Biomedical Engineering and Bioengineering Commons^™

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

All Dissertations

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

All Dissertations

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

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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 …

Surgical Suturing Skill Assessment Using Estimated Hand Roll Angle From A Deep-Learning Computer Vision Algorithm, Jianxin Gao, Amir Mehdi Shayan, Simar P. Singh, Joe Bible, Ravikiran Singapogu, Richard E. Groff

Publications

This paper proposes a deep-learning computer vision algorithm to estimate hand roll angles for metric-based assessment of surgical suturing skills. The number of rolls metric, previously calculated directly from IMU data, counts the number of hand roll reversals during a single suture. To calculate this metric using computer vision, we apply a deep-learning algorithm that can reliably estimate hand roll angles after training on suturing videos collected on the SutureCoach simulator. Results show that the estimation accuracy of the deep-learning algorithm is robust to different video backgrounds. The number of rolls metrics were used to analyze suturing performance in the …

The Effect Of Pressure Gradients On Perceived Discomfort, Zachary Bush

All Theses

Introduction:

A pressure gradient is where high and low pressure meet. It is responsible for displacement and irritation of the skin commonly caused by tight bandages, bracelets, or socks. The irritation is at the edge where the skin is displaced by the high and low pressure. An analysis of the effect pressure gradients have on discomfort would have significant medical relevance for any device, fixture, or clothing pressed against the skin at high pressure. This primarily includes prosthetic and orthotic devices.

The bottom surface of the heel provides a naturally circular, uniform pressure profile. This makes it the optimal testing …

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

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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 …

Hyperspectral Image Classification Of Bacteria Using A Deep Convolutional Neural Network, Bruce S. Vogelsberg Jr

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Hyperspectral imaging is a non-invasive imaging method capable of collecting both spatial and spectral information. However, because of the large volume of data collected, much of it is redundant or not useful for classification. Deep learning is a subset of machine learning that uses artificial neurons in a multilayered structure to learn representations from data. One of the main advantages of deep learning is the powerful feature extraction capabilities, which allow the model to learn both high- and low-level features. Convolutional neural networks are a type of deep learning model that have alternating convolutional and pooling layers capable of extracting …

Expandable Tissue-Engineered Living Surgical Pulmonary Heart Valve For Pediatric Patients, Jacob M. Lautenschlager

All Theses

Cardiovascular disease is the most common cause of mortality in developed countries, with 607.74 million cases globally in 2020.^1,2 Advances in medicine have changed the current demographic suffering from heart valve disease into an aging population suffering from degenerative heart valve disease, creating a growing population treated by surgical or transcatheter intervention.^3-6 Current treatments of valvular heart disease are therefore directed toward valve replacements for the adult population, leaving a treatment gap for pediatric patients suffering from heart valve disease.^7-10

Congenital heart defects are defined as structural abnormalities of the heart or intrathoracic great vessels and are …

A Benchtop Analysis Of Pressure Offloading Associated With Custom Socket Inlays In Transtibial Prostheses, Sarah G. Hill

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Approximately 78% of people with lower limb amputations are dissatisfied with the comfort of their prostheses (Quintero-Quiroz & Perez 2019). In the case of lower limb amputations, the residual limb tissue bears far more weight than it was before the amputation. The pressure put on the soft tissue of the residual limb causes discomfort (Brown et al. 2021). In previous work, custom inlays were created, which fit inside the prosthesis and offload pressure, with the goal of helping to increase the comfort and satisfaction of the prosthesis user (Brown et al. 2021). In this project, a benchtop prosthetic socket loading …

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

All Dissertations

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

All Dissertations

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 …

Evaluation And Development Of Tourniquet Test Methods, Catherine Pitts

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Since the beginning of the 21^st century the general perspective on tourniquets has changed to a more positive outlook on their life saving abilities. The US has seen a greater number of mass casualty events, and conflicts across the globe have led to an increased use of tourniquets. The increased demand has also led to faulty counterfeit tourniquets and improvised tourniquets that don not properly occlude blood flow or cause significant nerve damage to the injured limb.

ASTM started designing a tourniquet testing standard with experts in the tourniquet community to cut down on the dangers of tourniquet use. …

The Effect Of Central Screw And Post Vault Containment On Reverse Total Shoulder Arthroplasty (Rsta) Baseplate Stability, Mickaela J. Gunnison

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Reverse total shoulder arthroplasty (RTSA) is a procedure that aims to fix irreversible rotator cuff damage and degenerative glenohumeral joint diseases that hinder arm abduction. One major complication of RTSA is glenoid baseplate failure resulting from increased movement at the bone-baseplate interface. This study examined 36, 12 PCF composite Sawbones® scapulae. The specimens were split equally into 6 study groups, each having different implant configurations with varying baseplate lateralization and central screws or posts. Each specimen was subjected to cyclic shear loading and failure testing on an Instron to determine implant micromotion and load values.

After testing, ANOVA tests were …

Light-Induced Phase Separation Purification For Monoclonal Antibodies, Xuyang Chen

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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

All Dissertations

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 …

Mammary Epithelial Cell Derived Extracellular Vesicles Influence Tumorigenic Phenotype Suppression In Her2-Positive Breast Cancer Cells, Brenda Okereke

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On a global scale, breast cancer remains the most commonly diagnosed cancer in the world. In 2020 alone, there were over 2.3 million new cases of breast cancer seen and a total of 685,000 deaths globally, this represents 16% or 1 in every 6 cancer deaths seen in women. By 2040 it is projected that the breast cancer burden will rise by over 40% to exceed 3 million new cases a year. Further understanding of the underlying biology and mechanisms behind tumor progression and breast cancers such as HER2+ breast cancer would allow for new therapeutic treatment targets to emerge. …

Development Of Advanced Simulator-Based Metrics For Suturing Skills Assessment And Feedback, Simar Singh

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Vascular surgery demands highly skilled suturing to manipulate and connect delicate vasculature. However, inadequate methods for open suturing skills training necessitate efficient and objective methods to develop skills. To address this need, medical training simulators for objective surgical skills training are gaining popularity for their formative assessment.

This research details the development of a system to classify suturing performance and provide feedback on a suturing skills measurement and feedback platform (called the SutureCoach). The SutureCoach simulator offers a comprehensive assessment of skill through sensors measuring needle driver motions, membrane forces and torques, subcutaneous suture needle movement, and hand motions. We …

Mesenchymal Stromal Cell Response To Degenerated Intervertebral Disc-Like Ph, Kyle Cannon

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Intervertebral disc degeneration (IVDD) has become increasingly prevalent and is a common contributing factor to low back pain. There are currently no clinical treatment options for IVDD that alleviate the symptoms of IVDD while simultaneously promoting repair of IVD tissue. One treatment option being explored is intradiscal administration of mesenchymal stromal cells (MSCs). However, the microenvironment of the degenerating IVD places significant stress on both native IVD cells and implanted cells. There are several questions that need to be addressed which may help further inform the development of efficacious intradiscal MSC therapies for IVDD. These questions include: 1) Do MSCs …

Identifying Temporomandibular Disorder Morphological Risk Factors Via Explainable Deep Learning And Multiscale Biomechanical Modeling, Shuchun Sun

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Clarifying multifactorial musculoskeletal disorder etiologies supports risk analysis and development of targeted prevention and treatment modalities. Deep learning enables comprehensive risk factor identification through systematic analysis of disease datasets but does not provide sufficient context for mechanistic understanding, limiting clinical applicability for etiological investigations. Conversely, multiscale biomechanical modeling can evaluate mechanistic etiology within the relevant biomechanical and physiological context. We propose a hybrid approach combining 3D explainable deep learning and multiscale biomechanical modeling; we applied this approach to investigate temporomandibular joint (TMJ) disorder etiology by systematically identifying risk factors and elucidating mechanistic relationships between risk factors and TMJ biomechanics and …