Centimeter‐Scale Self‐Assembling Tendon Organoids Drive Tissue Regeneration
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.
Authors
- Yuanhao Xie
- Tingyun Lei (ORCID: https://orcid.org/0000-0002-8358-0551)
- Xiongfeng Li (ORCID: https://orcid.org/0000-0002-6432-0762)
- Yiwen Xue
- Zi Yin (ORCID: https://orcid.org/0000-0003-2892-8962)
- Yanan Du (ORCID: https://orcid.org/0000-0003-2627-9727)
- Xiaohui Xia (ORCID: https://orcid.org/0000-0003-0298-9417)
- Xiao Chen (ORCID: https://orcid.org/0000-0002-4438-5286)
- Zetao Wang (ORCID: https://orcid.org/0000-0002-8080-3027)
- Hong Zhang (ORCID: https://orcid.org/0000-0002-3342-5377)
- Xi Liu (ORCID: https://orcid.org/0000-0002-8654-0774)
- Weiliang Shen (ORCID: https://orcid.org/0000-0001-8131-325X)
- Zichen Wang (ORCID: https://orcid.org/0000-0002-1415-1286)
- Yishan Chen (ORCID: https://orcid.org/0000-0002-7162-9645)
- Bingbing Wu (ORCID: https://orcid.org/0000-0002-0250-104X)
- Tianshun Fang
- Ruifu Lin
Institutions
- Zhejiang International Studies University (CN)
- Sir Run Run Shaw Hospital (CN)
- Institute for Stem Cell Biology and Regenerative Medicine (IN)
- Huzhou Central Hospital (CN)
- Blood Center of Zhejiang Province (CN)
- Zhejiang Provincial People's Hospital (CN)
- Second Affiliated Hospital of Zhejiang University (CN)
- Zhejiang University-University of Edinburgh Institute (CN)
- Center for Life Sciences (CN)
- Hangzhou Medical College (CN)
Publication Details
- Journal
- Advanced Science
- Published
- 2025-08-29
- DOI
- https://doi.org/10.1002/advs.202509453
- Citations
- 1
- Primary Topic
- Tendon Structure and Treatment
- Type
- article
- Field-Weighted Citation Impact
- 1.72
Funders
- National Natural Science Foundation of China
- National Key Research and Development Program of China