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http://hdl.handle.net/11375/28242
Title: | Synthetic Dynamic Covalent Hydrogel Bioinks For Extrusion Bioprinting Applications |
Authors: | Mueller, Eva |
Advisor: | Hoare, Todd |
Department: | Chemical Engineering |
Publication Date: | 2022 |
Abstract: | Soft hydrogels provide a favorable environment for cells to grow, proliferate and differentiate. However, in the context of 3D bioprinting, hydrogels are often limited by templates, weak mechanics, and/or a need to work at non-physiological temperature/pH to enable gelation. Recently, we have developed in situ-gelling poly(oligoethylene glycol methacrylate) (POEGMA) and zwitterionic hydrogels based on dynamic hydrazone chemistry that occurs without UV crosslinking, templating, or catalysts, providing an excellent platform for directly incorporating cells during printing. However, the mixing of any dynamic covalent hydrogels presents a challenge to ensure sufficient crosslinking during the 3D printing process. This research highlights the first demonstration of using dynamic covalent POEGMA and zwitterionic hydrogels as a synthetic bioink platform for extrusion bioprinting using a customized extrusion printer. Three mixing strategies were employed: (1) using a modified coaxial needle for diffusion-based mixing of low-viscosity functional polymers; (2) using an embedded strategy via the FRESH (freeform reversible embedding of suspended hydrogels) bioprinting method to 3D print hydrazone-crosslinked POEGMA hydrogels; and (3) using a pre-mixing approach to print pre-formed zwitterionic hydrogels to fabricate small-scale liver mimics, which showed excellent cell viability (>90%, human hepatoma cells) after two weeks and improved albumin secretion when co-printed with fibroblast cells. The tunable gelation kinetics (from instantaneous to several minutes) allowed for these mixing modalities to be evaluated and optimized in terms of print fidelity, homogeneity of the printed constructs, and overall cell viability/functionality. To overcome the immiscibility of zwitterionic-only polymers with common ionic polysaccharides, a copolymer system (comprised of DMAPS and OEGMA) was developed and evaluated in terms of swelling, protein uptake, and anti-coagulant properties. Dual-crosslinked hydrogels based on ionic crosslinking (from calcium-crosslinked sodium alginate) and covalent crosslinking (from the functional synthetic copolymers) have potential benefits in creating cell-based therapeutics that maintain high cell viability and avoid fibrotic responses. |
URI: | http://hdl.handle.net/11375/28242 |
Appears in Collections: | Open Access Dissertations and Theses |
Files in This Item:
File | Description | Size | Format | |
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Mueller_Eva_finalsubmission2022Dec_PhD.pdf | 11.64 MB | Adobe PDF | View/Open |
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