4D bioprintable self-healing hydrogel with shape memory and cryopreserving properties

Four-dimensional (4D) bioprinting is an emerging biofabrication technology that integrates time as a fourth dimension with three-dimensional (3D) bioprinting for fabricating customizable tissue-engineered implants. 4D bioprinted implants are expected to possess self-healing and shape memory properties for new application opportunities, for instance, fabrication of devices with good shape integrity for minimally invasive surgery. Herein, we developed a self-healing hydrogel composed of biodegradable polyurethane (PU) nanoparticles and photo-/thermo-responsive gelatin-based biomaterials. The self-healing property of hydrogel may be associated with the formation of reversible ionomeric interaction between the COO- group of PU nanoparticles and NH3+ group on the gelatin chains. The self-healing hydrogel demonstrated excellent 3D printability and filament resolution. The UV-crosslinked printed hydrogel showed good stackability (>80 layers), structural stability, elasticity, and tunable modulus (1-60 kPa). The shape-memorizable 4D printed constructs revealed good shape fixity (~95%) and shape recovery (~98%) through the elasticity as well as forming and collapsing of water lattice in the hydrogel. The hydrogel and the printing process supported the continuous proliferation of neural stem cells (NSCs) (~3.7-fold after 14 days). Moreover, the individually bioprinted NSCs and mesenchymal stem cells in the adjacent, self-healed filaments showed mutual migration and such interaction promoted the cell differentiation behavior. The cryopreserved (-20 ~C or-80 ~C) 4D bioprinted hydrogel after awakening and shape recovery at 37 ~C demonstrated cell proliferation similar to that of the non-cryopreserved control. This 4D bioprintable, self-healable hydrogel with shape memory and cryopreserving properties may be employed for customized biofabrication. ? 2021 IOP Publishing Ltd.