Biomedical Engineering and Bioengineering Commons^™

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 …

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 …

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 …

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 …

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, …

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 …

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, …

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 …

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 …

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, …

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 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 …

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 …

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. …

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 …

Porous Silicon Photonics For Label-Free Interferometric Biosensing And Flat Optics, Tahmid Hassan Talukdar

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This dissertation uses porous silicon as a material platform to explore novel optical effects in three domains: (i) It studies dispersion engineering in integrated waveguides to achieve high performance group index sensing. With proper design parameters, the sensor waveguides can theoretically achieve 6 times larger group index shift compared to the actual bulk effective refractive index shift. We demonstrate the guided mode confinement factor to be a key parameter in design and implementation of these waveguides. (ii) It explores multicolor laser illumination to experimentally demonstrate perceptually enhanced colorimetric sensing, overcoming the limitations faced by many contemporary colorimetric sensors. Our technique …

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 …

Single Asperity Fretting Corrosion Of Traditional And Additively Manufactured Metallic Biomaterials: Quantitative Analysis From Acetabular Tapers To Micron And Nanometer Scale Tribocorrosion, Annsley Mace

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Mechanically assisted crevice corrosion (MACC) of metallic biomaterials continues to be a significant degradation mode. This is, in part, due to a lack of understanding of fundamental micron- and sub-micron scale mechanisms of metal degradation in biological environments. Metal-metal (or metal-hard) load bearing surfaces of hip arthroplasties are subjected to fretting crevice corrosion (FCC, one form of MACC). Current work in tribocorrosion involves large contact area tests with multiple asperities, with a distribution of load and wear that changes over time. A more systematic and controlled study of the FCC micro- and nanomechanics is needed.

Therefore, the goal of this …

Nonviral Approaches For Delivery Of Crispr-Cas9 Into Hepatocytes For Treatment Of Inherited Metabolic Disease, Tanner R. Rathbone

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Inherited metabolic diseases (IMDs) of the liver have a collective occurrence of about 1 in 800 births. Current therapies for IMDs of the liver are limited, and the only curative option for patients is orthotopic liver transplantation. Due to shortages of organ donors, immunosuppression following the transplantation, and mortality risks associated with the procedure, alternative treatment options are necessary for curing IMDs of the liver. Therapeutic gene editing has been proposed as a potential strategy for treating IMDs of the liver. Adeno-associated viral vectors (AAVs) are the most widely used delivery method for liver-targeted gene therapies. Although widely used for …

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 …

Influencing The Inflammatory Response Through Multi-Scale Geometry, Antibiotic Release, And Fluid Management In A Textile-Based Biomaterial Wound Dressing, Elizabeth Gianino

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The total population of diagnosed and undiagnosed diabetes mellitus in the United states is expected to rise by 54% between the years of 2015 and 2030 contributing to $200 billion in health care expense. The exponential rise in common diabetic wounds, such as diabetic foot ulcers, puts a large population at risk for complications such as infection, amputation, and even death. Peripheral neuropathy leading to late diagnoses, patient non-compliance, and lack of holistic treatment options all contribute to complications with the incidence of new ulcer formation after treatment reaching 50%. This work explores the design, development, and in vitro evaluation …

Development Of Solution Blow Spun Nanofibers As Electrical And Whole Cell Biosensing Interfaces, Craig Levar Miller

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Infectious pathogens place a huge burden on the US economy with more than $120 billion spent annually for direct and indirect costs for the treatment of infectious diseases. Rapid detection schemes continue to evolve in order to meet the demand of early diagnosis. In chronic wound infections, bacterial load is capable of impeding the healing process. Additionally, bacterial virulence production works coherently with bacterial load to produce toxins and molecules that prolongs the healing cycle. This work examines the use of nonwoven polymeric conductive and non-conductive nanofiber mats as synthetic biosensor scaffolds, drug delivery and biosensor interface constructs. A custom-made …

Time-Lapse Observation Of Sarcomeric Addition In Hypertrophic Models Based On A Tissue Like Cardiomyocyte Culture, Ailin Wei

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Cardiac hypertrophy is the response of the heart to increased mechanical stress exerted on the heart. In a hypertrophic heart, the muscles elongate or/and thicken with cardiomyocytes growing sizes. It is assumed that cardiomyocytes elongate by adding sarcomeres in series; the cardiomyocytes thicken with the addition of sarcomeres in the parallel position.

In this study, a tissue-like culture model was achieved with step-like ICDs. Uniaxial static stretch has been applied to our unique culture model for studying mechanical-load-induced cardiac hypertrophy. Hypertrophic responses of these cardiomyocytes have been confirmed on transcriptional and translational levels in our tissue-like model. The two-photon excitation …

Development Of A Nucleus Pulposus Implant For Intervertebral Disc Repair, Joshua Dillon Walters

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The intervertebral disc (IVD) is a fibrocartilaginous tissue connecting adjacent vertebrae in the spinal column. It comprises three distinct tissues: a gelatinous core known as the nucleus pulposus (NP), concentric fibrous rings encircling the NP known as the annulus fibrosus (AF), and the superior/inferior cartilaginous endplates (CEPs). The complex mechanical interplay of these tissues allows the IVD to withstand complex loading in the spine while maintaining trunk stability and flexibility. IVD pathologies, such as IVD degeneration (IDD) and herniation, are associated with cell-mediated inflammation in vivo. This inflammation creates a catabolic environment which degrades the extracellular matrix (ECM) of the …

Chemically Active Rheological Modifiers For The Improved Clinical Use Of Cyanoacrylates, Kyle Joseph Garcia

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Over 100 million surgical incisions, 50 million traumatic wounds, and 20 million minor lacerations from cuts and grazes are treated globally each year. One study determined that globally internal and external wounds occur for 40% and 37% of cases respectively for a total of 111 million patients that were treated for wounds. The remaining 23% of patients were treated for minor lacerations and trauma in the emergency room. These wounds require immediate medical attention including pressure application, sutures, clips, tissue cautery, and/or topical hemostatic agents to cease hemorrhage or the exit of other bodily fluids. With blood flow ceased, wound …

Target-Specific Capture Of Relevant Gaseous Compounds Using Natural And Synthetic Nano And Micro Materials, Fernanda Delbuque Guerra

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By definition, volatile organic compounds (VOCs) are organic compounds that easily become vapor or gases. Many VOCs are hazardous air pollutants and often known for their low, often unpleasant, threshold odor, which can be below parts per billion in some cases. Nanotechnology-based materials for the remediation of gaseous pollutants has been the focus of many researchers due to their unique chemical and physical properties and enhanced reactivity when compared to bulkier materials. Among the many challenges preventing the global use of nanomaterials are the high costs of fabrication, on-site recovery, limited scale-up, potential toxicity since many of them rely on …

Low Cost, Carbon-Based Micro- And Nano-Structured Electrodes For High Performance Supercapacitors, Kryssia Pamela Díaz Orellana

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Advances in the development of sustainable, low-cost, and reliable energy storage technologies have become a high priority as the demand for high power, and high energy storage devices has risen with emerging technologies in electronics, transportation, and renewable energy systems. Supercapacitors, due to their relatively high energy density and power density, provide an attractive alternative to bridge the gap between conventional batteries and capacitors. Materials ranging from high surface area, inert carbons to Faradaic metal oxides and conducting polymers have been used to achieve a range of performance properties in supercapacitors. However, the development of new technologies faces many challenges, …