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REVIEW ARTICLE

Tendon organoids: Advances in bioengineering strategies and translational applications

Yiwen Xue1 ,  Yixi Wu2 ,  Hong Zhang3 ,  Xiao Chen4,5,6* ,  Huanhuan Liu7,8* ,  Zi Yin1,4,9*
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1 Department of Orthopedic Surgery of Sir Run Run Shaw Hospital and Liangzhu Laboratory, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
2 Zhejiang University-University of Edinburgh Institute, Zhejiang University, Jiaxing, Zhejiang, China
3 Center for Rehabilitation Medicine, Rehabilitation & Sports Medicine Research Institute of Zhejiang Province, Department of Rehabilitation Medicine, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China
4 Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cells and Regenerative Medicine, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
5 Department of Sports Medicine & Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
6 Zhejiang Key Laboratory of Motor System Disease Precision Research and Therapy, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
7 Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University, Athens, Ohio, United States of America
8 Ohio Musculoskeletal and Neurological Institute, Ohio University, Athens, Ohio, United States of America
9 Institute of Cell Biology, Zhejiang University, Hangzhou, Zhejiang, China
OR 2025, 1(3), 025170016 https://doi.org/10.36922/OR025170016
Received: 27 April 2025 | Revised: 21 June 2025 | Accepted: 26 August 2025 | Published online: 23 September 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/ )
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Abstract

As critical connective tissues transmitting from muscles to bones, tendons play a central role in movement and postural stability. However, their low cellularity, limited metabolic activity, and propensity for degeneration render them vulnerable to acute and chronic injuries. Traditional therapeutic approaches, such as autografts and allografts, are constrained by donor scarcity, immune rejection, and suboptimal functional recovery, driving the emergence of tissue engineering and organoid technologies as innovative solutions. Tendon organoids, which recapitulate the native tendon’s three-dimensional (3D) structure, cellular complexity, and biomechanical niche, offer a physiologically relevant in vitro model for advancing our understanding of tendon development and pathology. This comprehensive review systematically examines recent advances in tendon organoid research, highlighting four key determinants in the construction of tendon organoids: (i) Selection and optimization of cell sources, particularly tendon stem/progenitor cells; (ii) regulation of biochemical cues through spatiotemporal coordination and signaling pathway modulation; (iii) design of biomimetic 3D microenvironments, including physical scaffolds and mechanical stimulation; and (iv) integration of engineering strategies, such as single-cell omics, gene editing, 3D bioprinting, and artificial intelligence (AI) for system optimization. Notably, tendon organoids demonstrate multidimensional potential in translational applications, including regenerative medicine, disease modeling, drug screening, and biomechanical research. To overcome current technical bottlenecks, future investigations should prioritize AI-driven organoid design, standardized manufacturing protocols, and solutions for clinical translation challenges. By bridging fundamental research and clinical therapeutics, this review outlines a theoretical framework and technical roadmap for the refined construction and application of tendon organoids, highlighting their transformative potential in regenerative medicine and precision healthcare.

Keywords
Tendon organoid
Tissue engineering
Regenerative medicine
Tendon stem/progenitor cells
Funding
This work was supported by the National Key Research and Development Program of China (2022YFA1106800), National Natural Science Foundation of China grants (82222044, T2121004, 32271406), Key R&D Program of Zhejiang (2024SSYS0026), and Fundamental Research Funds for the Zhejiang Provincial Universities (K20240141).
Conflict of interest
The authors declared that they have no competing interests.
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