Master of Science, The Ohio State University, 2009, Civil Engineering

As part of the Ohio Department of Transportation's (ODOT's) ongoing effort to solve engineering problems for the Ohio transportation system through research, The Ohio State University has undertaken a study entitled “Bioengineering for Land Stabilization” under the direction of Professor Patrick J. Fox and Professor Emeritus T. H. Wu. A large number of slopes and embankments throughout Ohio are experiencing shallow slope failures and/or erosion problems. The aim of this study is to identify bioengineering methods to address ODOT's slope stabilization needs in response to these occurrences. Bioengineering is an ecologically, and often economically, attractive alternative to conventional slope stabilization techniques. The objectives of this research are: 1) to identify important factors that control success or failure of bioengineering methods, 2) to develop installation techniques and designs for successful application of bioengineering methods, and 3) to provide thorough documentation to aid in the development of future design guides for bioengineering work for ODOT. Three field installations were conducted and monitored at demonstration sites located in Muskingum, Logan and Union Counties. Results indicate that biostabilization methods can be effective for the stabilization of shallow (less than 3 – 4 ft.) slides if vegetation can be established. Establishment of vegetation is dependent on local soil and climate conditions, especially during the first growing season after installation. The use of instrumentation (tensiometers, piezometers) can be effective in predicting vegetation survivability. Side-by-side panel comparisons indicated that varying installation techniques do not affect the survivability of live willow poles. The cost of bioengineering stabilization is expected to be approximately 25% less than that of conventional methods.

Committee: Patrick Fox (Advisor); Tien Wu (Committee Member); Halil Sezen (Committee Member) Subjects: Civil Engineering; Engineering

PhD, University of Cincinnati, 2022, Pharmacy: Pharmaceutical Sciences

It is becoming increasingly evident that rapid detection of bacteria and subsequent visualization of their cellular and molecular functions are key to unraveling bacterial pathogenesis and development of innovative treatment strategies. In this context, molecular imaging technologies allow noninvasive access to crucial information found deep inside patients' body. Herein, we present how bacterial biology can be exploited to develop radiopharmaceutical agents that have the potential for both bacteria-specific imaging and therapy in vivo. Our first specific aim was to develop a 64Cu-based positron emission tomography probe that would target the copper acquisition pathway employed by certain species of bacteria for preclinical imaging. We demonstrated a high affinity of the bacterial metal chelator, yersiniabactin (YbT) to chelate copper stably. This allowed us to target the ferric yersiniabactin uptake receptor A (FyuA), which is responsible for metal import in pathogenic Escherichia coli UTI89, Klebsiella pneumoniae and nonpathogenic Escherichia coli Nissle, to specifically image these bacteria in infected lungs and muscles of mice. Our second aim focused on repurposing the same metal-uptake pathway in probiotic E. coli Nissle for 67Cu-based cancer therapy. We genetically encoded our microbe to overexpress FyuA in order to maximize retention of the anti-cancer cargo (67Cu) in solid tumors following intratumoral administration of our engineered construct in mice. Bioengineered E. coli Nissle persisted in tumors and sequestered sufficient 67Cu-YbT to hamper tumor progression. This bacterial platform also elicited anti-tumor immunity and exhibited great potential as a novel targeted radionuclide therapeutic platform.

Committee: Nalinikanth Kotagiri Ph.D. (Committee Chair); Pankaj Desai Ph.D. (Committee Member); Mathieu Sertorio Ph.D. (Committee Member); Timothy Phoenix (Committee Member); Harshita Kumari Ph.D. (Committee Member) Subjects: Surgery

Doctor of Philosophy, The Ohio State University, 2023, Chemical Engineering

Minimal residual disease (MRD) is the persistence of latent cancer cells in distant sites originating from a primary tumor. In the case of breast cancer, the tumor cells originate in the breast tissue, such as the lobules or the ducts, traverse circulation, and invade distant organs, such as the liver, lung, bones, and brain, which are considered traditional metastatic sites. While treating cancerous cells in the primary site has encouraging survival rates of ~ 99%, once cancer metastasizes to distant organs, the survival rates plummet to ~ 30%. The drastic decrease in survival is due to the biological differences of the cancer cells responsible for MRD, such as evasion of the immune system, drug resistance, and dormancy, whereby the latter is characterized as the cessation of proliferation by cell cycle arrest. The extracellular matrix (ECM) and intercellular communication have been associated with the induction of dormancy. Furthermore, extracellular vesicles (EVs), which are cell-derived nanoparticles, are carriers of bioactive molecules and are thus a part of intercellular communication systems. Therefore, engineering the tumor microenvironment to actuate cell-ECM and cell-cell interactions has profound implications for understanding and simplifying the complexity of cancer dormancy. Herein, we present novel in vitro methods for engineering the tumor microenvironment to promote intercellular interaction, provide physiologically relevant models for EV secretion, develop novel methods to phenotype blood-derived particles, delineate a signature for dormant tumor cells, and efficiently screen therapies that target the inherent biology of tumor cells.

Committee: Eduardo Reátegui Ph.D. (Advisor); Bhuvaneswari Ramaswamy M.D., M.R.C.P. (Committee Member); Andre F. Palmer Ph.D. (Committee Member); Natarajan Muthusamy Ph.D., D.V.M. (Committee Member) Subjects: Chemical Engineering

PHD, Kent State University, 2020, College of Arts and Sciences / School of Biomedical Sciences

Background: Animal agriculture is an industrialized, globalized system of meat production that will continue to increase in demand through the 21st century. This is a greatly resource intensive process that produces greenhouse gases and zoonotic disease development that contribute to climate change and public health pandemics. Since the demand for meat shows no sign of slowing in the coming years, alternative methods of meat production are required to feed a growing human population. Cell-based meat is one possible solution, which is meat grown from cell culture technology. Cell-based meat can be grown from developing edible cell lines and expanding them in bioreactors using biomedical techniques and equipment. The field in in its infancy, however, and many questions remain about how to develop useful cell lines and which are the most effective ways to grow them. This work demonstrates a research framework from which to characterize and compare two of the main cell types in meat: skeletal muscle cells and intramuscular fat cells. Methods were developed to analyze the difference between porcine and bovine cells, what characterizes their sensory and pigment properties, and how to efficiently grow them skeletal muscle tissue form. Methods: Bovine and porcine myoblasts and intramuscular fibroblast were isolated from the hind leg of 2 month old pigs and cows. Myoblasts were used for myogenesis assays, and intramuscular fibroblasts were used for adipogenesis assays. Gene and protein expression and volumetric hypertrophy data was obtained for myoblasts and lipid staining was quantified for fibroblasts. Meat color and pigment was determined for pork, beef, and cultured cells using colorimetry. Myoglobin gene and protein expression was assessed during myogenesis assays with and without electrical stimulation, mimicking an exercise regimen. Conditioned media from polarized porcine macrophages was used to characterize the potential for developing serum free media for myobl (open full item for complete abstract)

Committee: Min-Ho Kim Dr. (Advisor); Kristy Welshhans Dr. (Committee Member); Oleg Lavrentovich Dr. (Committee Member); Feng Dong Dr. (Committee Member); Songping Huang Dr. (Committee Member) Subjects: Biomedical Engineering; Biomedical Research; Food Science

Master of Science, University of Toledo, 2018, Bioengineering

The clinical incidence of large-scale bone defects has increased over the past few decades to both an increasingly aging population and an associated rise in the number of traumatic injuries. These defects require surgical intervention and can be complicated by post-operative surgical site infections; while these infections were originally managed with intravenous antibiotics, overuse of antibiotic drugs in both livestock and hospital environments has contributed to the creation of antibiotic resistant pathogens such as methicillin resistant Staphylococcus aureus. In craniofacial applications, especially, the lack of a synthetic, biocompatible and osteoconductive graft material that could address infections via a non-pharmaceutical approach provided a niche for exploration. The objective of this study was to synthesize a novel glass series, characterize the series to determine whether it would be biologically feasible and if so, identify the antibacterial efficacy and cytocompatibility of the material. A novel Zn-based bioactive glass series was created, as Zn has proven antibacterial capacity in previous studies. Molten mixtures of SiO2, Na2O, SrO, CaO and ZnO with varying CaO and ZnO concentrations, from 0-30% Zn, were quenched in room temperature water and ground to dental cement standards of sub-45 microns. X-ray diffraction revealed broad humps for each composition indicating that each was an amorphous solid. Scanning electron microscopy, energy dispersive spectroscopy and particle size analyses validated that the particle size of each composition was 45 microns, containing a uniform distribution of both large and small particles of the appropriate elemental compositions. BET surface area analysis confirmed that the surface areas of the samples were between 0.4163 m2/g and 0.6671 m2/g from RC-Control to RC-3; similarity in surface areas implied that reactivity differences were likely attributable to other factors. Differential thermal analysis indicated that th (open full item for complete abstract)

Committee: Aisling Coughlan (Committee Chair); Sarit Bhaduri (Committee Member); Eda Yildirim-Ayan (Committee Member) Subjects: Biomedical Engineering; Engineering; Materials Science

Master of Science, University of Akron, 2017, Biomedical Engineering

Delivery of therapeutic fluids such as surfactant solutions into lungs is a major strategy to treat various respiratory disorders. Instilled solutions form liquid plugs in lung airways. The plugs propagate downstream in airways by inspired air or forced ventilation, continuously split at airway bifurcations to smaller daughter plugs and simultaneously lose mass from their trailing menisci, and eventually rupture. A uniform distribution of the instilled liquid in lung airways is expected to increase the treatments success. The uniformity of distribution of instilled liquid in the lungs greatly depends on the splitting of liquid plugs between daughter airways, especially in the first few generations of airways from which airways of different lobes of lungs emerge. To mechanistically understand the liquid plug splitting process, we develop a novel bioengineering approach to computationally design three-dimensional bifurcating airway models using morphometric data of human lungs, fabricate seamless physical models using additive manufacturing, and examine effects of geometry of airways, fluid properties, and flow characteristics on liquid plug splitting. We find that the orientation of bifurcating airways has a major effect on the splitting of liquid plugs between daughter airways and discuss the role of various forces including inertia, gravity, and surface tension using several dimensionless groups. This work provides a fundamental understanding toward developing delivery strategies for uniform distribution of therapeutic fluids in the lungs.

Committee: Hossein Tavana PhD (Advisor); Marnie Saunders PhD (Committee Member); Jae-Won Choi PhD (Committee Member) Subjects: Biomedical Engineering; Biomedical Research; Fluid Dynamics

Master of Science, The Ohio State University, 2017, Mechanical Engineering

Our current understanding of electrophysiological phenomena is limited by our ability to measure particular processes. There are a number of electrophysiological intracellular and extracellular measuring techniques which currently exist; however, they are not without limitations. These techniques, such as patch-clamping, involve the careful isolation of a singular cell (which removes the cell from its native environment) and subsequent puncturing or suctioning of the cell membrane (which can damage the cellular structure). This research focuses on the development of conducting polymer sensors for in vivo measurements of electrophysiological phenomena. The goal of this work is to create a system by which ion concentration dynamics can be directly measured and analyzed to quantify metrics of biological processes without harming tissues of the organism. Quasi-potentiostatic amperometric sensors were developed using polypyrrole doped with dodecylbenzenesulfonate (DBS) to form PPy(DBS). By applying a cyclic pulse voltage input to the conducting polymer measurement system, and measuring the resulting current response, system parameters can be correlated to deviations from an equilibrium concentration as a function of time. This research will lay the foundation for more complex measurement techniques, both in electrophysiology, as well as in energy storage technology.

Committee: Vishnu Baba Sundaresan (Committee Member); Daniel Gallego-Perez (Committee Member) Subjects: Biomedical Engineering; Cellular Biology; Engineering; Mechanical Engineering; Neurobiology; Neurology; Neurosciences

Master of Science (M.S.), University of Dayton, 2015, Bioengineering

Bioreactor systems used for tissue engineering applications are an essential component of understanding the development of new tissues and studying the biochemical interactions between cells and their environment. A bioreactor is typically designed to mimic physiological, environmental, and mechanical stimuli that occur in vivo, and bioreactors are generally created for a specific application, such as for studying 3-dimensional tissues or dynamic fluid flow in 1-dimensional cell monolayers. The leading cause of death in the United States is coronary artery disease, which is treated with bypass graft surgery using a left internal mammary artery or human saphenous vein as the graft. Since human saphenous vein grafts often fail, investigating vascular function as a whole will help to understand more about the method of graft failure. A bioreactor system to study vascular function was successfully developed using the application of endothelial cells under shear stress in a microfluidic slide. The temperature control and diffusion rate of CO2 were recorded inside the bioreactor to confirm the system could stay within a temperature range of 37ºC +/- 0.5ºC and a CO2 concentration between 56,000 ppm and 45,000 ppm. Also, a physiological level of shear stress was determined to be feasible with the peristaltic pump. The performance characteristics of the bioreactor were analyzed, and the apparatus was determined to be successful in generating physiological relevant conditions. Then, human umbilical vein endothelial cells were exposed to both static conditions and venous shear stress conditions for up to four days in an IBIDI® microfluidic chamber. The cell morphology, alignment, and elongation were also evaluated. The cells stayed viable during the duration of all of the dynamic flow experiments, and the cells showed evidence of cell division. The cells were also more aligned and elongated towards the direction of flow for the 48 and 72 hour flow experiments compared to th (open full item for complete abstract)

Committee: Robert Wilkens (Advisor); Carissa Krane (Advisor); Kristen Comfort (Committee Member) Subjects: Biology; Biomedical Engineering; Biomedical Research; Chemical Engineering; Engineering

Doctor of Philosophy, The Ohio State University, 2015, Biomedical Engineering

Electrospun fibers are currently utilized in a wide range of biomedical and commercial applications. The unique microstructure and morphology of electrospun nanofibers produce nanoscale inter-fiber porosity and large surface areas that promote cellular attachment and growth. This is significant in applications requiring improved drug adsorption, infusion, and release for drug delivery, and as an aid in filtration processes. Numerous polymers have been electrospun allowing considerable mechanical and chemical tailoring, thus expanding the already wide-range of applications. Polycaprolactone (PCL) is commonly used due to its inherent long-term stability, mechanical strength, and cellular integration in tissue engineering, drug delivery, and other-biomedical applications. In addition, electrospun fiber microstructure and morphology closely resembles and mimics the extracellular matrix (ECM) of human tissues and tumors. In my work, supercritical carbon dioxide (SCCO2) mediated infusion of small molecules; gelatin and thermal-sintering facilitated mechanical stability; aligned electrospun PCL fiber topography stimulated tumor cell migration was studied. Supercritical fluids present an approach capable of enhancing the chemical activity of composite tissue engineering scaffolds. Previous attempts to embed test compounds into electrospun polycaprolactone (PCL) alone at pressures above 6.20 MPa and temperatures above 25°C resulted in loss of biomimicry. Gelatin shrinks and dehydrates in the presence of SCCO2 restricting PCL polymer-chain mobility preventing melting and allowing enhanced small molecule infusion and release. In addition gelatin-PCL blended nanofibers allow for increased stability of modulus through hydrolytic induced crystallinity, that drives polymer chain rearrangement and mobility. Thermally driven-sintering below the melting point of PCL increased crystallinity and enhanced nanofiber strength. High-throughput in vitro tools allowing rapid, acc (open full item for complete abstract)

Committee: John Lannutti (Advisor); Tim Eubank (Committee Member); Heather Powell (Committee Member); Samir Ghadiali (Committee Member) Subjects: Biomedical Engineering; Biomedical Research; Cellular Biology; Materials Science

Doctor of Philosophy (Ph.D.), University of Dayton, 2013, Mechanical Engineering

The growing demand for superior materials that function as scaffolds for tissue repair and regeneration has served as a catalyst in medicine. The need for artificial or natural replacement or repair of organs, limbs and tissue presents an opportunity to deliver materials with superior biologics, architecture and mechanical properties. Current biomaterials utilized to repair damaged tissue or augment function commonly fail to meet the optimal combination of biomechanical and healing potential. Additionally, limited donor tissue availability and the increased cost of healthcare are driving factors for improving material processing and diagnostic assessment. Currently, metallic materials, such as titanium and stainless steel, function as implants and reinforcements. However, these materials are permanent and rigid and may inhibit natural healing of damaged tissue. Moreover, metallic implants corrode and fracture, causing repetitive injury and excess scar tissue formation. Conversely, polymer-based materials have shown promising results. A limited number of polymer biomaterials have been approved for scaffold and implant applications. Additionally, some polymers have the ability to degrade, an advantageous characteristic for biological applications. Nevertheless, most natural and synthetic biopolymers lack high strength and cannot be utilized as primary scaffolds in load bearing applications. The materials described earlier present shortcomings. The importance of the presented work is that it utilized mass producible materials, modified them for unique cellular environments and developed a computational model to predict cell behavior and facilitate future design endeavors. Specifically, the current analysis focused on preparing carbon-based scaffolds from monolithic, textile, composite, and nanoartifact derivatives. This work was the first to present an understanding between critical properties of carbon materials: crystallinity, orientation, surface (open full item for complete abstract)

Committee: Khalid Lafdi (Advisor); Robert Brockman (Committee Member); Wiebke Diestelkamp (Committee Member); Kevin Hallinan (Committee Member); Panagiotis Tsonis (Committee Member) Subjects: Biomedical Engineering; Materials Science; Mechanical Engineering; Medicine

Master of Science, The Ohio State University, 2009, Civil Engineering

As part of the Ohio Department of Transportation's (ODOT's) ongoing effort to solve engineering problems for the Ohio transportation system through research, The Ohio State University has undertaken a Bio-Engineering for Land Stabilization study under the direction of Professor Patrick J. Fox and Professor Emeritus T. H. Wu. Bioengineering is the use of vegetation for slope stabilization and has been used with success throughout the world; however, not much work on this topic has been performed in the mid-western United States. The aim of this study is to identify bioengineering methods to address ODOT's land stabilization needs in response to the all too common occurrence of shallow landslides. Bioengineering methods offer environmentally and economically attractive alternatives to traditional approaches to remediate and prevent such landslides. This research plans to achieve several objectives through the construction of three field demonstration projects: (1) to identify important factors that control success or failure of bioengineering methods, (2) to develop installation techniques and designs for successful application of bioengineering methods, (3) to provide thorough documentation to guide future work in bioengineering for ODOT, and (4) to develop new monitoring and testing methods that may be required for bioengineering projects. To date, research demonstration sites have been selected in Muskingum, Logan, and Union Counties and design and construction efforts are underway. Initial results of the project indicate that bioengineering installations, such as live willow poles, can be effective for the stabilization of shallow slides if the vegetation can be established.

Committee: Patrick Fox PhD (Advisor); Tien Wu PhD (Committee Co-Chair); William Wolfe PhD (Committee Member) Subjects: Civil Engineering