Year: 2022
Type: dissertation
Abstract: Chondroitinase-ABC (ChABC) is a bacterial enzyme that has immense potential as a therapy for central nervous system injuries due to its ability to degrade the chondroitin sulfate proteoglycans of the glial scar; however, its clinical translation has been thwarted by its thermal instability and lack of an optimal delivery strategy. In this thesis, we compared two delivery vehicles for the affinity-release of thermostabilized ChABC expressed with a Src homology 3 domain (ChABC-37-SH3): a tetrazine-norbornene-crosslinked carboxymethylcellulose hydrogel (CMC), and a biodegradable, oxime-crosslinked dextrin-gelatin-based hydrogel (Dexime). Cytocompatibility of both gels was demonstrated using neural progenitor cells and microglia in vitro. Rigorous mechanical characterization revealed their tuneability with crosslink density. Notably, sustained release of bioactive ChABC-37-SH3 was achieved from CMC over 7 days. In contrast, limited release was observed from Dexime due to the potential adsorption of ChABC-37-SH3 to gelatin. Based on these studies, CMC was the preferred hydrogel for affinity-release of ChABC-37-SH3.
Source: TSpace (University of Toronto)
Author: Zuccaro, Sabrina M
Institution: University of Toronto
Language: English
Subfield: Biomaterials
Field: Materials Science
Domain: Physical Sciences
Open Access status: green
OpenAlex ID: W7132919648