Biomedical Engineering and Bioengineering Commons^™

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

All Dissertations

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

Development Of A Tissue Engineered Cardiac Patch, Howard Herbert

All Dissertations

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

All Dissertations

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 …

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

All Dissertations

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 …

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

All Dissertations

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

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

All Dissertations

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

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

A Protocol For Coupling Volumetrically Dynamic In Vitro Experiments To Numerical Physiology Simulation For A Hybrid Cardiovascular Model, Abraham Umo, Ethan Kung

Publications

Objective: The Physiology Simulation Coupled Experiment (PSCOPE) is a hybrid modeling framework that enables a physical fluid experiment to operate in the context of a closed-loop computational simulation of cardiovascular physiology. Previous PSCOPE methods coupled rigid experiments to a lumped parameter network (LPN) of physiology but are incompatible with volumetrically dynamic experiments where fluid volume varies periodically. We address this limitation by introducing a method capable of coupling rigid, multi-branch, and volumetrically dynamic in-vitro experiments to an LPN. Methods: Our proposed method utilizes an iterative weighted-averaging algorithm to identify the unique solution waveforms for a given PSCOPE model. We confirm …

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

All Dissertations

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. …

Optimizing Crispr/Cas9-Mediated Knockdown Of Angptl3 In Liver Cell Lines And Mouse Hepatocytes, Meredith Reeves

All Theses

Familial hypercholesterolemia (FH) is a genetic condition characterized by elevated levels of low-density lipoprotein cholesterol (LDL-C) that leads to an increased risk of developing cardiac disease early in life (Shah et al., 2020). Current treatments such as statins and PCSK9 inhibitors have helped lower LDL-C levels, however they require repeated administration every 4-6 weeks to remain effective (Raal et al., 2018). Angiopoietin-like 3 (ANGPTL3) is an inhibitor of plasma lipid metabolism that has become a promising molecular target for the treatment of FH. Individuals with non-functional copies of ANGPTL3 demonstrate low levels of plasma LDL-C and triglycerides, indicating a protective …

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

All Dissertations

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 …

Soft Robotic Arms For Fall Mitigation: Design, Control And Evaluation, Param Malhotra

All Theses

Most fall mitigation devices present a heavy system that avoid injuries to the user by preventing the impact of a fall. They are dependent on the user capability or on the probability that the user falls in the assumed manner the system was designed for. Often that is not the case, hence this project initiates a novel concept of using soft robotic arms to prevent falls from happening in the first place itself and save the user from any injuries. This thesis describes the prototype and development of a soft continuum robotic backpack system. The system can validate its use …

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

All Dissertations

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

All Dissertations

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 …

Characterization Of Thermal Gelation Properties In Bioresorbable Thermally Activated Hydrogel Polymers For Hernia Surgery Applications, Alexander Mayfield

All Theses

Hydrogel adhesives are a new class of materials with excellent biocompatibility, which makes them very attractive for biomaterial applications. It has been previously shown that Tetronic T1107, a four-arm poly (propylene oxide)-poly (ethylene oxide) (PPO-PEO) block copolymer, is useful as a chemical crosslinking thermo-responsive hydrogel for bioadhesive applications. The end groups of this polymer are modified with acrylate and N-hydroxysuccinimide (NHS) functional groups. The acrylate end group gives the polymer cohesive properties with long-range chemical crosslinking using dithiothreitol (DTT), while the NHS end group gives the polymer adhesive properties through bonding with amines found in organic tissue. It was found …

Tissue-Engineered Living Pulmonary Valve For Young Adult Patients, Erica Hoskins

All Theses

Cardiovascular disease (CVD) is a non-communicable disease responsible for 659,000 deaths annually in the United States. While CVD can affect all components of the cardiovascular system, heart valve disease is responsible for 25,000 deaths yearly. Of specific interest is the pulmonary valve since there is limited research on resolving pathologies that affect it. Like the aortic and mitral valves, common pathologies include stenosis, regurgitation, and atresia. Notably, the pulmonary valve requires repair and replacement in pediatric patients and young adults due to congenital disabilities. Even with technological advances in valve replacements, limitations still present themselves for use with younger patients …

A 3d Tissue Engineering Model To Study Mitral Valve Annulus Calcification Under Diabetic Conditions, Erin James

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The most complex heart valve is the mitral valve (MV). Many pathologies can affect the MV, including stenosis, regurgitation, prolapse, and mitral annulus calcification (MAC). MAC is chronic degeneration of the annulus, which is the fibrous, saddle-shaped “ring” that can contract and relax with the myocardium. The prevalence of MAC is around 15% but increases in patients with other cardiovascular diseases and risk factors. It is also thought to increase in patients with type 2 diabetes, but MAC has not been properly characterized within this population because of confounding factors such as cardiac disease and kidney disease. The goal of …

Variations In Surgeon-Applied Loads During Passive Range Of Motion Following Total Knee Replacement With Relevance To Computational Modeling, Cj Bakle Ii

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Total knee replacement (TKR) is generally considered a successful treatment for musculoskeletal disorders of the knee. However, as many as 20% of patients report some dissatisfaction in their physical function after TKR. And approximately 50% of early revisions needed to address conditions related to component alignment and soft tissue tension to stabilize the knee. During TKR, surgeons manually perform passive range of motion (ROM) assessments to gain feedback perceived as tension in ligaments and other soft tissues. Such assessments are highly subjective and rely on the surgeon's perception of soft tissue tension rather than quantitative objective means. The variability in …

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

All Dissertations

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 …

Toward Sustainable Urban Food Production: Integrating Hydroponic Cultivation With Wastewater Reuse, Amanda Tan

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The growing crisis of freshwater scarcity together with the increasing global food demand directs attention to the need for alternative water sources for agriculture. The research presented here engages this need by carrying out indoor cultivation of food crops in Nutrient Film Technique (NFT) hydroponic systems using residential wastewater. Randomized single factor experimental designs were used to investigate the physiochemical and microbiological makeup of the hydroponic nutrient solution throughout the cultivation cycle and their relationship with different plant development parameters.

For agricultural wastewater reuse to be of low risk to human health there must be some advancement in pathogen monitoring …

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

All Dissertations

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 …

Nonlinear Optical Microscopy Assessment Of Tissue Structure And Chondrocyte Viability Of Articular Cartilage, Michael Le

All Theses

Articular cartilage functions to protect the ends of bones by providing a surface that can withstand compressive forces and minimize friction during movement. Collagen fibers form the organizational backbone of the extracellular matrix (ECM) in cartilage. Proteoglycans within the ECM function to retain water and provide the tissue with the swelling pressure needed to withstand compressional forces. Chondrocytes, the only type of cell found in articular cartilage, produces these collagen fibers and proteoglycans to maintain the tissue structure and function. Significant injuries to articular cartilage can damage the chondrocytes and disrupt their ability to maintain homeostasis in the tissue. Therefore, …

Insect Antennae As Bioinspirational Superstrong Fiber-Based Microfluidics, Griffin J. Donley

All Theses

Nature is frequently turned to for inspiration for the creation of new materials. Insect antennae are hollow, blood-filled fibers with complex shape, and are cantilevered at the head. The antenna is muscle-free, but the insect can controllably flex, twist, and maneuver it laterally. To explain this behavior, a comparative study of structural and tensile properties of the antennae of Periplaneta americana (American cockroach), Manduca sexta (Carolina hawkmoth), and Vanessa cardui (painted lady butterfly) was performed. These antennae demonstrate a range of distinguishable tensile properties, responding either as brittle fibers (Manduca sexta) or strain-adaptive fibers that stiffen when stretched (Vanessa cardui …

Fabrication Of Hydrogel Microparticles For Acute Treatment Of Penetrating Brain Injuries, Isabell Foulger

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Traumatic brain injuries (TBIs) are a type of acquired head trauma that results from an external force to the head. The development and severity of the secondary injury increases the risk of neurodegeneration and reduced cognitive recovery. Glucocorticoids are potent antiinflammatory therapeutics that have been investigated for potential treatment of TBIs, strokes, and other neuroinflammatory pathologies. However, their clinical application has been limited due to their ability to induce a variety of side effects, including adrenal suppression, edema, and reduced plasticity of the hippocampus. The use of a localized drug delivery system would overcome these systemic concerns. In previous studies, …

Design Of A Four Channel Pulsatile Perfusion Bioreactor For Ex-Vivo Study Of Vascular Grafts, Thomas M. Fair

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Cardiovascular diseases are the leading cause of death in the United States. Atherosclerosis in peripheral arteries is a major contributing factor. Autologous saphenous vein grafts are the most common bypass grafts for treating peripheral artery diseases. A quarter of these grafts fail within a year, and around half have failed within 10 years of the initial surgery. Graft failure is attributed to the development of intimal hyperplasia indicated by the migration and proliferation of vascular smooth muscle cells, fibroblasts, and the deposition of extracellular proteins.

Increases in flow, pressure, the pulse frequency, and the differential of pressure that model an …

Portable U-Bent Optical Fiber Biosensor For Detecting Microcystin-Lr, Quan Dio Anh Le

All Theses

Cyanobacteria are the only known prokaryotes that can photosynthesize. Due to their unique ability, they are important entities in the global carbon and nitrogen cycles. However, two factors can turn cyanobacteria into a nuisance. In general, eutrophication is the process that supplies external nutrients that are needed for cyanobacteria blooms into bodies of water from the surrounding environment. Climate warming intensifies this process by producing carbon dioxide, methane, and nitrous oxide. With cyanobacteria blooms occurring worldwide, they are becoming a bigger threat to human health, and there has been increased interest in detecting cyanobacteria and their toxic byproducts.

For instance, …

Tunable Blood Shunt For Neonates With Complex Congenital Heart Defects, Ellen Garver, Christopher B. Rodell, Kristen Shema, Krianthan Govender, Samantha E. Cassel, Bryan Ferrick, Gabriella Kupsho, Ethan Kung, Kara L. Spiller, Randy Stevens, Amy L. Throckmorton

Publications

Despite advancements in procedures and patient care, mortality rates for neonatal recipients of the Norwood procedure, a palliation for single ventricle congenital malformations, remain high due to the use of a fixed-diameter blood shunt. In this study, a new geometrically tunable blood shunt was investigated to address limitations of the current treatment paradigm (e.g., Modified Blalock-Taussig Shunt) by allowing for controlled modulation of blood flow through the shunt to accommodate physiological changes due to the patient’s growth. First, mathematical and computational cardiovascular models were established to investigate the hemodynamic requirements of growing neonatal patients with shunts and to inform design …