Tough 3D Printable Hydrogels Based on Force Responsive Protein Unfolding

The field of mechanochemistry has primarily focused on small molecules as the mechanophores that undergo mechanically-induced chemical transformations. Nature, however, uses macromolecules, such as proteins, as mechanically responsive elements in biological signaling and response. 3D printed thermosets based on the globular protein bovine serum albumin (BSA) as a biologically-derived mechanophore crosslinker have demonstrated high strength, ductility and shape memory, attributed to mechanically-responsive protein unfolding and refolding; however, these properties were not observed for the associated hydrogel. Herein, we develop a photopolymerizable hydrogel with a highly defined network topology based on norbornene functionalized BSA and poly(ethylene glycol) dithiol and a loosely-crosslinked interpenetrating network to observe mechanically-induced BSA unfolding. Harnessing BSA as a force-responsive crosslinker imparts high strength, toughness, ductility and tear resistance in 3D printable hydrogels, due to the disruption of the protein native structure and subsequent release of stored length as an energy dissipation mechanism to resist material failure. The development of this network enables the incorporation of a vast array of proteins as stimuli-responsive crosslinkers in vat photopolymerizable hydrogels.