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

Tissue engineering (TE) is a promising strategy to repair large bone defects by inducing endogenous bone regeneration. The ideal bone TE scaffold should possess high porosity (90%), suitable stiffness (1 MPa), and most importantly, a composition that mimics natural bone, including the same components (mineralized collagen) and cross-macro- and microscale structures. However, existing 3D-printed mineralized collagen bone TE scaffold hardly reproduces the cross-scale structure of natural bone, leading to low porosity (60%) and poor stiffness (100 kPa). To address this challenge, this study applied cryogenic 3D printing, also known as low-temperature field-assisted direct ink writing, to achieve 3D mineralized collagen scaffolds with cross-macro- and microscale structures. The inclusion of numerous micro-pores within the extruded fibers resulted in a porosity of 95%. In addition, through the control of scaffold microstructure and in situ mineralization, Young’s modulus of the cryogenic-printed collagen scaffold can be increased by 240% while maintaining the porosity at 95%, matching the properties of an 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, the high porosity of the scaffolds produced by this technology enables these scaffolds to be used in various fields, including impact resistance, wave absorption, thermal insulation, flexible materials, and piezoelectric ceramics, among others.

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