Temperature-Responsive Dynamic Granular Hydrogels for 4D Printing Applications

4D printing is an emerging technology to fabricate dynamic objects that can change their shape and properties in response to external stimuli (e.g., temperature). Such 4D printed materials have a wide range of potential applications, including soft robotics, active drug delivery systems, and pharmaceutical models. Granular hydrogels, comprised of jammed microgels, are promising as 3D printable materials due to their shear-thinning and self-healing properties, as well as unique micropore structure. By introducing stimuli responsiveness (e.g., volume transitions) into individual microgels, we anticipated that printed granular hydrogels would exhibit dynamic macroscopic and micropore structures; such dynamic granular hydrogels remain largely unexplored. To investigate this, we developed temperature-responsive microgels and assembled them into granular hydrogels to explore their application for 4D printing. Specifically, temperature responsiveness was achieved by crosslinking norbornene-modified hyaluronic acid (NorHA) with dithiol-terminated poly(N-isopropyl acrylamide) (DTPN) via a thiol-ene reaction, which showed a low critical solution temperature (LCST) transition. To form microgels, an emulsion of NorHA, DTPN, and photoinitiator was formed in stirring mineral oil and crosslinked via UV irradiation, which produced microgels with an average diameter of ~155 µm at room temperature (rt) after washing from the oil. Microgel diameters decreased by ~20% when heated (41°C), which was reversible when cooled back to rt. Granular hydrogels were prepared by centrifuging microgels, with structures exhibiting porosity and pore sizes of ~18 % and ~5360 µm², respectively, at rt. The porosity and the pore sizes significantly increased (~28 % and ~10300 µm², respectively) when heated (41°C), presumably due to microgel shrinkage and disconnection. To enhance the stability of granular hydrogels toward 4D printing, inter-particle photocrosslinking was introduced using a tetra-arm PEG thiol in the presence of a photoinitiator and light. Post-crosslinked granular hydrogels were stable and exhibited a bulk volume decrease by ~23% when heated. Interestingly, unlike granular hydrogels without post-crosslinking, increased temperatures reduced pore sizes (5848 µm²to 4283 µm²) within post-crosslinked granular hydrogels. This is likely because there is no disconnection between the covalently crosslinked microgels during heating, resulting in isotopic shrinkage of micropores. Finally, control granular hydrogels (i.e., non-responsive to temperature) were used as suspension baths (i.e., shear-yielding and self-healing materials) to receive temperature-responsive granular hydrogel inks to create multi-material objects that actuate in response to temperature based on patterned responsivity. We envisage that our findings will facilitate the rational design of dynamic hydrogels that respond to various stimuli based on an innovative 4D printing approach that exploits the benefits of granular hydrogels.