Synthesis of a cell-adhesive dextran scaffold crosslinked with protease-susceptible oligopeptides for use in neural tissue engineering applications.
Published: 2006
Language: eng
Number of pages: 253
ISBN-13: 9780494217795
Description: Novel macroporous dextran hydrogels were created by exploiting the liquid-liquid immiscibility of poly(ethylene glycol) (PEG) and methacrylated dextran during radical crosslinking of the methacrylate moieties. A series of formulation diagrams were prepared to gain insight into which conditions led to the formation of macroporous interconnected-beaded scaffolds.This thesis investigates a neural tissue engineering strategy that would mimic aspects of the extracellular environment. Using a dextran hydrogel as a novel material to build extracellular matrix (ECM) analogues, different aspects of the ECM were investigated, including physical support, cell-adhesive character, and the potential for remodeling.The following study demonstrates that dextran hydrogels can not only be modified to be both macroporous and cell adhesive but also to be enzymatically remodeled, thereby mimicking different aspects of the extracellular environment. In conclusion, chemically-modified dextran hydrogels show great promise for neural tissue-engineering applications.Finally, p-maleimidophenyl isocyanate (PMPI)-modified dextran hydrogels crosslinked with collagen-derived peptides, GCRDGPQGIASQDRCG, were used to mimic ECM enzymatic degradation. These hydrogels were found to be hydrolytically stable for more than 200 days yet degraded when exposed to bacterial collagenase, within 30 hours, or human MMP-2 within 16 days, demonstrating enzyme-mediated digestion of the peptide crosslinks. Incorporating the laminin-based peptides enhanced cell adhesion and survival.Although the physical structure of the created macroporous dextran scaffolds was advantageous for tissue engineering, their application was limited due to their non-cell-adhesive nature. To overcome this, macroporous scaffolds of Dex-MA were copolymerized with aminoethyl methacrylate (AEMA) to introduce reactive primary amine groups for covalent immobilization of extracellular-matrixderived peptides (CGRGDS or a combination of CDPGYIGSR/CQAASIKVAV) while maintaining the macroporous geometry of the scaffolds. Both cell adhesion and neurite outgrowth increased significantly for CDPGYIGSR/CQAASIKVAV-derived poly(Dex-MA- co-AEMA) hydrogels. Moreover, dorsal root ganglia (DRG) neurons penetrated the scaffolds, thereby demonstrating the potential of this scaffold for guided cell and axonal regeneration in vivo.
Notes: Source: Dissertation Abstracts International, Volume: 68-01, Section: B, page: 0436.

Thesis (Ph.D.)--University of Toronto, 2006.

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