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REVIEW ARTICLE

Toward functional bone bioprinting: Addressing the overlooked challenges of mechanical compliance

Amin Ebrahimi Sadrabadi1,2 ,  Payam Baei3 ,  Yalda Alibeigian1 ,  Mohamadreza Baghaban Eslaminejad1* ,  Samaneh Hosseini1,3*
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1 Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
2 Department of Tissue Engineering, Faculty of Basic Sciences and Advanced Technologies in Medicine, Royan Institute, ACECR, Tehran, Iran
3 Department of Cell Engineering, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
IJB, 025420425 https://doi.org/10.36922/IJB025420425
Received: 15 October 2025 | Accepted: 3 December 2025 | Published online: 12 December 2025
© 2025 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/ )
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Abstract

Three-dimensional bioprinting has emerged as a transformative biofabrication technology capable of engineering complex tissue constructs for regenerative medicine. While considerable progress has been made in replicating soft tissues using hydrogel-based bioprinting, the fabrication of mechanically robust bone-mimicking constructs remains a significant challenge. The mechanical heterogeneity of bone, including its anisotropic structure, varying mineral density, and intricate extracellular matrix composition, complicates the development of bioinks that can simultaneously achieve printability, structural integrity, and cellular viability. Recent advancements have focused on optimizing the mechanical properties of bioinks through composite hydrogels, osteoinductive nanomaterials, and bioactive moieties that enhance cell adhesion and differentiation. This review examines the role of mechanical cues in directing mesenchymal stem cell fate, the interplay between material stiffness and osteogenesis, and strategies to enhance bioink performance. We highlight limitations in mechanical compliance and propose novel biomaterial designs, crosslinking strategies, and scaffold functionalization to overcome these barriers. This review aims to bridge the gap between biomaterials science and clinical translation, with the ultimate goal of advancing functional bone graft substitutes.

Graphical abstract
Keywords
3D bioprinting
Bioinks
Bone tissue engineering
Extracellular matrix
Mechanical compliance
Regenerative medicine
Funding
The authors did not receive support from any organization for the submitted work.
Conflict of interest
The authors declare that they have no competing interests.
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International Journal of Bioprinting, Electronic ISSN: 2424-8002 Print ISSN: 2424-7723, Published by AccScience Publishing
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