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DC Field | Value | Language |
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dc.contributor.advisor | Hoare, Dr. Todd R. | - |
dc.contributor.author | Paron, Emilia | - |
dc.date.accessioned | 2017-10-05T13:01:53Z | - |
dc.date.available | 2017-10-05T13:01:53Z | - |
dc.date.issued | 2017-11 | - |
dc.identifier.uri | http://hdl.handle.net/11375/22090 | - |
dc.description.abstract | Injectable hydrogels are 3D water swollen polymeric networks formed through in situ gelling mechanisms. The minimally invasive nature of their delivery into the body, coupled with their highly tunable chemical properties, offer broad promise in mimicking or stimulating native tissue functions, essential to effectively treat organ failures resulting from injuries, aging, and disease. Alternately, injectable hydrogels can act as depot-based drug delivery vehicles for various therapeutics including drugs or cells that can be injected directly at a desired site of action for long-term efficacy. While such hydrogels can be formed from a variety of materials (both natural and synthetic) and through a variety of in situ crosslinking mechanisms (both physical and covalent), combining the chemical flexibility of synthetic polymers with reversible covalent gelation in which gel degradation can be better programmed according to its environment offers an attractive combination of properties to rationally engineer in situ gelling hydrogels for a variety of applications. This thesis presents the development of degradable, thermoresponsive and injectable hydrogels based on poly(oligo ethylene glycol methacrylate) (POEGMA), using the rapid covalent cross-linking of hydrazide and aldehyde functionalized POEGMA precursors to form a hydrazone bond capable of undergoing hydrolytic degradation at physiological pH/temperature. First, a new method to make synthetic and degradable hydrogels based on POEGMA is presented, demonstrating that POEGMA in situ-gelling systems can offer the advantageous biological interactions of current state-of-the-art poly (ethylene glycol) (PEG) hydrogels while also offering superior flexibility to control gel properties. The thesis then proceeds to show the facile modulation of POEGMA hydrogel volume phase transition temperatures (VPTT) through varying the length of the ethylene oxide side chains of the OEGMA monomers used during copolymerization. A thermoresponsive gel (similar to the conventional poly(N-isopropylacrylamide) networks) can be achieved while maintaining the excellent stealth like properties in vitro and in vivo of PEG hydrogels. By mixing POEGMA precursor polymers with different phase transition temperatures together, hydrogels with additive properties and the potential for the rational formation of internal microdomains are generated, domains that can be leveraged to control the kinetics of protein release. Next, the microscopic and macroscopic effects of incorporating the charged moieties N,N-dimethylamino ethyl methacrylate (DMAEMA) and acrylic acid (AA) into the POEGMA backbone are explored. We identify both the potential for secondary network formation that enhances gel mechanics as well as the potential to modulate cell responses with the hydrogels as a function of charge type and density, including the application of these charged hydrogels as injectable delivery vehicles for human retinal epithelial cells. Finally, mixed natural-synthetic hydrogels were reported by the incorporation of natural polymer dextran (DEX) into the POEGMA hydrogel platform. We show the resulting hydrogels offer the benefits of both POEGMA (low non-specific adsorption, thermoresponsivity) and dextran (cell interactions and enzymatic degradability), facilitating the generation of hydrogels with desirable in vivo properties. Based on the demonstrated capacity throughout this thesis to rationally change the properties of in situ-gelling hydrogels (often independent of other properties), this research has significant implications for the improvement of hydrogel materials for drug delivery and tissue engineering. | en_US |
dc.language.iso | en | en_US |
dc.title | DESIGNING INJECTABLE POLY(OLIGO ETHYLENE GLYCOL METHACRYLATE)-BASED HYDROGELS FOR DRUG DELIVERY AND TISSUE ENGINEERING APPLICATIONS | en_US |
dc.type | Thesis | en_US |
dc.contributor.department | Chemical Engineering | en_US |
dc.description.degreetype | Thesis | en_US |
dc.description.degree | Doctor of Philosophy (PhD) | en_US |
dc.description.layabstract | Injectable hydrogels are 3D water swollen gel networks formed by simple mixing of water-soluble polymers. Such hydrogels have the potential to mimic or stimulate native tissue functions and thus hold enormous promise in treating organ failures resulting from injuries, aging, and disease. Injectable hydrogels can also act as vehicles for various therapeutics including drugs or cells, and they can be administered minimally invasively. They can be formed from a variety of materials of natural and synthetic origins and through rapid physical or chemical crosslinking mechanisms. This thesis presents the development of degradable, thermoresponsive and injectable hydrogels using poly(oligo ethylene glycol methacrylate) (POEGMA). We demonstrate that by modifying the chemistry of POEGMA as well as how it is combined with other materials (e.g. charged functional groups or natural polymers like dextran) can significantly change the swelling, degradation, mechanical, protein interaction, cell interaction, and in vivo tissue response properties of the hydrogels, allowing them to be customized for various applications in drug delivery, cell delivery, or tissue engineering to improve efficacy relative to current materials. | en_US |
Appears in Collections: | Open Access Dissertations and Theses |
Files in This Item:
File | Description | Size | Format | |
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Paron_Emilia_2017August_PhD.pdf | 9.3 MB | Adobe PDF | View/Open |
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