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Investigation of Cell Media and Aminoglycoside Hydrogel Properties for Cancer Cell Dormancy

Description
In a dormant state, cancer cells survive chemotherapy leaving the opportunity for cancer cell relapse and metastasis ultimately leading to patient death. A novel aminoglycoside-based hydrogel ‘Amikagel’ developed in Dr. Rege’s lab serves as a platform for a 3D tumor microenvironment (3DTM) mimicking cancer cell dormancy and relapse. Six Amikagels…

In a dormant state, cancer cells survive chemotherapy leaving the opportunity for cancer cell relapse and metastasis ultimately leading to patient death. A novel aminoglycoside-based hydrogel ‘Amikagel’ developed in Dr. Rege’s lab serves as a platform for a 3D tumor microenvironment (3DTM) mimicking cancer cell dormancy and relapse. Six Amikagels of varying mechanical stiffness and adhesivities were synthesized and evaluated as platforms for 3DTM formation through cell viability and cell cycle arrest analyses. The impact of fetal bovine serum concentration and bovine serum albumin concentration in the media were studied for their impact on 3DTM formation. These experiments allow us to identify the best possible Amikagel formulation for 3DTM.
ContributorsGjertsen, Haley Nicole (Author) / Rege, Kaushal (Thesis director) / Grandhi, Taraka Sai Pavan (Committee member) / Chemical Engineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
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COMBINATORIAL SYNTHESIS OF INTRINSICALLY PHOTOLUMINESCENT POLY(AMINO ETHER)S AND THERMOSET RESINS

Description
Increased investigation into the development of macromolecular fluorophores has resulted in the synthesis and discovery of several potential candidates. These include modified and polymeric based dendritic structures, hyperbranched polymers and linear polymers. Strong inherent blue photoluminescence has been recently described in linear polyamine polymers in the absence of any chemical…

Increased investigation into the development of macromolecular fluorophores has resulted in the synthesis and discovery of several potential candidates. These include modified and polymeric based dendritic structures, hyperbranched polymers and linear polymers. Strong inherent blue photoluminescence has been recently described in linear polyamine polymers in the absence of any chemical modifications. Here we describe the screening of amine/polyamine compounds for inherent photoluminescence. Several compounds that exhibited strong inherent blue photoluminescence following excitation with UV light were identified. Furthermore we demonstrated successful synthesis of poly(amino ether) polymers as well as chemically cross-linked poly(amino ether) thermosets with the lead Pentaethylenehexamine which was found to have strong inherent blue photoluminescence. The polymers and thermosets were found to retain the photoluminescent properties of the original lead compound. The polymers and thermosets were investigated for their ability to sequester heavy metals from aqueous solutions. An increased decrease in initial photoluminescence was observed as the materials were incubated with increasing metal salt concentration as a result of metal binding sequestration. The poly(amino ether) polymers were found to have higher sensitivity for metal sequestration when compared to equivalent amount of linear 25 kDa polyethylenimine. The strong inherent blue photoluminescence and the ease of synthesis of the poly(amino ether) polymers and thermosets give these materials strong potential for future applications as sensors.
ContributorsVu, Jeffrey (Co-author) / Ramos, James (Co-author) / Rege, Kaushal (Thesis director) / Godeshala, Sudakhar (Committee member) / Barrett, The Honors College (Contributor) / Chemical Engineering Program (Contributor)
Created2015-05
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Amino Acid Templated Gold Nanoparticles as Sensors of Ionizing Radiation

Description
This research addresses the need for improvement in radiation sensors for applications of ionizing radiation such as radiotherapy. The current sensors involved are polymer gel dosimeters, MOSFETs, radio-chromic films, etc. Most of the sensors involved require expensive equipment's and processing facilities for readout. There is still a need to develo…

This research addresses the need for improvement in radiation sensors for applications of ionizing radiation such as radiotherapy. The current sensors involved are polymer gel dosimeters, MOSFETs, radio-chromic films, etc. Most of the sensors involved require expensive equipment's and processing facilities for readout. There is still a need to develop better sensors that can be clinically applied. There are numerous groups around the world trying to conceive a better dosimeter. One of the radiation sensors that was developed recently was based on fluorescence signal emitted from the sensor. To advance the field of radiation sensors, a visual indicator has been developed in-lab as a method of detect ionizing radiation. The intensity of change in color is directly dependent on the amount of incident ionizing radiation. An aqueous gold nanoparticle sensor can be used to accurately determine the incident amount of ionizing radiation1. A gold nanoparticle sensor has been developed in lab with the use of hexadecyltrimethylammonium bromide (C16TAB) as the templating molecule. In the presence of ionizing radiation, the colorless gold salt is reduced and templated, creating a dispersion within the fluid1. The formation of suspended nanoparticles leads to a color change that can be visually detected and accurately analyzed through the employment of a spectrometer. Unfortunately, the toxicity of C16TAB is high. It is expected the toxicity can be reduced by replacing C16TAB with an amino acid, as amino acids can act as templating molecules in the solution and many are naturally occuring2. The experiments included a screening of 20 natural amino acids and 12 unnatural amino acids with the gold salt solution in the presence of ionizing radiation. Stability and absorbance testing was conducted on the amino acid sensors. Additional screening of lead amino acid sensors at various concentrations of irradiation was conducted.
ContributorsGupta, Saumya (Co-author) / Rege, Kaushal (Co-author, Thesis director) / Pushpavanam, Karthik (Co-author, Committee member) / Chemical Engineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2017-05
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Light-Activated Sealants for Internal Organ Repair and Healing

Description

The current clinical gold standards for tissue sealing include sutures, staples, and glues, however several adverse effects limit their use. Sutures and staples inherently cause additional trauma to tissue surrounding the wound, and glues can be lacking in adhesion and are potentially inflammatory. All three also introduce risk of infection.…

The current clinical gold standards for tissue sealing include sutures, staples, and glues, however several adverse effects limit their use. Sutures and staples inherently cause additional trauma to tissue surrounding the wound, and glues can be lacking in adhesion and are potentially inflammatory. All three also introduce risk of infection. Light-activated tissue sealing, particularly the use of near-infrared light, is an attractive alternative, as it localizes heat, thereby preventing thermal damage to the surrounding healthy tissue. Previous work identified a glutaraldehyde-crosslinked chitosan film as a lead sealant for gastrointestinal incision sealing, but in vivo testing resulted in tissue degradation in and around the wound. The suggested causes for this degradation were excess acetic acid, endotoxins in the chitosan, and thermal damage. A basic buffer wash protocol was developed to remove excess acid from the films following fabrication. UV-Vis spectroscopy demonstrated that following the wash, films had the same concentration of Indocyanine green as unwashed films, allowing them to absorb light at the same wavelength, therefore showing the wash did not affect the film’s function. However subsequent washes led to degradation of film mass of nearly 20%. Standard chitosan films had significantly greater mass gain (p = 0.028) and significantly less subsequent loss (p= 0.012) than endotoxin free chitosan-films after soaking in phosphate buffered saline for varying durations , while soaking duration had no effect (p = 0.332). Leak pressure testing of films prepared with varying numbers of buffer washes, laser temperature, and lasering time revealed no significant interaction between any of the 3 variables. As such, it was confirmed that proceeding with in vivo testing with the buffer wash, various lasering temperatures, and laser times would not affect the sealing performance of the films. Future investigation will involve characterization of additional materials that may be effective for sealing of internal wounds, as well as drug loading of agents that may hasten the healing process.
ContributorsSira, Antara (Author) / Rege, Kaushal (Thesis director) / Weaver, Jessica (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor)
Created2022-05