Biomedical Engineering and Bioengineering Commons^™

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

All Dissertations

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

All Dissertations

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 …

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

All Dissertations

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 …

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

All Dissertations

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 …

Photodynamic Therapy To Treat Triple Negative Breast Cancer In Vitro, Hunter S. Warren

All Theses

Triple negative breast cancer (TNBC) is the most resilient form of breast cancer, being one of the leading causes of death for women and making up 7% of all cancer deaths. Photodynamic therapy (PDT) offers a minimally invasive solution to TNBC as a passive-targeting treatment that reduces the need for other well established yet harsh treatments that can be taxing on the patient. PDT involves the use of a high-energy red light on the area of a tumor injected with photosensitizers (PS) that generate reactive oxygen species (ROS) in the tumor, triggering cell death. The PS tetra(hydroxyphenyl)chlorin (m-THPC) was used …

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

All Dissertations

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, …

The Effects Of Compression Wrapping Techniques And Primary Wound Dressings On Leg Skin Interface Pressure, James Cox

All Theses

Peripheral edema affects approximately 20% of people in the US over the age of 50 and is frequently encountered among individuals with conditions such as heart disease, prolonged immobility, and venous insufficiency.¹ Compression is an established therapeutic tool utilized for the management of several chronic edema presentations including lymphedema and venous leg ulcers.^2,3 Therapeutic efficacy of compressive applications can be evaluated by defining interface pressure (IP) and IP distributions associated with specific textile combinations.² During compressive applications where an open wound is present, primary wound dressings should be used in combination with compressive wraps. Primary wound dressings …

Investigating The Potential Of A Cell-Based Gene Editing Therapy For Inherited Metabolic Liver Disease, Ilayda Ates

All Dissertations

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 …

Predicting Corrosion Damage In The Human Body Using Artificial Intelligence: In Vitro Progress And Future Applications Applications, Michael A. Kurtz, Ruoyu Yang, Mohan S. R. Elapolu, Audrey C. Wessinger, William Nelson, Kazzandra Alaniz, Rahul Rai, Jeremy L. Gilbert

Publications

Artificial intelligence (AI) is used in the clinic to improve patient care. While the successes illustrate the impact AI can have, few studies have led to improved clinical outcomes. A gap in translational studies, beginning at the basic science level, exists. In this review, we focus on how AI models implemented in non-orthopedic fields of corrosion science may apply to the study of orthopedic alloys. We first define and introduce fundamental AI concepts and models, as well as physiologically relevant corrosion damage modes. We then systematically review the corrosion/AI literature. Finally, we identify several AI models that may be Preprint …

An In Vivo Biocompatibility Analysis Of A Novel Tissue Regeneration Matrix Using A Pig Model, Shamar Thomas

All Theses

The goal of this project is to develop an injectable bead scaffold to promote tissue regeneration in the void created by lumpectomy and to alleviate post lumpectomy problems by preventing local recurrence and minimizing surgical-related infections. Microbeads were synthesized from collagen type I and crosslinked with tannic acid to form the basis for this injectable therapeutic. Tannic acid acts as a therapeutic anticancer agent. The action mechanisms of tannins in breast cancer cells have been studied with studies showing tannins to be cytotoxic to cancer cells in a dose-dependent manner. Tannic acid induces apoptosis in breast cancer cells via caspase …

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

All Dissertations

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 …

Development Of 3d Ovarian Cancer Spheroids In Vitro And Investigation Of Their Physiological Relevance As Models Of Inherent Chemoresistance, Amanda Murray

Honors College Theses

Ovarian cancer is the sixth leading cause of death among women worldwide, with an average 5-year survival rate of less than 48%. Current clinical treatment methods for this disease are often deemed ineffective because of the innate chemoresistance of tumors due to their microenvironment and architecture. Accurately mimicking chemoresistance with traditional 2D cultures is difficult; therefore, recent years have seen an increase in 3D culturing methods that create cellular spheroids. These spheroids can serve as models of in vivo tumor characteristics due to their hypoxic core, acidic microenvironment, and increased cell-to-cell interactions. This research aims to (1) refine a 3D …

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. …

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

All Theses

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 …

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 …

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 …

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 …

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 …

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

All Dissertations

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 …

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

All Theses

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 …