AccScience Publishing / IJB / Online First / DOI: 10.36922/IJB026280296
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REVIEW ARTICLE
Early Access

Multiscale 3D printing for hierarchical reconstruction and functional regeneration of bone tissue

Yueyang Wang1 Yazhe Fan1 Yue Wang2 Maisha Feng2 Li Ji3 Jinfan Wei1 Linyi Wang1 Lin Zhu4* Yujie Wang2* Pengbei Fan5,6*
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1 School of Bone and Joint Medicine, Henan University of Chinese Medicine, Zhengzhou 450046, China
2 School of Traditional Chinese Medicine, Henan University of Chinese Medicine, Zhengzhou 450046, China
3 The Third Clinical Medical College of Henan University of Chinese Medicine, Zhengzhou 450046, China
4 Department of Orthopedics, The Third Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou 450046, China
5 School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China
6 Wangqi Academy of Beijing University of Chinese Medicine, National Institute of TCM Constitution and Preventive Treatment of Disease, Beijing University of Chinese Medicine, Beijing 100029, China
Received: 8 July 2026 | Revised: 29 July 2026 | Accepted: 5 August 2026 | Published online: 6 August 2026
© 2026 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
Abstract

Bone tissue engineering (BTE) has emerged as a promising approach for repairing critical bone defects that remain challenging to treat using conventional grafting strategies. Recent advances in three-dimensional (3D) printing have enabled the fabrication of patient-specific and biomimetic bone constructs with precise control over structural architecture, material composition, and biological functionality. However, native bone exhibits a highly hierarchical organization spanning multiple length scales, and current 3D printing approaches often remain limited by insufficient integration between macroscopic mechanical reconstruction, microscale cellular regulation, and nanoscale bioactive signaling. In this review, we provide a comprehensive overview of multiscale 3D printing strategies for bone tissue reconstruction, highlighting how additive manufacturing technologies facilitate the recapitulation of hierarchical bone structures. We first summarize the historical evolution of 3D printing in BTE and discuss advances in bioinks, biomaterials, and printing technologies. Subsequently, we analyze multiscale reconstruction strategies from three perspectives: macroscale fabrication for personalized anatomical restoration and mechanical support, microscale construction for cellular organization and vascular network formation, and nanoscale engineering for biomimetic extracellular matrix interfaces and molecular regulation. Furthermore, we discuss emerging strategies integrating smart responsive materials, bioactive cues, and computational design to enhance the regenerative capacity of 3D-printed bone constructs. Finally, current challenges and future perspectives are presented, focusing on vascularization, immune regulation, artificial intelligence-assisted scaffold optimization, four-dimensional bioprinting, and clinical translation. This review highlights the potential of multiscale 3D printing as a transformative platform for developing functional bone tissues and advancing personalized regenerative medicine.

Keywords
Multiscale 3D bioprinting
Bone tissue engineering
Biofabrication
Tissue reconstitution
Regenerative medicine
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International Journal of Bioprinting, Electronic ISSN: 2424-8002 Print ISSN: 2424-7723, Published by AccScience Publishing