Barrett, The Honors College Thesis/Creative Project Collection
Barrett, The Honors College at Arizona State University proudly showcases the work of undergraduate honors students by sharing this collection exclusively with the ASU community.
Barrett accepts high performing, academically engaged undergraduate students and works with them in collaboration with all of the other academic units at Arizona State University. All Barrett students complete a thesis or creative project which is an opportunity to explore an intellectual interest and produce an original piece of scholarly research. The thesis or creative project is supervised and defended in front of a faculty committee. Students are able to engage with professors who are nationally recognized in their fields and committed to working with honors students. Completing a Barrett thesis or creative project is an opportunity for undergraduate honors students to contribute to the ASU academic community in a meaningful way.
Displaying 1 - 10 of 48
Description
Traumatic brain injury (TBI) may result in numerous pathologies that cannot currently be mitigated by clinical interventions. Stem cell therapies are widely researched to address TBI-related pathologies with limited success in pre-clinical models due to limitations in transplant survival rates. To address this issue, the use of tissue engineered scaffolds as a delivery mechanism has been explored to improve survival and engraftment rates. Previous work with hyaluronic acid \u2014 laminin (HA-Lm) gels found high viability and engraftment rates of mouse fetal derived neural progenitor/stem cells (NPSCs) cultured on the gel. Furthermore, NPSCs exposed to the HA-Lm gels exhibit increased expression of CXCR4, a critical surface receptor that promotes cell migration. We hypothesized that culturing hNPCs on the HA-Lm gel would increase CXCR4 expression, and thus enhance their ability to migrate into sites of tissue damage. In order to test this hypothesis, we designed gel scaffolds with mechanical properties that were optimized to match that of the natural extracellular matrix. A live/dead assay showed that hNPCs preferred the gel with this optimized formulation, compared to a stiffer gel that was used in the CXCR4 expression experiment. We found that there may be increased CXCR4 expression of hNPCs plated on the HA-Lm gel after 24 hours, indicating that HA-Lm gels may provide a valuable scaffold to support viability and migration of hNPCs to the injury site. Future studies aimed at verifying increased CXCR4 expression of hNPCs cultured on HA-Lm gels are necessary to determine if HA-Lm gels can provide a beneficial scaffold for stem cell engraftment therapy for treating TBI.
ContributorsHemphill, Kathryn Elizabeth (Author) / Stabenfeldt, Sarah (Thesis director) / Brafman, David (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
Abstract
The aim of the research performed was to increase research potential in the field of cell stimulation by developing a method to adhere human neural progenitor cells (hNPC’s) to a sterilized stretchable microelectrode array (SMEA). The two primary objectives of our research were to develop methods of sterilizing the polydimethylsiloxane (PDMS) substrate being used for the SMEA, and to derive a functional procedure for adhering hNPC’s to the PDMS. The proven method of sterilization was to plasma treat the sample and then soak it in 70% ethanol for one hour. The most successful method for cell adhesion was plasma treating the PDMS, followed by treating the surface of the PDMS with 0.01 mg/mL poly-l-lysine (PLL) and 3 µg/cm2 laminin. The development of these methods was an iterative process; as the methods were tested, any problems found with the method were corrected for the next round of testing until a final method was confirmed. Moving forward, the findings will allow for cell behavior to be researched in a unique fashion to better understand the response of adherent cells to physical stimulation by measuring changes in their electrical activity.
The aim of the research performed was to increase research potential in the field of cell stimulation by developing a method to adhere human neural progenitor cells (hNPC’s) to a sterilized stretchable microelectrode array (SMEA). The two primary objectives of our research were to develop methods of sterilizing the polydimethylsiloxane (PDMS) substrate being used for the SMEA, and to derive a functional procedure for adhering hNPC’s to the PDMS. The proven method of sterilization was to plasma treat the sample and then soak it in 70% ethanol for one hour. The most successful method for cell adhesion was plasma treating the PDMS, followed by treating the surface of the PDMS with 0.01 mg/mL poly-l-lysine (PLL) and 3 µg/cm2 laminin. The development of these methods was an iterative process; as the methods were tested, any problems found with the method were corrected for the next round of testing until a final method was confirmed. Moving forward, the findings will allow for cell behavior to be researched in a unique fashion to better understand the response of adherent cells to physical stimulation by measuring changes in their electrical activity.
ContributorsBridgers, Carson (Co-author) / Peterson, Mara (Co-author) / Stabenfeldt, Sarah (Thesis director) / Graudejus, Oliver (Committee member) / Harrington Bioengineering Program (Contributor) / School of Human Evolution and Social Change (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
The primary objective of this research project is to develop dual layered polymeric microparticles with a tunable delayed release profile. Poly(L-lactic acid) (PLA) and poly(lactic-co-glycolic acid) (PLGA) phase separate in a double emulsion process due to differences in hydrophobicity, which allows for the synthesis of double-walled microparticles with a PLA shell surrounding the PLGA core. The microparticles were loaded with bovine serum albumin (BSA) and different volumes of ethanol were added to the PLA shell phase to alter the porosity and release characteristics of the BSA. Different amounts of ethanol varied the total loading percentage of the BSA, the release profile, surface morphology, size distribution, and the localization of the protein within the particles. Scanning electron microscopy images detailed the surface morphology of the different particles. Loading the particles with fluorescently tagged insulin and imaging the particles through confocal microscopy supported the localization of the protein inside the particle. The study suggest that ethanol alters the release characteristics of the loaded BSA encapsulated in the microparticles supporting the use of a polar, protic solvent as a tool for tuning the delayed release profile of biological proteins.
ContributorsFauer, Chase Alexander (Author) / Stabenfeldt, Sarah (Thesis director) / Ankeny, Casey (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor)
Created2015-05
Description
This project aims to address the current protocol regarding the diagnosis and treatment of traumatic brain injury (TBI) in medical industries around the world. Although there are various methods used to qualitatively determine if TBI has occurred to a patient, this study attempts to aid in the creation of a system for quantitative measurement of TBI and its relative magnitude. Through a method of artificial evolution/selection called phage display, an antibody that binds highly specifically to a post-TBI upregulated brain chondroitin sulfate proteoglycan called neurocan has been identified. As TG1 Escheria Coli bacteria were infected with KM13 helper phage and M13 filamentous phage in conjunction, monovalent display of antibody fragments (ScFv) was performed. The ScFv bind directly to the neurocan and from screening, phage that produced ScFv's with higher affinity and specificity to neurocan were separated and purified. Future research aims to improve the ScFv characteristics through increased screening toward neurocan. The identification of a highly specific antibody could lead to improved targeting of neurocan post-TBI in-vivo, aiding researchers in quantitatively defining TBI by visualizing its magnitude.
ContributorsSeelig, Timothy Scott (Author) / Stabenfeldt, Sarah (Thesis director) / Ankeny, Casey (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor)
Created2015-05
Description
The endogenous response of neural stem cell/progenitor (NPSC) recruitment to the brain injury environment following a traumatic brain injury (TBI) is currently under heavy investigation. Mechanisms controlling NPSC proliferation and migration to the brain injury environment remain unclear; however, it is thought that the vascular extracellular matrix proteins (e.g. laminin, fibronectin, and vitronectin) and vascular endothelial growth factor (VEGF) play a role in mediating NPSC behavior through vasophillic interactions. This project attempts to uncover potential VEGF-ECM crosstalk in mediating migration and proliferation. To investigate migration, neurospheres were seeded on ECM-coated wells supplemented with VEGF and without VEGF, and neural outgrowth was measured at days 0, 1, 3, and 8 using differential interference contrast microscopy. Furthermore, single-cell NPSCs were seeded on ECM-coated Transwell membranes with VEGF supplemented media on one side and without VEGF to look at chemotactic migration. Migrated NPSCs were visualized with DAPI nuclear stain and imaged with an inverted fluorescent microscope. To investigate NPSC proliferation, NPSCs were seeded on ECM coated plates as in the radial migration assay and visualized with EdU on day 8. Total proliferation was measured by seeding NPSCs on ECM coated 96-well plates and incubating them with MTT on days 3 and 6. Proliferation was measured using a spectrophotometer at 630nm and 570nm wavelengths. It was found that VEGF-laminin crosstalk synergistically increased radial migration, but may not play a role in chemotactic migration. Understanding the mechanisms behind VEGF-laminin crosstalk in NPSC proliferation and migration may provide crucial information for the design of stem cell transplantation therapies in the future.
ContributorsMillar-Haskell, Catherine Susan (Author) / Stabenfeldt, Sarah (Thesis director) / Addington, Caroline (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor)
Created2015-05
Description
The main objective of this research is to develop and characterize a targeted contrast agent that will recognize acute neural injury pathology (i.e. fibrin) after traumatic brain injury (TBI). Single chain fragment variable antibodies (scFv) that bind specifically to fibrin have been produced and purified. DSPE-PEG micelles have been produced and the scFv has been conjugated to the surface of the micelles; this nanoparticle system will be used to overcome limitations in diagnosing TBI. The binding and imaging properties will be analyzed in the future to determine functionality of the nanoparticle system in vivo.
ContributorsRumbo, Kailey Michelle (Author) / Stabenfeldt, Sarah (Thesis director) / Kodibagkar, Vikram (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor)
Created2014-05
Description
The brain is the most important part of the central nervous system in the human body. It is the center of consciousness and controls all voluntary motor activity of the body. Mechanical trauma sustained to the head during a car accident, fall, or sports injury can lead to a traumatic brain injury (TBI) that may have long ranging and sustained physical, cognitive and emotional effects. TBI is the most common form of brain injury and it contributes to one third of all injury related deaths in the United States. The Stabenfeldt lab aims to develop regenerative strategies that will harness inherent endogenous repair mechanisms in traumatic brain injury to improve functional outcomes in cognitive and motor functions. Previous research has demonstrated that the acute inflammatory response after TBI releases soluble cytokines that mediate regeneration after TBI. One of such soluble signal is stromal cell derived factor-1α (SDF-1α) and its receptor CXCR4. The SDF-1α/CXCR4 signaling axis directs the migration and organization of neural progenitor/ stem cells which is important in the regeneration of the injury area. In this study, we probed this paradigm by injecting bolus and nanoparticle exogenous SDF-1α intracortically into mice then sacrificing at 1, 3, and 7 days’ post-injection. Increased CXCR4 positive cells were expressed around the SDF-1α injection area. This study specifically focused on characterizing microglia and macrophage population in the brains that expressed CXCR4 via immunohistochemistry. Data from this study showed that the bolus group initiated microglial activation within the injection tract particularly at day 3 post injection which was resolved by day 7. However, the nanoparticle group initiated the activation of microglial/macrophages as early as day 1 post injection which proceeded to day 7. This shows that the nanoparticle groups initiated an
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inflammatory reaction in the injection tract irrespective of SDF-1α since the blank nanoparticle (nanoparticle with no SDF-1α) group exhibited the identical trend.
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inflammatory reaction in the injection tract irrespective of SDF-1α since the blank nanoparticle (nanoparticle with no SDF-1α) group exhibited the identical trend.
ContributorsSalifu, Mariama (Author) / Stabenfeldt, Sarah (Thesis director) / Dutta, Dipankar (Committee member) / Barrett, The Honors College (Contributor)
Created2017-05
Description
Traumatic brain injury (TBI) can result in many pathologies, one of which being coagulopathy. TBI can progress to hemorrhagic lesions and increased intercranial pressure leading to coagulopathy. The coagulopathy has been linked to poor clinical outcomes and occurs in 60% of severe TBI cases. To improve hemostasis, synthetic platelets (SPs) have been repurposed. SPs are composed of a poly(N-isopropylacrylamide-co-acrylic-acid) microgel, conjugated with a fibrin-specific antibody and are biomimetic in their ability to deform and collapse within a fibrin matrix. The objective of this study is to diminish coagulopathy with a single, intravenous injection of SPs, and subsequently decrease neuropathologies. TBI was modeled in animal cohorts using the well-established controlled cortical impact and SPs were injected 2-3 hours post-injury. Control cohorts received no injection. Brain tissue was harvested at acute (24h) and delayed (7 days) time points post-TBI, and fluorescently imaged to quantify reactive astrocytes (GFAP+), microglial morphology and presence (Iba1+), and tissue lesion spared. SP-treatment resulted in significant reduction of GFAP expression at 7 days post-TBI. Furthermore, SP-treatment significantly reduced the percent difference from 24h to 7 days in microglia/macrophage per field compared to the control. For microglial morphology, SP-treated cohorts observed a significant percent difference in endpoints per soma from 24h to 7 days compared to untreated cohorts. However, microglial branch length significantly decreased in percent difference from 24h to 7 days when compared to the control. Finally, tissue sparing did not significantly decrease between 24h and 7 day for SP-treated cohorts as was observed in untreated cohorts, implying inhibition of delayed necrosis. Overall, these results suggest decreased neuroinflammation by 7 days, supporting SPs as potentially therapeutic post-TBI.
ContributorsTodd, Jordan Cecile (Author) / Stabenfeldt, Sarah (Thesis director) / Bharadwaj, Vimala (Committee member) / Harrington Bioengineering Program (Contributor, Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
Traumatic brain injury (TBI) is a major concern in public health due to its prevalence and effect. Every year, about 1.7 million TBIs are reported [7]. According to the According to the Centers for Disease Control and Prevention (CDC), 5.5% of all emergency department visits, hospitalizations, and deaths from 2002 to 2006 are due to TBI [8]. The brain's natural defense, the Blood Brain Barrier (BBB), prevents the entry of most substances into the brain through the blood stream, including medicines administered to treat TBI [11]. TBI may cause the breakdown of the BBB, and may result in increased permeability, providing an opportunity for NPs to enter the brain [3,4]. Dr. Stabenfeldt's lab has previously established that intravenously injected nanoparticles (NP) will accumulate near the injury site after focal brain injury [4]. The current project focuses on confirmation of the accumulation or extravasation of NPs after brain injury using 2-photon microscopy. Specifically, the project used controlled cortical impact injury induced mice models that were intravenously injected with 40nm NPs post-injury. The MATLAB code seeks to analyze the brain images through registration, segmentation, and intensity measurement and evaluate if fluorescent NPs will accumulate in the extravascular tissue of injured mice models. The code was developed with 2D bicubic interpolation, subpixel image registration, drawn dimension segmentation and fixed dimension segmentation, and dynamic image analysis. A statistical difference was found between the extravascular tissue of injured and uninjured mouse models. This statistical difference proves that the NPs do extravasate through the permeable cranial blood vessels in injured cranial tissue.
ContributorsIrwin, Jacob Aleksandr (Author) / Stabenfeldt, Sarah (Thesis director) / Bharadwaj, Vimala (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
Traumatic brain injury (TBI) is a serious health problem around the world with few available treatments. TBI pathology can be divided into two phases: the primary insult and the secondary injury. The primary insult results from the bump or blow to the head that causes the initial injury. Secondary injury lasts from hours to months after the initial injury and worsens the primary insult, creating a greater area of tissue damage and cell death. Many current treatments focus on lessening the severity of secondary injury. Secondary injury results from the cyclical nature of tissue damage. Inflammatory pathways cause damage to tissue, which in turn reinforces inflammation. Since many inflammatory pathways are interconnected, targeting individual products within these pathways is impractical. A target at the beginning of the pathway, such as a receptor, must be chosen to break the cycle. This project aims to identify novel nanobodies that could temporarily inactivate the CD36 receptor, which is a receptor found on many immune and endothelial cells. CD36 initiates and perpetuates the immune system's inflammatory responses. By inactivating this receptor temporarily, inflammation and immune cell entry could be lessened, and therefore secondary injury could be attenuated. This project utilized phage display as a method of nanobody selection. The specific phage library utilized in this experiment consists of human heavy chain (V_H) segments, also known as domain antibodies (dAbs), displayed on M13 filamentous bacteriophage. Phage display mimics the process of immune selection. The target is bound to a well as a means of displaying it to the phage. The phage library is then incubated with the target to allow antibodies to bind. After, the well is washed thoroughly to detach any phage that are not strongly bound. The remaining phage are then amplified in bacteria and run again through the same assay to select for mutations that resulted in higher affinity binding. This process, called biopanning, was performed three times for this project. After biopanning, the library was sequenced using Next Generation sequencing (NGS). This platform enables the entire library to be sequenced, as opposed to traditional Sanger sequencing, which can only sequence single select clones at a time thereby limiting population sampling. This type of genetic sequencing allows trends in the complementarity determining regions (CDRs) of the domain antibody library to be analyzed, using bioinformatics programs such as RStudio, FastAptamer, and Swiss Model. Ultimately, two nanobody candidates were identified for the CD36 receptor.
ContributorsLundgreen, Kendall (Author) / Stabenfeldt, Sarah (Thesis director) / Ugarova, Tatiana (Committee member) / School of Life Sciences (Contributor) / School of International Letters and Cultures (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05