Biomedical Engineering and Bioengineering Commons^™

A Surface-Bound Detection Architecture For Label-Free Evanescent-Wave Sensing Of Cobalt In Complex Fluids, Jeremiah W. Carpenter

All Dissertations

Cobalt exposure is a clinical concern in orthopedic implant surveillance, where cobalt-chromium wear debris can release ions detectable in blood and urine, and an environmental concern in mining-affected and industrial water systems. Reference laboratory methods, including inductively coupled plasma mass spectrometry, provide sensitive quantification but require centralized instrumentation, trained personnel, and controlled sample handling, which limits their availability for routine screening in decentralized clinical and environmental contexts. This dissertation develops a surface-bound detection architecture for label-free evanescent-wave sensing of cobalt in complex fluids. The architecture rests on a physical necessity argument grounded in interfacial optics: at physiologically and environmentally relevant …

Baseline Cervical Intervertebral Disc Biomechanics And Implications For Allograft Preservation, Nathan F. Buchweitz

All Dissertations

Neck pain has become an increasingly common orthopaedic healthcare issue. Evidence shows that degeneration of cervical intervertebral discs (the cartilage between the spinal vertebrae in the neck) may be associated. While disc degeneration in the lumbar spine has been extensively studied in relation to low back pain, it has received less attention in the cervical spine. Biomechanically, the cervical (neck) and lumbar (lower back) regions of the spine differ in function. Lumbar discs resist a greater burden of body weight, whereas cervical discs are adapted for mobility to aid flexible head orientation. Despite these key differences, disc injury and degeneration …

Degradation Of Cobalt Chrome Molybdenum Hip And Knee Implants In Vivo And In Vitro, Peter William Kurtz

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Cobalt Chrome Molybdenum (CoCrMo) remains a popular material choice for femoral condyles in total knee arthroplasty and for acetabular liners in dual mobility total hip designs. CoCrMo has been phased out of conventional THA designs due to its correlation with adverse effects such as ALTR and ALVAL. It is less understood if the mechanisms (i.e. abrasive wear to the surface of the implant) that release metal ions into the surrounding tissue occur at similar rates as seen in conventional THA. Additionally, it is unknown what effect the secondary damage modes such as electrocautery damage and adhesive wear have on these …

Reverse (Bio)Engineering: A Machine Learning Approach To Optimize Baseball Pitcher Health And Performance, Robert C. Moore

All Dissertations

Ball tracking systems are becoming ubiquitous in sport, creating an unprecedented opportunity for big data applications to optimize human health and performance. These applications are especially common in baseball, a sport known for analyzing ball flight data to quantify performance. Analysts routinely use ball flight data to identify the attributes of top performing pitchers, finding that the best pitchers throw with optimal combinations of release speed and spin to precise locations. However, for certain pitchers, the throwing motion required to produce optimal ball flight places exceedingly high biomechanical load on the elbow, and consequently injury rates continue to rise. This …

Crevice Corrosion Mechanisms Of Cocrmo Alloys In Orthopedic Implants: Retrieval Analysis, Nano-Tribocorrosion And Cellular Responses, Hwaran Lee

All Dissertations

Mechanically assisted corrosion and non-mechanically (chemically) driven corrosion in modular junctions of orthopedic implants using cobalt-chromium-molybdenum (CoCrMo) alloys remain clinical concerns and may contribute to implant failure. The underlying corrosion mechanisms are not yet fully understood, leaving a critical research gap. We hypothesized that corrosion in modular junctions may be driven by aggressive local environments, including fretting, metal ion release (cobalt ion, Co²⁺), low pH and reactive oxygen species (ROS). This dissertation aims to (1) analyze corrosion modes and potential causes in modular junctions; (2) identify chemically driven corrosion modes on CoCrMo alloys using simulated inflammatory modular taper …

Synthesis And Characterization Of Magnetic Nanoparticles To Study Effective Magnetic Anisotropy For Biomedical And Catalytic Applications, Alexander Malaj

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This dissertation focuses on understanding how to tune the magnetic properties of nanoparticles through controlling the effective magnetic anisotropy (Keff), which is a key variable in determining a nanoparticle’s Néel relaxation time, which will dictate its magnetic behavior in various applications. In this work, magnetocrystalline anisotropy is tuned by synthesizing tri-metallic substituted ferrite (Fe3-x-yMnxCoyO4) nanoparticles with specific metallic compositions that were informed by computer simulations using density functional theory (DFT) to target magnetocrystalline anisotropy values. A drip synthesis was used to control the size and composition of the tri-metallic ferrites, which were revealed to be monodisperse and compositionally mixed by …

3d Bioprinting Of Hydrogel Scaffold Skin Equivalents For Cosmetic And Drug Testing, Allison Reno

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Tissue engineering scaffolds are a crucial element of generating larger 3D tissue equivalents for modeling and clinical grafting. Currently, much of scaffold technology has not been significantly updated since the introduction of manually pipetted hydrogels and electrospun fiber scaffolds. Both of these approaches have their advantages and disadvantages, but neither utilize emerging biofabrication techniques such as advanced 3D bioprinting and plotting. In addition to more precision in the outer geometries of the scaffold, the use of bioprinting also introduces the ability to shape hydrogels into very intricate porous inner patterns within the outer geometries. This allows for the design of …

Development Of Rolipram Loaded Pgp Nanoparticles For Spinal Cord Injury Repair, Zhen Liao

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Spinal cord injury (SCI) leads to devastating neurological deficits due to primary mechanical damage and secondary injury mechanisms, including inflammation, oxidative stress, excitotoxicity, and inhibitory scarring, which collectively impede neural regeneration. One key aspect of SCI pathology is a significant reduction in cyclic adenosine monophosphate (cAMP) levels, primarily due to increased phosphodiesterase (PDE 4) activity. As a ubiquitous second messenger, cAMP regulates key signaling pathways, including protein kinase A (PKA) / cAMP response element-binding protein (CREB) and exchange protein activated by cAMP 2 (EPAC2). Therefore, restoring/increasing cAMP level is one of the major therapeutic strategies to reduce neurotrauma and restore …

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 …

Toward The Application Of Natural Language Processing In Electronic Health Record Analysis For Taxonomy Development, Latoya Mcdonald

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Electronic health records (EHRs) are pivotal resources for nurse practice because they increase the timeliness and reliability of patient information at the point of care and support access by multiple healthcare providers and the individual patients themselves. However, it is widely recognized that data extraction from EHRs is challenging due to the variability in the language used in clinical care notes and the lack of standardized terminology across healthcare systems. The broad objective of this dissertation is to develop taxonomy-based classification models for nursing care by applying feature engineering approaches to EHRs that include nursing care of ostomy patients following …

Ex Vivo Multiplex Knockdown Of Angptl3 And Cypor In Hepatocytes As A Novel Cell Therapy For Familial Hypercholesterolemia, Callie D. Clark

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Inherited metabolic diseases (IMDs) affect approximately 1 in 800 individuals. The only curative treatment for IMDs is liver transplantation. However, transplantation carries significant risks, including organ rejection and a lifelong need for immunosuppression. Therefore, gene editing has emerged as a promising alternative to liver transplantation for treating IMDs.

Familial hypercholesterolemia (FH) is and IMD characterized by elevated LDL-C levels resulting in premature cardiovascular disease. CRISPR-Cas9-mediated gene editing to disrupt the gene encoding angiopoietin-like 3 (ANGPTL3) in the liver represents a novel therapeutic approach for FH. Nonviral delivery performed ex vivo is safer than systemic delivery because gene editing is in …

Deciphering And Translating Bioinspired Structures For Engineering Materials Design Via Computational Modeling And Machine Learning, Zhangke Yang

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Nature has evolved extraordinary structural materials—such as nacre, bone, and the mantis shrimp’s dactyl club—that achieve remarkable combinations of strength, toughness, and impact resistance. These properties arise from sophisticated synergies between structure and composition. Inspired by these biological systems, this dissertation presents a comprehensive investigation into bioinspired materials, uncovering fundamental mechanisms and providing guidance on designing materials with superior mechanical properties.

This dissertation begins by examining the "brick-and-mortar" structure of nacre, which informs the design of layered polymer-graphene nanocomposite films. Using coarse-grained molecular dynamics simulations, I elucidate mechanisms of dynamic wave propagation and energy dissipation in these systems, providing critical …

Understanding The Role Of Ligamentous Constraint In Trapeziometacarpal Pathomechanics, Lizzie Walker

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The trapeziometacarpal (TMC) joint is the most common site for osteoarthritis (OA) in the upper limb. This joint is characterized by its wide range of motion and limited bony stability, making it susceptible to OA. The TMC joint relies mostly on ligaments and muscles for its static and dynamic stability, respectively. While importance of both volar and dorsal capsular TMC stabilizers has been demonstrated, the role of TMC ligamentous tissues in the development of thumb basal joint OA remains unclear.

The goal of this work was to identify morphometric and mechanical changes in key TMC ligament stabilizers, including the volar …

The Effects Of Cigarette Smoke Extract On Osteoarthritis In A Primary Joint Tissue Explant Model, Emily Sawvell

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Osteoarthritis (OA) is the most common degenerative joint disease in the world with an economic burden of nearly $140 billion annually. Factors identified to increase the risk of developing OA include age, obesity, sex, race, genetics, and previous joint injury. However, one risk factor that has been scarcely studied in OA etiology is cigarette smoking. While some studies have reported smoking to protect against OA, increasing evidence suggests that cigarette smoking results in more severe and painful OA, increases the rate of developing OA, and reduces the efficacy of pain medications and arthritis-targeting therapies. Despite this, the impact of cigarette …

Understanding Dimensional Stability Of Polymer Surgical Mesh, Simeon J. Mckelvey

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Polymer surgical mesh is a biomedical implant that has revolutionized the repair of the abdominal wall and pelvic floor. Each year, over 1.6 million Americans undergo surgical procedures using polymer surgical mesh to treat conditions where internal organs protrude through weakened tissues. This material is used in approximately 90% of hernia repairs, 80% of stress urinary incontinence procedures, and 30% of pelvic organ prolapse surgeries.

Despite this widespread use of polymer surgical mesh, post-implantation complications have prompted regulatory investigation and scrutiny. These complications stem from the mesh's behavior within the human body, including wrinkling, contraction, and loss of fixation, which …

The Clot Thickens: Investigation Of The Mechanism Behind Hypercoagulation In Covid-19 Patients, Toni Warnick

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Since its emergence in 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been associated with cardiovascular complications, which correlate with illness severity and increased mortality. It was initially thought that this hypercoagulable state was induced by endothelial dysfunction or cytokine storm because of SARS-CoV-2 infection. Although platelets have been reported to express the SARS-CoV-2 primary target receptor, angiotensin-converting enzyme 2 (ACE2), this remains controversial due to conflicting findings that suggest minimal to no ACE2 expression on platelets. This ambiguity has led to exploring alternative entry pathways, notably via the virus’s RGD (arginine-glycine-aspartic acid) sequence within its spike protein receptor-binding …

Optimization Of Polymeric Micelles As A Delivery System For Crispr/Cas9 Ribonucleoprotein, Lucian Williams

All Dissertations

Clustered regularly interspaced short palindromic repeats (CRISPR) is an adaptive immune system in bacteria that has been harnessed to perform precise genetic modifications in mammalian cells. Among CRISPR-associated (Cas) proteins, Cas9 has emerged as a transformative tool in gene editing due to its simplicity, high specificity, and versatility compared to the other Cas proteins and gene-editing technologies. Despite its potential to cure genetic disorders, the clinical application of Cas9 has been hindered by challenges such as immunogenicity, off-target effects, and low delivery efficiency. To address these issues, this dissertation explores using polymeric nanoparticle systems to encapsulate and protect Cas9 and …

Multifunctional Peptides To Improve Nucleic Acid Delivery For Ovarian Cancer Treatment, Kharimat Lora Alatise

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RNA interference (RNAi) therapies, such as small interfering RNA (siRNA), offer a high-precision approach to reducing the expression of disease-promoting genes with minimal off-target effects. For aggressive diseases like ovarian cancer, RNAi therapy can serve as a robust treatment modality if delivered successfully. Over 70% of ovarian cancer patients are diagnosed in stages three and four, where the disease becomes more difficult to treat. High relapse rates and drug resistance in these stages demonstrate the need for novel strategies to sensitize tumors to chemotherapy, making siRNA a promising avenue for targeting resistance-associated oncogenes.

However, the delivery of siRNA remains a …

Modeling Instrument Design Risks In Medical Device Reprocessing, Manuel Andres Gutierrez

All Dissertations

Medical device reprocessing is an essential practice in healthcare delivery. While FDA regulations require device manufacturers to develop and validate reprocessing procedures, the increasing complexity of medical device designs and their use environments can increase the risks of inadequate reprocessing and associated device malfunctions and potential patient injury. While some design features present known difficulties for reprocessing, critical information needed to define relative risks or feature-specific parameters that increase or decrease risks of inadequate reprocessing is lacking. There is an urgent need for tools to quantify and predict reprocessing risks associated with design features used in surgical instruments.

The broad …

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

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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 …

Measuring Cannulation Behavior On A Sensorized Simulator: Development, Verification, And Testing Of System Components, Lydia Petersen

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End Stage Kidney Disease (ESKD) is a significant public health burden in the United States. Life-sustaining hemodialysis, required up to three times a week for ESKD patients, necessitates a functioning vascular access. For proper cannulation, cannulators have many factors to consider, including an AVF’s geometry, depth, diameter, and other details. Poor cannulation can lead to infiltration, where the needle punctures the vessel wall. Infiltration occurs in as many as 50% of cannulations, causing complications ranging from hematoma and swelling to delayed treatment or loss of vascular access. This highlights the need for objective, standardized training methods to improve cannulation skills …

Fluid-Solid Coupled Analysis Of Biological Samples In A Flow Chamber Using Optical Coherence Tomography, Reece W. Fratus

All Dissertations

Forces from fluid flow on a tissue or cellular boundary can drive remodeling processes through mechanotransduction pathways. In most cases, the exact mechanisms are not understood, such as in marine biofilm development or vascular remodeling. To gain a better understanding of these interactions, the flow profile at a solid boundary and the mechanical changes of that solid can be coupled together to determine the impact of fluid flow on mechanical remodeling. To achieve this, optical coherence tomography (OCT) is used to image the fluid and solid simultaneously. Fluid seeded with particles can be imaged and run through a particle image …

Contribution Of Collagen Type I To The Mechanical Properties Of Myocardial Tissues At The Micron Level, Adam Baker

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Collagen is a critical component of the organization and one of the key factors contributing to the mechanical stability of the myocardium. Where cardiomyocytes actuate to contract the heart and deliver blood to the lungs and the entire body, the local collagen network must be able to support the mechanical needs of the heart by enhancing rigidity, reducing the mechanical responsibility of cells, and increasing compliance to add loading capacity during diastole. At an organ-wide level, this has been measured and modeled in many ways. At the tissue level, the mechanical properties have been evaluated using techniques such as bi-axial …

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 …

Computer Vision Algorithms For Assessment Of Surgical Suturing Skill Using Hand And Needle Motion, Jianxin Gao

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Surgical suturing skill assessment is a crucial part of surgical education. Vascular surgery educators have developed a simulation-based examination called Fundamentals of Vascular Surgery, which includes a clock-face model for assessing open surgical suturing skills. The clock-face model, however, requires the valuable time of expert surgeons to determine examinees' skills. Moreover, expert surgeons have different judgments for appropriate sutures, which leads to inconsistent grading. These limitations motivate us to use sensors to measure examinees' needle motions and hand motions during the clock-face suturing exercises, and then use the measurements for objective suturing skill assessment.

To assess suturing skills based on …

Novel Meta-Materials Application For Pressure-Offloading Of Diabetic Foot Ulcers, Kyle Walker

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Diabetes and its associated complications have seen their prevalence sharply rise in the United States over the past few decades. In fact, the prevalence of diagnosed diabetes has nearly doubled from 5.1% of the US population in 1988, to 9% in the most recent CDC report, which does not include the large percentage of the population with undiagnosed or prediabetes. Of this diabetic population, it is estimated that up to 34% will experience at least one foot ulcer during their lifetime. In worst case scenarios, these ulcers can become infected and eventually require amputation of a portion of, or the …

The Development Of A Novel Cartilage Analog Scaffold For Chondral Regeneration, Vishal Thomas

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Focal Chondral Defects (FCDs) are cartilage injuries that affect about 900,000 Americans every year. Left untreated, these may lead to osteoarthritis and eventually necessitate painful knee replacements. Current treatment options are limited in terms of durability, cost, and availability of grafts. Tissue engineering, using natural scaffolds, are a highly attractive alternative promising cost efficiency, abundance, and long-term benefits. However, their low mechanical strength and dense matrices are impediments that could lead to sub-optimal repair.

In this work, a natural biomaterial, the bovine nucleus pulposus (bNP), derived from intervertebral disc tissue, was identified as a candidate scaffold for cartilage regeneration. Mechanical …

An In Vitro Investigation Of Urothelial Cell Function In Response To Hypoxia And Pressure In Relation To Bladder Outlet Obstruction, Britney Hudson

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Bladder outlet obstruction (BOO) is a prevalent urological condition and can be characterized by the presence of lower urinary tract symptoms (LUTS), such as hesitancy, weak stream, and nocturia. The main cause of BOO is a partial blockage of the urethra, which results in elevated voiding pressure, high storage pressure, and tissue ischemia, which are thought to be the triggers of bladder inflammation and subsequent fibrosis. Often patients do not seek treatment until the conditions get severe. Thus, it would be ideal to have an early diagnostic tool to detect changes in the bladder due to BOO. Extracellular vesicles (EVs) …

Locally Injectable Peptide Hydrogel For Conversion Of Temozolomide And Codelivery Of Sirna In Glioblastoma Multiforme Treatment, Megan Pitz

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Traditional treatment methods for glioblastoma multiforme (GBM) are largely unsuccessful, with a 5-year survival rate of 5.6%. Temozolomide (TMZ), the only chemotherapy FDA-approved for GBM treatment, is a hydrophobic prodrug that is stable in an acidic pH and begins converting to its active form at a physiological pH of 7.4. However, complete conversion of TMZ is observed only at a higher pH, and only about 30% of administered TMZ reaches the central nervous system. Therefore, there is a need for new treatment methods that maximize TMZ delivery to and efficacy at the tumor site. Self-assembling peptides are a unique class …

Tin-Silver As A Novel Biodegradable Metallic Biomaterial, Charley Goodwin

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The Essure device is a non-hormonal, minimally-invasive, permanent female sterilization implant, removed from the market due to an increase in adverse events, hypothesized to be caused by corrosion of the Sn-Ag component of the implant. The goals of this dissertation were to first develop implant retrieval methods for Essure devices and surrounding tissue, documenting signs of degradation and metallic degradation products, then to characterize the electrochemical behavior of Sn-Ag in biologically representative environments and finally, to assess the biological interaction of Sn-Ag. Retrieval analyses developed successful methods, qualifying the degree of corrosion, primarily of the Sn-Ag component and finding Sn …