Chemically-induced Jamming and 3D printing of Granular Hydrogels: Microgels as Reservoirs of Volume

Granular hydrogels, made of jammed soft microparticles, are of great interest for 3D (bio)printing, as they combine ideal rheological properties and extensive modularity, yielding favorable microstructures for tissue engineering. Typically, the yield-stress properties of these materials, which facilitate printability, are defined by the preparation state and the initial particle content of the hydrogel. Here, we propose a granular hydrogel whose yield-stress and, consequently, printability and printed scaffolds shape retention can be controlled not only by the initial weight fraction of particles but also by their stimuli-responsive swelling. The responsive microgels are prepared from poly(N-isopropylacrylamide) crosslinked by dynamic covalent disulfide bonds. The particles swelling is triggered by reduction-induced cleavage of the disulfide bonds into two pendant thiol groups, enabling printing of multilayer scaffolds with high shape fidelity. Without chemically induced swelling, the same formulation requires higher particle concentrations to be printable. Importantly, the printed structures can be annealed by oxidizing the thiol units back into disulfide inter-particle bonds. The printed scaffolds are compatible with human dermal fibroblasts (HDF) and support cell-material interactions. This system offers a unique opportunity for on-demand modulation of both printability and scaffold microstructure, enabling unique control over local stiffness, packing density, and porosity in granular scaffolds.