Page 152 - OR-1-3

A B

C

Figure 2. Construction and application of skeletal muscle organoids. (A) The construction of muscle organoids; (B) muscle organoid; (C) the applications
of muscle organoids. Created in BioRender. Shi, Q. (2025) https://BioRender.com/82y9pxc.
Abbreviations: CTM: Cascade tube microfluidics; hPSC: Human pluripotent stem cells; iPSC: Induced pluripotent stem cells.

rise to the structure of tendon. 42,43 Tendons contain a small a three-step method (2D expansion, 2D stimulation, 3D
amount of cells, mainly tendon cells, which are responsible maturation), and these organoids possess an extracellular
for synthesizing collagen, as well as some cell types such matrix (ECM) and microenvironment similar to that of the
as endothelial cells, pericytes, and immune cells, which are native tendon structure and are suitable for tendon-related
distributed in different regions and have unique functions. research. Kroner-Weigl et al. similarly adopted the three-
44
48
Some studies have shown that stem or progenitor cells are step protocol, i.e., expansion, stimulation, and maturation,
present in tendons and can be isolated. The tendon can be to construct tendon organoid models using purchased
45
divided into two parts: the midsubstance, which is mainly human dermal fibroblasts as the source cells, which were
dense fibrous connective tissue formed by type I collagen used to study the effect of dexamethasone on tendon
fibrils aligned parallel to the long axis of the tendon, and differentiation of human dermal fibroblasts. In addition,
the tendon-bone interface, which can be subdivided into the construction of tendon organoids is not yet mature,
four sequential transition areas: tendon, fibrocartilage, and the optimization studies of the construction protocol
calcified fibrocartilage, and mineralized bone. The are underway. For example, Yan et al. constructed in
49
46
primary function of tendons is to transmit the tension vitro tendon organoids using young tendon stem cells and
generated by muscle contraction, thereby assisting in the senescent tendon stem cells, respectively, as cell sources,
completion of motion. Furthermore, tendons possess which resulted in a higher failure rate, low cell density,
47
proprioceptive function, allowing them to play a crucial and disorganized matrix in the model constructed from
role in the adjustment of movements. 43 senescent stem cells. Zhao et al. evaluated the suitability of
52
porcine tendon-derived decellularized ECM (dECM) with
2.2.2. Construction of tendon organoids different digestibility for 3D bioprinting and demonstrated
Tendon organoids are important components of rotator that the “high-viscosity slurry” state was more suitable and
cuff organoids, and their cell sources include human enhanced targeted differentiation of stem cells, suggesting
dermal fibroblasts, tendon-derived stem cells (TDSCs), its potential as a promising biomaterial for organoid
49
48
and bone marrow mesenchymal stem cells (BMSCs), construction (Table 3).
50
which can generate tendon organoids in suitable matrix
materials that meet the needs for research and therapeutic 2.2.3. Application of tendon organoids
purposes through a pre-designed cultivation strategy. Tendon damage is a high-impact injury with inherently
Graça et al. established 3D rod-like organoids of tendon limited regenerative capacity, and traditional repair
51
using commercially available dermal fibroblasts through modalities such as surgical treatment are difficult to fully

Volume 1 Issue 3 (2025) 5 doi: 10.36922/OR025320025