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- Member of: ASU Electronic Theses and Dissertations
Description
Aqueous solutions of temperature-responsive copolymers based on N-isopropylacrylamide (NIPAAm) hold promise for medical applications because they can be delivered as liquids and quickly form gels in the body without organic solvents or chemical reaction. However, their gelation is often followed by phase-separation and shrinking. Gel shrinking and water loss is a major limitation to using NIPAAm-based gels for nearly any biomedical application. In this work, a graft copolymer design was used to synthesize polymers which combine the convenient injectability of poly(NIPAAm) with gel water content controlled by hydrophilic side-chain grafts based on Jeffamine® M-1000 acrylamide (JAAm). The first segment of this work describes the synthesis and characterization of poly(NIPAAm-co-JAAm) copolymers which demonstrates controlled swelling that is nearly independent of LCST. The graft copolymer design was then used to produce a degradable antimicrobial-eluting gel for prevention of prosthetic joint infection. The resorbable graft copolymer gels were shown to have three unique characteristics which demonstrate their suitability for this application. First, antimicrobial release is sustained and complete within 1 week. Second, the gels behave like viscoelastic fluids, enabling complete surface coverage of an implant without disrupting fixation or movement. Finally, the gels degrade rapidly within 1-6 weeks, which may enable their use in interfaces where bone healing takes place. Graft copolymer hydrogels were also developed which undergo Michael addition in situ with poly(ethylene glycol) diacrylate to form elastic gels for endovascular embolization of saccular aneurysms. Inclusion of JAAm grafts led to weaker physical crosslinking and faster, more complete chemical crosslinking. JAAm grafts prolonged the delivery window of the system from 30 seconds to 220 seconds, provided improved gel swelling, and resulted in stronger, more elastic gels within 30 minutes after delivery.
ContributorsOverstreet, Derek (Author) / Caplan, Michael (Thesis advisor) / Massia, Stephen (Committee member) / Mclaren, Alexander (Committee member) / Vernon, Brent (Committee member) / McLemore, Ryan (Committee member) / Arizona State University (Publisher)
Created2012
Description
Current treatment methods for cerebral aneurysms are providing life-saving measures for patients suffering from these blood vessel wall protrusions; however, the drawbacks present unfortunate circumstances in the invasive procedure or with efficient occlusion of the aneurysms. With the advancement of medical devices, liquid-to-solid gelling materials that could be delivered endovascularly have gained interest. The development of these systems stems from the need to circumvent surgical methods and the requirement for improved occlusion of aneurysms to prevent recanalization and potential complications. The work presented herein reports on a liquid-to-solid gelling material, which undergoes gelation via dual mechanisms. Using a temperature-responsive polymer, poly(N-isopropylacrylamide) (poly(NIPAAm), the gelling system can transition from a solution at low temperatures to a gel at body temperature (physical gelation). Additionally, by conjugating reactive functional groups onto the polymers, covalent cross-links can be formed via chemical reaction between the two moieties (chemical gelation). The advantage of this gelling system comprises of its water-based properties as well as the ability of the physical and chemical gelation to occur within physiological conditions. By developing the polymer gelling system in a ground-up approach via synthesis, its added benefit is the capability of modifying the properties of the system as needed for particular applications, in this case for embolization of cerebral aneurysms. The studies provided in this doctoral work highlight the synthesis, characterization and testing of these polymer gelling systems for occlusion of aneurysms. Conducted experiments include thermal, mechanical, structural and chemical characterization, as well as analysis of swelling, degradation, kinetics, cytotoxicity, in vitro glass models and in vivo swine study. Data on thermoresponsive poly(NIPAAm) indicated that the phase transition it undertakes comes as a result of the polymer chains associating as temperature is increased. Poly(NIPAAm) was functionalized with thiols and vinyls to provide for added chemical cross-linking. By combining both modes of gelation, physical and chemical, a gel with reduced creep flow and increased strength was developed. Being waterborne, the gels demonstrated excellent biocompatibility and were easily delivered via catheters and injected within aneurysms, without undergoing degradation. The dual gelling polymer systems demonstrated potential in use as embolic agents for cerebral aneurysm embolization.
ContributorsBearat, Hanin H (Author) / Vernon, Brent L (Thesis advisor) / Frakes, David (Committee member) / Massia, Stephen (Committee member) / Pauken, Christine (Committee member) / Preul, Mark (Committee member) / Solis, Francisco (Committee member) / Arizona State University (Publisher)
Created2012
Description
Proton beam therapy (PBT) is a state-of-the-art radiotherapy treatment approach that uses focused proton beams for tumor ablation. A key advantage of this approach over conventional photon radiotherapy (XRT) is the unique dose deposition characteristics of protons, resulting in superior healthy tissue sparing. This results in fewer unwanted side effects and improved outcomes for patients. Current available dosimeters are intrinsic, complex and expensive; hence cannot be used to determine the dose delivered to the tumor routinely. Here, we report a hydrogel based plasmonic nanosensor for measurements of clinical doses in ranges between 2-4 GyRBE. In this nanosensor, gold ions, encapsulated in a hydrogel, are reduced to gold nanoparticles following irradiation with proton beams. Formation of gold nanoparticles renders a color change to the originally colorless hydrogel. The intensity of the color can be used to calibrate the hydrogel nanosensor in order to quantify different radiation doses employed during treatment. The potential of this nanosensor for clinical translation was demonstrated using an anthropomorphic phantom mimicking a clinical radiotherapy session. The simplicity of fabrication, detection range in the fractionated radiotherapy regime and ease of detection with translational potential makes this a first-in-kind plasmonic colorimetric nanosensor for applications in clinical proton beam therapy.
ContributorsInamdar, Sahil (Author) / Rege, Kaushal (Thesis advisor) / Anand, Aman (Committee member) / Nannenga, Brent (Committee member) / Arizona State University (Publisher)
Created2017
Description
When air is supplied to a conditioned space, the temperature and humidity of the air often contribute to the comfort and health of the occupants within the space. However, the vapor compression system, which is the standard air conditioning configuration, requires air to reach the dew point for dehumidification to occur, which can decrease system efficiency and longevity in low temperature applications.
To improve performance, some systems dehumidify the air before cooling. One common dehumidifier is the desiccant wheel, in which solid desiccant absorbs moisture out of the air while rotating through circular housing. This system improves performance, especially when the desiccant is regenerated with waste or solar heat; however, the heat of regeneration is very large, as the water absorbed during dehumidification must be evaporated. N-isopropylacrylamide (NIPAAm), a sorbent that oozes water when raised above a certain temperature, could potentially replace traditional desiccants in dehumidifiers. The heat of regeneration for NIPAAm consists of some sensible heat to bring the sorbent to the regeneration temperature, plus some latent heat to offset any liquid water that is evaporated as it is exuded from the NIPAAm. This means the NIPAAm regeneration heat has the potential to be much lower than that of a traditional desiccant.
Models were created for a standard vapor compression air conditioning system, two desiccant systems, and two theoretical NIPAAm systems. All components were modeled for simplified steady state operation. For a moderate percent of water evaporated during regeneration, it was found that the NIPAAm systems perform better than standard vapor compression. When compared to the desiccant systems, the NIPAAm systems performed better at almost all percent evaporation values. The regeneration heat was modeled as if supplied by an electric heater. If a cheaper heat source were utilized, the case for NIPAAm would be even stronger.
Future work on NIPAAm dehumidification should focus on lowering the percent evaporation from the 67% value found in literature. Additionally, the NIPAAm cannot exceed the lower critical solution temperature during dehumidification, indicating that a NIPAAm dehumidification system should be carefully designed such that the sorbent temperature is kept sufficiently low during dehumidification.
To improve performance, some systems dehumidify the air before cooling. One common dehumidifier is the desiccant wheel, in which solid desiccant absorbs moisture out of the air while rotating through circular housing. This system improves performance, especially when the desiccant is regenerated with waste or solar heat; however, the heat of regeneration is very large, as the water absorbed during dehumidification must be evaporated. N-isopropylacrylamide (NIPAAm), a sorbent that oozes water when raised above a certain temperature, could potentially replace traditional desiccants in dehumidifiers. The heat of regeneration for NIPAAm consists of some sensible heat to bring the sorbent to the regeneration temperature, plus some latent heat to offset any liquid water that is evaporated as it is exuded from the NIPAAm. This means the NIPAAm regeneration heat has the potential to be much lower than that of a traditional desiccant.
Models were created for a standard vapor compression air conditioning system, two desiccant systems, and two theoretical NIPAAm systems. All components were modeled for simplified steady state operation. For a moderate percent of water evaporated during regeneration, it was found that the NIPAAm systems perform better than standard vapor compression. When compared to the desiccant systems, the NIPAAm systems performed better at almost all percent evaporation values. The regeneration heat was modeled as if supplied by an electric heater. If a cheaper heat source were utilized, the case for NIPAAm would be even stronger.
Future work on NIPAAm dehumidification should focus on lowering the percent evaporation from the 67% value found in literature. Additionally, the NIPAAm cannot exceed the lower critical solution temperature during dehumidification, indicating that a NIPAAm dehumidification system should be carefully designed such that the sorbent temperature is kept sufficiently low during dehumidification.
ContributorsKocher, Jordan Daniel (Author) / Wang, Robert (Thesis advisor) / Phelan, Patrick (Committee member) / Parrish, Kristen (Committee member) / Arizona State University (Publisher)
Created2019
Description
Traumatic brain injury (TBI) is a significant public health concern in the U.S., where approximately 1.7 million Americans sustain a TBI annually, an estimated 52,000 of which lead to death. Almost half (43%) of all TBI patients report experiencing long-term cognitive and/or motor dysfunction. These long-term deficits are largely due to the expansive biochemical injury that underlies the mechanical injury traditionally associated with TBI. Despite this, there are currently no clinically available therapies that directly address these underlying pathologies. Preclinical studies have looked at stem cell transplantation as a means to mitigate the effects of the biochemical injury with moderate success; however, transplants suffer very low retention and engraftment rates (2-4%). Therefore, transplants need better tools to dynamically respond to the injury microenvironment.
One approach to develop new tools for stem cell transplants may be to look towards the endogenous repair response for inspiration. Specifically, activated cell types surrounding the injury secrete the chemokine stromal cell-derived factor-1α (SDF-1α), which has been shown to play a critical role in recruiting endogenous neural progenitor/stem cells (NPSCs) to the site of injury. Therefore, it was hypothesized that improving NPSC response to SDF-1α may be a viable mechanism for improving NPSC transplant retention and migration into the surrounding host tissue. To this end, work presented here has 1. identified critical extracellular signals that mediate the NPSC response to SDF-1α, 2. incorporated these findings into the development of a transplantation platform that increases NPSC responsiveness to SDF-1α and 3. observed increased NPSC responsiveness to local exogenous SDF-1α signaling following transplantation within our novel system. Future work will include studies investigating NSPC response to endogenous, injury-induced SDF-1α and the application of this work to understanding differences between stem cell sources and their implications in cell therapies.
One approach to develop new tools for stem cell transplants may be to look towards the endogenous repair response for inspiration. Specifically, activated cell types surrounding the injury secrete the chemokine stromal cell-derived factor-1α (SDF-1α), which has been shown to play a critical role in recruiting endogenous neural progenitor/stem cells (NPSCs) to the site of injury. Therefore, it was hypothesized that improving NPSC response to SDF-1α may be a viable mechanism for improving NPSC transplant retention and migration into the surrounding host tissue. To this end, work presented here has 1. identified critical extracellular signals that mediate the NPSC response to SDF-1α, 2. incorporated these findings into the development of a transplantation platform that increases NPSC responsiveness to SDF-1α and 3. observed increased NPSC responsiveness to local exogenous SDF-1α signaling following transplantation within our novel system. Future work will include studies investigating NSPC response to endogenous, injury-induced SDF-1α and the application of this work to understanding differences between stem cell sources and their implications in cell therapies.
ContributorsAddington, Caroline (Author) / Stabenfeldt, Sarah E (Thesis advisor) / Kleim, Jeffrey A (Committee member) / Caplan, Michael R (Committee member) / Lifshitz, Jonathan (Committee member) / Massia, Stephen P (Committee member) / Arizona State University (Publisher)
Created2015
Description
Both molecular structure of macromolecular materials and subsequent processing of these materials dictate resulting material properties. In this work novel synthetic strategies combined with detailed analytical methodology reveal fundamental structure-processing-property relationships in thermoplastic polyesters, thermoplastic polyurethanes, covalently crosslinked acetal functionalized networks, and small molecule surfactants. 4,4’ dimethyloxybisbenzoate afforded a series of novel polyester structures, and the incorporation of this monomer both increased the Tg and decreased the crystallinity in cyclohexane dimethanol based polyesters. Solubility and dynamic light scattering experiments combined with oscillatory rheology techniques provided methodology to validate polyurethane extrusion in commercial polyurethanes. Acid catalyzed hydroxyl addition to vinyl ethers provided two families of acetal functionalized poly(ethylene glycol hydrogels). Stoichiometric control of binary thiol-acrylate polymerizations afforded hydrogels with both tunable mechanical properties and predictable degradation profiles. Following this work, a photoacid generator catalyzed cationic catalysis provided acetal functionalized organogels whose mechanical properties were predicted by excess vinyl ether monomers which underwent cationic polymerization under the same reaction conditions that yielded acetal functionalization. Time resolved FT-IR spectroscopy provided new understanding in hydroxyl vinyl ether reactions, where both hydroxyl addition to a vinyl ether and vinyl ether cationic polymerization occur concurrently. This work inspired research into new reactive systems for photobase generator applications. However, current photobase generator technologies proved incompatible for carbon-Michael reactions between acetoacetate and acrylate functionalities as a result of uncontrollable acrylate free radical polymerization. The fundamental knowledge and synthetic strategies afforded by these investigations were applied to small molecule surfactant systems for fire-fighting applications. Triethylsilyl-containing zwitterionic and cationic surfactants displayed surface tensions lower than hydrocarbon surfactants, but larger than siloxane-containing surfactants. For the first time, oscillatory rheology and polarized optical light imagine rheology highlighted shear-induced micelle alignment in triethylsilyl surfactants, which provided more stable foams than zwitterionic analogues. The knowledge gained from these investigations provided fundamental structure-processing-property relationships in small molecule surfactant solutions applied as fire-fighting foams. This discovery regarding the effect of self-assembled structures in foam solutions informs the design and analysis of next generation surfactants to replace fluorocarbon surfactants in fire-fighting foam applications.
ContributorsBrown, James Robert (Author) / Long, Timothy E (Thesis advisor) / Bortner, Michael J (Committee member) / Biegasiewicz, Kyle F (Committee member) / Jin, Kailong (Committee member) / Arizona State University (Publisher)
Created2023
Description
Emerging interest in research of polymeric biomaterials towards human health has intrigued me to pursue my graduate research, primarily towards a few biomedical applications like radiation dosimetry, drug & gene delivery systems. Although Radiotherapy remains a foundation of cancer treatment procedures in clinic; overdosing of radiation can induce toxicity to sensitive organs and underexposure can lead to low efficacies of tumor treatment. Commercial sensors consist of several intrinsic disadvantages due to their sensitivity to heat and light, long processing times, and high costs. For real-time dose detection, a novel colorimetric hydrogel sensor was developed with formation of maroon-colored gold nanoparticles (templated by a variety of surfactants and amino acids) within an agarose-based polymeric hydrogel, upon exposure of ionizing radiation. Translational potential of sensor was demonstrated using anthropomorphic phantoms and in live canine patients undergoing radiotherapy treatments by qualitatively and quantitatively measuring the delivered dose.
Combination therapy by simultaneously using drug & gene delivery with a single multifunctional carrier can lead to novel treatment modalities for various diseases like Cancer, Alzheimer etc. A library of lipid-based Aminoglycoside-derived cationic self-assembling polymer nanoparticles (LPNs) was developed with size ranging from (50-150) nm. Lead LPNs showed great potential for concurrent delivery of nucleic acids along with small molecule drug such as histone deacetylase (HDAC) inhibitor, AR-42 as a combination treatment to cancer cells.
ContributorsDutta, Subhadeep (Author) / Yarger, Jeffery JL (Thesis advisor) / Stephanopoulos, Nicholas NS (Committee member) / Pannala, Rahul RP (Committee member) / Arizona State University (Publisher)
Created2022
Description
Encapsulation is a promising technology to deliver cell-based therapies to patients safely and with reduced need for immunosuppression. Macroencapsulation devices are advantageous due to their ease of retrieval, and thus enhanced safety profile, relative to microencapsulation techniques. A major challenge in macroencapsulation device design is ensuring sufficient oxygen transport to encapsulated cells, requiring high surface area-to-volume device geometries. In this work, a hydrogel injection molding biofabrication method was modified to design and generate complex three-dimensional macroencapsulation devices that have greater complexity in the z-axis. The rheological properties of diverse hydrogels were evaluated and used to perform computational flow modeling within injection mold devices to evaluate pressure regimes suitable for cell viability. 3D printed device designs were evaluated for the reproducibility of hydrogel filling and extraction. This work demonstrated that injection molding biofabrication to construct complex three-dimensional geometries is feasible in pressure regimes consistent with preserving cell viability. Future work will evaluate encapsulated cell viability after injection molding.
ContributorsBrowning, Blake (Author) / Weaver, Jessica D (Thesis advisor) / Vernon, Brent (Committee member) / Nikkhah, Mehdi (Committee member) / Arizona State University (Publisher)
Created2022
Description
Nanostructured zeolites, in particular nanocrystalline zeolites, are of great interest due to their efficient use in conventional catalysis, separations, and emerging applications. Despite the recent advances, fewer than 20 zeolite framework types have been synthesized in the form of nanocrystallites and their scalable synthesis has yet to be developed and understood. Geopolymers, claimed to be “amorphous cousins of zeolites”, are a class of ceramic-like aluminosilicate materials with prominent application in construction due to their unique chemical and mechanical properties. Despite the monolith form, geopolymers are fundamentally nanostructured materials and contain zeolite nanocrystallites.
Herein, a new cost-effective and scalable synthesis of various types of nanocrystalline zeolites based on geopolymer chemistry is presented. The study includes the synthesis of highly crystalline discrete nanorods of a CAN zeolite framework structure that had not been achieved hitherto, the exploration of the Na−Al−Si−H2O kinetic phase diagram of hydrogels that gives SOD, CAN and FAU nanocrystalline zeolites, and the discovery of a unique formation mechanism of highly crystalline nanostructured FAU zeolite with intermediate gel products that possess an unprecedented uniform distribution of elements. This study demonstrated the possibility of using high-concentration hydrogels for the synthesis of nanocrystalline zeolites of additional framework structures.
Moreover, a comprehensive study on nanostructured FAU zeolites ion-exchanged with Ag+, Zn2+, Cu2+ and Fe2+ for antibacterial applications is presented, which comprises metal ion release kinetics, antibacterial properties, and cytotoxicity. For the first time, superior metal ion release performance was confirmed for the nanostructured zeolites compared to their micron-sized counterparts. The metal ion-exchanged FAU nanostructured zeolites were established as new effective antibacterial materials featuring their unique physiochemical, antibacterial, and cytotoxic properties.
Herein, a new cost-effective and scalable synthesis of various types of nanocrystalline zeolites based on geopolymer chemistry is presented. The study includes the synthesis of highly crystalline discrete nanorods of a CAN zeolite framework structure that had not been achieved hitherto, the exploration of the Na−Al−Si−H2O kinetic phase diagram of hydrogels that gives SOD, CAN and FAU nanocrystalline zeolites, and the discovery of a unique formation mechanism of highly crystalline nanostructured FAU zeolite with intermediate gel products that possess an unprecedented uniform distribution of elements. This study demonstrated the possibility of using high-concentration hydrogels for the synthesis of nanocrystalline zeolites of additional framework structures.
Moreover, a comprehensive study on nanostructured FAU zeolites ion-exchanged with Ag+, Zn2+, Cu2+ and Fe2+ for antibacterial applications is presented, which comprises metal ion release kinetics, antibacterial properties, and cytotoxicity. For the first time, superior metal ion release performance was confirmed for the nanostructured zeolites compared to their micron-sized counterparts. The metal ion-exchanged FAU nanostructured zeolites were established as new effective antibacterial materials featuring their unique physiochemical, antibacterial, and cytotoxic properties.
ContributorsChen, Shaojiang (Author) / Seo, Dong Kyun (Thesis advisor) / Trovitch, Ryan (Committee member) / Thomas, MaryLaura Lind (Committee member) / Arizona State University (Publisher)
Created2019
Description
Soft materials are matters that can easily deform from their original shapes and structures under thermal or mechanical stresses, and they range across various groups of materials including liquids, foams, gels, colloids, polymers, and biological substances. Although soft materials already have numerous applications with each of their unique characteristics, integrating materials to achieve complementary functionalities is still a growing need for designing advanced applications of complex requirements. This dissertation explores a unique approach of utilizing intermolecular interactions to accomplish not only the multifunctionality from combined materials but also their tailored properties designed for specific tasks. In this work, multifunctional soft materials are explored in two particular directions, ionic liquids (ILs)-based mixtures and interpenetrating polymer network (IPN).
First, ILs-based mixtures were studied to develop liquid electrolytes for molecular electronic transducers (MET) in planetary exploration. For space missions, it is challenging to operate any liquid electrolytes in an extremely low-temperature environment. By tuning intermolecular interactions, the results demonstrated a facile method that has successfully overcome the thermal and transport barriers of ILs-based mixtures at extremely low temperatures. Incorporation of both aqueous and organic solvents in ILs-based electrolyte systems with varying types of intermolecular interactions are investigated, respectively, to yield optimized material properties supporting not only MET sensors but also other electrochemical devices with iodide/triiodide redox couple targeting low temperatures.
Second, an environmentally responsive hydrogel was synthesized via interpenetrating two crosslinked polymer networks. The intermolecular interactions facilitated by such an IPN structure enables not only an upper critical solution temperature (UCST) transition but also a mechanical enhancement of the hydrogel. The incorporation of functional units validates a positive swelling response to visible light and also further improves the mechanical properties. This studied IPN system can serve as a promising route in developing “smart” hydrogels utilizing visible light as a simple, inexpensive, and remotely controllable stimulus.
Over two directions across from ILs to polymeric networks, this work demonstrates an effective strategy of utilizing intermolecular interactions to not only develop multifunctional soft materials for advanced applications but also discover new properties beyond their original boundaries.
First, ILs-based mixtures were studied to develop liquid electrolytes for molecular electronic transducers (MET) in planetary exploration. For space missions, it is challenging to operate any liquid electrolytes in an extremely low-temperature environment. By tuning intermolecular interactions, the results demonstrated a facile method that has successfully overcome the thermal and transport barriers of ILs-based mixtures at extremely low temperatures. Incorporation of both aqueous and organic solvents in ILs-based electrolyte systems with varying types of intermolecular interactions are investigated, respectively, to yield optimized material properties supporting not only MET sensors but also other electrochemical devices with iodide/triiodide redox couple targeting low temperatures.
Second, an environmentally responsive hydrogel was synthesized via interpenetrating two crosslinked polymer networks. The intermolecular interactions facilitated by such an IPN structure enables not only an upper critical solution temperature (UCST) transition but also a mechanical enhancement of the hydrogel. The incorporation of functional units validates a positive swelling response to visible light and also further improves the mechanical properties. This studied IPN system can serve as a promising route in developing “smart” hydrogels utilizing visible light as a simple, inexpensive, and remotely controllable stimulus.
Over two directions across from ILs to polymeric networks, this work demonstrates an effective strategy of utilizing intermolecular interactions to not only develop multifunctional soft materials for advanced applications but also discover new properties beyond their original boundaries.
ContributorsXu, Yifei (Author) / Dai, Lenore L. (Thesis advisor) / Forzani, Erica (Committee member) / Holloway, Julianne (Committee member) / Jiang, Hanqing (Committee member) / Zhuang, Houlong (Committee member) / Arizona State University (Publisher)
Created2020