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http://hdl.handle.net/11375/24055
Title: | ENGINEERING HYDROGEL CHEMISTRIES AND STRUCTURES FOR BIOMEDICAL APPLICATIONS |
Authors: | XU, Fei |
Advisor: | Hoare, Todd Sheardown, Heather |
Department: | Chemical Engineering |
Publication Date: | 2018 |
Abstract: | Hydrogels have been widely applied for drug delivery and tissue engineering given their highly relevant physiochemical and biological properties such as hydrophilicity, biomimetic mechanics, low protein absorption, and non-toxicity. However, the practical and effective use of hydrogels in such applications demands the development of methods to (1) rapidly identify hydrogel compositions that can exhibit a desired set of properties and (2) fabricate hydrogels with the internal morphology, degradability, and mechanics required to match the needs of the application. In this thesis, new strategies for high-throughput hydrogel synthesis and characterization techniques and reactive electrospinning of reactive pre-polymers directly into hydrogel nanofibers have been developed and applied for drug delivery and tissue engineering applications, using hydrazide and aldehyde-functionalized precursor polymers as the basis for investigations. To optimize injectable hydrogels for protein delivery, high throughput robotics were used to mix 14 different types of precursor polymers functionalized with hydrazide or aldehyde groups to create 126 hydrogels within 30 mins. Coupled with the development of corresponding high-throughput screening strategies for measuring key hydrogel physicochemical and pharmacokinetic properties (e.g. swelling, degradation, mechanics, transparency, and protein release), correlations were identified between hydrogel composition and protein release. To better mimic the nanofibrous nature of native extracellular matrix, a reactive electrospinning method was developed to co-extrude hydrazide and aldehyde-functionalized polymers based on poly(oligoethylene glycol methacrylate) (POEGMA) into well-defined nanofibrous hydrogels with fast swelling responses. Reactive electrospinning of thermoresponsive POEGMA precursors resulted in fast reversible temperature-responsive macroporous nanofibrous hydrogels that could be reversibly thermally cycled and act as highly effective substrates for cell growth and triggered delamination. The inclusion of cells within the precursor polymers enables the direct development of cell-loaded scaffolds that maintain very high cell viability even when dried, facilitate effective cell proliferation, and can be stored in liquid nitrogen for a long period without any added cryoprotectants while preserving high cell viability, representing a “ready-to-use” tissue patch for the clinic. Finally, the morphologies of electrospun scaffolds can also be tuned from microbeads to nanofibers by controlling concentration of POEGMA in the system, enabling precise nanostructural control over the resulting scaffolds. Overall, this work provides new insight into the design of hydrogels with more biologically-relevant properties for clinical applications. |
URI: | http://hdl.handle.net/11375/24055 |
Appears in Collections: | Open Access Dissertations and Theses |
Files in This Item:
File | Description | Size | Format | |
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Xu_Fei_finalsubmission_2018 September_PhD.pdf | 37.49 MB | Adobe PDF | View/Open |
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