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

Wei Chang , Zhiwei Huang , Wei Huang , Kai Ren , Jing Ye , Bing Ye , Zheng Zhu , Xianglin Zhang , Bin Wu

International Journal of Bioprinting ›› 2025, Vol. 11 ›› Issue (3) : 199 -217.

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International Journal of Bioprinting ›› 2025, Vol. 11 ›› Issue (3) : 199 -217. DOI: 10.36922/ijb.8123
RESEARCH ARTICLE
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Microstructure control during cryogenic 3D printing to obtain biomimetic porous and tough cross-scale mineralized collagen bone scaffold

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Abstract

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.

Keywords

Bone-mimetic cross-scale structure / Cryogenic 3D printing / Mineralized collagen

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Wei Chang, Zhiwei Huang, Wei Huang, Kai Ren, Jing Ye, Bing Ye, Zheng Zhu, Xianglin Zhang, Bin Wu. Microstructure control during cryogenic 3D printing to obtain biomimetic porous and tough cross-scale mineralized collagen bone scaffold. International Journal of Bioprinting, 2025, 11(3): 199-217 DOI:10.36922/ijb.8123

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Funding

This work was supported by the National Natural Science Foundation of China (Grant No. 52305359, 52305558, 82472440), National Medical Products Administration Key Laboratory for Dental Materials (PKUSS20240401), Hubei Provincial Natural Science Foundation of China (No. 2023AFB141), Key Research and Development Plan of Zhejiang Province (2023C01169), the startup funding, and the Cross-Research Support Program from the Huazhong University of Science and Technology (HUST).

Conflict of interest

The authors declare they have no competing interests.

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