Bioinspired glycosaminoglycan hydrogels via click chemistry for 3D dynamic cell encapsulation.

ABSTRACT: Cell encapsulation within 3D hydrogels is an attractive approach to develop effective cell-based therapies. However, little is known about how cells respond to the dynamic microenvironment resulting from hydrogel gelation-based cell encapsulation. Here, a tunable biomimetic hydrogel system that possesses alterable gelation kinetics and biologically relevant matrix stiffness is developed to study 3D dynamic cellular responses during encapsulation. Hydrogels are synthesized by cross-linking thiolated hyaluronic acid and thiolated chondroitin sulfate with polyethylene glycol diacrylate under cell-compatible conditions. Hydrogel properties are tailored by altering thiol substitution degrees of glycosaminoglycans or molecular weights of cross-linkers. Encapsulation of human mesenchymal stem cells through hydrogel gelation reveals high cell viability as well as a three-stage gelation-dependent cellular response in real-time focal adhesion kinase (FAK) phosphorylation in live single cells. Furthermore, stiffer hydrogels result in higher equilibrium FAK activity and enhanced actin protrusions. Our results demonstrate the promise of hydrogel-mediated cellular responses during cell encapsulation.

SUBMITTER: Kuang L 

PROVIDER: S-EPMC6749605 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature