Hydrogels are promising materials for a number of biomedical applications, including tissue engineering, controlled drug delivery, and wound healing. Due to the semi-permeable nature of the water-swollen crosslinked polymer network, hydrogels have the unique ability to encapsulate materials, while allowing passage of any necessary resources, such as the import of oxygen or nutrients and the export of waste or therapeutic agents. Hydrogel properties vary greatly depending on the polymer material and crosslinking chemistry chosen, all of which can be tuned for a particular application. Current hydrogel systems typically involve either natural or synthetic polymers. Synthetic polymers afford more structural control to the resulting hydrogel, however the employed crosslinking chemistry is often non-ideal, due to the high temperatures required or the presence of cytotoxic catalysts. Click chemistry, particularly the strain-promoted alkyne-azide cycloaddition (SPAAC), is ideal for hydrogel crosslinking as it is fast at physiological temperatures, bio-orthogonal, doesn’t produce any byproducts, and doesn’t require a catalyst or external stimuli. For the hydrogel material, synthetic poly(ethylene glycol) (PEG) is most appealing since it is non-toxic, easy to functionalize, and physiologically stable. At the time of this thesis, there were few examples of PEG hydrogels prepared via SPAAC, with limited characterization of the physical properties of these gels and the parameters that dictate their gelation behavior.
The work presented in this thesis involved the optimized synthesis of a cyclooctyne derivative, aza-dibenzocyclooctyne (DIBAC), which was subsequently used for the preparation and characterization of a series of PEG hydrogels crosslinked via SPAAC. We showed that the PEG chain length and number of crosslinking groups had a significant effect on the swelling, degradation time and stiffness of the resulting hydrogels. Additionally, there was very little protein adsorption on the surface of the hydrogels, and the polymer components proved non-cytotoxic.
A second objective of this work was to investigate reproducible hydrogels. We created novel, SPAAC crosslinked PEG hydrogels that contained well-defined dendritic crosslinking groups, making them more reproducible than the previous linear analogs. These hydrogels have short gelation times at low polymer concentration, minimal swelling at physiological temperatures, and kept human mesenchymal stem cells (hMSCs) viable for over 15 days. / Thesis / Doctor of Philosophy (PhD)
| Identifer | oai:union.ndltd.org:mcmaster.ca/oai:macsphere.mcmaster.ca:11375/22048 |
| Date | 11 1900 |
| Creators | Hodgson, Sabrina M. |
| Contributors | Adronov, Alex, Chemistry |
| Source Sets | McMaster University |
| Language | English |
| Detected Language | English |
| Type | Thesis |
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