Hybrid Microgels with Thermo-Tunable Elasticity for Controllable Cell Confinement.

Stimuli-responsive hydrogels are able to change their physical properties such as their elastic moduli in response to changes in their environment. If biocompatible polymers are used to prepare such materials and if living cells are encapsulated within these networks, their switchability allows the cell-matrix interactions to be investigated with unprecedented consistency. In this paper, thermo-responsive macro- and microscopic hydrogels are presented based on azide-functionalized copolymers of poly(N-(2-hydroxypropyl)-methacrylamide) and poly(hydroxyethyl methacrylate) grafted with poly(N-isopropylacrylamide) side chains. Crosslinking of these comb polymers is realized by bio-orthogonal strain-promoted azide-alkyne cycloaddition with cyclooctyne-functionalized poly(ethylene glycol). The resulting hybrid hydrogels exhibit thermo-tunable elasticity tailored by the polymer chain length and grafting density. This bio-orthogonal polymer crosslinking strategy is combined with droplet-based microfluidics to encapsulate living cells into stimuli-responsive microgels, proving them to be a suitable platform for future systematic stem-cell research.