Matching Items (28)
Filtering by
- All Subjects: Biomedical Engineering
- Genre: Academic theses
- Creators: Brafman, David
- Member of: Theses and Dissertations
- Status: Published
Description
The objective of this research is to investigate the relationship among key process design variables associated with the development of nanoscale electrospun polymeric scaffolds capable of tissue regeneration. To date, there has been no systematic approach toward understanding electrospinning process parameters responsible for the production of 3-D nanoscaffold architectures with desired levels quality assurance envisioned to satisfy emerging regenerative medicine market needs. , As such, this study encompassed a more systematic, rational design of experiment (DOE) approach toward the identification of electrospinning process conditions responsible for the production of dextran-polyacrylic acid (DEX-PAA) nanoscaffolds with desired architectures and tissue engineering properties. The latter includes scaffold fiber diameter, pore size, porosity, and degree of crosslinking that together can provide a range of scaffold nanomechanical properties that closely mimics the cell microenvironment. The results obtained from this preliminary DOE study indicate that there exist electrospinning operation conditions capable of producing Dex-PAA nanoarchitecture having potential utility for regenerative medicine applications.
ContributorsEspinoza, Roberta (Author) / Pizziconi, Vincent (Thesis advisor) / Massia, Stephen (Committee member) / Garcia, Antonio (Committee member) / Arizona State University (Publisher)
Created2013
Description
The overall goal of this research project was to assess the feasibility of investigating the effects of microgravity on mineralization systems in unit gravity environments. If possible to perform these studies in unit gravity earth environments, such as earth, such systems can offer markedly less costly and more concerted research efforts to study these vitally important systems. Expected outcomes from easily accessible test environments and more tractable studies include the development of more advanced and adaptive material systems, including biological systems, particularly as humans ponder human exploration in deep space. The specific focus of the research was the design and development of a prototypical experimental test system that could preliminarily meet the challenging design specifications required of such test systems. Guided by a more unified theoretical foundation and building upon concept design and development heuristics, assessment of the feasibility of two experimental test systems was explored. Test System I was a rotating wall reactor experimental system that closely followed the specifications of a similar test system, Synthecon, designed by NASA contractors and thus closely mimicked microgravity conditions of the space shuttle and station. The latter includes terminal velocity conditions experienced by both innate material systems, as well as, biological systems, including living tissue and humans but has the ability to extend to include those material test systems associated with mineralization processes. Test System II is comprised of a unique vertical column design that offered more easily controlled fluid mechanical test conditions over a much wider flow regime that was necessary to achieving terminal velocities under free convection-less conditions that are important in mineralization processes. Preliminary results indicate that Test System II offers distinct advantages in studying microgravity effects in test systems operating in unit gravity environments and particularly when investigating mineralization and related processes. Verification of the Test System II was performed on validating microgravity effects on calcite mineralization processes reported earlier others. There studies were conducted on calcite mineralization in fixed-wing, reduced gravity aircraft, known as the `vomit comet' where reduced gravity conditions are include for very short (~20second) time periods. Preliminary results indicate that test systems, such as test system II, can be devised to assess microgravity conditions in unit gravity environments, such as earth. Furthermore, the preliminary data obtained on calcite formation suggest that strictly physicochemical mechanisms may be the dominant factors that control adaptation in materials processes, a theory first proposed by Liu et al. Thus the result of this study may also help shine a light on the problem of early osteoporosis in astronauts and long term interest in deep space exploration.
ContributorsSeyedmadani, Kimia (Author) / Pizziconi, Vincent (Thesis advisor) / Towe, Bruce (Committee member) / Alford, Terry (Committee member) / Arizona State University (Publisher)
Created2013
Description
Flow measurement has always been one of the most critical processes in many industrial and clinical applications. The dynamic behavior of flow helps to define the state of a process. An industrial example would be that in an aircraft, where the rate of airflow passing the aircraft is used to determine the speed of the plane. A clinical example would be that the flow of a patient's breath which could help determine the state of the patient's lungs. This project is focused on the flow-meter that are used for airflow measurement in human lungs. In order to do these measurements, resistive-type flow-meters are commonly used in respiratory measurement systems. This method consists of passing the respiratory flow through a fluid resistive component, while measuring the resulting pressure drop, which is linearly related to volumetric flow rate. These types of flow-meters typically have a low frequency response but are adequate for most applications, including spirometry and respiration monitoring. In the case of lung parameter estimation methods, such as the Quick Obstruction Method, it becomes important to have a higher frequency response in the flow-meter so that the high frequency components in the flow are measurable. The following three types of flow-meters were: a. Capillary type b. Screen Pneumotach type c. Square Edge orifice type To measure the frequency response, a sinusoidal flow is generated with a small speaker and passed through the flow-meter that is connected to a large, rigid container. True flow is proportional to the derivative of the pressure inside the container. True flow is then compared with the measured flow, which is proportional to the pressure drop across the flow-meter. In order to do the characterization, two LabVIEW data acquisition programs have been developed, one for transducer calibration, and another one that records flow and pressure data for frequency response testing of the flow-meter. In addition, a model that explains the behavior exhibited by the flow-meter has been proposed and simulated. This model contains a fluid resistor and inductor in series. The final step in this project was to approximate the frequency response data to the developed model expressed as a transfer function.
ContributorsHu, Jianchen (Author) / Macia, Narciso (Thesis advisor) / Pollat, Scott (Committee member) / Rogers, Bradley (Committee member) / Arizona State University (Publisher)
Created2013
Description
The objective of this research is to develop a biocompatible scaffold based on dextran and poly acrylic acid (PAA) with the potential to be used for soft tissue repair. In this thesis, physical and chemical properties of the scaffold were investigated. The scaffolds were made using electrospinning and cross-linked under high temperature. After heat treatment, Scanning Electron Microscope (SEM) was used to observe the structures of these scaffolds. Fourier transform infrared spectroscopy (FTIR) was used to measure the cross-linking level of scaffold samples given different times of heat treatment by detecting and comparing the newly formed ester bonds. Single-walled carbon nanotubes (SWCNT) were added to enhance the mechanical properties of dextran-PAA scaffolds. Attachment of NIH-3T3 fibroblast cells to the scaffold and the response upon implantation into rabbit vaginal tissue were also evaluated to investigate the performance of SWCNT dextran-PAA scaffold. SEM was then used to characterize morphology of fibroblast cells and rabbit tissues. The results suggest that SWCNT could enhance cell attachment, distribution and spreading performance of dextran-PAA scaffold.
ContributorsLiu, Chongji (Author) / Massia, Stephen (Thesis advisor) / Pizziconi, Vincent (Committee member) / Pauken, Christine (Committee member) / Arizona State University (Publisher)
Created2014
Description
The effects of specific histone deacetylase inhibitors (HDACi) on transgene expression in combination with a novel polymer as a delivery vehicle are investigated in this research. Polymer vectors, although safer than viruses, are notorious for low levels of gene expression. In this investigation, the use of an emerging chemotherapeutic anti-cancer drug molecule, HDACi, was used to enhance the polymer-mediated gene expression. HDACi are capable of inhibiting deacetylation activities of histones and other non-histone proteins in the cytoplasm and nucleus, as well as increase transcriptional activities necessary for gene expression. In a prior study, a parallel synthesis and screening of polymers yielded a lead cationic polymer with high DNA-binding properties, and even more attractive, high transgene expressions. Previous studies showed the use of this polymer in conjunction with cytoplasmic HDACi significantly enhanced gene expression in PC3-PSMA prostate cancer cells. This led to the basis for the investigation presented in this thesis, but to use nuclear HDACi to potentially achieve similar results. The HDACi, HDACi_A, was a previously discovered lead drug that had potential to significantly enhance luciferase expression in PC3-PSMA cells. The results of this study found that the 20:1 polymer:plasmid DNA weight ratio was effective with 1 uM and 2 uM HDACI_A concentrations, showing up to a 9-fold enhancement. This enhancement suggested that HDACi_A was effectively aiding transfection. While not an astounding enhancement, it is still interesting enough to investigate further. Cell viabilities need to be determined to supplement the results.
ContributorsLehrman, Jennifer (Author) / Rege, Kaushal (Thesis advisor) / Caplan, Michael (Committee member) / Pizziconi, Vincent (Committee member) / Arizona State University (Publisher)
Created2012
Description
Multiple Sclerosis, an autoimmune disease, is one of the most common neurological disorder in which demyelinating of the axon occurs. The main symptoms of MS disease are fatigue, vision problems, stability issue, balance problems. Unfortunately, currently available treatments for this disease do not always guarantee the improvement of the condition of the MS patient and there has not been an accurate mechanism to measure the effectiveness of the treatment due to inter-patient heterogeneity. The factors that count for varying the performance of MS patients include environmental setting, weather, psychological status, dressing style and more. Also, patients may react differently while examined at specially arranged setting and this may not be the same while he/she is at home. Hence, it becomes a major problem for MS patients that how effectively a treatment slows down the progress of the disease and gives a relief for the patient. This thesis is trying to build a reliable system to estimate how good a treatment is for MS patients. Here I study the kinematic variables such as velocity of walking, stride length, variability and so on to find and compare the variations of the patient after a treatment given by the doctor, and trace these parameters for some patients after the treatment effect subdued.
ContributorsYin, Siyang (Author) / He, Jiping (Thesis advisor) / Pizziconi, Vincent (Committee member) / Towe, Bruce (Committee member) / Arizona State University (Publisher)
Created2012
Description
In the search for chemical biosensors designed for patient-based physiological applications, non-invasive diagnostic approaches continue to have value. The work described in this thesis builds upon previous breath analysis studies. In particular, it seeks to assess the adsorptive mechanisms active in both acetone and ethanol biosensors designed for breath analysis. The thermoelectric biosensors under investigation were constructed using a thermopile for transduction and four different materials for biorecognition. The analytes, acetone and ethanol, were evaluated under dry-air and humidified-air conditions. The biosensor response to acetone concentration was found to be both repeatable and linear, while the sensor response to ethanol presence was also found to be repeatable. The different biorecognition materials produced discernible thermoelectric responses that were characteristic for each analyte. The sensor output data is presented in this report. Additionally, the results were evaluated against a mathematical model for further analysis. Ultimately, a thermoelectric biosensor based upon adsorption chemistry was developed and characterized. Additional work is needed to characterize the physicochemical action mechanism.
ContributorsWilson, Kimberly (Author) / Guilbeau, Eric (Thesis advisor) / Pizziconi, Vincent (Thesis advisor) / LaBelle, Jeffrey (Committee member) / Arizona State University (Publisher)
Created2011
Description
The portability of genetic tools from one organism to another is a cornerstone of synthetic biology. The shared biological language of DNA-to-RNA-to-protein allows for expression of polypeptide chains in phylogenetically distant organisms with little modification. The tools and contexts are diverse, ranging from catalytic RNAs in cell-free systems to bacterial proteins expressed in human cell lines, yet they exhibit an organizing principle: that genes and proteins may be treated as modular units that can be moved from their native organism to a novel one. However, protein behavior is always unpredictable; drop-in functionality is not guaranteed.
My work characterizes how two different classes of tools behave in new contexts and explores methods to improve their functionality: 1. CRISPR/Cas9 in human cells and 2. quorum sensing networks in Escherichia coli.
1. The genome-editing tool CRISPR/Cas9 has facilitated easily targeted, effective, high throughput genome editing. However, Cas9 is a bacterially derived protein and its behavior in the complex microenvironment of the eukaryotic nucleus is not well understood. Using transgenic human cell lines, I found that gene-silencing heterochromatin impacts Cas9’s ability to bind and cut DNA in a site-specific manner and I investigated ways to improve CRISPR/Cas9 function in heterochromatin.
2. Bacteria use quorum sensing to monitor population density and regulate group behaviors such as virulence, motility, and biofilm formation. Homoserine lactone (HSL) quorum sensing networks are of particular interest to synthetic biologists because they can function as “wires” to connect multiple genetic circuits. However, only four of these networks have been widely implemented in engineered systems. I selected ten quorum sensing networks based on their HSL production profiles and confirmed their functionality in E. coli, significantly expanding the quorum sensing toolset available to synthetic biologists.
My work characterizes how two different classes of tools behave in new contexts and explores methods to improve their functionality: 1. CRISPR/Cas9 in human cells and 2. quorum sensing networks in Escherichia coli.
1. The genome-editing tool CRISPR/Cas9 has facilitated easily targeted, effective, high throughput genome editing. However, Cas9 is a bacterially derived protein and its behavior in the complex microenvironment of the eukaryotic nucleus is not well understood. Using transgenic human cell lines, I found that gene-silencing heterochromatin impacts Cas9’s ability to bind and cut DNA in a site-specific manner and I investigated ways to improve CRISPR/Cas9 function in heterochromatin.
2. Bacteria use quorum sensing to monitor population density and regulate group behaviors such as virulence, motility, and biofilm formation. Homoserine lactone (HSL) quorum sensing networks are of particular interest to synthetic biologists because they can function as “wires” to connect multiple genetic circuits. However, only four of these networks have been widely implemented in engineered systems. I selected ten quorum sensing networks based on their HSL production profiles and confirmed their functionality in E. coli, significantly expanding the quorum sensing toolset available to synthetic biologists.
ContributorsDaer, René (Author) / Haynes, Karmella (Thesis advisor) / Brafman, David (Committee member) / Nielsen, David (Committee member) / Kiani, Samira (Committee member) / Arizona State University (Publisher)
Created2017
Description
Myocardial infarction (MI) remains the leading cause of mortality and morbidity in the U.S., accounting for nearly 140,000 deaths per year. Heart transplantation and implantation of mechanical assist devices are the options of last resort for intractable heart failure, but these are limited by lack of organ donors and potential surgical complications. In this regard, there is an urgent need for developing new effective therapeutic strategies to induce regeneration and restore the loss contractility of infarcted myocardium. Over the past decades, regenerative medicine has emerged as a promising strategy to develop scaffold-free cell therapies and scaffold-based cardiac patches as potential approaches for MI treatment. Despite the progress, there are still critical shortcomings associated with these approaches regarding low cell retention, lack of global cardiomyocytes (CMs) synchronicity, as well as poor maturation and engraftment of the transplanted cells within the native myocardium. The overarching objective of this dissertation was to develop two classes of nanoengineered cardiac patches and scaffold-free microtissues with superior electrical, structural, and biological characteristics to address the limitations of previously developed tissue models. An integrated strategy, based on micro- and nanoscale technologies, was utilized to fabricate the proposed tissue models using functionalized gold nanomaterials (GNMs). Furthermore, comprehensive mechanistic studies were carried out to assess the influence of conductive GNMs on the electrophysiology and maturity of the engineered cardiac tissues. Specifically, the role of mechanical stiffness and nano-scale topographies of the scaffold, due to the incorporation of GNMs, on cardiac cells phenotype, contractility, and excitability were dissected from the scaffold’s electrical conductivity. In addition, the influence of GNMs on conduction velocity of CMs was investigated in both coupled and uncoupled gap junctions using microelectrode array technology. Overall, the key contributions of this work were to generate new classes of electrically conductive cardiac patches and scaffold-free microtissues and to mechanistically investigate the influence of conductive GNMs on maturation and electrophysiology of the engineered tissues.
ContributorsNavaei, Ali (Author) / Nikkhah, Mehdi (Thesis advisor) / Brafman, David (Committee member) / Migrino, Raymond Q. (Committee member) / Stabenfeldt, Sarah (Committee member) / Vernon, Brent (Committee member) / Arizona State University (Publisher)
Created2018
Description
The advent of medical imaging has enabled significant advances in pre-procedural planning, allowing cardiovascular anatomy to be visualized noninvasively before a procedure. However, absolute scale and tactile information are not conveyed in traditional pre-procedural planning based on images alone. This information deficit fails to completely prepare clinicians for complex heart repair, where surgeons must consider the varied presentations of cardiac morphology and malformations. Three-dimensional (3D) visualization and 3D printing provide a mechanism to construct patient-specific, scale models of cardiovascular anatomy that surgeons and interventionalists can examine prior to a procedure. In addition, the same patient-specific models provide a valuable resource for educating future medical professionals. Instead of looking at idealized images on a computer screen or pages from medical textbooks, medical students can review a life-like model of patient anatomy.
In cases where surgical repair is insufficient to return the heart to normal function, a patient may proceed to advanced heart failure, and a heart transplant may be required. Unfortunately, a finite number of available donor hearts are available. A mechanical circulatory support (MCS) device can be used to bridge the time between heart failure and reception of a donor heart. These MCS devices are typically constructed for the adult population. Accordingly, the size associated to the device is a limiting factor for small adults or pediatric patients who often have smaller thoracic measurements. While current eligibility criteria are based on correlative measurements, the aforementioned 3D visualization capabilities can be leveraged to accomplish patient-specific fit analysis.
The main objectives of the work presented in this dissertation were 1) to develop and evaluate an optimized process for 3D printing cardiovascular anatomy for surgical planning and medical education and 2) to develop and evaluate computational tools to assess MCS device fit in specific patients. The evaluations for objectives 1 and 2 were completed with a collection of qualitative and quantitative validations. These validations include case studies to illustrate meaningful, qualitative results as well as quantitative results from surgical outcomes. The latter results present the first quantitative supporting evidence, beyond anecdotal case studies, regarding the efficacy of 3D printing for pre-procedural planning; this data is suitable as pilot data for clinical trials. The products of this work were used to plan 200 cardiovascular procedures (including 79 cardiothoracic surgeries at Phoenix Children's Hospital), via 3D printed heart models and assess MCS device fit in 29 patients across 6 countries.
In cases where surgical repair is insufficient to return the heart to normal function, a patient may proceed to advanced heart failure, and a heart transplant may be required. Unfortunately, a finite number of available donor hearts are available. A mechanical circulatory support (MCS) device can be used to bridge the time between heart failure and reception of a donor heart. These MCS devices are typically constructed for the adult population. Accordingly, the size associated to the device is a limiting factor for small adults or pediatric patients who often have smaller thoracic measurements. While current eligibility criteria are based on correlative measurements, the aforementioned 3D visualization capabilities can be leveraged to accomplish patient-specific fit analysis.
The main objectives of the work presented in this dissertation were 1) to develop and evaluate an optimized process for 3D printing cardiovascular anatomy for surgical planning and medical education and 2) to develop and evaluate computational tools to assess MCS device fit in specific patients. The evaluations for objectives 1 and 2 were completed with a collection of qualitative and quantitative validations. These validations include case studies to illustrate meaningful, qualitative results as well as quantitative results from surgical outcomes. The latter results present the first quantitative supporting evidence, beyond anecdotal case studies, regarding the efficacy of 3D printing for pre-procedural planning; this data is suitable as pilot data for clinical trials. The products of this work were used to plan 200 cardiovascular procedures (including 79 cardiothoracic surgeries at Phoenix Children's Hospital), via 3D printed heart models and assess MCS device fit in 29 patients across 6 countries.
ContributorsRyan, Justin Robert (Author) / Frakes, David (Thesis advisor) / Collins, Daniel (Committee member) / LaBelle, Jeffrey (Committee member) / Pizziconi, Vincent (Committee member) / Pophal, Stephen (Committee member) / Arizona State University (Publisher)
Created2015