Micro-structure control during cryogenic 3D printing to obtain biomimetic porous and tough cross-scale mineralized collagen bone scaffold

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Tissue engineering (TE) is a promising strategy to repair large bone defects through inducing endogenous bone regeneration. The ideal bone TE scaffold should possess high porosity (90%), suitable stiffness (1 MPa), and most importantly, the same components (mineralized collagen) and macro to micro cross-scale structures similar to natural bone. However, existing 3D-printed mineralized collagen bone TE scaffold hardly reproduces the cross-scale structure of natural bone, resulting in a small porosity (60%) and poor stiffness (100 kPa). To address this challenge, this study applied cryogenic 3D printing, also being known as low-temperature field-assisted ink direct writing, to achieve 3D mineralized collagen scaffolds with macro to micro cross-scale structure. The inclusion of numerous micro-pores within the extruded fibres resulted in a porosity of 95%. In addition, through the control of scaffold micro-structure and in situ mineralization, the Young’s modulus of cryogenic printed collagen scaffold can be increased by 240% while keeping the porosity of 95%, matching the properties of ideal bone TE scaffold. In summary, this work provides new guidelines for technological innovation and application of cryogenic 3D printing, achieving a biomimetic mineralized collagen bone TE scaffold. In addition, because of the high porosity of the scaffolds produced by this technology, these scaffolds can be used in the fields of impact resistance, wave absorption, thermal insulation, flexible materials, piezoelectric ceramics, and so on.