Biomedical Engineering and Bioengineering Commons^™

A Study On The Applications And Toxicity Assessments Of Carbon Nanotubes In Tissue Engineering, Rena Baktur

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

Carbon nanotubes (CNTs) are one of the most popular nanomaterials. There has been increasing interest in the development and applications of carbon nanotubes due to their huge potential in industrial and medical applications. Recent applications of carbon nanotubes include development of scaffolds and drug delivery systems. Despite rapidly emerging applications of CNTs, little is known about the impact of CNTs on cellular processes, especially mesenchymal stem cell (MSC)'s differentiation. Also, the effects of nanoparticle exposure under different conditions on cellular responses have not been well characterized yet.

To characterize the effects of CNTs on creating nanoscale scaffolds for tissue engineering, …

Evaluation Of Delivery Conditions For Cutaneous Plasmid Electrotransfer Using A Multielectrode Array, Bernadette Ferraro, Loree C. Heller, Yolmari L. Cruz, Siqi Guo, Amy Donate, Richard Heller

Bioelectrics Publications

Electroporation (EP) is a simple in vivo method to deliver normally impermeable molecules, such as plasmid DNA, to a variety of tissues. Delivery of plasmid DNA by EP to a large surface area is not practical because the distance between the electrode pairs, and therefore the applied voltage, must be increased to effectively permeabilize the cell membrane. The design of the multielectrode array (MEA) incorporates multiple electrode pairs at a fixed distance to allow for delivery of plasmid DNA to the skin, potentially reducing the sensation associated with in vivo EP. In this report, we evaluate the effects of field …

Construction And Use Of A Direct Calorimeter To Estimate Energy Expenditure In Hibernators, Mark S. Burger, Frank Van Breukelen

Festival of Communities: UG Symposium (Posters)

Metabolic rates have traditionally been estimated through indirect calorimetry (gas exchange or respirometry) due to its ease and availability. Oxygen consumption neglects the contributions of anaerobic metabolism, while direct calorimetry (heat production) estimates both anaerobic and aerobic metabolism. Walsberg and Hoffman (2005) report anaerobic metabolism may be more important to small rodents than was previously thought. During the non-steady state of mammalian hibernation, we hypothesize that anaerobic processes may play an even greater role in fueling metabolism. To address this question, we constructed a very sensitive calorimeter that utilizes the Seebeck effect from a thermoelectric element (Peltier device). We describe …

Bacterial Killing By Dry Metallic Copper Surfaces, Christophe Espírito Santo, Ee Wen Lam, Christian Elowsky, Davide Quaranta, Dylan W. Domaille, Christopher J. Chang, Gregor Grass

Nebraska Center for Biotechnology: Faculty and Staff Publications

Metallic copper surfaces rapidly and efficiently kill bacteria. Cells exposed to copper surfaces accumulated large amounts of copper ions, and this copper uptake was faster from dry copper than from moist copper. Cells suffered extensive membrane damage within minutes of exposure to dry copper. Further, cells removed from copper showed loss of cell integrity. Acute contact with metallic copper surfaces did not result in increased mutation rates or DNA lesions. These findings are important first steps for revealing the molecular sensitive targets in cells lethally challenged by exposure to copper surfaces and provide a scientific explanation for the use of …

Electroporation-Induced Electrosensitization, Olga N. Pakhomova, Betsy W. Gregory, Vera A. Khorokhorina, Anglela M. Bowman, Shu Xiao, Andrei G. Pakhomov

Bioelectrics Publications

BACKGROUND: Electroporation is a method of disrupting the integrity of cell membrane by electric pulses (EPs). Electrical modeling is widely employed to explain and study electroporation, but even most advanced models show limited predictive power. No studies have accounted for the biological consequences of electroporation as a factor that alters the cell's susceptibility to forthcoming EPs.

METHODOLOGY/PRINCIPAL FINDINGS: We focused first on the role of EP rate for membrane permeabilization and lethal effects in mammalian cells. The rate was varied from 0.001 to 2,000 Hz while keeping other parameters constant (2 to 3,750 pulses of 60-ns to 9-micros duration, 1.8 …

Finite Element Reconstruction Of Real World Aortic Injury In Near-Side Lateral Automotive Crashes With Conceptual Countermeasures, Aditya Neelakanta Belwadi

Wayne State University Dissertations

Traumatic rupture of the aorta (TRA) remains the second most common cause of death associated with motor vehicle crashes after brain injury. On an average, nearly 8,000 people die annually in the United States due to blunt injury to the aorta. It is observed that more than 80% of occupants who suffer an aortic injury die at the scene due to exsanguination into the chest. With the advent of more accurate and established human body finite element (FE) models, FE crash reconstruction methods may become a valuable tool when assessing crash scenarios and occupant injury mechanisms.

The current study is …

Nanosecond Pulsed Electric Field Induced Cytoskeleton, Nuclear Membrane And Telomere Damage Adversely Impact Cell Survival, Michael W. Stacey, P. Fox, S. Buescher, Juergen F. Kolb

Bioelectrics Publications

We investigated the effects of nanosecond pulsed electric fields (nsPEF) on three human cell lines and demonstrated cell shrinkage, breakdown of the cytoskeleton, nuclear membrane and chromosomal telomere damage. There was a differential response between cell types coinciding with cell survival. Jurkat cells showed cytoskeleton, nuclear membrane and telomere damage that severely impacted cell survival compared to two adherent cell lines. Interestingly, disruption of the actin cytoskeleton in adherent cells prior to nsPEF exposure significantly reduced cell survival. We conclude that nsPEF applications are able to induce damage to the cytoskeleton and nuclear membrane. Telomere sequences, regions that tether and …

Role Of Hydrodynamic Behavior Of Dna Molecules In Dielectrophoretic Polarization Under The Action Of An Electric Field, Hui Zhao

Mechanical Engineering Faculty Research

A continuum model is developed to predict the dielectrophoretic polarizability of coiled DNA molecules under the action of an alternating current electric field. The model approximates the coiled DNA molecule as a charged porous spherical particle. The model explains the discrepancies among scaling laws of polarizability of different-sized DNA molecules with contour length and such discrepancies are attributed to different hydrodynamic behavior. With zero or one fitting parameter, theoretical predictions are in good agreement with various experimental data, even though in experiments there are some uncertainties in regard to certain parameters.

A Multi-Species Analysis Of Biomechanical Responses Of The Head To A Shock Wave, Richard Bolander

Wayne State University Dissertations

Shock wave induced brain injury remains a field of research that has great consequences for the rehabilitation of soldiers and civilians that are exposed to an explosion. As such, for the research to be successful in developing strategies to mitigate the effects of these injuries, appropriate research methods need to be developed. Animal models are currently employed to understand the brain's response to a shock wave exposure. Unfortunately no criteria have been established that indicates in what way the mechanical inputs that the cells in an animal's brain are subjected to are similar to a human. The purpose of this …

Computational Simulation Of Skull Fracture Patterns In Pediatric Subjects Using A Porcine Model, Christina Devito Wagner

Wayne State University Dissertations

In cases of suspected child abuse with skeletal trauma, it is often the role of the injury biomechanist, forensic pathologist, clinical radiologist, and forensic anthropologist to determine the mechanism of injury when the child victims cannot speak for themselves. This is a challenging task, especially for the head, as comprehensive biomechanical data on skull fracture in infants and children do not currently exist, and frequently the determination regarding cause of injury is based on anecdotal evidence from the medical literature and unsubstantiated eyewitness accounts. The current process may result in unreliable autopsy interpretation and miscarriages of justice due to a …

Nanosecond Pulse Electrical Fields Used In Conjunction With Multi-Wall Carbon Nanotubes As A Potential Tumor Treatment, Michael W. Stacey, Christopher Osgood, Bhargava Subhash Kalluri, Wei Cao, Hani Elsayed-Ali, Tarek Abdel-Fattah

Bioelectrics Publications

The objectives of this communication were to fabricate pure samples of multi-walled carbon nanotubes (MWCNTs) and to determine their toxicity in tumor cell lines. MWCNTs were dispersed in a concentration of the surfactant T80 that was minimally toxic. Cell-type variation in toxicity to MWCNTs was observed but was not significantly different to unexposed controls. Additionally, we investigated the increased cell killing of the pancreatic cancer cell line PANC1 when exposed to ultrashort (nanosecond) pulsed electrical fields (nsPEF) in the presence of MWCNTs as a potential form of cancer therapy. We hypothesized that the unique electronic properties of MWCNTs disrupt cell …

Electro-Gene Transfer To Skin Using A Noninvasive Multielectrode Array, Siqi Guo, Amy Donate, Gaurav Basu, Cathryn Lundberg, Loree Heller, Richard Heller

Bioelectrics Publications

Because of its large surface area and easy access for both delivery and monitoring, the skin is an attractive target for gene therapy for cutaneous diseases, vaccinations and several metabolic disorders. The critical factors for DNA delivery to the skin by electroporation (EP) are effective expression levels and minimal or no tissue damage. Here, we evaluated the non-invasive multielectrode array (MEA) for gene electrotransfer. For these studies we utilized a guinea pig model, which has been shown to have a similar thickness and structure to human skin. Our results demonstrate significantly increased gene expression 2 to 3 logs above injection …

A Microfluidic Device For Impedance Spectroscopy, Ahmet Can Sabuncu

Mechanical & Aerospace Engineering Theses & Dissertations

Recently, microfluidics has become a versatile tool to investigate cellular biology and to build novel biomedical devices. Dielectric spectroscopy, on the other hand, allows non-invasive probing of biological cells. Information on the cell membrane, cytoplasm, and nucleus can be obtained by dielectric spectroscopy provided that appropriate tools are used in specific frequency ranges. This dissertation includes fabrication, characterization, and testing of a simple microfluidic device to measure cell dielectric properties. The dielectric measurements are performed on human T-cell leukemia (Jurkat), mouse melanoma (B16), mouse hepatoma (Hepa), and human costal chondrocyte cells. Dielectric measurements consist of measuring the complex impedance of …

A Novel Device For Cell-Cell Electrofusion, Justin T. Stewart

USF Tampa Graduate Theses and Dissertations

Cell transplantation therapy is a potentially powerful tool and can be used to replace defective cells with healthy cells. This offers the possibility of alleviating the destructive symptoms for many diseases such as Parkinson's disease, Alzheimer's disease, stroke, spinal cord trauma, Type I diabetes and many more. While there are many diseases that could be positively impacted from cell transplantation therapy, the focus of this research is insulin dependent, Type I Diabetes.

The Islets of Langerhans are composed of various types of cells located in the pancreas and are responsible for a variety of biochemical functions. Specifically, the beta Islet …

The Incidence Of Type-1 Diabetes In Nod Mice Is Modulated By Restricted Flora Not Germ-Free Conditions., Cecile King, Nora Sarvetnick

Journal Articles: Regenerative Medicine

In the NOD mouse, the incidence of type-1 diabetes is thought to be influenced by the degree of cleanliness of the mouse colony. Studies collectively demonstrate that exposure to bacterial antigen or infection in the neonatal period prevents diabetes [1], [2], [3], [4], [5], [6], [7], [8], [9], [10], supporting the notion that immunostimulation can benefit the maturation of the postnatal immune system [11]. A widely accepted extrapolation from this data has been the notion that NOD mice maintained under germ-free conditions have an increased incidence of diabetes. However, evidence supporting this influential concept is surprisingly limited [12]. In this …

Fus Transgenic Rats Develop The Phenotypes Of Amyotrophic Lateral Sclerosis And Frontotemporal Lobar Degeneration, Cao Huang, Hongxia Zhou, Jianbin Tong, Han Chen, Yong-Jian Liu, Dian Wang, Xiaotao Wei, Xugang Xia

Nebraska Center for Biotechnology: Faculty and Staff Publications

Fused in Sarcoma (FUS) proteinopathy is a feature of frontotemporal lobar dementia (FTLD), and mutation of the fus gene segregates with FTLD and amyotrophic lateral sclerosis (ALS). To study the consequences of mutation in the fus gene, we created transgenic rats expressing the human fus gene with or without mutation. Overexpression of a mutant (R521C substitution), but not normal, human FUS induced progressive paralysis resembling ALS. Mutant FUS transgenic rats developed progressive paralysis secondary to degeneration of motor axons and displayed a substantial loss of neurons in the cortex and hippocampus. This neuronal loss was accompanied by ubiquitin aggregation and …

Comparative Manufacture And Cell-Based Delivery Of Antiretroviral Nanoformulations, Shantanu Balkundi, Ari S. Nowacek, Ram S. Veerubhotla, Han Chen, Andrea Martinez-Skinner, Upal Roy, R. Lee Mosley, Georgette Kanmogne, Xinming Liu, Alexander V. Kabanov, Tatiana Bronich, Joellyn Mcmillan, Howard E. Gendelman

Nebraska Center for Biotechnology: Faculty and Staff Publications

Nanoformulations of crystalline indinavir, ritonavir, atazanavir, and efavirenz were manufactured by wet milling, homogenization or sonication with a variety of excipients. The chemical, biological, immune, virological, and toxicological properties of these formulations were compared using an established monocyte-derived macrophage scoring indicator system. Measurements of drug uptake, retention, release, and antiretroviral activity demonstrated differences amongst preparation methods. Interestingly, for drug cell targeting and antiretroviral responses the most significant difference among the particles was the drug itself. We posit that the choice of drug and formulation composition may ultimately affect clinical utility.

Longissimus Muscle Fatigue And Injury Response Due To Electrical Stimulation With Varied Work/Rest Ratios, Peter Wawrow

Wayne State University Dissertations

LONGISSIMUS MUSCLE FATIGUE AND INJURY RESPONSE DUE TO ELECTRICAL STIMULATION WITH VARIED WORK/REST RATIOS

BY

PETER WAWROW

May 2011

Advisor: John Cavanaugh, MD

Major: Biomedical Engineering

Degree: Doctor of Philosophy

The estimated yearly cost of lost-time work injuries and illnesses is $140 billion. The average cost of musculoskeletal disorders (MSDs) exceeds all other claims. These injuries persist in spite of ergonomic interventions addressing known risk factors. Work/rest ratios have not received a significant amount of attention, particularly in low back disorders, and it is hypothesized that the lack of adequate rest within a work cycle may contribute to muscle fatigue …

Analysis Of The Performance Of Peanut Fame In A Single Cylinder Idi Engine And Investigations Of Neat Methyl Ester Influence On Fuel Quality, Jeffery Lewis

College of Graduate Studies: Theses & Dissertations

Author's abstract: To meet evolving standards set forth by the U.S. EPA and U.S. Energy Policy it is necessary to consider a variety of feedstock for biofuels synthesis and to understand the role individual fatty acids contribute to the overall performance. It is the belief of the authors that excess peanut production would provide an excellent source for high quality biodiesel feedstock, and the complete property and combustion analysis of the fatty acid components will provide insight for future biofuel developments. The preliminary investigations of the project focused on the combustion performance and thermal efficiency of peanut FAME and its …

Bcc Skin Cancer Diagnosis Based On Texture Analysis Techniques, Shao-Hui Chuang, Xiaoyan Sun, Wen-Yu Chang, Gwo-Shing Chen, Adam Huang, Jiang Li, Frederic D. Mckenzie

Electrical & Computer Engineering Faculty Publications

In this paper, we present a texture analysis based method for diagnosing the Basal Cell Carcinoma (BCC) skin cancer using optical images taken from the suspicious skin regions. We first extracted the Run Length Matrix and Haralick texture features from the images and used a feature selection algorithm to identify the most effective feature set for the diagnosis. We then utilized a Multi-Layer Perceptron (MLP) classifier to classify the images to BCC or normal cases. Experiments showed that detecting BCC cancer based on optical images is feasible. The best sensitivity and specificity we achieved on our data set were 94% …

Modeling And Quantitative Analysis Of White Matter Fiber Tracts In Diffusion Tensor Imaging, Xuwei Liang

University of Kentucky Doctoral Dissertations

Diffusion tensor imaging (DTI) is a structural magnetic resonance imaging (MRI) technique to record incoherent motion of water molecules and has been used to detect micro structural white matter alterations in clinical studies to explore certain brain disorders. A variety of DTI based techniques for detecting brain disorders and facilitating clinical group analysis have been developed in the past few years. However, there are two crucial issues that have great impacts on the performance of those algorithms. One is that brain neural pathways appear in complicated 3D structures which are inappropriate and inaccurate to be approximated by simple 2D structures, …

Modeling Heat Transfer During Cooling Of Ready-To-Eat Meat And Poultry Products Using Three-Dimensional Finite Element Analysis And Web-Based Simulation, Jihan F. Cepeda Jimenez

Department of Agricultural and Biological Systems Engineering: Dissertations, Theses, and Student Research

The meat industry is required to comply with processing performance standards for preventing the growth of foodborne pathogens in products. These performance standards, established by the United States Department of Agriculture - Food Safety and Inspection Service (USDA-FSIS) require a reduction of Salmonella spp (lethality standard) and limit the growth of sporeforming bacteria (stabilization standard) in certain processed meat products. In general, strategies used to comply with these standards are associated with thermal processing. Meat processors have difficulties complying with these performance standards. Moreover, thermal processing deviations are an issue in the meat industry that generate uncertainty regarding the safety …

Development Of Near Real-Time Assessment System For Cancer Cells., Nahrizul Adib Kadri

Student Works (2010-2019)

Dielectrophoresis (DEP) is an electrical phenomenon that occurs when a polarisable particle is placed in non-uniform electrical fields, generating DEP force (FDEP) that is dependent upon the electrophysiological make-up of the particle in use. In cell cytometry studies, DEP offers the advantage of conducting various cell manipulations in vitro without the need of specific surface markers. Its drawbacks, namely the time-consuming processes involved and the inability to conduct large batch cell assays, had limited its usage. This thesis presents the work that offered solution to the said obstacles, by developing a system capable of conducting DEP experiments within a very …

Development Of Software To Estimate Pressures On The Residual Limbs Of Amputees By Means Of A Pylon Mounted Transducer, Malli K. Yalamanchili

UNLV Theses, Dissertations, Professional Papers, and Capstones

The alignment of prosthesis has been recognized as one of the main factors that determine successful prosthetic outcomes for trans-tibial amputees. Alignment is defined as the relative position and orientation of the prosthetic components. Misalignment can result in changes in the position and orientation of the joints of the leg and moments experienced by them during gait, increases in energy use, and discomfort or even tissue breakdown at the socket/stump interface. Hence it is very important to align the prosthesis in correct manner. Gait analysis can be used to examine the effects of incorrect alignment of the prosthesis during gait. …

Deletion Of The Cel48s Cellulase From Clostridium Thermocellum, Daniel G. Olson, Shital A. Tripathi, Richard J. Giannone, Jonathan Lo, Nicky C. Caiazza, David A. Hogsett, Robert L. Hettich, Adam M. Guss, Genia Dubrovsky, Lee R. Lynd

Dartmouth Scholarship

Clostridium thermocellum is a thermophilic anaerobic bacterium that rapidly solubilizes cellulose with the aid of a multienzyme cellulosome complex. Creation of knockout mutants for Cel48S (also known as CelS, S(S), and S8), the most abundant cellulosome subunit, was undertaken to gain insight into its role in enzymatic and microbial cellulose solubilization. Cultures of the Cel48S deletion mutant (S mutant) were able to completely solubilize 10 g/L crystalline cellulose. The cellulose hydrolysis rate of the S mutant strain was 60% lower than the parent strain, with the S mutant strain also exhibiting a 40% reduction in cell yield. The cellulosome produced …

Alterations In Multiple Measures Of White Matter Integrity In Normal Women At High Risk For Alzheimer's Disease, Brian T. Gold, David K. Powell, Anders H. Andersen, Charles D. Smith

Neuroscience Faculty Publications

There is evidence that disruption of white matter (WM) microstructure is an early event in the course of Alzheimer's disease (AD). However, the neurobiological bases of WM microstructural declines in presymptomatic AD are unknown. In the present study we address this issue using a multimodal imaging approach to the study of presymptomatic AD. Participants were 37 high-risk (both family history of dementia and one or more APOE4 alleles) women and 20 low-risk (neither family history nor APOE4) women. Groups were matched for age, education, neuropsychological performance, and vascular factors that could affect white matter. Whole-brain analyses of diffusion tensor imaging …

Selective Biochlorination Of Hydroxyquinolines By A Flavin-Dependent Halogenase, Fuchao Xu, Amanda Merkley, Dayu Yu, Jixun Zhan

Biological Engineering Faculty Publications

Rdc2 is a flavin-dependent halogenase from Pochonia chlamydosporia. Through the introduction of a His₆-tag to both the N- and C-termini, the isolation yield of Rdc2 from Escherichia coli using Ni-NTA affinity chromatography was increased by three-fold. In vitro reaction of Rdc2 and a flavin reductase (Fre) with seven different hydroxyquinolines revealed that 3-hydroxyquinoline (3), 5-hydroxyquinoline (5), 6-hydroxyquinoline (6), and 7-hydroxyquinoline (7) can be specifically halogenated. These products were prepared by incubating the corresponding substrates with IPTG-induced E. coli BL21(DE3)/Rdc2. They were respectively characterized as 3-hydroxy-4-chloroquinoline (3a), 5-hydroxy-6-chloroquinoline (5a), 5-chloro-6-hydroxyquinoline (6a), and 7-hydroxy-8-chloroquinoline (7a) by NMR and MS …

Dispersion Of Cytotoxic Properties Of Multi-Walled Carbon Nanotubes Suspended In Biological Solutions With Tween 80: Their Role In Enhancing Killing Effects Of Nanosecond Pulse Electric Fields On Tumor Cell Lines, Bhargava S. Kalluri

Biological Sciences Theses & Dissertations

The objective of this study was to determine whether multi-walled carbon nanotubes (MWCNTs) suspended in the surfactant Tween 80 give an additive killing effect on tumor cells when exposed to nsPEFs. In this study, MWCNTs were suspended in DMEM and RPMI with or without T80 (surfactant). The size distribution of MWCNTs suspended in these solutions was evaluated with a Delsa™ Nano Zeta potential and sub micro particle Size Analyzer and confirmed with microscopy. The cytotoxicity of MWCNTs dispersed in different concentrations of T80 was evaluated in PANC1 (Human pancreatic cancer cell line) and Jurkat cell lines (Human T-cell lymphoblast cell …

Development Of Pyrf-Based Genetic System For Targeted Gene Deletion In Clostridium Thermocellum And Creation Of A Pta Mutant, Shital A. Tripathi, Daniel G. Olson, D. Aaron Argyros, Bethany B. Miller, Trisha F. Barrett, Daniel M. Murphy, Jesse D. Mccool, Anne K. Warner, Vineet B. Rajgarhia, Lee R. Lynd, David A. Hogsett, Nicky C. Caiazza

Dartmouth Scholarship

We report development of a genetic system for making targeted gene knockouts in Clostridium thermocellum, a thermophilic anaerobic bacterium that rapidly solubilizes cellulose. A toxic uracil analog, 5-fluoroorotic acid (5-FOA), was used to select for deletion of the pyrF gene. The ΔpyrF strain is a uracil auxotroph that could be restored to a prototroph via ectopic expression of pyrF from a plasmid, providing a positive genetic selection. Furthermore, 5-FOA was used to select against plasmid-expressed pyrF, creating a negative selection for plasmid loss. This technology was used to delete a gene involved in organic acid production, namely pta, which encodes …

3d Micro-Mr And Micro-Ct Models For Determining In-Vivo Function In The Guinea Pig Knee Model Of Osteoarthritis (Oa), Kristoffer W. Dean

Undergraduate Research Opportunities Program (UROP)

Osteoarthritis (OA) is a debilitating disease that affects an estimated 27 million adults in the United States. OA causes damage to cartilage in the joints resulting in bones that rub together. This creates pain, swelling, loss of motion of the joint, and bone spurs. As the number of adults above 65 grows (an estimated 72 million people by 2030) even more people will be at high risk for OA. It is the most common type of arthritis by far yet very little is known about it including relationships between joint structure and function. In 2004, the NIH created the Osteoarthritis …