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 NH(3)(+)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.
Date:
2021-10-04
Relation:
Biofabrication. 2021 Oct 4;13(4):Article number 045029.
