Engineering bone organoids: Recent advances and future prospects

Abstract

Bone organoids have emerged as powerful three-dimensional (3D) culture systems that recapitulate key aspects of bone physiology and pathology, offering superior translational relevance compared with traditional two-dimensional cultures and animal models. By integrating stem cell-derived lineages with biomimetic matrices that mimic the native extracellular matrix, bone organoids faithfully reproduce cellular heterogeneity, structural organization, and dynamic remodeling. Recent advances in natural and synthetic hydrogels, bioactive signaling, and diverse cell sources—including osteogenic, osteoclastic, hematopoietic, and adipogenic populations—have further enhanced organoid fidelity. Biofabrication strategies, such as scaffold-assisted assembly, 3D bioprinting, and organ-on-a-chip platforms enable spatial control and vascularization, while CRISPR-based gene editing and artificial intelligence-driven optimization offer unprecedented precision and scalability. The development of vascularized, innervated, and multi-system-integrated bone organoids holds great promise for disease modeling, drug screening, and regenerative therapies. This review outlines present strategies, technological advances, and future directions in bone organoid engineering.

Keywords

Bone organoids / Biofabrication strategies / Prospects

Acknowledgments

None.

Funding

This work was supported by Grants from Shandong Postdoctoral Science Foundation (SDCX-ZG-202400008), Shandong University Second Hospital Cultivation Fund (2023YP17), National Natural Science Foundation of China (82402801), Shandong Provincial Education Department Project (2024KJJ078), Young Talent of Lifting engineering for Science and Technology in Shandong (SDAST2025QTA009) and Foundation of National Center for Translational Medicine (Shanghai) SHU Branch (No. SUITM202505).

Conflict of interest

The authors declare that they have no conflicts of interest.

Author contributions

Conceptualization: All authors

Visualization: Wei Wang, Juehan Wang

Writing - original draft: Wei Wang, Tehan Zhang

Writing - review & editing: Wenzhao Wang, Haijian Sun

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Availability of data

Not applicable.

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