Molecular Engineering Mechanically Programmable Hydrogels with Orthogonal Functionalization

A unique orthogonally tunable synthetic polymer hydrogel with programmable elasticity is described herein. The temporal modulation of mechanical properties was achieved by an orthogonal sulfonium-containing synthon, acting both as crosslinkable motifs and as functionalizable handles for chemical modification of the gel. The kinetic formation of iin situ covalent cross-linked hydrogels with ionic features enabled time-dependent mechanical behavior over weeks, a critical parameter of biomimetic substrates for cell development. The elasticity of the dynamic hydrogel was approximately 2 orders of magnitude greater than that of the ionically cross-linked sample with constant stiffness. In addition, we achieved on-demand control of the elastic properties of the hydrogels by application of a thermal stimulus of 37 °C, which provides new avenues to regulate cell behavior and fate. Furthermore, sulfonium groups and styrenyl moieties within the network provided covalent attachment sites for molecules of interest via highly efficient nucleophilic substitution and thiol-ene chemistry. This robust and orthogonal strategy has been demonstrated for temporal control of elasticity and molecular functionalization of the hydrogels as potential substrates for cell development