Biomedical Engineering and Bioengineering Commons^™

Synthesis Of Monodisperse Nanoscintillators At High Temperatures For Biomedical Relevant Applications, Eric Zhang

All Dissertations

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 …

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

All Dissertations

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 …

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

All Dissertations

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 …

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 …

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 …

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 …

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 …

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, …

Effects Of Growth Factor Supplementation And Environmental Conditions On Human Adipose-Derived Stem Cell Differentiation Towards Urothelial Lineage, James Turner

All Dissertations

In recent years, tissue engineering of the bladder has undergone many technological advances. Autologous urothelial cells have been used in animal models and have shown increased performance for ureteral reconstruction compared to unseeded grafts. However, since patients may lack a reliable source of native urothelial cells due to the nature of their specific bladder disease, autologous cells are not an ideal source clinically, and an alternate cell source must be explored. Adipose derived stem cells (ADSCs) are an attractive cell source for such regenerative medicine applications as they have been extensively studied for their multipotential differentiation, immunosuppressive properties, ease of …

Manipulation Of The Electrical Double Layer For Control And Sensing In A Solid State Nanopore, Samuel L. Bearden

All Dissertations

Nanopores have been explored with the goal of achieving non-functionalized, sub-molecular sensors, primarily with the purpose of producing fast, low-cost DNA sequencers. Because of the nanoscale volume within the nanopore structure, it is possible to isolate individual molecular and sub-molecular analytes. Nanopore DNA sequencing has remained elusive due to high noise levels and the challenge of obtaining single-nucleotide resolution. However, the complete electrical double layer within the nanopore is a key feature of fluid-nanopore interaction and has been neglected in previous studies. By exploring interactions with the electrical double layer in various nanopore systems, we characterize the material, electrical, and …

Understanding The Fusion And Maturation Of Tissue Engineered Linear Blood Vessels Using Magnetic Cellular Spheroids, Timothy R. Olsen

All Dissertations

Cellular spheroids are attractive for tissue fabrication due to having precise control over cell and extracellular matrix (ECM) composition, the ability for upscaled production and repeatability, their three-dimensional nature and the fact that spheroids will produce their own ECM over time. A critical process in the fabrication of complex tissue structures with cellular spheroids is related to their fusion and maturation. Tissue fusion is a self-assembly process in which two or more distinct cell populations, or tissues, make contact and coalesce to form a single cohesive structure. Maturation of tissue engineered constructs involves developing the mechanical properties and ECM compositions …

Development Of A Transport System For Advancing Tissue Engineering And Cell Identification, Suzanne Mae Tabbaa

All Dissertations

This work centers on the development of a novel passive transport system for two tissue engineering applications – cell distribution and cell separation. This approach relies on a wicking fiber-based system, derived from the textile field that functions by directing and maintaining transport of cells as well as fluids and biomolecules. This system has the ability to enhance cell movement for both the purpose of cell seeding distribution as well as to isolate specific cell types from heterogeneous cell populations.

The success of spinal fusions and large bone defects is often limited by the decreased surrounding vasculature and the ability …

Platform Technologies To Advance Clinically Relevant Tissue Engineered Heart Valve Products, Leslie Neil Sierad

All Dissertations

Diseased heart valves are commonly replaced by mechanical, bioprosthetic, or allograft heart valves. These replacements provide major improvements in cardiac function and quality of life, but have significant limitations and eventually require surgical replacement within 15-20 years. These risks are particularly prominent in pediatric patients and young adults. The field of tissue engineering and regenerative medicine, which combines scaffolds and cells, holds great promise in developing living replacement heart valves that would self-repair and grow in size along with the growing children.

The long-term goal of this project is to generate living, tissue-engineered heart valves from biological scaffolds and autologous …

In Vitro Simulation Of Pathological Bone Conditions To Predict Clinical Outcome Of Bone Tissue Engineered Materials, Duong Nguyen

All Dissertations

According to the Centers for Disease Control, the geriatric population of ≥65 years of age will increase to 51.5 million in 2020; 40% of white women and 13% of white men will be at risk for fragility fractures or fractures sustained under normal stress and loading conditions due to bone disease, leading to hospitalization and surgical treatment. Fracture management strategies can be divided into pharmaceutical therapy, surgical intervention, and tissue regeneration for fracture prevention, fracture stabilization, and fracture site regeneration, respectively. However, these strategies fail to accommodate the pathological nature of fragility fractures, leading to unwanted side effects, implant failures, …

Vascular Nanomedicine: Site Specific Delivery Of Elastin Stabilizing Therapeutics To Damaged Arteries, Aditi Sinha

All Dissertations

Elastin, a structural protein in the extra-cellular matrix, plays a critical role in the normal functioning of blood vessels. Apart from performing its primary function of providing resilience to arteries, it also plays major role in regulating cell-cell and cell-matrix interactions, response to injury, and morphogenesis. Medial arterial calcification (MAC) and abdominal aortic aneurysm (AAA) are two diseases where the structural and functional integrity of elastin is severely compromised. Although the clinical presentation of MAC and AAA differ, they have one common underlying causative mechanism--pathological degradation of elastin. Hence prevention of elastin degradation in the early stages of MAC and …

Biological Scaffolds For Peripheral Vascular Surgery, George Fercana

All Dissertations

The gold standards for small diameter peripheral vascular graft replacement are autologous arteries or veins; however, one-third of patients lack such vessels due to previous vessel harvesting or advanced vascular disease. A promising approach for patients in this category is tissue engineering with off-the-shelf biological vascular grafts. Three small diameter acellular scaffolds were developed and evaluated as vascular grafts. Porcine renal arteries (2-3 mm diameter, 20 mm length) were decellularized by immersion and stabilized with penta-galloyl glucose (PGG) with and without subsequent heparinization via carbodiimide chemistry. Bovine mammary (4-6 mm ID, 250 mm length) and femoral arteries (6-8 mm ID, …

Identification Of Novel Genes Regulating Elastic Fiber Formation Through Expression Profiling Analysis Of Elastogenic Models, Erin Sproul

All Dissertations

Background: Particularly important to the mechanical performance of native arterial blood vessels is elastin, an extracellular matrix (ECM) protein deposited by VSMCs in the form of elastic fibers, arranged in concentric lamellae in the media of the vessel wall. In addition to serving as major structural elements of arterial walls, providing extensibility and elastic recoil, elastic fibers also influence vascular cell behaviors. For these reasons tissue engineers are attempting to exploit elastic fiber biology to enhance vascular graft design and patency. Therefore, developing a greater understanding of the molecular mechanisms of elastogenesis may offer opportunities to control elastogenesis in tissue …

Engineering Beta-Cell Spheroids For Type 1 Diabetes Treatment, Xiaoyan Liu

All Dissertations

Diabetes mellitus, the third most common disease in the world, is a chronic metabolic disorder caused by a failure of insulin production and/or an inability to respond to insulin. Specifically, type 1 diabetes is a disorder characterized by targeted autoimmune-directed destruction of a patient's beta-cell population within the pancreatic islets of Langerhans. The current primary treatment for type 1 diabetes is daily multiple insulin injections. However, this treatment cannot provide sustained physiological release, and the insulin amount is not finely tuned to glycemia. Pancreatic transplants or islet transplants would be the preferred treatment method but the lack of donor tissue …

Implantable Biosensors For Physiologic Status Monitoring During Hemorrhage, Christian Kotanen

All Dissertations

Trauma diagnostics and management are major aims of research for implantable amperometric enzyme biosensor technology. Biosensors are capable of monitoring metabolic variables in a minimally invasive manner and have great potential to augment current wireless vital sign monitoring technologies in order to make a more robust physiologic status monitoring platform. The dual responsive Electrochemical Cell-on-a-Chip Microdisc Electrode Array (ECC MDEA 5037) is a recently developed electrochemical transducer for use in a wireless, implantable biosensor system for the continuous measurement of interstitial glucose and lactate. Hyperglycemia arising from insulin resistance and hyperlactatemia arising from anaerobic metabolism both occur following trauma and …

Biofabrication Of Scaffolds For Intervertebral Disc (Ivd) Tissue Regeneration, Benjamin Whatley

All Dissertations

The ultimate goal of tissue regeneration is to replace damaged or diseased tissue with a cell-based or biomaterial-based tissue that accurately mimics the functionality, biology, mechanics, and cellular and extracellular matrix (ECM) composition of the native tissue. Specifically, the ability to control the architecture of tissue engineered constructs plays a vital role in all of these issues as scaffold architecture has an affect on function, biomechanics, and cellular behavior. Many tissue engineered scaffolds focus on the ability to mimic natural tissue by simulating the ECM due to the fact that in each distinct tissue, the ECM serves as a structural …

Feeling For Failure: Haptic Force Perception Of Soft Tissue Constraints In A Simulated Minimally Invasive Surgery Task, Lindsay Long

All Dissertations

In minimally invasive surgery (MIS), the ability to accurately interpret haptic information and apply appropriate force magnitudes onto soft tissue is critical for minimizing bodily trauma. Force perception in MIS is a dynamic process in which the surgeon's administration of force onto tissue results in useful perceptual information which guides further haptic interaction and it is hypothesized that the compliant nature of soft tissue during force application provides biomechanical information denoting tissue failure. Specifically, the perceptual relationship between applied force and material deformation rate specifies the distance remaining until structural capacity will fail, or indicates Distance-to-Break (DTB). Two experiments explored …

Ion Channel-Mediated Hydrostatic Pressure Mechanotransduction In Urothelial Cells, Kevin Champaigne

All Dissertations

A majority of men and women aged 40 and over experience lower urinary tract symptoms, including urgency, incontinence, and frequency, which often affect the individual's quality of life. Although often considered a simple structure, the bladder is a complex system with sophisticated sensory and motor feedback mechanisms that allow for the sensation of fullness and pain, reflexive responses to bladder filling, and conscious control over the time and place of micturition. Although disruptions of these sensory mechanisms are believed to cause certain lower urinary tract dysfunctions, the specific mechanisms involved in sensing bladder fullness, distension, tension, or pressure at the …

A Novel Hybrid Hydrogel For Scaffold-Mediated Gene Delivery, Jeremy Zhang

All Dissertations

Scaffold-mediated nonviral gene delivery avoids several drawbacks of systemic injection such as clearance by the reticulo-endothelial system and serum aggregation. Existing synthetic and natural polymers used in gene delivery scaffolds are primarily derived from other tissue engineering applications with design parameters focused on the physicochemical properties of the scaffold and its biocompatibility. Common synthetic materials used in polymeric scaffolds such as PEG are practically bio-inert with minimal cell and protein interaction. Therefore, an opportunity exists for the rational design novel gene delivery scaffolds with components capable of increasing the expression of incorporated transgene by including scaffold components that interact with …

Spatial Control Of Magnetic Nanoparticles Integrated With Cellular Spheroids As Tissue Engineered Building Blocks, Brandon Mattix

All Dissertations

Magnetic nanoparticles (MNPs) have been investigated in tissue engineering applications to provide in situ imaging, drug delivery, and tissue patterning, but direct and prolonged interaction between cells and MNPs can have adverse effects on cell function. Therefore, methods which reduce or limit the interaction of MNPs with cells, or utilize more biocompatible MNP-based strategies will improve upon the commonly used iron oxide MNPs. We investigated a variety of methods to improve upon the use of MNPS in tissue engineering.
Cell aggregates, or spheroids, have been used as tissue engineered building blocks that can closely mimic the native three-dimensional in vivo …

Multifunctional Nanophosphors For Tissue Imaging And Drug Delivery, Hongyu Chen

All Dissertations

X-rays have been used for non-invasive high-resolution imaging of thick biological specimens since their discovery in 1895. They are widely used for structural imaging of bone, metal implants, and cavities in soft tissue. Recently, a number of new contrast methodologies have emerged which are expanding X-ray's biomedical applications to functional as well as structural imaging. However, traditional X-ray imaging provides high spatial resolution imaging through tissue but do not measure chemical concentrations. In this dissertation, we describe an X-ray excited optical luminescence (XEOL) technique which uses a scanning X-ray beam to irradiate Gd2O2S phosphors and detect the resulting visible luminescence …

Sustained Release Of Estrogens From Pegylated Nanoparticles For Treatment Of Secondary Spinal Cord Injury, John Barry

All Dissertations

Spinal Cord Injury (SCI) is a debilitating condition which causes neurological damage and can result in paralysis. SCI results in immediate mechanical damage to the spinal cord, but secondary injuries due to inflammation, oxidative damage, and activated biochemical pathways leading to apoptosis exacerbate the injury. The only currently available treatment, methylprednisolone, is controversial because there is no convincing data to support its therapeutic efficacy for SCI treatment. In the absence of an effective SCI treatment option, 17β-estradiol has gained significant attention for its anti-oxidant, anti-inflammatory, and anti-apoptotic abilities, all events associated with secondary. Sadly, 17β-estradiol is associated with systemic adverse …

Highly Sensitive Fiber-Based Devices For Gene And Protein Analysis, Victor Maximov

All Dissertations

Single cell probing has found a number of applications in different areas of research. It can help us to better understand cell-to-cell interactions; it has found numerous applications in immunology, cancer research, detection of pathogenic infections and genetic abnormalities. The single cell analysis is very important in stem cells research and development of cells. The main obstacle in the single cell analysis is the small amount of analyte that a single cell could provide. Another difficulty is connected to the cell-to-cell variability inside the uniform population due to the differences of single cells in size, activity, mitotic stage, and functions. …