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restore the structure and function of the tendon and are cells can enable personalized therapeutic strategies, assist
associated with many complications. Thus, organoids in exploring clinical intervention and treatment methods in
exhibiting a high degree of similarity emerge as potential a targeted manner, and promote the realization of optimal
transplantation therapies. Qiu et al. cultured mesenchymal repair outcomes (Figure 3).
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stem cells (MSCs) on collagen fiber scaffolds under cyclic
tensile stimulation, directing them to undergo fibroblast 2.3. Bone organoids
differentiation, suggesting their significant potential for 2.3.1. Physiological structure of bone
application as regenerative grafts for tendon repair. Similar
to skeletal muscle organoids, another pivotal application Bone is a mineralized connective tissue that provides
of tendon organoids lies in their utility as a platform for structural support and protection to vital organs while
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drug screening and toxicity assessment. Kroner-Weigl participating in the movement of the body. Bone serves
et al. constructed tendon organoids for testing the effect as a reservoir of calcium and phosphorus, which regulates
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of glucocorticoids on tendon cell differentiation to validate calcium and phosphorus homeostasis in body fluids. In
their role in inducing tendon differentiation, although the addition, the bone marrow contained in the bone plays
results did not show obvious advantages. Furthermore, a hematopoietic role. The bone matrix is the basic non-
tendon organoids constructed from patient-derived stem cellular structure that constitutes bone tissue, and is
composed of organic (about 35%) and inorganic (about

Table 3. Construction of tendon organoids 65%) components that provide mechanical strength and
Cell source Inducing factor Matrix material References metabolic regulatory functions to bone. The cellular
components of bone primarily comprise osteoblasts,
Human dermal TGF-β3 N/A 48 osteoclasts, and osteocytes. Among them, osteocytes are
fibroblasts the fully matured form of osteoblasts, accounting for about
TSPCs TGF-β3 N/A 49 90–95% of skeletal cells, while osteoblasts and osteoclasts
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Human dermal TGF-β3 N/A 51 are responsible for bone formation and resorption,
fibroblasts respectively, through tightly coupled cellular activities that
MSCs N/A NDGA-crosslinked 53 drive the skeletal remodeling process. Various skeletal
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collagen fiber
scaffolds stem/progenitor cells have also been identified, which are
Abbreviations: MSC: Mesenchymal stem cell; present in specialized compartments including periosteum
NDGA: Nordihydroguaiaretic acid; TGF-β3: Transforming growth and bone marrow cavity, playing a critical role in bone
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factor beta 3; TSPC: Tendon stem/progenitor cells. development. Macroscopically, bones can be categorized

Figure 3. Construction and application of tendon organoids. Created in BioRender. Shi, Q. (2025) https://BioRender.com/6id61yz.
Abbreviations: BMSCs: Bone marrow mesenchymal stem cells; dECM: Decellularized extracellular matrix; TDSCs: Tendon-derived stem cells.

Volume 1 Issue 3 (2025) 6 doi: 10.36922/OR025320025