Document Type
Article
Publication Date
3-12-2018
Publication Title
Biomacromolecules
Volume
19
Issue
3
First Page
926
Last Page
935
Abstract
Engineered hydrogels have been extensively used to direct cell function in 3D cell culture models, which are more representative of the native cellular microenvironment than conventional 2D cell culture. Previously, hyaluronan-furan and bis-maleimide polyethylene glycol hydrogels were synthesized via Diels-Alder chemistry at acidic pH, which did not allow encapsulation of viable cells. In order to enable gelation at physiological pH, the reaction kinetics were accelerated by replacing the hyaluronan-furan with the more electron-rich hyaluronan-methylfuran. These new click-cross-linked hydrogels gel faster and at physiological pH, enabling encapsulation of viable cells, as demonstrated with 3D culture of 5 different cancer cell lines. The methylfuran accelerates Diels-Alder cycloaddition yet also increases the retro Diels-Alder reaction. Using computational analysis, we gain insight into the mechanism of the increased Diels-Alder reactivity and uncover that transition state geometry and an unexpected hydrogen-bonding interaction are important contributors to the observed rate enhancement. This cross-linking strategy serves as a platform for bioconjugation and hydrogel synthesis for use in 3D cell culture and tissue engineering.
DOI
10.1021/acs.biomac.7b01715
ISSN
15257797
E-ISSN
15264602
Recommended Citation
Smith, Laura J.; Taimoory, S. Maryamdokht; Tam, Roger Y.; Baker, Alexander E.G.; Binth Mohammad, Niema; Trant, John F.; and Shoichet, Molly S.. (2018). Diels-Alder Click-Cross-Linked Hydrogels with Increased Reactivity Enable 3D Cell Encapsulation. Biomacromolecules, 19 (3), 926-935.
https://scholar.uwindsor.ca/chemistrybiochemistrypub/199
PubMed ID
29443512