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REVIEW ARTICLE
Advancing musculoskeletal organoids

research: Overcoming barriers to reduce animal
model dependency

Dachuan Liu 1† , Shijie Gao 1† , Jingxi Xu 1† , Wei Xia 2 , Song Chen * , and Bin Li *
1
1
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
*Corresponding authors: Bin Li (binli@suda.edu.cn); Song Chen (chensong@suda.edu.cn)

† These authors contributed equally to Abstract
this work.
Citation: Liu D, Gao S, Xu J, Musculoskeletal (MSK) disorders represent a leading cause of disability worldwide,
Xia W, Chen S, Li B. Advancing with their incidence increasing steadily each year. While animal models have
musculoskeletal organoids research: been instrumental in replicating various aspects of MSK pathologies, they face
Overcoming barriers to reduce animal
model dependency. Organoid Res. significant limitations, including interspecies variations, ethical concerns, and
2025;1(3):025280024. prolonged modeling timelines. The emergence of MSK organoids presents promising
doi: 10.36922/OR025280024 complementary models for pathophysiological research, disease modeling,
Received: July 11, 2025 drug screening, and regenerative medicine. As a valuable adjunct for traditional
Revised: August 1, 2025 two-dimensional cultures and animal experiments, organoids provide novel
mechanistic insights into MSK biology in a more physiologically relevant context.
Accepted: August 7, 2025 This review provides a comprehensive overview of current modeling strategies for
Published online: August 25, 2025 MSK diseases and highlights the potential of organoids to reduce reliance on animal
Copyright: © 2025 Author(s). models. We critically assess the advantages and limitations of MSK organoids in
This is an Open-Access article disease recapitulation, identify key challenges in their development, and propose
distributed under the terms of the potential strategies for refinement. Finally, future directions and opportunities in this
Creative Commons Attribution
License, permitting distribution, and rapidly evolving field have been discussed.
reproduction in any medium, which
provided that the original work is
properly cited. Keywords: Musculoskeletal system; Organoid; Animal model; Standardization
Publisher’s Note: AccScience
Publishing remains neutral with regard
to jurisdictional claims in published
maps and institutional affiliations.

1. Introduction global population in 2024, and the number of OA cases
in the working-age population represented a growth rate
Musculoskeletal (MSK) system diseases refer to of 116.16% from 1990 to 2021. Moreover, as of 2024,
7,8
pathological conditions affecting MSK structures, including the total number of osteoporosis (OP) patients worldwide
bones, joints, muscles, and ligaments. These disorders has surpassed 200 million, with a global prevalence rate
1,2
are generally categorized into degenerative, traumatic, of 18.3%. From a socioeconomic perspective, MSK
9
metabolic, or inflammatory diseases. They may also system diseases impose staggering healthcare costs, with
3-5
include systemic issues, such as diabetes, hypertension, annual expenditures for OA and OP management alone
and even cardiac conditions. The global burden of these surpassing billions of dollars worldwide. Furthermore,
6
10
conditions has risen substantially due to demographic these conditions contribute significantly to workforce
aging and increasing unhealthy lifestyles. For example, productivity losses and long-term care burdens, thereby
osteoarthritis (OA) affected approximately 7.6% of the emerging as critical public health challenges.

Volume 1 Issue 3 (2025) 1 doi: 10.36922/OR025280024