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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

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
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Description
Cardiac tissue engineering is an emerging field that has the potential to regenerate and repair damaged cardiac tissues after myocardial infarction. Numerous studies have introduced hydrogel-based cardiac tissue constructs featuring suitable microenvironments for cell growth along with precise surface topographies for directed cell organization. Despite significant progress, previously developed cardiac

Cardiac tissue engineering is an emerging field that has the potential to regenerate and repair damaged cardiac tissues after myocardial infarction. Numerous studies have introduced hydrogel-based cardiac tissue constructs featuring suitable microenvironments for cell growth along with precise surface topographies for directed cell organization. Despite significant progress, previously developed cardiac tissue constructs have suffered from electrically insulated matrices and low cell retention. To address these drawbacks, we fabricated micropatterned hybrid hydrogel constructs (uniaxial microgrooves with 50 µm with) using a photocrosslinkable gelatin methacrylate (GelMA) hydrogel incorporated with gold nanorods (GNRs). The electrical impedance results revealed a lower impedance in the GelMA-GNR constructs versus the pure GelMA constructs. Superior electrical conductivity of GelMA-GNR hydrogels (due to incorporation of GNRs) enabled the hybrid tissue constructs to be externally stimulated using a pulse generator. Furthermore, GelMA-GNR tissue hydrogels were tested to investigate the biological characteristics of cultured cardiomyocytes. The F-actin fiber analysis results (area coverage and alignment indices) revealed higher directed (uniaxial) cytoskeleton organization of cardiac cells cultured on the GelMA-GNR hydrogel constructs in comparison to pure GelMA. Considerable increase in the coverage area of cardiac-specific markers (sarcomeric α-actinin and connexin 43) were observed on the GelMA-GNR hybrid constructs compared to pure GelMA hydrogels. Despite substantial dissimilarities in cell organization, both pure GelMA and hybrid GelMA-GNR hydrogel constructs provided a suitable microenvironment for synchronous beating of cardiomyocytes.
ContributorsMoore, Nathan Allen (Author) / Nikkhah, Mehdi (Thesis director) / Smith, Barbara (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
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Description
Cancer is one of the leading causes of death globally according to the World Health Organization. Although improved treatments and early diagnoses have reduced cancer related mortalities, metastatic disease remains a major clinical challenge. The local tumor microenvironment plays a significant role in cancer metastasis, where tumor cells respond and

Cancer is one of the leading causes of death globally according to the World Health Organization. Although improved treatments and early diagnoses have reduced cancer related mortalities, metastatic disease remains a major clinical challenge. The local tumor microenvironment plays a significant role in cancer metastasis, where tumor cells respond and adapt to a plethora of biochemical and biophysical signals from stromal cells and extracellular matrix (ECM) proteins. Due to these complexities, there is a critical need to understand molecular mechanisms underlying cancer metastasis to facilitate the discovery of more effective therapies. In the past few years, the integration of advanced biomaterials and microengineering approaches has initiated the development of innovative platform technologies for cancer research. These technologies enable the creation of biomimetic in vitro models with physiologically relevant (i.e. in vivo-like) characteristics to conduct studies ranging from fundamental cancer biology to high-throughput drug screening. In this review article, we discuss the biological significance of each step of the metastatic cascade and provide a broad overview on recent progress to recapitulate these stages using advanced biomaterials and microengineered technologies. In each section, we will highlight the advantages and shortcomings of each approach and provide our perspectives on future directions.
ContributorsPeela, Nitish (Author) / Nikkhah, Mehdi (Thesis director) / LaBaer, Joshua (Committee member) / Harrington Bioengineering Program (Contributor, Contributor) / Barrett, The Honors College (Contributor)
Created2017-05
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Description
Glioblastoma multiforme (GBM) is a malignant, aggressive and infiltrative cancer of the central nervous system with a median survival of 14.6 months with standard care. Diagnosis of GBM is made using medical imaging such as magnetic resonance imaging (MRI) or computed tomography (CT). Treatment is informed by medical images and

Glioblastoma multiforme (GBM) is a malignant, aggressive and infiltrative cancer of the central nervous system with a median survival of 14.6 months with standard care. Diagnosis of GBM is made using medical imaging such as magnetic resonance imaging (MRI) or computed tomography (CT). Treatment is informed by medical images and includes chemotherapy, radiation therapy, and surgical removal if the tumor is surgically accessible. Treatment seldom results in a significant increase in longevity, partly due to the lack of precise information regarding tumor size and location. This lack of information arises from the physical limitations of MR and CT imaging coupled with the diffusive nature of glioblastoma tumors. GBM tumor cells can migrate far beyond the visible boundaries of the tumor and will result in a recurring tumor if not killed or removed. Since medical images are the only readily available information about the tumor, we aim to improve mathematical models of tumor growth to better estimate the missing information. Particularly, we investigate the effect of random variation in tumor cell behavior (anisotropy) using stochastic parameterizations of an established proliferation-diffusion model of tumor growth. To evaluate the performance of our mathematical model, we use MR images from an animal model consisting of Murine GL261 tumors implanted in immunocompetent mice, which provides consistency in tumor initiation and location, immune response, genetic variation, and treatment. Compared to non-stochastic simulations, stochastic simulations showed improved volume accuracy when proliferation variability was high, but diffusion variability was found to only marginally affect tumor volume estimates. Neither proliferation nor diffusion variability significantly affected the spatial distribution accuracy of the simulations. While certain cases of stochastic parameterizations improved volume accuracy, they failed to significantly improve simulation accuracy overall. Both the non-stochastic and stochastic simulations failed to achieve over 75% spatial distribution accuracy, suggesting that the underlying structure of the model fails to capture one or more biological processes that affect tumor growth. Two biological features that are candidates for further investigation are angiogenesis and anisotropy resulting from differences between white and gray matter. Time-dependent proliferation and diffusion terms could be introduced to model angiogenesis, and diffusion weighed imaging (DTI) could be used to differentiate between white and gray matter, which might allow for improved estimates brain anisotropy.
ContributorsAnderies, Barrett James (Author) / Kostelich, Eric (Thesis director) / Kuang, Yang (Committee member) / Stepien, Tracy (Committee member) / Harrington Bioengineering Program (Contributor) / School of Mathematical and Statistical Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
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Description
Spasticity is a neurological disorder in which a target group of muscles remain in a contracted state. In addition to interfering with the function of these muscles, spasticity causes chronic pain and discomfort. Often found in patients with cerebral palsy, multiple sclerosis, or stroke history, spasticity affects an estimated twelve

Spasticity is a neurological disorder in which a target group of muscles remain in a contracted state. In addition to interfering with the function of these muscles, spasticity causes chronic pain and discomfort. Often found in patients with cerebral palsy, multiple sclerosis, or stroke history, spasticity affects an estimated twelve million people worldwide. Not only does spasticity cause discomfort and loss of function, but the condition can lead to contractures, or permanent shortenings of the muscle and connective tissue, if left untreated. Current treatments for spasticity are primarily different forms of muscle relaxant pharmaceuticals. Almost all of these drugs, however, carry unwanted side effects, including total muscle weakness, liver toxicity, and possible dependence. Additionally, kinesiotherapy, conducted by physical therapists at rehabilitation clinics, is often prescribed to people suffering from spasticity. Since kinesiotherapy requires frequent practice to be effective, proper treatment requires constant professional care and clinic appointments, discouraging patient compliance. Consequently, a medical device that could automate relief for spasticity outside of a clinic is desired in the market. While a number of different dynamic splints for hand spasticity are currently on the market, research has shown that these devices, which simply brace the hand in an extended position, do not work through any mechanism to decrease spastic tension over time. Two methods of temporarily reducing spasticity that have been observed in clinical studies are cryotherapy, or the decrease of temperature on a target area, and electrotherapy, which is the delivery of regulated electrical pulses to a target area. It is possible that either of these mechanisms could be incorporated into a medical device aimed toward spastic relief. In fact, electrotherapy is used in a current market device called the SaeboStim, which is advertised to help stroke recovery and spastic reduction. The purpose of this paper is to evaluate the viability of a potential spastic relief device that utilizes cryotherapy to a current and closest competitor, the SaeboStim. The effectiveness of each device in relieving spasticity is reviewed. The two devices are also compared on their ability to address primary customer needs, such as convenience, ease of use, durability, and price. Overall, it is concluded that the cryotherapy device more effectively relieves hand spasticity in users, although the SaeboStim's smaller size and better convenience gives it market appeal, and reveals some of the shortcomings in the preliminary design of the cryotherapy device.
ContributorsWiedeman, Christopher Blaise (Author) / Kleim, Jeffrey (Thesis director) / Buneo, Christopher (Committee member) / W.P. Carey School of Business (Contributor) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
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Description
With an increased demand for more enzyme-sensitive, bioresorbable and more biodegradable polymers, various studies of copolymers have been developed. Polymers are widely used in various applications of biomedical engineering such as in tissue engineering, drug delivery and wound healing. Depending on the conditions in which polymers are used, they are

With an increased demand for more enzyme-sensitive, bioresorbable and more biodegradable polymers, various studies of copolymers have been developed. Polymers are widely used in various applications of biomedical engineering such as in tissue engineering, drug delivery and wound healing. Depending on the conditions in which polymers are used, they are modified to accommodate a specific need. For instance, polymers used in drug delivery are more efficient if they are biodegradable. This ensures that the delivery system does not remain in the body after releasing the drug. It is therefore crucial that the polymer used in the drug system possess biodegradable properties. Such modification can be done in different ways including the use of peptides to make copolymers that will degrade in the presence of enzymes. In this work, we studied the effect of a polypeptide GAPGLL on the polymer NIPAAm and compare with the previously studied Poly(NIPAAm-co-GAPGLF). Both copolymers Poly(NIPAAm-co-GAPGLL) were first synthesized from Poly(NIPAAm-co-NASI) through nucleophilic substitution by the two peptides. The synthesis of these copolymers was confirmed by 1H NMR spectra and through cloud point measurement, the corresponding LCST was determined. Both copolymers were degraded by collagenase enzyme at 25 ° C and their 1H NMR spectra confirmed this process. Both copolymers were cleaved by collagenase, leading to an increase in solubility which yielded a higher LCST compared to before enzyme degradation. Future studies will focus on evaluating other peptides and also using other techniques such as Differential Scanning Microcalorimetry (DSC) to better observe the LCST behavior. Moreover, enzyme kinetics studies is also crucial to evaluate how fast the enzyme degrades each of the copolymers.
ContributorsUwiringiyimana, Mahoro Marie Chantal (Author) / Vernon, Brent (Thesis director) / Nikkhah, Mehdi (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
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Description
Smart contrast agents allow for noninvasive study of specific events or tissue conditions inside of a patient's body using Magnetic Resonance Imaging (MRI). This research aims to develop and characterize novel smart contrast agents for MRI that respond to temperature changes in tissue microenvironments. Transmission Electron Microscopy, Nuclear Magnetic Resonance,

Smart contrast agents allow for noninvasive study of specific events or tissue conditions inside of a patient's body using Magnetic Resonance Imaging (MRI). This research aims to develop and characterize novel smart contrast agents for MRI that respond to temperature changes in tissue microenvironments. Transmission Electron Microscopy, Nuclear Magnetic Resonance, and cell culture growth assays were used to characterize the physical, magnetic, and cytotoxic properties of candidate nanoprobes. The nanoprobes displayed thermosensitve MR properties with decreasing relaxivity with temperature. Future work will be focused on generating and characterizing photo-active analogues of the nanoprobes that could be used for both treatment of tissues and assessment of therapy.
ContributorsHussain, Khateeb Hyder (Author) / Kodibagkar, Vikram (Thesis director) / Stabenfeldt, Sarah (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor) / School of Mathematical and Statistical Sciences (Contributor)
Created2014-05
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Description
Glioblastoma Multiforme (GBM) is an aggressive and deadly form of brain cancer with a median survival time of about a year with treatment. Due to the aggressive nature of these tumors and the tendency of gliomas to follow white matter tracks in the brain, each tumor mass has a unique

Glioblastoma Multiforme (GBM) is an aggressive and deadly form of brain cancer with a median survival time of about a year with treatment. Due to the aggressive nature of these tumors and the tendency of gliomas to follow white matter tracks in the brain, each tumor mass has a unique growth pattern. Consequently it is difficult for neurosurgeons to anticipate where the tumor will spread in the brain, making treatment planning difficult. Archival patient data including MRI scans depicting the progress of tumors have been helpful in developing a model to predict Glioblastoma proliferation, but limited scans per patient make the tumor growth rate difficult to determine. Furthermore, patient treatment between scan points can significantly compound the challenge of accurately predicting the tumor growth. A partnership with Barrow Neurological Institute has allowed murine studies to be conducted in order to closely observe tumor growth and potentially improve the current model to more closely resemble intermittent stages of GBM growth without treatment effects.
ContributorsSnyder, Lena Haley (Author) / Kostelich, Eric (Thesis director) / Frakes, David (Committee member) / Barrett, The Honors College (Contributor) / School of Mathematical and Statistical Sciences (Contributor) / Harrington Bioengineering Program (Contributor)
Created2014-05
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Description
As the rates of anxiety in adults rapidly swell, new and creative treatment methods become increasingly relevant. Individuals with an anxiety disorder may experience challenging symptoms that interfere with daily activities and impede academic and social success. The purpose of this project is to design and engineer a portable heart

As the rates of anxiety in adults rapidly swell, new and creative treatment methods become increasingly relevant. Individuals with an anxiety disorder may experience challenging symptoms that interfere with daily activities and impede academic and social success. The purpose of this project is to design and engineer a portable heart rate monitor that communicates with an iOS mobile application for use by individuals suffering from anxiety or panic disorders. The proposed device captures the innovation of combining biosensor feedback with new, creative therapy methods on a convenient iOS application. The device is implemented as an Arduino Uno which translates radial pulse information onto an LCD screen from a wristband. Additionally, the iOS portion uses a slow expanding and collapsing animation to guide the user through a calming breathing exercise while displaying their pulse in beats per minute. The user's awareness or his or her ability to control one's own physiological state supports and facilitates an additional form of innovative therapy. The current design of the iOS app uses a random-number generator between 40 to 125 to imitate a realistic heart rate. If the value is less than 60 or greater than 105, the number is printed in red; otherwise the heart rate is displayed in green. Future versions of this device incorporate bluetooth capabilities and potentially additional synchronous methods of therapy. The information presented in this research provides an excellent example of the integrations of new mobile technology and healthcare.
ContributorsTadayon, Ramesh (Author) / Muthuswamy, Jit (Thesis director) / Towe, Bruce (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
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Description
Engineers have a strong influence on everyday lives, ranging from electronics and trains to chemicals and organs [1]. However, in the United States, there is a large knowledge gap in the roles of engineers, especially in K-12 students [2] [3]. The National Academy of Engineering (NAE) recognizes the current problems

Engineers have a strong influence on everyday lives, ranging from electronics and trains to chemicals and organs [1]. However, in the United States, there is a large knowledge gap in the roles of engineers, especially in K-12 students [2] [3]. The National Academy of Engineering (NAE) recognizes the current problems in engineering, such as the dominance of white males in the field and the amount of education needed to become a successful engineer [4]. Therefore, the NAE encourages that the current engineering community begin to expose the younger generations to the real foundation of engineering: problem-solving [4]. The objective of this thesis is to minimize the knowledge gap by assessing the current perception of engineering amongst middle school and high school students and improving it through engaging and interactive presentations and activities that build upon the students’ problem-solving abilities.

The project was aimed towards middle school and high school students, as this is the estimated level where they learn biology and chemistry—key subject material in biomedical engineering. The high school students were given presentations and activities related to biomedical engineering. Additionally, within classrooms, posters were presented to middle school students. The content of the posters were students of the biomedical engineering program at ASU, coming from different ethnic backgrounds to try and evoke within the middle school students a sense of their own identity as a biomedical engineer. To evaluate the impact these materials had on the students, a survey was distributed before the students’ exposure to the materials and after that assesses the students’ understanding of engineering at two different time points. A statistical analysis was conducted with Microsoft Excel to assess the influence of the activity and/or presentation on the students’ understanding of engineering.
ContributorsLlave, Alison Rose (Author) / Ganesh, Tirupalavanam (Thesis director) / Parker, Hope (Committee member) / Harrington Bioengineering Program (Contributor, Contributor) / Barrett, The Honors College (Contributor)
Created2017-05