Engineering Commons^™

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 …

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 …

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

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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 …

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 …

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) …

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 …

Experimental And Computational Platforms For Studying Systems Mechanobiology, Brendyn Miller

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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 …

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

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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 …

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

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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 …

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

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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 …

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 …

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

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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 …

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

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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, …

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 …

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

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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 …

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

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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 …

Investigating Spatial Heterogeneity In Myocardial Wound Environments To Improve Therapy, Michael Potter

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Heart failure is a broad pathology manifestation categorized by an inability of the heart to successfully pump blood throughout the vast vessel network of the body. Within the United States, heart failure is projected to increase by approximately 46% from 2012 to 2030. Modalities of heart failure are generally related to wall mechanics that are impacted following myocardial infarction events. Interplay exists between the wall mechanics, responding cell populations, and the spatial heterogeneities in the resultant scar. This interplay directs the myocardium towards heart failure modalities governed by overly stiff or compliant states. It is essential to elucidate details underlying …

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

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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

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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, …

Development Of A Tissue Engineered Cardiac Patch, Howard Herbert

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Cardiovascular Disease(CVD) is the leading cause of mortality in the developed world. CVD is most commonly manifested as atherosclerosis of the coronary arteries leading to Myocardial Infarction(MI). After MI, fibrosis of the ventricular wall leads to heart failure(HF), a pandemic affecting 26 million people globally. While therapies are continuously developed to combat HF, the treatment of choice, whole heart transplant, is limited by the availability of donor hearts. It is clear that there is a need to develop a long-term solution to combat HF and its enormous economic burden. Tissue Engineering and Regenerative Medicine holds promise as a possible solution …

Highly Adherent Antimicrobial Coatings For Orthopedic Implants, Mikhail Bredikhin

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Fracture-related infections (FRIs) are the most devasting sort of complications associated with fracture fixation devices, as they lead to patients’ morbidity, prolonged hospitalization, amputations, and even death.External fixators additionally suffer from pin site infections (PSIs), which initiate at the skin entry points of the skin-metallic pin interface present in the external fixation of the damaged bones, often causing deep tissue infection and osteomyelitis. Small percutaneous pins, commonly known as Kirschner wires (K-wires), are used to treat complex fractures and deformities.They are drilled inside the diseased bone for the healing period and are left protruding outside the skin for fixation adjustments …

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

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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, …

Using In Vitro, In Silico, And In-Classroom Techniques To Address The Gender Data Gap In Health Care, Kelsey Watts

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Cardiovascular diseases (CVDs) are the leading cause of death worldwide in males (XY) and females (XX). Prior to menopause, females have a relative protection against serious cardiac pathologies compared to age-matched males. This phenomenon is widely attributed to the ovarian hormone estrogen. Unfortunately, hormone replacement therapy to maintain estrogen levels in postmenopausal females has overall adverse effects, and it is not recommended for long-term use or as a preventative measure for eCVDs. A major driver of CVDs, specifically heart failure, is cardiac fibrosis: the continued buildup of scar tissue that reduces the heart’s ability to pump. There are currently no …

The Development And Analysis Of Methods Used To Evaluate American Football Facemasks, Alexander Bina

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The motivation for this Ph.D. dissertation is to provide football equipment managers, coaches, parents, athletes, and relevant industry personnel with an understanding of the implication a chosen football facemask design will have on the safety of the athlete. As athletes have increased their capacity for speed, size, and strength, so too has the head injury risk increased in American football. To align with the increase in head impact injury in American football, the protective head impact community must expand its capacity to evaluate protective equipment systems. This dissertation focuses specifically on one helmet system component: the football facemask. This dissertation …

Development Of A Reverse Engineered, Parameterized, And Structurally Validated Computational Model To Identify Design Parameters That Influence American Football Faceguard Performance, William Ferriell

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Traumatic brain injury (TBI) continues to have the greatest incidence among athletes participating in American football. The headgear design research community has focused on developing accurate computational and experimental analysis techniques to better assess the ability of headgear technology to attenuate impacts and protect athletes from TBI. Despite efforts to innovate the headgear system, minimal progress has been made to innovate the faceguard. Although the faceguard is not the primary component of the headgear system that contributes to impact attenuation, faceguard performance metrics, such as weight, structural stiffness, and visual field occlusions, have been linked to athlete safety. To improve …

Multi-Scale Vertebral-Kinematics Based Simulation Pipeline Of The Human Spine With Application To Spine Tissues Analysis, Mohd Jaradat

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This study developed an analytical tool for understanding spine tissues’ behavior in response to vertebral kinematics and spine pathology over a range of body postures. It proposed a novel pipeline of computational models based on predicting individual vertebral kinematics from measurable body-level motions, using musculoskeletal dynamics simulations to drive the vertebrae in corresponding spine FEMs.

A reformulated elastic surface node (ESN) lumbar model was developed for use in MSD simulations. The ESN model modifies the lumbar spine within an existing MSD model by removing non-physiological kinematic constraints and including elastic IVD behavior. The model was scaled using subject-specific anthropometrics and …

Mitral Valve Tissue Engineering - A Dynamic Model For Investigating The Mechanism Of Valvular Pathology, Collin Owens

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Heart valve disease affects an average of 2.5% of the population in the United States. The mitral valve (MV) is the most complex of the heart’s four valves and is most associated with the disease by exhibiting altered extracellular matrix (ECM) which translates into stenosis or regurgitation. These diseases are typically degenerative in nature and can be accelerated by risk factors such as diabetes and hypertension. With diabetes and hypertension affecting 425 million and 1.39 billion people worldwide, further investigation into these risk factors is warranted. This study aims to develop and test an in vitro model of MV disease. …

Synthesis Of Monodisperse Nanoscintillators At High Temperatures For Biomedical Relevant Applications, Eric Zhang

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Luminescent sub-100 nm particulates continuously generate immense research interest in the biomedical field for imaging, theranostics, and optogenetics. Conventionally, upconversion nanoparticles or UV activated semiconductors are studied, however these materials are limited by biological barriers such as the skin which reduces the penetration depth of these excitation sources, tissue's auto- fluorescence, and toxicity. One approach to overcome these challenges is to use nanoscintillators (sub-100 nm materials that can generate visible light using high energy excitation sources such as x-rays) which can generate light locally to the human body. Numerous scintillators have been reported since the discovery of x-rays from the …

Development And Application Of 3d Kinematic Methodologies For Biomechanical Modelling In Adaptive Sports And Rehabilitation, Anne Marie Severyn

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Biomechanical analysis is widely used to assess human movement sciences, specifically using three-dimensional motion capture modelling. There are unprecedented opportunities to increase quantitative knowledge of rehabilitation and recreation for disadvantaged population groups. Specifically, 3D models and movement profiles for human gait analysis were generated with emphasis on post-stroke patients, with direct model translation to analyze equivalent measurements while horseback riding in use of the alternative form of rehabilitation, equine assisted activities and therapies (EAAT) or hippotherapy (HPOT). Significant improvements in gait symmetry and velocity were found within an inpatient rehabilitation setting for patients following a stroke, and the developed movement …