Theses and Dissertations from UMD
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New submissions to the thesis/dissertation collections are added automatically as they are received from the Graduate School. Currently, the Graduate School deposits all theses and dissertations from a given semester after the official graduation date. This means that there may be up to a 4 month delay in the appearance of a give thesis/dissertation in DRUM
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Item Bringing New Chemistry to Guanosine Hydrogels(2020) Xiao, Songjun; Davis, Jeffery T; Chemistry; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Molecular self-assembly is a powerful method to construct functional materials such as supramolecular hydrogels. Hydrogels contain mostly water but show solid-like rheology. Nucleosides and nucleotides contain rich recognition information, which opens up opportunities for gelator design. Hydrogels derived from these natural products have seen a resurgence in the past decade due to the high biodegradability and biocompatibility. Guanosine (G 1) and its analogs are powerful supramolecular hydrogelators. The structural basis for most guanosine hydrogels is G4•M+ quartet with K+ being the best metal to stabilize such a structure. These hydrogen-bonded macrocycles further stack to form 1D G-quadruplex that traps water to give hydrogels. Guanosine hydrogels have been used for applications such as bioactive molecule trap and release, environmental remediation, sensing and cell culture. While the H-bonded G-quadruplex is critical for gelation, G 1 can be synthetically modified to introduce new functions. The work presented here is focused on G-quartet hydrogels made from synthetic guanosine analogs. Guanosine analogs containing sulfur on 8- and 5ʹ-position are purified and their hydrogelation properties in water were examined. The resulting hydrogels can potentially be applied to environmental remediation. Substitution of 5ʹ-OH in G 1 into a hydrazine group in HG 2 significantly improves the hydrogelation properties. The resulting HG 2 KCl hydrogel can be used to non-covalently bind anionic dyes and covalently trap toxic electrophiles such as acrolein. A binary mixture of G 1 and HAG 15 forms a stable hydrogel with KCl. The hydroxamic acid group in HAG 15 serves as a pH-switchable group that can be applied as a carboxylic acid substitute in hydrogelator design. Furthermore, the hydrogel serves as a supramolecular siderophore and binds Fe3+ to generate patterns on the gel surface. The surface can be erased with a reducing agent and rewritten with Fe3+.Item Colloid Assembly Strategies For Structurally Colored Materials And Protease Detection(2019) Torres, Leopoldo; Kofinas, Peter; Bioengineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)The goal of this dissertation is to better understand a mechanism that produces large color changes in a protease responsive nanoparticle hydrogel (PRNH) with structural color. The outcomes of this research can lead in the development of a peptide-based hydrogel optical sensor for the detection of toxic proteases in solution to prevent public exposure by means of water or food source contamination, and a potential terrorist event. Towards this application, a structural color changing SiO2 nanoparticle hydrogel film was made with a 4-arm poly(ethylene glycol) terminated with carboxylic acid norbornene (4PEGN), and a degradable dicysteine peptide. To fabricate the PRNHs, a rapid and tunable centrifugation-based assembly was developed. The color of centrifuged colloids of a single particle diameter was precisely controlled within 50 nm by modulating the particle concentration. The peak wavelength reflected by the material was further tuned by altering the centrifugal rate and assembly time. When placed in a protease solution, the peptide crosslinks degrade causing electrostatic binding and adsorption of the polymer to the particle surface which leads to the assembly of particles into compact amorphous arrays with structural color. Only PRNHs with highly negative particle surface charge exhibit color changes after degradation. Ultra-small angle x-ray scattering revealed that the particles become coated in polymer after degradation, producing a material with less order compared to the initial state. Altering the particle diameter modulates the composites' color, and all sizes investigated (178–297 nm) undergo the degradation-directed assembly. Varying the amount of 4PEGN adjusts the swollen PRNH color and has no effect on the degradation-directed assembly. Next, a botulinum neurotoxin (Botox) responsive nanoparticle hydrogel was developed. Its stability, optical properties, and response time were characterized and optimized for detecting 10 µg/mL of BoTox in solution. Last, a new method to produce bright full-spectrum structurally colored fluids that are non-iridescent is presented. The color was modulated by altering the particle volume fraction and a model predicting the peak wavelength reflected by the colloid was developed. Collectively, this body of work advances the development of responsive structurally colored detection platforms and particle assembly strategies for the production of structural color.Item PHOTO-GUIDED SHAPE TRANSFORMATION OF COMPOSITE HYDROGEL SHEETS(2018) Guo, Hongyu; Nie, Zhihong; Chemistry; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Shape-changing hydrogel material has numerous potential applications in biomimetics, soft robotics, biomedicine, etc. Light as a clean energy source can be remotely delivered to material with high spatial and temporal resolution, which brings new controllability to shape-transformation of hydrogel material. However, the current strategy of using light to control deformation of hydrogel is limited. This dissertation aims to develop new approaches to program shape-transformation of hydrogel material by using light. First, I developed a simple and efficient approach to re-program shape-transformation of composite hydrogel sheet with homogeneously distributed silver nanoparticle. By modulating light irradiation pattern, the same hydrogel sheet transformed to multiple distinct geometries, which were verified by finite element method. Secondly, I developed a simple and reliable approach to pattern various types of photo-thermal converting nanoparticles in hydrogel sheet. The approach enables nanoparticle patterning in both lateral and thickness-direction of hydrogel, which cannot be readily achieved by other approaches such as microcontact printing and photo-lithography. Thirdly, I explored shape transformation of composite hydrogel sheet with spatially patterned plasmonic gold nanoparticles fabricated by using the approach mentioned above. The same patterned composite hydrogel sheet can be designed to exhibit distinct shape transformation modes, highly depending on light irradiation direction, which has not been reported before. Fourthly, I studied shape transformation of composite hydrogel sheet spatially patterned with erasable and rewritable iron oxide nanoparticles. The same hydrogel sheet was re-programmed to exhibit various distinct shape transformations by changing nanoparticle pattern. This provides a new method to reprogram shape transitions of hydrogel material by using external light source. In addition, a hydrogel tube was also readily patterned with iron oxide nanoparticles and its deformation was studied as well. Lastly, I developed a simple and general approach to fabricate multifunctional composite hydrogel tube. The hydrogel tube was formed via self-rolling of 2D hydrogel sheet after releasing stress introduced during photo-polymerization. The introduced magnetic nanorod brought multi-functionality to the hydrogel tube. The self-rolled tube was used to load, transport and release cargo manipulated by capillary force, magnet and light, respectively. This dissertation provides a new, simple and efficient toolset to program and re-program shape transformation of composite hydrogel material by using external light. It is believed that the toolset and concept developed in this dissertation can be applied to other light-responsive hydrogel material.Item Tailoring Guanosine Hydrogels for Various Applications(2018) Plank, Taylor Nicole; Davis, Jeffery T; Chemistry; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Supramolecular hydrogels are of current interest for their ease of use, potential biocompatibility, and reactivity to stimuli. These gel materials have found use in a number of fields ranging from drug delivery and tissue engineering to sensing and environmental remediation. For over a century, guanosine (G 1) and its derivatives have been known to form hydrogels based on self-assembled G4-quartet structures. Recent research has focused on extending the lifetime stability of these hydrogels and modifying their properties to better suit the gels for applications in multiple fields. One such method involves the mixing of G 1 (or G-derivatives) with 0.5 eq of KB(OH)4, which results in the formation of guanosine-borate (GB) diesters. The GB-diesters self-assemble into G4-quartets stabilized by K+, the G4-quartets then stack to form wires that entangle to make a fibrous hydrogel network. This thesis details modifications of this GB-hydrogel system and explores applications of the resulting hydrogels. Modification of the 5ʹ-OH group of G 1 to form 5ʹ-deoxy-5ʹ-iodoguanosine (5ʹ-IG 2) results in a hydrogel that self-destructs via intramolecular cyclization to 5ʹ-deoxy-N3,5ʹ-cycloguanosine (5ʹ-cG 3). Guanine analog drugs can be incorporated into this hydrogel network and then released upon self-destruction of the gel. Substitution of boric acid with benzene-1,4-diboronic acid (BDBA 4) to form hydrogels with G 1 and K+ results in hydrogels that can be crosslinked with Mg2+. These G-BDBA-Mg hydrogels have a lower critical gelator concentration (cgc) than their non-crosslinked counterparts and can be used for cell growth applications. Utilizing binary mixtures of 8-aminoguanosine (8AmG 5) with G 1 allows for the formation of hydrogels with various salts. Hydrogels made of different salts preferentially absorb either cationic or anionic dyes from water, making them candidates for use in environmental remediation. Other 8-substituted G-analogs, including, 8-bromoguanosine (8BrG 6), 8-iodoguanosine (8IG 7), and 8-morpholinoguanosine (8morphG 8) can be used in binary mixtures with G 1 to form gels at room temperature upon mixing with KB(OH)4. Room temperature hydrogels have potential applications in enzyme immobilization, drug encapsulation, and environmental cleanup.Item Guanosine-borate hydrogels- Form and function(2015) Peters, Gretchen Marie; Davis, Jeffery T; Chemistry; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Due to their biocompatibility and stimuli-responsive nature, supramolecular hydrogels derived from natural products are attractive for a number of biomedical applications, including diagnostics, targeted drug delivery and tissue engineering. Nucleosides, the building blocks of nucleic acids, are desirable candidates for forming supramolecular gels as they readily engage in reversible, noncovalent interactions. Guanosine (G 1), in particular, is unique in that it has multiple faces for noncovalent interactions and can self-associate into stable higher-order assemblies, such as G4-quartets and G-quadruplexes. This self-assembly of G 1 and its derivatives into G4-quartets has long been known to induce hydrogelation. However, the requirement of excess salt and the propensity of G 1 to crystallize persist as limitations for G4-hydrogels. Thus, recent interest has focused on developing G4-hydrogels with improved lifetime stabilities and lower salt concentrations. The work described here focuses on a long-lived G4-hydrogel made from G 1 and 0.5 equiv. of KB(OH)4. Gelation occurs through the formation of guanosine-borate (GB) diesters and subsequent assembly into cation-templated G4•K+-quartets. The physical properties and stability of the GB hydrogel can be readily manipulated by varying the gelation components. For example, merely altering the identity of the cation drastically alters the gel’s physical properties. Namely, while GB hydrogels formed with K+ are self-supporting and robust, mixing G 1 with LiB(OH)4 results in a weak gel that readily dissociates upon physical agitation. Small molecules, such as cationic dyes and nucleosides, could be selectively incorporated into the GB hydrogel through reversible noncovalent and covalent interactions. One such dye and known G4-quartet binding ligand, thioflavin T (ThT) fluoresces in the presence of the GB hydrogel. The ThT fluorescence increases as a function of gelator concentration with a sharp increase correlating to the gel point. Thus, this ThT fluorescence assay is a new method for probing the formation of G4-hydrogels. Additionally, ThT acts as a molecular chaperone for Li+ GB hydrogelation. Substoichiometric amounts of ThT results in faster hydrogelation, increased gel strength and improved recovery of a hydrogel destroyed by external stress. Insights gained from this research have implications towards development of biomaterials, biomolecule sensing, and drug delivery.Item Development of food polymer-based colloidal delivery systems for nutraceuticals(2012) Luo, Yangchao; Wang, Qin; Food Science; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Colloidal delivery systems have drawn increasing attention in food science area. Biopolymers, i.e. proteins and polysaccharides originated from foods, with low toxicity, high biocompatibility and biodegradability, are the ideal biomaterials to develop delivery systems for nutraceuticals. The present work is dedicated to develop delivery systems for nutraceuticals, using food derived biopolymers, e.g. chitosan and zein. In the first part of this study, different core-shell structured nanoparticles were developed for encapsulating both hydrophilic and hydrophobic nutracetuicals. For chitosan nanoparticles with zein coating, the hydrophilic nutraceutical, selenite, was encapsulated and the physicochemical properties was improved after zein coating. Then, zein nanoparticles with chitosan (CS) or carboxymethyl chitosan (CMCS) coating were developed to encapsulate hydrophobic nutraceuticals, including vitamin E, vitamin D3, indole-3-carbinol and diindolylmethane. The fabrication parameters were systematically studied and the effects of encapsulation on stabilities of nutraceuticals were investigated under different conditions. Subsequently, a novel approach to prepare CMCS hydrogel beads was developed. CMCS, a water-soluble derivative of CS, was known as unable to form hydrogel beads by itself in aqueous solution due to chain rigidity and inefficient entanglement. In this part, the formation of CMCS hydrogel beads was studied in aqueous-alcohol binary solutions. Chemical crosslinking was required to maintain its integrity upon drying. Different drying methods (i.e. freeze and air drying) were also investigated to understand their effects on swelling and release profile in simulated gastrointestinal conditions. Some possible mechanisms were discussed. Lastly, cellular evaluation of zein nanoparticles stabilized by caseinate was carried out. The zein-caseinate nanoparticles had a good redispersibility after freeze-drying and were able to maintain original particle size in different cell culture medium and buffer at 37°C over time. The zein-caseinate nanoparticles had no cytotoxicity at concentrations up to 1 mg/ml over 3 days. Then, coumarin 6, a fluorescent marker, was encapsulated into zein-caseinate nanoparticles to investigate their cell uptake and epithelial transport. The cell uptake was clearly visualized by fluorescent microscopy and the uptake mechanisms were investigated. The epithelial transport was investigated on Caco-2 cell monolayers. The results suggested caseinate not only stabilized zein nanoparticles in different buffers, but also improved cell uptake and epithelial transport.Item Lipid-Hydrogel Nanoparticles: Synthesis Methods and Characterization(2009) Hong, Jennifer S.; Raghavan, Srinivasa R; Bioengineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)This dissertation focuses on the directed self-assembly of nanoscale soft matter particles using methods based on liposome-templating. Nanoscale liposomes, nano-sized hydrogel particles ("nanogels"), and hybrids of the two have enormous potential as carriers in drug delivery and nanotoxicity studies, and as nanovials for enzyme encapsulation and single molecule studies. Our goal is to develop assembly methods that produce stable nanogels or hybrid lipid-polymer nanoparticles, using liposomes as size and shape templates. First we describe a bulk method that employs liposomes to template relatively monodisperse nanogels composed of the biopolymer, alginate, which is a favorable material for nanogel formation because it uses a gentle ionic crosslinking mechanism that is suitable for the encapsulation of cells and biomolecules. Liposomes encapsulating sodium alginate are suspended in aqueous buffer containing calcium chloride, and thermal permeabilization of the lipid membrane facilitates transmembrane diffusion of Ca2+ ions from the surrounding buffer into the intraliposomal space, ionically crosslinking the liposome core. Subsequent lipid removal results in bare calcium alginate nanogels with a size distribution consistent with that of their liposome template. The second part of our study investigates the potential for microfluidic-directed formation of lipid-alginate hybrid nanoparticles by adapting the above bulk self-assembly procedure within a microfluidic device. Specifically we investigated the size control of alginate nanogel self-assembly under different flow conditions and concentrations. Finally, we investigate the microfluidic directed self-assembly of lipid-polymer hybrid nanoparticles, using phospholipids and an N-isopropylacrylamide monomer as the liposome and hydrogel precursors, respectively. Microfluidic hydrodynamic focusing is used to control the convective-diffusive mixing of the two miscible nanoparticle precursor solutions to form nanoscale vesicles with encapsulated hydrogel precursor. The encapsulated hydrogel precursor is polymerized off-chip and the resultant hybrid nanoparticle size distributions are highly monodisperse and precisely controlled across a broad range relevant to the targeted delivery and controlled release of encapsulated therapeutic agents. Given the ability to modify liposome size and surface properties by altering the lipid components and the many polymers of current interest for nanoparticle synthesis, this approach could be adapted for a variety of hybrid nanoparticle systems.Item SYNTHESIS, CHARACTERIZATION, AND KINETIC STUDIES OF IONIZING RADIATION-INDUCED INTRA- AND INTER-CROSSLINKED POLY(VINYL PYRROLIDONE) NANOHYDROGELS(2007-11-26) An, Jung-Chul; Al-Sheikhly, Mohamad; Material Science and Engineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)A polymer nanohydrogel can be defined as a three-dimensional polymer network composed of hydrophilic crosslinked macromolecular chains filled with liquid and possessing a diameter of 1-102 nanometers. Nanohydrogels have drawn huge interest due to their potential applications, such as target-specific drug delivery carriers, absorbents, chemical/biological sensors, and bio-mimetic materials. However, the conventional methods of nanohydrogel synthesis require toxic chemicals (e.g., initiators, crosslinking agents) to form the gel structure. The additional steps required to remove unreacted or residual (undesired) substances cause nanohydrogel fabrication to be complicated, environmentally unfriendly, and unsuitable for biomedical use. This study aims to develop simple and efficient methods of producing nanohydrogels from polymeric, aqueous solutions using ionizing radiation. Poly(vinyl pyrrolidone) (PVP) nanohydrogels of various sizes and molecular weights were prepared by pulsed electron beam and steady-state gamma irradiation at different doses (5 and 10 kGy; 1Gy = 1 J kg-1) and temperatures (20 to 77 °C). The pervaded volume of the PVP chains becomes smaller at high temperatures (above 50 °C) due to the disruption of hydrogen bonds between water and PVP molecules which reduces the size and the molecular weight of the synthesized PVP nanohydrogels. The synthesis parameters (e.g., irradiation temperature, pulse repetition rate, dose rate, and solution concentration) were varied in order to control the size and the average molecular weight of the irradiated sample. In the absence of oxygen, the radiolytically produced free radicals of the thermally collapsed PVP molecules primarily underwent intra-crosslinking reactions, along with a minor contribution from inter-crosslinking reactions. The predominance of the intra-crosslinking mechanism was exhibited at high irradiation temperature (77 °C) in dilute solutions (c = 0.9 x 10-2 mol L-1). The formation of carbon-centered free radicals along the backbone of the PVP chain at higher pulse repetition rate (300 pulses per second) was found to enhance the intra-crosslinking reaction, thereby leading to the formation of smaller nanohydrogel molecules containing an average hydrodynamic radius (Rh) of 9.9 ± 0.1 nm.