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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

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
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Description
One of the most prominent biological challenges for the field of drug delivery is the blood-brain barrier. This physiological system blocks the entry of or actively removes almost all small molecules into the central nervous system (CNS), including many drugs that could be used to treat diseases in the CNS.

One of the most prominent biological challenges for the field of drug delivery is the blood-brain barrier. This physiological system blocks the entry of or actively removes almost all small molecules into the central nervous system (CNS), including many drugs that could be used to treat diseases in the CNS. Previous studies have shown that activation of the adenosine receptor signaling pathway through the use of agonists has been demonstrated to increase BBB permeability. For example, regadenoson is an adenosine A2A receptor agonist that has been shown to disrupt the BBB and allow for increased drug uptake in the CNS. The goal of this study was to verify this property of regadenoson. We hypothesized that co-administration of regadenoson with a non-brain penetrant macromolecule would facilitate its entry into the central nervous system. To test this hypothesis, healthy mice were administered regadenoson or saline concomitantly with a fluorescent dextran solution. The brain tissue was either homogenized to measure quantity of fluorescent molecule, or cryosectioned for imaging with confocal fluorescence microscopy. These experiments did not identify any significant difference in the amount of fluorescence detected in the brain after regadenoson treatment. These results contradict those of previous studies and highlight potential differences in injection methodology, time windows, and properties of brain impermeant molecules.
ContributorsWohlleb, Gregory Michael (Author) / Sirianni, Rachael (Thesis director) / Stabenfeldt, Sarah (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor)
Created2015-05
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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 microspheres growing in popularity as viable systems for targeted drug therapeutics, there exist a host of diseases and pathology induced side effects which could be treated with poly(lactic-co-glycolic acid) [PLGA] microparticle systems [6,10,12]. While PLGA systems are already applied in a wide variety the clinical setting [11], microparticles still

With microspheres growing in popularity as viable systems for targeted drug therapeutics, there exist a host of diseases and pathology induced side effects which could be treated with poly(lactic-co-glycolic acid) [PLGA] microparticle systems [6,10,12]. While PLGA systems are already applied in a wide variety the clinical setting [11], microparticles still have some way to go before they are viable systems for drug delivery. One of the main reasons for this is a lack of fabrication processes and systems which produce monodisperse particles while also being feasible for industrialization [10]. This honors thesis investigates various microparticle fabrication techniques \u2014 two using mechanical agitation and one using fluid dynamics \u2014 with the long term goal of incorporating norepinephrine and adenosine into the particles for metabolic stimulatory purposes. It was found that mechanical agitation processes lead to large values for dispersity and the polydispersity index while fluid dynamics methods have the potential to create more uniform and predictable outcomes. The research concludes by needing further investigation into methods and prototype systems involving fluid dynamics methods; however, these systems yield promising results for fabricating monodisperse particles which have the potential to encapsulate a wide variety of therapeutic drugs.
ContributorsRiley, Levi Louis (Author) / Vernon, Brent (Thesis director) / VanAuker, Michael (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2018-12
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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
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Description
Previous research has shown that a loud acoustic stimulus can trigger an individual's prepared movement plan. This movement response is referred to as a startle-evoked movement (SEM). SEM has been observed in the stroke survivor population where results have shown that SEM enhances single joint movements that are usually performed

Previous research has shown that a loud acoustic stimulus can trigger an individual's prepared movement plan. This movement response is referred to as a startle-evoked movement (SEM). SEM has been observed in the stroke survivor population where results have shown that SEM enhances single joint movements that are usually performed with difficulty. While the presence of SEM in the stroke survivor population advances scientific understanding of movement capabilities following a stroke, published studies using the SEM phenomenon only examined one joint. The ability of SEM to generate multi-jointed movements is understudied and consequently limits SEM as a potential therapy tool. In order to apply SEM as a therapy tool however, the biomechanics of the arm in multi-jointed movement planning and execution must be better understood. Thus, the objective of our study was to evaluate if SEM could elicit multi-joint reaching movements that were accurate in an unrestrained, two-dimensional workspace. Data was collected from ten subjects with no previous neck, arm, or brain injury. Each subject performed a reaching task to five Targets that were equally spaced in a semi-circle to create a two-dimensional workspace. The subject reached to each Target following a sequence of two non-startling acoustic stimuli cues: "Get Ready" and "Go". A loud acoustic stimuli was randomly substituted for the "Go" cue. We hypothesized that SEM is accessible and accurate for unrestricted multi-jointed reaching tasks in a functional workspace and is therefore independent of movement direction. Our results found that SEM is possible in all five Target directions. The probability of evoking SEM and the movement kinematics (i.e. total movement time, linear deviation, average velocity) to each Target are not statistically different. Thus, we conclude that SEM is possible in a functional workspace and is not dependent on where arm stability is maximized. Moreover, coordinated preparation and storage of a multi-jointed movement is indeed possible.
ContributorsOssanna, Meilin Ryan (Author) / Honeycutt, Claire (Thesis director) / Schaefer, Sydney (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2016-12
Description

Traumatic brain injury (TBI), a neurological condition that negatively affects neural capabilities, occurs when a blunt trauma impacts the head. Following the initial injury that immediately impacts neural cell function and survival, a series of secondary injury events lead to substantial sustained inflammation for weeks to years post-injury. To develo

Traumatic brain injury (TBI), a neurological condition that negatively affects neural capabilities, occurs when a blunt trauma impacts the head. Following the initial injury that immediately impacts neural cell function and survival, a series of secondary injury events lead to substantial sustained inflammation for weeks to years post-injury. To develop TBI treatments that may stimulate regenerative processes, a novel drug delivery system that efficiently delivers the appropriate drug/payload to injured tissue is crucial. Hyaluronic acid (HA) hydrogels are attractive when developing a biomaterial for tissue reparation and regeneration. HA is a natural polymer with physicochemical properties that can be tuned to match the properties of the extracellular matrix (ECM) of the many tissues including the central nervous system (CNS). Here, the project objective was to develop a HA hydrogel system for local delivery of a biological payload; this objective was completed by employing a composite system with two parts. The first part is an injectable, shear-thinning bulk hydrogel, and the second is microgels for loading biological payloads. The bulk hydrogel was composed of cyclodextrin modified HA (Cd-HA) and adamantane modified HA (Ad-HA) that give rise to guest-host interactions that facilitate physical crosslinking. The microgel, composed of norbornene-HA (Nor-HA) and sulfated-HA, crosslink via chemical crosslinks upon activation of a UV photoinitiator. The sulfated-HA microgels facilitate loading of biological payloads by mimicking heparin binding sites via the conjugated sulfated group. Neuregulin I, an epidermal growth factor with neuroprotective properties, is one such protein with a heparin binding domain that may be retained in the sulfated-HA microgels. Specifically, the project focused on mechanical testing of this composite microgel/hydrogel system and also developing protein affinity assays.

ContributorsKylat, Anna (Author) / Stabenfeldt, Sarah (Thesis director) / Holloway, Julianne (Committee member) / Jensen, Gregory (Committee member) / Barrett, The Honors College (Contributor) / School of Mathematical and Statistical Sciences (Contributor) / Harrington Bioengineering Program (Contributor)
Created2023-05
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Description
The aim of the present study was to review the symptoms and current treatment options of the most common skin infections seen in outpatient settings and develop a preliminary alternative treatment solution. The specific skin infections evaluated were those caused by Staphylococcus and Streptococcus bacterial species, and are frequently treated

The aim of the present study was to review the symptoms and current treatment options of the most common skin infections seen in outpatient settings and develop a preliminary alternative treatment solution. The specific skin infections evaluated were those caused by Staphylococcus and Streptococcus bacterial species, and are frequently treated with a wide variety of systemic antibiotics or topical ointments. Systemic antibiotics have shown increased occurrence of adverse side effects as well as the development of antibiotic-resistant bacteria. Additionally, these medications are usually overprescribed, which may further exacerbate negative side effects. Another issue that is addressed is the development of infections following treatment of a new laceration or other trauma to the skin. A patient may be treated for their wound with stitches or another alternative, but there is still the possibility of developing an infection later.
This study synthesizes information found from extensive research and provides a review of the most optimal techniques for developing an alternative to systemic antibiotics. The final deliverable is a report detailing the significant findings and discussing the ways that this solution may be developed further and implemented in a clinical setting. The solution is a hydrogel bandage designed to deliver antibiotics directly to the wound site, while also offering protection and enhanced wound healing. The target population is patients suffering from skin conditions in an outpatient setting. The antibiotics of interest for this solution are clindamycin, doxycycline, and trimethoprim-sulfamethoxazole (co-trimoxazole), as they offer excellent treatment against gram-positive bacteria and methicillin-resistant Staphylococcus aureus. However, other broad-spectrum antibiotics could potentially be incorporated to protect against gram-negative bacteria. The design features a polyvinyl alcohol (PVA) hydrogel that has shown many properties that are beneficial to biomedical applications, including biocompatibility, flexibility, high drug-loading capacity, high absorption of wound exudate, increased promotion of wound healing, and more. Preliminary mathematical models of the hydrogel’s drug delivery behaviors are also included. Due to the scope and timeframe of this project, the majority of findings herein are based on research of prior literature instead of development of the novel device. Future directions would include further research and development of the mechanisms behind the device, creation of a physical prototype, experimental testing, and statistical analyses to verify device specifications and capabilities.
ContributorsTanner, Emily Christine (Author) / Pizziconi, Vincent (Thesis director) / Nguyen, Eric (Committee member) / Harrington Bioengineering Program (Contributor, Contributor) / School of Mathematical and Statistical Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05
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Description
NIPAAm co-DEAEMA hydrogels are a potential solution for sustained, local delivery of ketorolac tromethamine. Current methods of postoperative pain management, such as local anesthetics, NSAIDs, and opioids, can be improved by minimizing side effects while still effectively treating severe and extreme pain. Though high doses of ketorolac can be toxic,

NIPAAm co-DEAEMA hydrogels are a potential solution for sustained, local delivery of ketorolac tromethamine. Current methods of postoperative pain management, such as local anesthetics, NSAIDs, and opioids, can be improved by minimizing side effects while still effectively treating severe and extreme pain. Though high doses of ketorolac can be toxic, sustained, local delivery via hydrogels offers a promising solution. Four ketorolac release studies were conducted using PNDJ hydrogels formulated by Sonoran Biosciences. The first two studies tested a range of JAAm concentration between 1.4 and 2.2 mole percent. Both had high initial release rates lasting less than 7 days and appeared to be unaffected by JAAm content. Tobramycin slowed down the release of ketorolac but was unable to sustain release for more than 6 days. Incorporating DEAEMA prolonged the release of ketorolac for up to 14 days with significant reductions in initial burst release rate. Low LCST of NIPAAM co-DEAEMA polymer is problematic for even drug distribution and future in vivo applications.
ContributorsHui, Nathan (Author) / Vernon, Brent (Thesis director) / Heffernan, John (Committee member) / School of International Letters and Cultures (Contributor) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05