical Simulation-Based Sensor Methods For Ultrasound-Guided Dialysis Cannulation Skill Assessment, Devansh Shukla

All Theses

End-stage kidney disease (EKSD) is the final, permanent stage of chronic kidney disease (CKD), where the body's kidneys cannot filter blood sufficiently. Hemodialysis treats ESKD by filtering wastes and water from your blood externally via a dialyzer. Patients on hemodialysis require a vascular access, typically an arteriovenous fistula (AVF) or arteriovenous graft (AVG) for dialysis, which is used three times a week for about four hours a session. These life-saving therapies can be quite tedious, especially for elderly patients and patients with co-morbidities. As such, successful cannulation is extremely important to ensure the longevity of the patient's vascular access and …

Controlled Manipulation And Transport By Microswimmers In Stokes Flows, Jake Buzhardt

All Dissertations

Remotely actuated microscale swimming robots have the potential to revolutionize many aspects of biomedicine. However, for the longterm goals of this field of research to be achievable, it is necessary to develop modelling, simulation, and control strategies which effectively and efficiently account for not only the motion of individual swimmers, but also the complex interactions of such swimmers with their environment including other nearby swimmers, boundaries, other cargo and passive particles, and the fluid medium itself. The aim of this thesis is to study these problems in simulation from the perspective of controls and dynamical systems, with a particular focus …

Structural Characterization Of Cardiomyocyte Microenvironment In Murine Myocardium By Multimodal Stimulated Emission Depletion Microscopy, Zhao Zhang

All Dissertations

Cardiomyopathy, a disease of the heart muscle, is characterized by structural and functional abnormalities of the myocardium, in the absence of coronary artery disease, hypertension, valvular disease or congenital heart disease. In 2020, there were approximately 6.11 million prevalent cases of cardiomyopathy and myocarditis, and 0.37 million related deaths worldwide. Many affected individuals are asymptomatic, and chronically treated patients are at risk of heart failure. Within the myocardium, cardiomyocytes reside in a complex and dynamic extracellular matrix (ECM), consisting of basement membrane and interstitial matrix. The interactions between cardiomyocytes and myocardial ECM play a critical role in maintaining cardiac geometry …

Ti-6al-4v Β Phase Selective Dissolution: In Vitro Mechanism And Prediction, Michael A Kurtz

All Dissertations

Retrieval studies document Ti-6Al-4V β phase dissolution within total hip replacement systems. A gap persists in our mechanistic understanding and existing standards fail to reproduce this damage. This thesis aims to (1) elucidate the Ti-6Al-4V selective dissolution mechanism as functions of solution chemistry, electrode potential and temperature; (2) investigate the effects of adverse electrochemical conditions on additively manufactured (AM) titanium alloys and (3) apply machine learning to predict the Ti-6Al-4V dissolution state. We hypothesized that (1) cathodic activation and inflammatory species (H₂O₂) would degrade the Ti-6Al-4V oxide, promoting dissolution; (2) AM Ti-6Al-4V selective dissolution would occur …

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 …

Experimental And Computational Platforms For Studying Systems Mechanobiology, Brendyn Miller

All Dissertations

Mechanical stimulation through physical activity has been shown to play an important role in treating and preventing several non-communicable diseases such as hypertension, lower back pain (LBP), type-2 diabetes mellitus, and several cancers. This is accomplished through the regulation of cellular behavior and tissue remodeling within the body at both the micro- and macro-scale levels. The goal of mechanobiology research is to gain in-depth knowledge and understanding of how cells sense physical forces in conjunction with other biochemical cues and translate those factors into important biological functions that either maintain tissue homeostasis or lead to pathological states. Understanding these processes …

Assessing Chondrocyte Viability Of Articular Cartilage Using Label-Free Imaging Methods, Hongming Fan

All Dissertations

ABSTRACT

Articular cartilage covers the ends of bones, providing a protective layer that can endure forces during movement. Chondrocytes, the only cell type found in articular cartilage, produce collagen fibers and proteoglycans that maintain the extracellular matrix (ECM). Cartilage damage impairs chondrocytes and their ability to maintain tissue stability. There are various factors that can cause cell death, which can be broadly classified into two categories: programmed cell death (apoptosis) and non-programmed cell death (necrosis). The consequences of cell death can have significant impacts on the extracellular matrix (ECM). The ECM is a complex network of proteins and carbohydrates that …

An In Vitro Platform To Characterize Myocardial Wound Remodeling, Jonathan Heywood

All Dissertations

Heart Failure, sometimes called Congestive Heart Failure, is a collection of pathological disruptions in which the heart is unable to pump blood properly. It affects over 6 million people in the United States, with the cost-per-patient at approximately $30,000 and the total cost estimated to be $160 billion by 2030. There is no single cause of heart failure, as it can manifest as a varying array of diseases, disorders, and syndromes. However, many of these underlying diseases result specifically from dysregulation of mechanically active cells called cardiac fibroblasts, which play a critical role in the remodeling of the extracellular matrix …

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 …

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 …

The Effects Of Compression Wrapping Techniques And Primary Wound Dressings On Leg Skin Interface Pressure, James Cox

All Theses

Peripheral edema affects approximately 20% of people in the US over the age of 50 and is frequently encountered among individuals with conditions such as heart disease, prolonged immobility, and venous insufficiency.¹ Compression is an established therapeutic tool utilized for the management of several chronic edema presentations including lymphedema and venous leg ulcers.^2,3 Therapeutic efficacy of compressive applications can be evaluated by defining interface pressure (IP) and IP distributions associated with specific textile combinations.² During compressive applications where an open wound is present, primary wound dressings should be used in combination with compressive wraps. Primary wound dressings …

Tandem Peptides Targeting Her2 For Delivery Of Cd44 Sirna Into Her2+ Breast Cancer Cells In Vitro, James Kalogeros

All Theses

More than 300,000 women will be diagnosed with breast cancer, and approximately 48,000 women will die this year due to the disease in the United States. HER2+ breast cancer accounts for 20-25% of invasive breast cancer, and it has a worse prognosis and higher early-stage mortality rate than other breast cancer subtypes. Common treatments for HER2+ breast cancer involve surgical removal of the breast or systemic therapy with chemotherapeutic drugs, both of which cause damage to healthy tissue. Due to the lack of a natural ligand for the HER2 receptor, there is a need for improved targeting strategies for the …

Development & Validation Of Needle-Based Metrics For Hemodialysis Cannulation Skill Assessment, Ziyang Zhang

All Dissertations

Dialysis is a vital medical treatment for patients with end-stage renal disease. An arteriovenous fistula, a surgically created connection between an artery and a vein, is the preferred vascular access for dialysis due to superior clinical outcomes. However, cannulation complications caused by needle-related errors are common and dangerous, necessitating the need for effective cannulation training. Despite cannulation being a challenging and complex clinical procedure, little is known about the quantitative aspects of needle insertion dynamics necessary for skilled cannulation. The aim of this study was to develop meaningful and instructive needle-based metrics for cannulation skill assessment and training.

Two iterations …

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 …

In Vitro And In Vivo Diabetic Models For Assessment Of Tissue Engineered Vascular Grafts, Juan Carlos Carrillo Garcia

All Dissertations

Diabetes has become one of the leading causes of lower-limb loss worldwide. Every 30 seconds, a person loses a limb due to diabetic-related vascular complications. About one-third of patients needing lower-limb bypass surgery have debilitated autologous vessels unsuitable for use, and no other good long-term options are available. These detrimental effects on the vasculature are caused mainly by the hyperglycemic and hyperlipidemic conditions derived from diabetes. Under these conditions, an increase in advanced glycation end products (AGEs) and reactive oxygen species leads to irreversible crosslinks of extracellular matrix proteins, accelerating vascular pathology through vascular stiffening, endothelial dysfunction, inflammation, atherosclerosis, fibrosis, …

Predicting Corrosion Damage In The Human Body Using Artificial Intelligence: In Vitro Progress And Future Applications Applications, Michael A. Kurtz, Ruoyu Yang, Mohan S. R. Elapolu, Audrey C. Wessinger, William Nelson, Kazzandra Alaniz, Rahul Rai, Jeremy L. Gilbert

Publications

Artificial intelligence (AI) is used in the clinic to improve patient care. While the successes illustrate the impact AI can have, few studies have led to improved clinical outcomes. A gap in translational studies, beginning at the basic science level, exists. In this review, we focus on how AI models implemented in non-orthopedic fields of corrosion science may apply to the study of orthopedic alloys. We first define and introduce fundamental AI concepts and models, as well as physiologically relevant corrosion damage modes. We then systematically review the corrosion/AI literature. Finally, we identify several AI models that may be Preprint …

Assesment Of Structure, Function, And Microevolutionary Dynamics Of Extrachromosomal Circular Dna In Chinese Hamster Ovary Cells, Dylan Chitwood

All Dissertations

Chinese hamster ovary (CHO) cell lines are among the most popular expression hosts used in biopharmaceutical manufacturing due to relative ease of culture, capacity to perform human-like post-translational modifications, and non-susceptibility to viruses. However, the intrinsic plasticity of the CHO genome can lead to undesired genetic rearrangements, phenotypic shifts, reduced product quality, and early culture termination that prevents continuous biomanufacturing. A characteristic of plastic and unstable genomes that is poorly understood in CHO cells is extrachromosomal circular DNA (eccDNA). EccDNAs are focal amplifications of the genome that reside in the extranuclear space. These plasmid-like entities are structurally complex and are …

Development Of 3d Ovarian Cancer Spheroids In Vitro And Investigation Of Their Physiological Relevance As Models Of Inherent Chemoresistance, Amanda Murray

Honors College Theses

Ovarian cancer is the sixth leading cause of death among women worldwide, with an average 5-year survival rate of less than 48%. Current clinical treatment methods for this disease are often deemed ineffective because of the innate chemoresistance of tumors due to their microenvironment and architecture. Accurately mimicking chemoresistance with traditional 2D cultures is difficult; therefore, recent years have seen an increase in 3D culturing methods that create cellular spheroids. These spheroids can serve as models of in vivo tumor characteristics due to their hypoxic core, acidic microenvironment, and increased cell-to-cell interactions. This research aims to (1) refine a 3D …

3d Printing With Photopolymerizable Polyester Resins For Resorbable Medical Device Applications, Mathew Murphy Stanford

All Dissertations

In the past decade, the healthcare industry has seen a significant increase in the use of additive manufacturing (AM or “3D printing”) with subsequent improvement in clinical outcomes.As an exceptional AM technology, vat-photopolymerization (VP), often called stereolithography, can create complex structures and has thus been adopted for a range of biomedical applications including surgical guides, temporary implants, and resorbable tissue scaffolds.However, limitations remain in the availability of photopolymerizable resin materials with appropriate mechanical performance, biodegradability, and biocompatibility for application to resorbable medical devices.

The objective of this work was to employ novel photopolymerizable polyester-based macromers in the development of resorbable …

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 …

An In Vivo Biocompatibility Analysis Of A Novel Tissue Regeneration Matrix Using A Pig Model, Shamar Thomas

All Theses

The goal of this project is to develop an injectable bead scaffold to promote tissue regeneration in the void created by lumpectomy and to alleviate post lumpectomy problems by preventing local recurrence and minimizing surgical-related infections. Microbeads were synthesized from collagen type I and crosslinked with tannic acid to form the basis for this injectable therapeutic. Tannic acid acts as a therapeutic anticancer agent. The action mechanisms of tannins in breast cancer cells have been studied with studies showing tannins to be cytotoxic to cancer cells in a dose-dependent manner. Tannic acid induces apoptosis in breast cancer cells via caspase …

Development Of Enzyme-Responsive Polymersomes As A Drug Delivery System For Gm1 Gangliosidosis, Bipin Chakravarthy Paruchuri

All Dissertations

GM1 gangliosidosis is a lysosomal storage disorder caused by deficiency of β-galactosidase (βgal) and subsequent accumulation of GM1 ganglioside in lysosomes. The rare nature of this disorder presents challenges with prognosis and treatment. Enzyme replacement therapy (ERT) can effectively treat systemic deficiencies, but the intravenously administered enzyme cannot cross the blood-brain barrier (BBB) to treat the central nervous system. A delivery system to encapsulate and deliver the enzyme can facilitate enzyme transport across the BBB with suitable surface modifications. One of the pathological aspects of GM1-affected cells is the upregulation of the lysosomal enzyme hexosaminidase A (HexA). In this dissertation, …

In Vitro Bioreactor For Mechanical Control And Characterization Of Tissue Constructs, Samuel Coeyman

All Dissertations

Heart failure (HF) currently affects over 6 million Americans, 50% of whom die within 5 years of their initial diagnosis. A major contributor to the onset of HF is cardiac fibrosis in the myocardium, which arises when fibroblasts (FBs) are activated in response to heightened mechanical stress from overload conditions like hypertension. Activated FBs remodel the extracellular matrix (ECM) and secrete ECM proteins including collagen. FB remodeling has been studied in the past by applying forces and/or deformations to three-dimensional, cell-seeded gels and tissue constructs in vitro. Unfortunately, previous stretching platforms have traditionally not enabled mechanical property assessment to be …

Scalable Data-Driven Predictive Modeling And Analytics For Cho Process Development Optimization, Sarah Mbiki

All Dissertations

In 1982, the FDA approved the first recombinant therapeutic protein, and since then, the biopharmaceutical industry has continued to develop innovative and highly effective biological drugs for various illnesses¹. These drugs are produced using host organisms that are modified to hold the genetic encoding of the targeted protein¹. Of the many host organisms, Chinese hamster ovary (CHO) cells are often used due to capability to perform posttranslational modification (PTM): which allows human-like synthesis of proteins unlikely to invoke immunogenicity in humans ^1,2.

Despite all the positive attributes, many challenges are associated with CHO cell cultures, …