AccScience Publishing / OR / Volume 1 / Issue 3 / DOI: 10.36922/OR025280024
REVIEW ARTICLE

Advancing musculoskeletal organoids research: Overcoming barriers to reduce animal model dependency

Dachuan Liu1 Shijie Gao1 Jingxi Xu1 Wei Xia2 Song Chen1* Bin Li1*
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1 Medical 3D Printing Center, Orthopedic Institute, Department of Orthopedic Surgery, The First Affiliated Hospital, School of Basic Medical Sciences, MOE Key Laboratory of Geriatric Diseases and Immunology, Suzhou Medical College, Soochow University, Suzhou, Jiangsu, China
2 Applied Materials Science, Department of Materials Science and Engineering, Uppsala University, Uppsala, Sweden
OR 2025, 1(3), 025280024 https://doi.org/10.36922/OR025280024
Received: 11 July 2025 | Revised: 1 August 2025 | Accepted: 7 August 2025 | Published online: 25 August 2025
© 2025 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution -Noncommercial 4.0 International License (CC-by the license) ( https://creativecommons.org/licenses/by-nc/4.0/ )
Abstract

Musculoskeletal (MSK) disorders represent a leading cause of disability worldwide, with their incidence increasing steadily each year. While animal models have been instrumental in replicating various aspects of MSK pathologies, they face significant limitations, including interspecies variations, ethical concerns, and prolonged modeling timelines. The emergence of MSK organoids presents promising complementary models for pathophysiological research, disease modeling, drug screening, and regenerative medicine. As a valuable adjunct for traditional two-dimensional cultures and animal experiments, organoids provide novel mechanistic insights into MSK biology in a more physiologically relevant context. This review provides a comprehensive overview of current modeling strategies for MSK diseases and highlights the potential of organoids to reduce reliance on animal models. We critically assess the advantages and limitations of MSK organoids in disease recapitulation, identify key challenges in their development, and propose potential strategies for refinement. Finally, future directions and opportunities in this rapidly evolving field have been discussed.

Keywords
Musculoskeletal system
Organoid
Animal model
Standardization
Funding
This research was supported by National Natural Science Foundation of China under the project titled “Intervertebral disc regeneration based on precise tissue analysis and spatiotemporal regulation on the materials-related mechanical microenvironment” and “The design of antibacterial and osteoimmunodulatory materials for repairing infectious bone defects with mucin hybrid materials” with grant number 32130059 and 32271421, respectively, and Priority Academic Program Development of Jiangsu Higher Education Institutions.
Conflict of interest
Bin Li is an Editorial Board Member of this journal, but was not in any way involved in the editorial and peer-review process conducted for this paper, directly or indirectly. Separately, other authors declared that they have no known competing financial interests or personal relationships that could have influenced the work reported in this paper.
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