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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
Description
Cardiac tissue engineering has major applications in regenerative medicine, disease modeling and fundamental biological studies. Despite the significance, numerous questions still need to be explored to enhance the functionalities of the engineered tissue substitutes. In this study, three dimensional (3D) cardiac micro-tissues were developed through encapsulating co-culture of cardiomyocytes and

Cardiac tissue engineering has major applications in regenerative medicine, disease modeling and fundamental biological studies. Despite the significance, numerous questions still need to be explored to enhance the functionalities of the engineered tissue substitutes. In this study, three dimensional (3D) cardiac micro-tissues were developed through encapsulating co-culture of cardiomyocytes and cardiac fibroblasts, as the main cellular components of native myocardium, within photocrosslinkable gelatin-based hydrogels. Different co-culture ratios were assessed to optimize the functional properties of constructs. The geometry of the micro-tissues was precisely controlled using micro-patterning techniques in order to evaluate their role on synchronous contraction of the cells. Cardiomyocytes exhibited a native-like phenotype when co-cultured with cardiac fibroblasts as compared to the mono-culture condition. Particularly, elongated F-actin fibers with abundance of sarcomeric α-actinin and troponin-I were observed within all layers of the hydrogel constructs. Higher expressions of connexin-43 and integrin β1 indicated improved cell-cell and cell-matrix interactions. Amongst co-culture conditions, 2:1 (cardiomyocytes: cardiac fibroblasts) ratio exhibited enhanced functionalities, whereas decreasing the construct size adversely affected the synchronous contraction of the cells. Therefore, this study indicated that cell-cell ratio as well as the geometrical features of the micropatterned constructs are among crucial parameters, which need to be optimized in order to enhance the functionalities of engineered tissue substitutes and cardiac patches.
ContributorsSaini, Harpinder (Author) / Nikkhah, Mehdi (Thesis advisor) / Vernon, Brent (Committee member) / Towe, Bruce (Committee member) / Arizona State University (Publisher)
Created2015
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Description

Pelvic Circumferential Compression Devices (PCCDs), an important medical device when caring for patients with pelvic fractures, play a crucial role in the stabilization and reduction of the fracture. During pelvic fracture cases, control of internal bleeding through access to the femoral artery is of utmost importance. Current designs of PCCDs

Pelvic Circumferential Compression Devices (PCCDs), an important medical device when caring for patients with pelvic fractures, play a crucial role in the stabilization and reduction of the fracture. During pelvic fracture cases, control of internal bleeding through access to the femoral artery is of utmost importance. Current designs of PCCDs do not allow vital access to this artery and in attempts to gain access, medical professionals and emergency care providers choose to cut into the PCCDs or place them in suboptimal positions with unknown downstream effects. We researched the effects on surface pressure and the overall pressure distribution created by the PCCDs when they are modified or placed incorrectly on the patient. In addition, we investigated the effects of those misuses on pelvic fracture reduction, a key parameter in stabilizing the patient during critical care. We hypothesized that incorrectly placing or modifying the PCCD will result in increased surface pressure and decreased fracture reduction. Our mannequin studies show that for SAM Sling and T-POD, surface pressure increases if a PCCD is incorrectly placed or modified, in support of our hypothesis. However, opposite results occurred for the Pelvic Binder, where the correctly placed PCCD had higher surface pressure when compared to the incorrectly placed or modified PCCD. Additionally, pressure distribution was significantly affected by the modification of the PCCDs. The cadaver lab measurements show that modifying or incorrectly placing the PCCDs significantly limits their ability to reduce the pelvic fracture. These results suggest that while modifying or incorrectly placing PCCDs allows access to the femoral artery, there are potentially dangerous effects to the patient including increased surface pressures and limited fracture reduction.

ContributorsRyder, Madison Taylor (Co-author) / Conley, Ian (Co-author) / Vernon, Brent (Thesis director) / Bogert, James (Committee member) / School of Mathematical and Statistical Sciences (Contributor) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
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Description

Pelvic Circumferential Compression Devices (PCCDs), an important medical device when caring for patients with pelvic fractures, play a crucial role in the stabilization and reduction of the fracture. During pelvic fracture cases, control of internal bleeding through access to the femoral artery is of utmost importance. Current designs of PCCDs

Pelvic Circumferential Compression Devices (PCCDs), an important medical device when caring for patients with pelvic fractures, play a crucial role in the stabilization and reduction of the fracture. During pelvic fracture cases, control of internal bleeding through access to the femoral artery is of utmost importance. Current designs of PCCDs do not allow vital access to this artery and in attempts to gain access, medical professionals and emergency care providers choose to cut into the PCCDs or place them in suboptimal positions with unknown downstream effects. We researched the effects on surface pressure and the overall pressure distribution created by the PCCDs when they are modified or placed incorrectly on the patient. In addition, we investigated the effects of those misuses on pelvic fracture reduction, a key parameter in stabilizing the patient during critical care. We hypothesized that incorrectly placing or modifying the PCCD will result in increased surface pressure and decreased fracture reduction. Our mannequin studies show that for SAM Sling and T-POD, surface pressure increases if a PCCD is incorrectly placed or modified, in support of our hypothesis. However, opposite results occurred for the Pelvic Binder, where the correctly placed PCCD had higher surface pressure when compared to the incorrectly placed or modified PCCD. Additionally, pressure distribution was significantly affected by the modification of the PCCDs. The cadaver lab measurements show that modifying or incorrectly placing the PCCDs significantly limits their ability to reduce the pelvic fracture. These results suggest that while modifying or incorrectly placing PCCDs allows access to the femoral artery, there are potentially dangerous effects to the patient including increased surface pressures and limited fracture reduction.

ContributorsConley, Ian Patrick (Co-author) / Ryder, Madison (Co-author) / Vernon, Brent (Thesis director) / Bogert, James (Committee member) / Harrington Bioengineering Program (Contributor) / School of Mathematical and Statistical Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
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Description

Polymer drug delivery system offers a key to a glaring issue in modern administration routes of drugs and biologics. Poly(lactic-co-glycolic acid) (PLGA) can be used to encapsulate drugs and biologics and deliver them into the patient, which allows high local concentration (compared to current treatment methods), protection of the cargo

Polymer drug delivery system offers a key to a glaring issue in modern administration routes of drugs and biologics. Poly(lactic-co-glycolic acid) (PLGA) can be used to encapsulate drugs and biologics and deliver them into the patient, which allows high local concentration (compared to current treatment methods), protection of the cargo from the bodily environment, and reduction in systemic side effects. This experiment used a single emulsion technique to encapsulate L-tyrosine in PLGA microparticles and UV spectrophotometry to analyze the drug release over a period of one week. The release assay found that for the tested samples, the released amount is distinct initially, but is about the same after 4 days, and they generally follow the same normalized percent released pattern. The experiment could continue with testing more samples, test the same samples for a longer duration, and look into higher w/w concentrations such as 20% or 50%.

ContributorsSeo, Jinpyo (Author) / Vernon, Brent (Thesis director) / Pal, Amrita (Committee member) / Dean, W.P. Carey School of Business (Contributor) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
Description

The goal of this research project is to create a Mathcad template file capable of statistically modelling the effects of mean and standard deviation on a microparticle batch characterized by the log normal distribution model. Such a file can be applied during manufacturing to explore tolerances and increase cost and

The goal of this research project is to create a Mathcad template file capable of statistically modelling the effects of mean and standard deviation on a microparticle batch characterized by the log normal distribution model. Such a file can be applied during manufacturing to explore tolerances and increase cost and time effectiveness. Theoretical data for the time to 60% drug release and the slope and intercept of the log-log plot were collected and subjected to statistical analysis in JMP. Since the scope of this project focuses on microparticle surface degradation drug release with no drug diffusion, the characteristic variables relating to the slope (n = diffusional release exponent) and the intercept (k = kinetic constant) do not directly apply to the distribution model within the scope of the research. However, these variables are useful for analysis when the Mathcad template is applied to other types of drug release models.

ContributorsHan, Priscilla (Author) / Vernon, Brent (Thesis director) / Nickle, Jacob (Committee member) / Harrington Bioengineering Program (Contributor, Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
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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