Wu S.-DSHAN-HUI HSU2022-03-222022-03-22202117585082https://www.scopus.com/inward/record.uri?eid=2-s2.0-85117239650&doi=10.1088%2f1758-5090%2fac2789&partnerID=40&md5=12f9496cd4e4ab8eb004b7d459bd028ahttps://scholars.lib.ntu.edu.tw/handle/123456789/600379Four-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.4D bioprintingbiodegradable polyurethanecryopreservationself-healingshape memory3D printersAmmoniaCell cultureCell proliferationCrosslinkingMolecular biologyNanoparticlesPolyurethanesRecoverySelf-healing materialsShape optimizationStabilityStem cells4d bioprintingBiodegradable polyurethanesBiofabricationBioprintingCryo-preservationNeural stem cellPropertySelf-healingShape recoveryShape-memoryHydrogelsgelatinbioprintinghydrogelthree dimensional printingtissue engineeringGelatinPrinting, Three-DimensionalTissue Engineeringjournal article10.1088/1758-5090/ac2789345304082-s2.0-85117239650