Programmable Tissue Folding in Magneto-Active Structured Hydrogels

Biological tissues are structurally complex and heterogeneous, making the in vitro recapitulation challenging if using a traditional flat cell-culture substrate. Although recent development in engineering tissue patterns has been achieved through top-down approaches including micro-molding and 3D bioprinting, reversible and on-demand dynamic patterning is still underdeveloped. Among soft actuation systems, magnetic actuation shows little toxicity to cells, and can penetrate tissue and media to generate pulling forces and torques remotely, enabling fast and reverse untethered actuation. In this study, we developed hydrogel cell-culture systems based on bilayer folding hydrogels composed of a rigid hyaluronic acid (HA) hydrogel and a stretchable double-network (DN) with ferromagnetic particle dopants. Building upon recent advances in the design of magnetoactive soft materials, our approach further uses magnetoactive hydrogels to provide dynamic patterning upon applying magnetic fields. Using this method, we generated cell-laden hydrogel substrates that display on-demand folding/unfolding reversible shape transformations, providing a culture system for mimicking dynamic tissue folding in vitro and recapitulating 3D complex structures to probe cellular mechanisms.