Biomedical Engineering and Bioengineering Commons^™

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

All Dissertations

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 …

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

All Dissertations

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

All Dissertations

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 …

Systematic Review And Regression Modeling Of The Effects Of Age, Body Size, And Exercise On Cardiovascular Parameters In Healthy Adults, Aseem Pradhan, John Scaringi, Patrick Gerard, Ross Arena, Jonathan Myers, Leonard A. Kaminsky, Ethan Kung

Publications

Purpose

Blood pressure, cardiac output, and ventricular volumes correlate to various subject features such as age, body size, and exercise intensity. The purpose of this study is to quantify this correlation through regression modeling.

Methods

We conducted a systematic review to compile reference data of healthy subjects for several cardiovascular parameters and subject features. Regression algorithms used these aggregate data to formulate predictive models for the outputs—systolic and diastolic blood pressure, ventricular volumes, cardiac output, and heart rate—against the features—age, height, weight, and exercise intensity. A simulation-based procedure generated data of virtual subjects to test whether these regression models built …

Plaque Contact Surface Area And Flow Lumen Volume Predict Stroke Risk In Extracranial Carotid Artery Stenosis, Ryan Gendey, Ethan Kung, Veena Mehta, Adam Brown, Matthew Bridges, Ravi Veeraswamy

Publications

The standard indication for intervention in asymptomatic disease is currently percent stenosis in the internal carotid artery as measured by the NASCET method, which remains limited in discriminating power. CT angiography (CTA) is widely used to calculate NASCET stenosis but also offers the opportunity to analyze carotid artery plaques from a morphological perspective that has not been widely utilized. We aim to improve stroke risk stratification of patients with carotid artery stenosis using plaque 3D modeling and image analysis. Patients with CTAs appropriate for 3D reconstruction were identified from an NIH designated stroke center database, and carotid arteries were segmented …

Hemodynamic Response To Device Titration In The Shunted Single Ventricle Circulation - A Patient Cohort Modeling Study, Chet Villa, Farha Zafar, Angela Lorts, Ethan Kung

Publications

Clinical outcomes of ventricular assist device (VAD) support for shunted single ventricle patients trail the larger population due in part to the challenges in optimizing VAD support and balancing systemic and pulmonary circulations. We sought to understand the response to VAD titration in the shunted circulation using a lumped-parameter network modeling six patient-specific clinical cases. Hemodynamic data from six patients (mean body surface area = 0.30 m²) with a systemic-to-pulmonary shunt was used to construct simulated cases of heart failure and hemodynamic response to increasing VAD flow from 5 to 10 L/min/m². With increasing VAD flow, …

A Comparison Of Methods To Measure Crop Water Use In South Carolina, Andrew C. Ewing

All Theses

The objective of this thesis was to compare cost-effective methods of measuring crop water use, known as evapotranspiration (ET), in South Carolina’s humid climate. The methods analyzed were the surface renewal method (SR), the Eddy Covariance method (EC), large in-field weighing lysimeters, a newly developed pressure differential device (PDD), a Class A Evaporation pan, and the Penman-Monteith equation. In the first chapter, ET measurements obtained by SR were compared to ET measured by EC and weighing lysimeters. For reference, EC and SR track the energy budget to estimate ET, while the weighing lysimeters used in this study are box-like containers …

Mechanical Analysis Of Double Network Hydrogels To Determine Suitability As An Articular Cartilage Substitute, Casey Virginia Young

All Theses

The Center for Disease Control has found that between 2013-2015, 26% of women and 19% of men reported doctor-diagnosed cartilage disease or damage. Currently, there exists a substantial population with cartilage damage or disease needing a solution to increasing pain and decreasing function and mobility. Many of these individuals are young and thus looking for a treatment to delay a total knee replacement. Many others are elderly and thus looking to avoid major surgeries, as the riskiness of these procedures increases with age. As researchers look towards a method of cartilage replacement, hydrogels show measurable potential as a synthetic substitute …

Target Flow-Pressure Operating Range For Designing A Failing Fontan Cavopulmonary Support Device, Masoud Farahmand, Minoo N. Kavarana, Phillip M. Trusty, Ethan Kung

Publications

Fontan operation as the current standard of care for the palliation of single ventricle defects results in significant late complications. Using a mechanical circulatory device for the right circulation to serve the function of the missing subpulmonary ventricle could potentially stabilize the failing Fontan circulation. This study aims to elucidate the hydraulic operating regions that should be targeted for designing cavopulmonary blood pumps. By integrating numerical analysis and available clinical information, the interaction of the cavopulmonary support via the IVC and full assist configurations with a wide range of simulated adult failing scenarios was investigated; with IVC and full assist …

Risks And Benefits Of Using A Commercially Available Ventricular Assist Device For Failing Fontan Cavopulmonary Support: A Modeling Investigation, Masoud Farahmand, Minoo N. Kavarana, Ethan Kung

Publications

Fontan patients often develop circulatory failure and are in desperate need of a therapeutic solution. A blood pump surgically placed in the cavopulmonary pathway can substitute the function of the absent sub-pulmonary ventricle by generating a mild pressure boost. However, there is currently no commercially available device designed for the cavopulmonary application; and the risks and benefits of implanting a ventricular assist device (VAD), originally designed for the left ventricular application, on the right circulation of failing Fontan patients is not yet clear. Moreover, further research is needed to compare the hemodynamics between the two clinically-considered surgical configurations for cavopulmonary …

High Gravity Fermentation Of Sugarcane Bagasse Hydrolysate By Saccharomyces Pastorianus To Produce Economically Distillable Ethanol Concentrations: Necessity Of Medium Components Examined, Sarah W. Harcum, Thomas P. Caldwell

Open Access Publishing Fund

A major economic obstacle in lignocellulosic ethanol production is the low sugar concentrations in the hydrolysate and subsequent fermentation to economically distillable ethanol concentrations. We have previously demonstrated a two-stage fermentation process that recycles xylose with xylose isomerase to increase ethanol productivity, where the low sugar concentrations in the hydrolysate limit the final ethanol concentrations. In this study, three approaches are combined to increase ethanol concentrations. First, the medium-additive requirements were investigated to reduce ethanol dilution. Second, methods to increase the sugar concentrations in the sugarcane bagasse hydrolysate were undertaken. Third, the two-stage fermentation process was recharacterized with high gravity …

An Algorithm For Coupling Multibranch In Vitro Experiment To Numerical Physiology Simulation For A Hybrid Cardiovascular Model, Ehsan Mirzaei, Masoud Farahmand, Ethan Kung

Publications

The hybrid cardiovascular modeling approach integrates an in vitro experiment with a computational lumped‐parameter simulation, enabling direct physical testing of medical devices in the context of closed‐loop physiology. The interface between the in vitro and computational domains is essential for properly capturing the dynamic interactions of the two. To this end, we developed an iterative algorithm capable of coupling an in vitro experiment containing multiple branches to a lumped‐parameter physiology simulation. This algorithm identifies the unique flow waveform solution for each branch of the experiment using an iterative Broyden's approach. For the purpose of algorithm testing, we first used mathematical …

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

All Dissertations

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 …

Factors Affecting Cardiovascular Physiology In Cardiothoracic Surgery: Implications For Lumped-Parameter Modeling, Joshua Kaufmann, Ethan Kung

Publications

Cardiothoracic surgeries are complex procedures during which the patient cardiovascular physiology is constantly changing due to various factors. Physiological changes begin with the induction of anesthesia, whose effects remain active into the postoperative period. Depending on the surgery, patients may require the use of cardiopulmonary bypass and cardioplegia, both of which affect postoperative physiology such as cardiac index and vascular resistance. Complications may arise due to adverse reactions to the surgery, causing hemodynamic instability. In response, fluid resuscitation and/or vasoactive agents with varying effects may be used in the intraoperative or postoperative periods to improve patient hemodynamics. These factors have …

A Hybrid Experimental‐Computational Modeling Framework For Cardiovascular Device Testing, Ethan Kung, Masoud Farahmand, Akash Gupta

Publications

Significant advances in biomedical science often leverage powerful computational and experimental modeling platforms. We present a framework named physiology simulation coupled experiment (“PSCOPE”) that can capitalize on the strengths of both types of platforms in a single hybrid model. PSCOPE uses an iterative method to couple an in vitro mock circuit to a lumped-parameter numerical simulation of physiology, obtaining closed-loop feedback between the two. We first compared the results of Fontan graft obstruction scenarios modeled using both PSCOPE and an established multiscale computational fluid dynamics method; the normalized root-mean-square error values of important physiologic parameters were between 0.1% and 2.1%, …

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

All Dissertations

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 …

Mechanically Assisted Electrochemical Degradation Of Alumina-Tic Composites, Hetal Umesh Maharaja, Guigen Zhang

Publications

Alumina-TiC composite material is a tough ceramic composite with excellent hardness, wear resistance and oxidation resistance in dry and high-temperature conditions. In aqueous conditions, however, it is likely to be electrochemically active facilitating charge transfer processes due to the conductive nature of TiC. For application as an orthopedic biomaterial, it is crucial to assess the electrochemical behavior of this composite, especially under a combined mechanical and electrochemical environment. In this study, we examined the mechanically assisted electrochemical performance of alumina-TiC composite in an aqueous environment. The spontaneous electrochemical response to brushing abrasion was measured. Changes in the magnitude of electrochemical …

Regeneration Of The Ventricular Endocardium Within Acellular Whole Rabbit Hearts Using A Layer-By-Layer Seeding Method, Clayton Lewis Compton

All Theses

In the United States, 1 out of every 9 death certificates in 2013 referenced heart failure.1 Despite the outstanding need of treatment options for heart failure, heart transplantation remains the optimal treatment method. However, there is a severe shortage of donor hearts available for transplantation.2 Other available treatment options are not ideal because they do not fully restore function and are associated with creating other complications.3 Thus, there is a need for developing a living tissue engineered whole heart for transplantation to provide an alternative option for patients on the waitlist to receive a donor heart.

Our solution is to …

Cardiovascular Biomechanical Models, Ethan Kung

Publications

Computational and in vitro methods offer powerful means to model the cardiovascular system and investigate biomechanics related to blood flow, cardiovascular tissue, and medical devices. These models can be constructed to directly describe human anatomy and physiology, and can be more highly controlled compared to animal models. Low-order models composed of lumped-parameter elements and simplified descriptions of cardiac function can capture the global physiology, while high-order models exhibiting detailed 3D anatomy and dynamics can provide highly realistic replication of biomechanical interactions in a small region of the circulation. Multiscale models offer the freedom to capture biomechanics in different regions at …

Multiscale Modeling Of Cardiovascular Flows, Alison Marsden, Ethan Kung

Publications

Simulations of blood flow in the cardiovascular system offer investigative and predictive capabilities to augment current clinical tools. Using image-based modeling, the Navier-Stokes equations can be solved to obtain detailed 3-dimensional hemodynamics in patient-specific anatomical models. Relevant parameters such as wall shear stress and particle residence times can then be calculated from the 3D results and correlated with clinical data for treatment planning and device evaluation. Reduced-order models such as open or closed loop 0D lumped-parameter models can simulate the dynamic behavior of the circulatory system using an analogy to electrical circuits. When coupled to 3D simulations as boundary conditions, …

The Effect Of Surface Roughness Modifications And Chitosan Surface Coatings On Biofilm Formation For Prevention Of Orthopaedic Infections, Nathan Dewayne Smith

All Theses

Infections have been reported to occur in up to 91% of patients after orthopaedic procedures. Many of these infections are caused by bacterial biofilm growth on the surface of the implanted device. Surface modifications of fracture fixation implants have been taken into consideration in order to reduce infection rates and improve clinical results in orthopaedic procedures. Effective surface treatments will also reduce the need for antibiotics and prevent formation of drug-resistant bacteria. Titanium alloy sample discs (N=144) were prepared with six surface roughness treatments through polishing as well as with four different concentrations of chitosan through spin coating. In vitro …

Cancer Cell Redirection Biomarker Discovery Using A Mutual Information Approach, Kimberly Roche, F. Alex Feltus, Jang Pyo Park, Marie-May Coissieux, Chenyan Chang, Vera B.S. Chan, Mohamed Bentires-Alj, Brian W. Booth

Publications

Introducing tumor-derived cells into normal mammary stem cell niches at a sufficiently high ratio of normal to tumorous cells causes those tumor cells to undergo a change to normal mammary phenotype and yield normal mammary progeny. This phenomenon has been termed cancer cell redirection. We have developed an in vitro model that mimics in vivo redirection of cancer cells by the normal mammary microenvironment. Using the RNA profiling data from this cellular model, we examined high-level characteristics of the normal, redirected, and tumor transcriptomes and found the global expression profiles clearly distinguish the three expression states. To identify potential redirection …

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

All Dissertations

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 …

Superior Performance Of Continuous Over Pulsatile Flow Ventricular Assist Devices In The Single Ventricle Circulation: A Computational Study, Tyler Schmidt, David Rosenthal, Olaf Reinhartz, Kirk Riemer, Fei He, Tain-Yen Hsia, Alison Marsden, Ethan Kung

Publications

This study compares the physiological responses of systemic-to-pulmonary shunted single ventricle patients to pulsatile and continuous flow ventricular assist devices (VADs). Performance differences between pulsatile and continuous flow VADs have been clinically observed, but the underlying mechanism remains poorly understood. Six systemic-to-pulmonary shunted single ventricle patients (mean BSA=0.30 m2) were computationally simulated using a lumped-parameter network tuned to match patient specific clinical data. A first set of simulations compared current clinical implementation of VADs in single ventricle patients. A second set modified pulsatile flow VAD settings with the goal to optimize cardiac output (CO). For all patients, the best-case continuous …

A Real-Time Programmable Pulsatile Flow Pump For In Vitro Cardiovascular Experimentation, Rahul Raj Mechoor, Tyler Schmidt, Ethan Kung

Publications

Benchtop in vitro experiments are valuable tools for investigating the cardiovascular system and testing medical devices. Accurate reproduction of the physiologic flow waveforms at various anatomic locations is an important component of these experimental methods. This study discusses the design, construction, and testing of a low-cost and fully programmable pulsatile flow pump capable of continuously producing unlimited cycles of physiologic waveforms. It consists of a gear pump actuated by an AC servomotor and a feedback algorithm to achieve highly accurate reproduction of flow waveforms for flow rates up to 300 ml/s across a range of loading conditions. The iterative feedback …

Development And Initial Validation Of A Surgical Instrument For In Situ Mechanical Characterization Of Surgical Mesh-Tissue Composites, Jorge Ivan Hernandez Sanchez

All Theses

Approximately 5 million Americans have an abdominal wall hernia, and over 700,000 undergo surgical procedures every year to treat them. Surgical procedures have evolved with the goal of preventing recurrences, leading to the current gold standard of treatment: hernia repair with mesh. Hernia repair with mesh consists on augmenting the weakened abdominal wall by implanting a synthetic or biological mesh. Although the adoption of hernia repair with mesh has improved outcomes, recurrence from primary repair procedures with large incisions (>10 cm) remains an alarming 32%.

The wide variety of implanted surgical mesh (materials, structure) and surgical variability (attachment method, …

Autologous Protein Solution Exhibits Potential To Mitigate Osteoarthritis (Oa) Progression In A Human Explant Co-Culture Model, Kathleen Emily Steckbeck

All Theses

Osteoarthritis (OA) is a debilitating and painful disease that affects upwards of one in every eight adults1,2. OA influences the entire joint, but is traditionally characterized by cartilage degradation3. OA is a multifactorial disease with genetic, biological, and biochemical consideration, but there has been a recent shift in scientific opinion that the pathological progression of OA stems from an inflammatory milieu produced by the feed-forward progressive pathway as evidenced by simultaneous cartilage and synovium co-culture4–7. Autologous protein solution (APS) poses as an intriguing potential OA therapy by possessing a high anti-inflammatory and anabolic mediator concentration profile that could potentially mitigate …

Engineering Xylose Utilization In Yarrowia Lipolytica By Understanding Its Cryptic Xylose Pathway, Gabriel M. Rodriguez, Murtaza Shabbir Hussain, Lauren Gambill, Difeng Gao, Allison Yaguchi, Mark Blenner

Publications

Background

The oleaginous yeast, Yarrowia lipolytica, has been utilized as an industrial host for about 60 years for various applications. Recently, the metabolic engineering of this host has become increasingly popular due to its ability to accumulate lipids as well as improvements made toward developing new genetic tools. Y. lipolytica can robustly metabolize glucose, glycerol, and even different lipid classes. However, little is known about its xylose metabolizing capability. Given the desirability of having a robust xylose utilizing strain of Y. lipolytica, we performed a comprehensive investigation and elucidation of the existing components of its xylose metabolic pathway. …

Fabrication And Characterization Of An Extracellular Matrix Hydrogel For Aortic Valve Applications, Brady Culbreth

All Theses

With an estimated 5 million people suffering from valve disease in the United, valve disease is currently the leading cause of cardiovascular disease. Each year, between 80,000 and 85,000 aortic valve replacements are performed in order to treat the stenotic heart valves. Despite this being a worldwide epidemic, the current valve replacement options that are on the market have distinct limitations. Furthermore, a viable alternative does not exist for the patients that are not candidates for the current treatment methods. Our proposed solution to this epidemic is to create a highly viable injectable scaffold that would allow for the minimally …

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

All Dissertations

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, …