Bioprinting with superelastic and fatigue-resistant bioinks for large-sized tissue delivery

3D bioprinting technology is advancing rapidly to construct multi-scale preformed architectures that satisfy the demands of tissue regeneration. However, challenges remain in accurately delivering large-sized preformed architectures to the defect sites without being damaged by the mechanical environment in vivo. In this study, we proposed a versatile bioprinting strategy to fabricate large-sized architectures with remarkable injection capacity for geometry-independent minimally invasive tissue delivery. We design a novel hydrogel by mixing gelatin methacryloyl with poly(ethylene glycol) diacrylate (PEGDA) and photocrosslinking the mixture under a white light source. The hydrogel forms a reinforced crosslinking network, exhibiting superelasticity and fatigue resistance. We infer that the flexible chains of high-molecular-weight PEGDA and interconnected macropores of hydrogel contribute to the reinforcement mechanisms. With a decoupled bioprinting strategy, the bioink can be 3D printed into large-sized architectures with different geometries and tunable Poisson’s ratio. The printing architectures displayed excellent deformation and shape recovery capacity by compressing to less than 1% of the original size and fully recovering after injection. The injection capacity is geometry-independent, indicating the intrinsic properties of the hydrogel and allowing higher freedom for the structural design and geometry size of the architectures. The bioprinting process is compatible with genome-edited hepatic cells with high cell-bioprinting suitability, demonstrating high cell viability, a minimally altered transcriptomic profile after bioprinting, and a biocompatible microenvironment that supports cell survival and hepatic function maintenance. The cell-laden architectures express uncompromised injection capacity with unaffected cell viability after injection. This study presents a generalizable strategy for preparing and bioprinting with superelastic and fatigue-resistant bioinks into customized cell-laden architectures to facilitate minimally invasive large-sized tissue delivery.