Page 121 - OR-1-3

REVIEW ARTICLE
Tendon organoids: Advances in bioengineering

strategies and translational applications

Yiwen Xue 1† , Yixi Wu 2† , Hong Zhang 3† , Xiao Chen 4,5,6 * , Huanhuan Liu * , and Zi Yin 1,4,9 *
7,8
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
*Corresponding authors: Xiao Chen (chenxiao-610@zju.edu.cn); Zi Yin (yinzi@zju.edu.cn); Huanhuan Liu (liuh1@ohio.edu)

† These authors contributed equally to Abstract
this work.
Citation: Xue Y, Wu Y, Zhang H, Chen As critical connective tissues transmitting from muscles to bones, tendons play a
X, Liu H, Yin Z. Tendon organoids: central role in movement and postural stability. However, their low cellularity,
Advances in bioengineering strategies limited metabolic activity, and propensity for degeneration render them vulnerable
and translational applications.
Organoid Res. 2025;1(3):025170016. to acute and chronic injuries. Traditional therapeutic approaches, such as autografts
doi: 10.36922/OR025170016 and allografts, are constrained by donor scarcity, immune rejection, and suboptimal
Received: April 27, 2025 functional recovery, driving the emergence of tissue engineering and organoid
technologies as innovative solutions. Tendon organoids, which recapitulate
1st revised: June 10, 2025 the native tendon’s three-dimensional (3D) structure, cellular complexity, and
2nd revised: June 21, 2025 biomechanical niche, offer a physiologically relevant in vitro model for advancing our
Accepted: August 26, 2025 understanding of tendon development and pathology. This comprehensive review
systematically examines recent advances in tendon organoid research, highlighting
Published online: September 23, four key determinants in the construction of tendon organoids: (i) Selection and
2025
optimization of cell sources, particularly tendon stem/progenitor cells; (ii) regulation
Copyright: © 2025 Author(s). of biochemical cues through spatiotemporal coordination and signaling pathway
This is an Open-Access article
distributed under the terms of the modulation; (iii) design of biomimetic 3D microenvironments, including physical
Creative Commons Attribution scaffolds and mechanical stimulation; and (iv) integration of engineering strategies,
License, permitting distribution, and such as single-cell omics, gene editing, 3D bioprinting, and artificial intelligence (AI)
reproduction in any medium, which
provided that the original work is for system optimization. Notably, tendon organoids demonstrate multidimensional
properly cited. potential in translational applications, including regenerative medicine, disease
Publisher’s Note: AccScience modeling, drug screening, and biomechanical research. To overcome current
Publishing remains neutral with regard technical bottlenecks, future investigations should prioritize AI-driven organoid
to jurisdictional claims in published design, standardized manufacturing protocols, and solutions for clinical translation
maps and institutional affiliations.
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

Volume 1 Issue 3 (2025) 1 doi: 10.36922/OR025170016