Matching Items (22)
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- All Subjects: Biomedical Engineering
- Creators: Rege, Kaushal
- Resource Type: Text
Description
Biological membranes are critical to cell sustainability by selectively permeating polar molecules into the intracellular space and providing protection to the interior organelles. Biomimetic membranes (model cell membranes) are often used to fundamentally study the lipid bilayer backbone structure of the biological membrane. Lipid bilayer membranes are often supported using inorganic materials in an effort to improve membrane stability and for application to novel biosensing platforms. Published literature has shown that a variety of dense inorganic materials with various surface properties have been investigated for the study of biomimetic membranes. However, literature does not adequately address the effect of porous materials or supports with varying macroscopic geometries on lipid bilayer membrane behavior. The objective of this dissertation is to present a fundamental study on the synthesis of lipid bilayer membranes supported by novel inorganic supports in an effort to expand the number of available supports for biosensing technology. There are two fundamental areas covered including: (1) synthesis of lipid bilayer membranes on porous inorganic materials and (2) synthesis and characterization of cylindrically supported lipid bilayer membranes. The lipid bilayer membrane formation behavior on various porous supports was studied via direct mass adsorption using a quartz crystal microbalance. Experimental results demonstrate significantly different membrane formation behaviors on the porous inorganic supports. A lipid bilayer membrane structure was formed only on SiO2 based surfaces (dense SiO2 and silicalite, basic conditions) and gamma-alumina (acidic conditions). Vesicle monolayer adsorption was observed on gamma-alumina (basic conditions), and yttria stabilized zirconia (YSZ) of varying roughness. Parameters such as buffer pH, surface chemistry and surface roughness were found to have a significant impact on the vesicle adsorption kinetics. Experimental and modeling work was conducted to study formation and characterization of cylindrically supported lipid bilayer membranes. A novel sensing technique (long-period fiber grating refractometry) was utilized to measure the formation mechanism of lipid bilayer membranes on an optical fiber. It was found that the membrane formation kinetics on the fiber was similar to its planar SiO2 counterpart. Fluorescence measurements verified membrane transport behavior and found that characterization artifacts affected the measured transport behavior.
ContributorsEggen, Carrie (Author) / Lin, Jerry Y.S. (Thesis advisor) / Dai, Lenore (Committee member) / Rege, Kaushal (Committee member) / Thornton, Trevor (Committee member) / Vogt, Bryan (Committee member) / Arizona State University (Publisher)
Created2011
Description
Cancer is the second leading cause of death in the United States and novel methods of treating advanced malignancies are of high importance. Of these deaths, prostate cancer and breast cancer are the second most fatal carcinomas in men and women respectively, while pancreatic cancer is the fourth most fatal in both men and women. Developing new drugs for the treatment of cancer is both a slow and expensive process. It is estimated that it takes an average of 15 years and an expense of $800 million to bring a single new drug to the market. However, it is also estimated that nearly 40% of that cost could be avoided by finding alternative uses for drugs that have already been approved by the Food and Drug Administration (FDA). The research presented in this document describes the testing, identification, and mechanistic evaluation of novel methods for treating many human carcinomas using drugs previously approved by the FDA. A tissue culture plate-based screening of FDA approved drugs will identify compounds that can be used in combination with the protein TRAIL to induce apoptosis selectively in cancer cells. Identified leads will next be optimized using high-throughput microfluidic devices to determine the most effective treatment conditions. Finally, a rigorous mechanistic analysis will be conducted to understand how the FDA-approved drug mitoxantrone, sensitizes cancer cells to TRAIL-mediated apoptosis.
ContributorsTaylor, David (Author) / Rege, Kaushal (Thesis advisor) / Jayaraman, Arul (Committee member) / Nielsen, David (Committee member) / Kodibagkar, Vikram (Committee member) / Dai, Lenore (Committee member) / Arizona State University (Publisher)
Created2013
Description
Ionizing radiation, such as gamma rays and X-rays, are becoming more widely used. These high-energy forms of electromagnetic radiation are present in nuclear energy, astrophysics, and the medical field. As more and more people have the opportunity to be exposed to ionizing radiation, the necessity for coming up with simple and quick methods of radiation detection is increasing. In this work, two systems were explored for their ability to simply detect ionizing radiation. Gold nanoparticles were formed via radiolysis of water in the presence of Elastin-like polypeptides (ELPs) and also in the presence of cationic polymers. Gold nanoparticle formation is an indicator of the presence of radiation. The system with ELP was split into two subsystems: those samples including isopropyl alcohol (IPA) and acetone, and those without IPA and acetone. The samples were exposed to certain radiation doses and gold nanoparticles were formed. Gold nanoparticle formation was deemed to have occurred when the sample changed color from light yellow to a red or purple color. Nanoparticle formation was also checked by absorbance measurements. In the cationic polymer system, gold nanoparticles were also formed after exposing the experimental system to certain radiation doses. Unique to the polymer system was the ability of some of the cationic polymers to form gold nanoparticles without the samples being irradiated. Future work to be done on this project is further characterization of the gold nanoparticles formed by both systems.
ContributorsWalker, Candace (Author) / Rege, Kaushal (Thesis advisor) / Chang, John (Committee member) / Kodibagkar, Vikram (Committee member) / Potta, Thrimoorthy (Committee member) / Arizona State University (Publisher)
Created2012
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
Gold nanoparticles as potential diagnostic, therapeutic and sensing systems have a long history of use in medicine, and have expanded to a variety of applications. Gold nanoparticles are attractive in biological applications due to their unique optical, chemical and biological properties. Particularly, gold nanorods (GNRs) are increasingly used due to superior optical property in the near infrared (NIR) window. Light absorbed by the nanorod can be dissipated as heat efficiently or re-emitted by the particle. However, the limitations for clinical translation of gold nanorods include low yields, poor stability, depth-restricted imaging, and resistance of cancer cells to hyperthermia, are severe. A novel high-throughput synthesis method was employed to significantly increase in yields of solid and porous gold nanorods/wires. Stable functional nanoassemblies and nanomaterials were generated by interfacing gold nanorods with a variety of polymeric and polypeptide-based coatings, resulting in unique properties of polymer-gold nanorod assemblies and composites. Here the use of these modified gold nanorods in a variety of applications including optical sensors, cancer therapeutics, and nanobiomaterials were described.
ContributorsHuang, Huang-Chiao (Author) / Rege, Kaushal (Thesis advisor) / Sierks, Michael (Committee member) / Dai, Lenore (Committee member) / Ramakrishna, B (Committee member) / Vogt, Bryan (Committee member) / Arizona State University (Publisher)
Created2012
Description
Oxygen delivery is crucial for the development of healthy, functional tissue. Low tissue oxygenation, or hypoxia, is a characteristic that is common in many tumors. Hypoxia contributes to tumor malignancy and can reduce the success of chemotherapy and radiation treatment. There is a current need to noninvasively measure tumor oxygenation or pO2 in patients to determine a personalized treatment method. This project focuses on creating and characterizing nanoemulsions using a pO2 reporter molecule hexamethyldisiloxane (HMDSO) and its longer chain variants as well as assessing their cytotoxicity. We also explored creating multi-modal (MRI/Fluorescence) nanoemulsions.
ContributorsGrucky, Marian Louise (Author) / Kodibagkar, Vikram (Thesis director) / Rege, Kaushal (Committee member) / Stabenfeldt, Sarah (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor)
Created2013-05
Description
Skin wounds can be caused by traumatic lacerations or incisions which disrupt the structural and functional integrity of the skin. Wound closure and primary intention treatment of the wound as soon as possible is crucial to avoid or minimize the risk of infection that can result in a compromised healing rate or advanced functional intricacy. The gold standard treatment for skin wound healing is suturing. Light-activated tissue sealing is an appealing alternative to sutures as it seals the wound edges minimizing the risk of infection and scarring, especially when utilized along with biodegradable polymeric biomaterials in the wound bed. Silk fibroins can be used as a biodegradable biomaterial that possesses properties supporting cell migration and proliferation in the tissue it interacts with. In addition, histamine treatment is shown to have extensive effects on cellular functions promoting wound healing. Here, the evaluation of Laser-activated Sealants (LASE) consisting of silk fibroin films induced with Indocyanine Green dye in a wound sealed with laser in the presence of Histamine receptor agonists H1R, H2R and H4R take place. The results were evaluated using Trans-epidermal Water Loss (TEWL), histological and analytical techniques where immune cell biomarkers Arginase-1, Ly6G, iNOS, Alpha-SMA, Proliferating Cell Nuclear Antigen (PCNA), and E-Cadherin were used to study the activity of specific cells such as macrophages, neutrophils, and myofibroblasts that aid in wound healing. PBS was used as a control for histamine receptor agonists. It was found that TEWL increased when treated with H1 receptor agonists while decreasing significantly in H2R and H4R-treated wounds. Arginase-1 activity improved, while it displayed an inverse relationship compared to iNOS. H4R agonist escalated Alpha-SMA cells, while others did not have any significant difference. Ly6G activity depleted in all histamine agonists significantly, while PCNA and E-Cadherin failed to show a positive or negative effect.
ContributorsPatel, Dirghau Manishbhai (Author) / Rege, Kaushal (Thesis advisor) / Massia, Stephen (Committee member) / Brafman, David (Committee member) / Arizona State University (Publisher)
Created2022
DescriptionThe primary objective of this research was to investigate the efficacy of heart rate variability biofeedback (HRVB) training interventions aimed to enhance resiliency across collegiate student athletes. This current work focuses on examining the effects of HRVB training and its effects on resiliency in collegiate student athletes.
ContributorsKilroy, Sarah (Author) / James, Dara (Thesis director) / Kim, Sunny (Committee member) / Koffer, Rachel (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor) / School for the Future of Innovation in Society (Contributor)
Created2023-12
Description
Combining 3D bio-printing and drug delivery are promising techniques tofabricate scaffolds with well controlled and patient-specific structures for tissue
engineering. In this study, silk derivatives of bioink were developed consisting of
silk fibroin and gelatin then 3D printed into scaffolds. The scaffolds would be
evaluated for small molecule release, cell growth, degradation, and morphology.
Preparations and design of the scaffolds are major parts of engineering and tissue
engineering. Scaffolds are designed to mimic extracellular matrix by providing
structural support as well as promoting cell attachment and proliferation with
minimum inflammation while degrading at a controlled rate. Scaffolds offers new
potentials in medicine by aiding in the preparation of personalized and controlled
release therapeutic systems.
ContributorsNg, Johnny (Author) / Rege, Kaushal (Thesis advisor) / Holloway, Julianne (Committee member) / Jin, Kailong (Committee member) / Arizona State University (Publisher)
Created2022
Description
Drug delivery has made a significant contribution to cancer immunotherapy and can have a tremendous impact on modulating immunometabolism, thereby affecting cancer outcomes. Notably, the science of delivery of cancer vaccines and immunotherapeutics, modulating immune cell functions has inspired development of several successful companies and clinical products. For example, cancer vaccines require activation of dendritic cells (DCs) and tumour associated Mɸs (TAMs) through modulation of their energy metabolism (e.g., glycolysis, glutaminolysis, Krebs cycle). Similar to activated immune cells, cancer cells also upregulate glucose and glutamine transporters for proliferation and survival. Cancer cells having accelerated energy metabolism, which has been exploited as a target for various therapeutic studies. In the first strategy, an immunometabolism strategy based on sustained release of succinate from biomaterials, which incorporate succinate in the backbone of the polymer was developed. This study demonstrates that succinate-based polymeric microparticles act as alarmins by modulating the immunometabolism of DCs and Mɸs to generate robust pro-inflammatory responses for melanoma treatment in immunocompetent young as well as aging mice. In the second strategy, a biomaterial-based strategy was developed to deliver metabolites one-step downstream of the node where the glycolytic pathway is inhibited, to specifically rescue DCs from glycolysis inhibition. The study successfully demonstrated for the first time that the glycolysis of DCs can be rescued both in vitro and in vivo using a biomaterial strategy of delivering metabolites downstream of the inhibitory node. Overall, it is believed that advanced drug delivery strategies will play an important role in marrying the fields of immunometabolism and immunotherapy to generate translatable anti-cancer treatments.
ContributorsInamdar, Sahil (Author) / Acharya, Abhinav P (Thesis advisor) / Rege, Kaushal (Committee member) / Green, Matthew (Committee member) / Curtis, Marion (Committee member) / Seetharam, Mahesh (Committee member) / Arizona State University (Publisher)
Created2022