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

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

Acknowledgments

None.

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.

Author contributions

Conceptualization: Bin Li, Song Chen

Writing-original draft: Dachuan Liu, Shijie Gao, Jingxi Xu

Writing-review & editing: All authors

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Availability of data

Data will be made available on request.

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