Biological Engineering Commons^™

Developing Droplet Based 3d Cell Culture Methods To Enable Investigations Of The Chemical Tumor Microenvironment, Jacqueline Alexandria De Lora

Biomedical Sciences ETDs

Adaptation of cancer cells to changes in the biochemical microenvironment in an expanding tumor mass is a crucial aspect of malignant progression, tumor metabolism, and drug efficacy. In vitro, it is challenging to mimic the evolution of biochemical gradients and the cellular heterogeneity that characterizes cancer tissues found in vivo. It is well accepted that more realistic and controllable in vitro 3D model systems are required to improve the overall cancer research paradigm and thus improve on the translation of results, but multidisciplinary approaches are needed for these advances. This work develops such approaches and demonstrates that new droplet-based cell-encapsulation …

Radical Social Ecology As Deep Pragmatism: A Call To The Abolition Of Systemic Dissonance And The Minimization Of Entropic Chaos, Arielle Brender

Student Theses 2015-Present

This paper aims to shed light on the dissonance caused by the superimposition of Dominant Human Systems on Natural Systems. I highlight the synthetic nature of Dominant Human Systems as egoic and linguistic phenomenon manufactured by a mere portion of the human population, which renders them inherently oppressive unto peoples and landscapes whose wisdom were barred from the design process. In pursuing a radical pragmatic approach to mending the simultaneous oppression and destruction of the human being and the earth, I highlight the necessity of minimizing entropic chaos caused by excess energy expenditure, an essential feature of systems that aim …

Exogenous Fniii 12-14 Regulates Tgf-Β1-Induced Markers, Hilmi M. Humeid

Theses and Dissertations

The extracellular matrix protein Fibronectin (FN) plays an important role in cell contractility, differentiation, growth, adhesion, and migration. The 12th -14th Type III repeats of FN (FNIII 12-14), also referred to as the Heparin-II domain, comprise a highly promiscuous growth factor (GF) binding region. This binding domain aids in cellular signaling initiated from the ECM. Additionally, FN has the ability to assemble into fibrils under certain conditions, mostly observed during cell contractile processes such as those that initiate due to upregulation of Transforming Growth Factor Beta 1 (TGF-β1) [1], [2]. Previous work from our lab has shown that self-assembly of …

The Effects Of Emerging Technology On Healthcare And The Difficulties Of Integration, Skyler J. Pavlish-Carpenter

Honors Undergraduate Theses

Background: Disruptive technology describes technology that is significantly more advanced than previous iterations, such as: 3D printing, genetic manipulation, stem cell research, innovative surgical procedures, and computer-based charting software. These technologies often require extensive overhauls to implement into older systems and must overcome many difficult financial and societal complications before they can be widely used. In a field like healthcare that makes frequent advancements, these difficulties can mean that the technology will not be utilized to its full potential or implemented at all.

Objective: To determine the inhibiting factors that prevent disruptive technology from being implemented in conventional healthcare.

Methods: …

Characterization Of Murine Breast Cancer Cell Lines For Anti-Cancer Vaccine, Haven N. Frazier

Biological Sciences Undergraduate Honors Theses

Breast cancer is the most commonly diagnosed cancer in women and the second leading cause of cancer death among women in the United States (1). While treatments involving radiation and chemotherapy currently exist, disease must be detected early in order for the treatments to be somewhat effective, and there is no effective treatment after metastasis occurs (2). Additionally, current therapies do not mitigate tumor immunosuppression. Decreasing the tumor-associated immunosuppressive conditions while activating antitumor immunity could prevent recurrence and metastasis, possibly leading to an effective treatment for cancer (3). Tumor cell vaccines could possibly address this issue and have become a …

Chitosan Nanoparticle Modifications For Improved Gene Delivery In An Oral Dna Vaccine Application, Austin Helmink

Honors Program: Senior Projects (Public)

Vaccines represent one of the most significant medical innovations of the 20^th century, resulting in the eradication or near eradication of a handful of deadly diseases. However, many infectious diseases remain resistant to effective vaccination, largely due to a lack full immune activation by traditional protein-based vaccines. A promising alternative vaccination strategy is the emerging development of DNA vaccines, which rely upon the delivery of exogenous genetic material to host cells encoding for a viral or bacterial antigen in order to induce a robust immune response by closely mimicking live infection. The delivery of genetic material requires a carrier …

Theoretically Proposed Optimal Frequency For Ultrasound Induced Cartilage Restoration, April D. Miller, Anuradha Subramanian, Hendrik J. Viljoen

Department of Chemical and Biomolecular Engineering: Faculty Publications

Background: Matching the frequency of the driving force to that of the system’s natural frequency of vibration results in greater amplitude response. Thus we hypothesize that applying ultrasound at the chondrocyte’s resonant frequency will result in greater deformation than applying similar ultrasound power at a frequency outside of the resonant bandwidth. Based on this resonant hypothesis, our group previously confirmed theoretically and experimentally that ultrasound stimulation of suspended chondrocytes at resonance (5 MHz) maximized gene expression of load inducible genes. However, this study was based on suspended chondrocytes. The resonant frequency of a chondrocyte does not only depend on the …

A Comprehensive Dosimetric Study On Switching From A Type-B To A Type-C Dose Algorithm For Modern Lung Sbrt, Christina Zhou, Nathan Bennion, Rongtao Ma, Xiaoying Liang, Shuo Wang, Kristina Zvolanek, Megan Hyun, Xiaobo Li, Sumin Zhou, Weining Zhen, Chi Lin, Andrew Wahl, Dandan Zheng

Department of Agricultural and Biological Systems Engineering: Faculty Publications

Background: Type-C dose algorithms provide more accurate dosimetry for lung SBRT treatment planning. However, because current dosimetric protocols were developed based on conventional algorithms, its applicability for the new generation algorithms needs to be determined. Previous studies on this issue used small sample sizes and reached discordant conclusions. Our study assessed dose calculation of a Type-C algorithm with current dosimetric protocols in a large patient cohort, in order to demonstrate the dosimetric impacts and necessary treatment planning steps of switching from a Type-B to a Type-C dose algorithm for lung SBRT planning.

Methods: Fifty-two lung SBRT patients were included, each …

Long-Term Biocompatibility, Imaging Appearance And Tissue Effects Associated With Delivery Of A Novel Radiopaque Embolization Bead For Image-Guided Therapy, Karun Sharma, Zainab Bascal, Hugh Kilpatrick, Koorosh Ashrafi, Sean L. Willis, Matthew R. Dreher, Andrew L. Lewis

Pediatrics Faculty Publications

The objective of this study was to undertake a comprehensive long-term biocompatibility and imaging assessment of a new intrinsically radiopaque bead (LC Bead LUMI™) for use in transarterial embolization. The sterilized device and its extracts were subjected to the raft of ISO10993 biocompatibility tests that demonstrated safety with respect to cytotoxicity, mutagenicity, blood contact, irritation, sensitization, systemic toxicity and tissue reaction. Intra-arterial administration was performed in a swine model of hepatic arterial embolization in which 0.22–1 mL of sedimented bead volume was administered to the targeted lobe(s) of the liver. The beads could be visualized during the embolization procedure with …

Nanobubbles Provide Theranostic Relief To Cancer Hypoxia, Christopher M. Long, Pushpak N. Bhandari, Joseph Irudayaraj

The Summer Undergraduate Research Fellowship (SURF) Symposium

Hypoxia is a common motif among tumors, contributing to metastasis, angiogenesis, cellular epigenetic abnormality, and resistance to cancer therapy. Hypoxia also plays a pivotal role in oncological studies, where it can be used as a principal target for new anti-cancer therapeutic methods. Oxygen nanobubbles were designed in an effort to target the hypoxic tumor regions, thus interrupting the hypoxia-inducible factor-1α (HIF-1α) regulatory pathway and inhibiting tumor progression. At less than 100nm, oxygen nanobubbles act as a vehicle for site-specific oxygen delivery, while also serving as an ultrasound contrast agent for advanced imaging purposes. Through in vitro and in vivo studies, …

Mechanical Reliability Of Implantable Polyimide-Based Magnetic Microactuators For Biofouling Removal, Christian G. Figueroa-Espada, Qi Yang, Hyowon Lee

The Summer Undergraduate Research Fellowship (SURF) Symposium

Hydrocephalus is a neurological disorder that typically requires a long-term implantation of a shunt system to manage its symptoms. These shunt systems are notorious for their extremely high failure rate. More than 40% of all implanted shunt systems fail within the first year of implantation. On average, 85% of all hydrocephalus patients with shunt systems undergo at least two shunt-revision surgeries within 10 years of implantation. A large portion of this high failure rate can be attributed to biofouling-related obstructions and infections. Previously, we developed flexible polyimide-based magnetic microactuators to remove obstructions formed on hydrocephalus shunts. To test the long-term …

Calcium Phosphate As A Key Material For Socially Responsible Tissue Engineering, Vuk Uskoković, Victoria M. Wu

Pharmacy Faculty Articles and Research

Socially responsible technologies are designed while taking into consideration the socioeconomic, geopolitical and environmental limitations of regions in which they will be implemented. In the medical context, this involves making therapeutic platforms more accessible and affordable to patients in poor regions of the world wherein a given disease is endemic. This often necessitates going against the reigning trend of making therapeutic nanoparticles ever more structurally complex and expensive. However, studies aimed at simplifying materials and formulations while maintaining the functionality and therapeutic response of their more complex counterparts seldom provoke a significant interest in the scientific community. In this review …

Inhibition Of Bacterial Growth And Prevention Of Bacterial Adhesion With Localized Nitric Oxide Delivery, Julia Osborne

Dissertations, Master's Theses and Master's Reports

Bacterial infections continue to be a problem at the site of an indwelling medical device, and over the years, various bacterial strains have become more resistant to current antibiotic treatments. Bacterial infection at an indwelling medical device can be dangerous and affect the performance of the medical device which can ultimately lead to the failure of the device due to bacterial resistance to treatment.

Nitric Oxide (NO) has been shown to possess antibacterial properties to prevent and inhibit bacterial growth. NO releasing coatings on indwelling medical devices could provide a reduction in bacterial infections that occur at the device site …

Design And Development Of Two Component Hydrogel Ejector For Three-Dimensional Cell Growth, Thomas Dunkle, Jessica Deschamps, Connie Dam

Honors Scholar Theses

Hydrogels are useful in wound healing, drug delivery, and tissue engineering applications, but the available methods of injecting them quickly and noninvasively are limited. The medical industry does not yet have access to an all-purpose device that can quickly synthesize hydrogels of different shapes and sizes. Many synthesis procedures that have been developed result in the formation of amorphous hydrogels. While generally useful, amorphous hydrogels exhibit limited capability in tissue engineering applications, especially due to their viscous properties. This endeavor aims to modulate the appropriate gelation parameters, optimize the injection process, and create a prototype that allows for the extrusion …

Selection Methods For Genetically-Modified T Cells: In Support Of Translational Therapy, David Rushworth

Dissertations and Theses (Open Access)

T cells are blood cells which organize the immune system of the host. These cells are necessary for the host to respond appropriately to threats from foreign organisms and cancerous growth. However, in the case of certain infections and cancer, T cells are unable to respond appropriately to a threat and establish immunity. This leads to disease when the infection or cancer is not sufficiently eliminated. On the other hand, T cells can lack tolerance for healthy tissue and perceive healthy tissue as infected. The ensuing over-reactive immune response also leads to disease. A delicate balance must exist between immunity …

Modeling The Adaptive Immune Response To Mutation-Generated Antigens, Rory J. Geyer

University Scholar Projects

Somatic mutations may drive tumorigenesis or lead to new, immunogenic epitopes (neoantigens). The immune system is thought to represses neoplastic growths through the recognition of neoantigens presented only by tumor cells. To study mutations as well as the immune response to mutation-generated antigens, we have created a conditional knockin mouse line with a gene encoding, 5’ to 3’, yellow fluorescent protein (YFP), ovalbumin (which is processed to the immunologically recognizable peptide, SIINFEKL), and cyan fluorescent protein (CFP), or, YFP-ovalbumin-CFP. A frame shift mutation has been created at the 5’ end of the ovalbumin gene, hence YFP should always be expressed, …

Modeling The Adaptive Immune Response To Mutation-Generated Antigens, Rory J. Geyer

Honors Scholar Theses

Somatic mutations may drive tumorigenesis or lead to new, immunogenic epitopes (neoantigens). The immune system is thought to represses neoplastic growths through the recognition of neoantigens presented only by tumor cells. To study mutations as well as the immune response to mutation-generated antigens, we have created a conditional knockin mouse line with a gene encoding, 5’ to 3’, yellow fluorescent protein (YFP), ovalbumin (which is processed to the immunologically recognizable peptide, SIINFEKL), and cyan fluorescent protein (CFP), or, YFP-ovalbumin-CFP. A frame shift mutation has been created at the 5’ end of the ovalbumin gene, hence YFP should always be expressed, …

Bioactivity And Cell-Mediated Targeting Of Multistage Nanoporous Silicon Particles, Jonathan O. Martinez

Dissertations and Theses (Open Access)

Progress in drug delivery approaches have not adequately translated into clinical advances in the diagnosis or treatment of inflammatory disorders (e.g., cancer). This disconnect is rooted in the inefficient delivery of imaging and therapeutic agents to the inflamed site upon systemic delivery. A multitude of biological barriers pose insurmountable obstacles limiting the ability of the agent to effectively reach and accumulate at the target site. Nanoparticles (NP) surfaced as potential vectors to encapsulate and deliver biological agents. However, even after surface decoration, NP have failed to evade biological barriers (i.e., MPS) and to accumulate at the tumor site at therapeutic …

Pretreatment Of Scenedesmus Sp. Biomass As A Potential Anaerobic Digestion Substrate, Xinyi E, Czarena Crofcheck

Biosystems and Agricultural Engineering Faculty Publications

Algal biomass can be a potential substrate for anaerobic digestion. However, raw algae cells show a resistance to biological degradation, resulting in a slower methane production rate. Varying thermal and chemical pretreatments of algal biomass were investigated in an attempt to increase soluble organic matter (SOM) yield, which would result in enhanced methane production during subsequent anaerobic digestion. Scenedesmus sp. was harvested using three different procedures: with flocculation, with flocculation and drying, and without flocculation or drying. For all pretreatments and algae types, fluorescence micrographs were obtained to visually confirm the degradation of the algal cell walls. A complete 2 …

Evaluation Of Tissue-Engineered Tendon Enthesis Polymer Constructs, Joshua A. Bundy Bs, Mary Beth Wade Phd, Hitomi Nakao Md, Phillip Mcclellan Phd, Qing Yu Phd, Robin Jacquet-Childs Ms, William J. Landis Phd

Williams Honors College, Honors Research Projects

Both scientists and clinicians have proposed tissue engineering as the future of medicine. The possibilities for tissue engineering, that is, fabrication of tissues and organs in the laboratory and their translation to patients, appear to be endless, and many believe that this new approach in medicine will result in abolishing many common ailments, injuries, and congenital defects. Injuries to a tendon enthesis, the normal tissue connection between tendon and bone, are of particular concern to clinicians because of their frequency and failure to repair as a result of surgery. While these injuries may not be life threatening, they can certainly …

Hybrid Nanostructured Textile Bioelectrode For Unobtrusive Health Monitoring, Pratyush Rai

Graduate Theses and Dissertations

Coronary heart disease, cardiovascular diseases and strokes are the leading causes of mortality in United States of America. Timely point-of-care health diagnostics and therapeutics for person suffering from these diseases can save thousands of lives. However, lack of accessible minimally intrusive health monitoring systems makes timely diagnosis difficult and sometimes impossible. To remedy this problem, a textile based nano-bio-sensor was developed and evaluated in this research. The sensor was made of novel array of vertically standing nanostructures that are conductive nano-fibers projecting from a conductive fabric. These sensor electrodes were tested for the quality of electrical contact that they made …

Beach Wheelchair Project, Rory Aronson, Joshua Marcum, Samuel Coyne, Alex Hayes, Alexa Colburn, Max Hessel, Benedikt Strauss, Marvin Rimmele, Marco Pietsch

Mechanical Engineering

The Beach Wheelchair, Sandcrawler, is a machine intended to help give people with disabilities the full beach experience. The non-profit organization Bridge II Sports sponsored this project, and tasked us with developing the design and fabricating a prototype. This chair has several features including a linkage mechanism that raises and lowers a chair relative to an external frame, hand crank drive with Gates Carbondrive belt and sprockets, buoyant Wheeleez balloon tires, and much more.

The Effects Of Hydrostatic Pressure On Early Endothelial Tubulogenic Processes, Ryan M. Underwood

Theses and Dissertations--Biomedical Engineering

The effects of mechanical forces on endothelial cell function and behavior are well documented, but have not been fully characterized. Specifically, fluid pressure has been shown to elicit physical and chemical responses known to be involved in the initiation and progression of endothelial cell-mediated vascularization. Central to the process of vascularization is the formation of tube-like structures. This process—tubulogenesis—is essential to both the physiological and pathological growth of tissues. Given the known effects of pressure on endothelial cells and its ubiquitous presence in the vasculature, we investigated pressure as a magnitude-dependent parameter for the regulation of endothelial tubulogenic activity. To …

Noninvasive Near-Infrared Diffuse Optical Monitoring Of Cerebral Hemodynamics And Autoregulation, Ran Cheng

Theses and Dissertations--Biomedical Engineering

Many cerebral diseases are associated with abnormal cerebral hemodynamics and impaired cerebral autoregulation (CA). CA is a mechanism to maintain cerebral blood flow (CBF) stable when mean arterial pressure (MAP) fluctuates. Evaluating these abnormalities requires direct measurements of cerebral hemodynamics and MAP. Several near-infrared diffuse optical instruments have been developed in our laboratory for hemodynamic measurements including near-infrared spectroscopy (NIRS), diffuse correlation spectroscopy (DCS), hybrid NIRS/DCS, and dual-wavelength DCS flow-oximeter. We utilized these noninvasive technologies to quantify CBF and cerebral oxygenation in different populations under different physiological conditions/manipulations. A commercial finger plethysmograph was used to continuously monitor MAP. For investigating …

Development Of A Protocol To Measure Gene Expression In The Mouse Tibia, Daniel Hoover

Biomedical Engineering

Numerous molecular factors active in bone tissue direct fracture repair and remodeling which can be altered by disease conditions such as Peripheral Arterial Disease (PAD) and Osteoporosis. Methods of molecular biology are commonly applied to investigate the expression and role of these molecular factors. This project presents a robust three-step protocol for examining gene expression in the mouse tibia. The protocol begins with isolating RNA from a flash frozen tibia sample. The isolated RNA is reverse transcribed into cDNA. Finally, PCR is performed to indentify expressed genes. Establishing this protocol will allow further research into the mechanisms of bone remodeling …

Aptamer-Based Spr Biosensor For Detection Of Avian Influenza Virus, Hua Bai

Graduate Theses and Dissertations

Rapid and specific detection of avian influenza (AI) virus is urgently needed with the concerns over the outbreaks of highly pathogenic H5N1 avian influenza in animal and human infection. Aptamers are artificial oligonucleic acid that can specifically bind to target molecules. They show comparable affinity for target virus and better thermal stability than monoclonal antibodies. Those advantages make aptamers promising candidates in diagnostic and detection applications. The goal of this research was to use DNA&ndashaptamer as the specific recognition element in a portable surface plasmon resonance (SPR) biosensor for detection of AI H5N1 virus in poultry.

A SPR biosensor was …

A Thousand Tiny Pieces: The Federal Circuit’S Fractured Myriad Ruling, Lessons To Be Learned, And The Way Forward, Jonathan R. K. Stroud

IP Theory

No abstract provided.

Design And Fabrication Of Nanofluidic Systems For Biomolecule Characterizations, Orain Ansel Hibbert

Graduate Theses and Dissertations

Nanofluidic channel systems were designed and fabricated by combining MEMS microfabrication with AFM nanolithography. In the fabrication process flow, photolithography was first utilized to pattern microfluidic channels and reservoirs on a 4" Pyrex substrate. Subsequently, atomic force microscopy (AFM) based nanolithography was used to mechanically fabricate nanochannels to connect the microreservoirs which formed the inlet and outlet of the nanofluidic system. A Tap190 Diamond-Like Carbon (DLC) AFM tip with a force constant of 48 N/m and a radius of less than 15 nm was used as the nanolithography tool. The resultant nanochannel ranges from 20 to 80 µm in length …

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 …

Robust Dynamic Balance Of Ap-1 Transcription Factors In A Neuronal Gene Regulatory Network., Gregory M Miller, Babatunde A Ogunnaike, James S Schwaber, Rajanikanth Vadigepalli

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: The octapeptide Angiotensin II is a key hormone that acts via its receptor AT1R in the brainstem to modulate the blood pressure control circuits and thus plays a central role in the cardiac and respiratory homeostasis. This modulation occurs via activation of a complex network of signaling proteins and transcription factors, leading to changes in levels of key genes and proteins. AT1R initiated activity in the nucleus tractus solitarius (NTS), which regulates blood pressure, has been the subject of extensive molecular analysis. But the adaptive network interactions in the NTS response to AT1R, plausibly related to the development of …