journal article·2025-11Open access

Centimeter‐Scale Self‐Assembling Tendon Organoids Drive Tissue Regeneration

Tianshun Fang, Hong Zhang, Yuanhao Xie, Xiongfeng Li, Xi Liu, Zichen Wang, Yiwen Xue, Xiaohui Xia, Zetao Wang, Tingyun Lei, Ruifu Lin, Weiliang Shen, Bingbing Wu, Yishan Chen, Yanan Du, Xiao Chen, Zi Yin

Advanced Science· Volume 12· Issue 43

Abstract

Abstract As a cell‐deficient tissue, the scarcity of endogenous stem cells significantly hampers the regeneration of tissue structure and restoration of motor function following tendon injury. To engineer large‐scale transplantable stem cell‐derived organoids in vitro would show tremendous potential in regenerative medicine. Here, by optimizing chemical signals and mimicking tendon extracellular matrix, transplantable tendon organoids exceeding 3 cm in human tissue‐scale dimensions are ultimately developed. This strategy empowers tendon organoids, with high cellular viability, proliferation, tenogenic phenotype, and remarkable enhancements in extracellular matrix (ECM) production enabled self‐assembly. At the single‐cell level, the majority cells in tendon organoids successfully achieve precise tendon‐specific lineage differentiation in vitro while retaining the exceptional regenerative capacity characteristic of fetal tendons. In a tendon defect model, the organoids increase the retention rate of stem cells by 7.9 times at 4 weeks and initiate the formation of a denser repaired tendon with enhanced mechanical properties. Overall, an efficient construction of centimeter‐scale human tendon organoids with superior regenerative potential is achieved, providing a promising strategy for the regenerative medicine.
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Research context

OpenAlex topics: Tendon Structure and Treatment · Cellular Mechanics and Interactions · 3D Printing in Biomedical Research

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Department of Orthopedic Surgery of Sir Run Run Shaw Hospital, and Liangzhu Laboratory Zhejiang University School of Medicine Hangzhou 310058 China

Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cells and Regenerative Medicine and Institute of Cell Biology, Zhejiang University School of Medicine Hangzhou 310058 P. R. China

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 310014 China

Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province Hangzhou Zhejiang Province 310058 China

Department of Sports Medicine & Orthopedic Surgery the Second Affiliated Hospital, and Liangzhu Laboratory Zhejiang University School of Medicine Hangzhou 310058 China

Huzhou Central Hospital Zhejiang University School of Medicine Huzhou Zhejiang 313000 China

International Institutes of Medicine The 4th Affiliated Hospital of Zhejiang University School of Medicine Hangzhou Zhejiang 322000 China

Zhejiang University‐University of Edinburgh Institute Zhejiang University International Campus Haining 314400 China

School of Biomedical Engineering Tsinghua‐Peking Joint Center for LifeSciences Tsinghua University Beijing 100084 China

Funding

National Key Research and Development Program of China · National Natural Science Foundation of China

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