Page 156 - OR-1-3

have also been explored: Chen et al. leveraged cartilage well as animal models—exhibit some limitations which
78
organoids by precisely engineering pro-/anti-angiogenic make it difficult to meet the needs of comprehensive
microenvironments to achieve osteochondral defect repair disease research. In addition, since rotator cuff tears
(Figure 5). predominantly occur at the tendon-bone interface and have
a high rate of postoperative re-tear, there is an urgent need
3. Construction of rotator cuff organoids for an innovative and effective strategy to achieve better
Similar to most diseases, existing in vitro models for rotator restoration of rotator cuff injuries. Based on this, multiple
cuff disorders—primarily conventional cell cultures as rotator cuff regeneration strategies are under constant
exploration, including stem cell-based therapies (MSCs,
Table 5. Construction of cartilage organoids ADSCs), scaffold materials (collagen matrices, nano/
Cell source Inducing factor Matrix References micro-fibrous matrices), PRP, and physical stimulation
Most of the strategies focus on developing
modalities.
79,80
material
BMSCs TGF-β3, RGD-SF-DNA 71 structural materials that recapitulate the properties of
natural tissues to improve the healing, while substantial
81
dexamethasone, hydrogel
ascorbic Acid microsphere evidence has demonstrated that these regeneration
Chondrocytes TGF-β1, IGF-1, Collagen 72 approaches have achieved some improvements, but some
hydrogel significant challenges persist in this domain. Given the
BMSCs CTCC-Y002 medium N/A 73 structural complexity of the rotator cuff, the creation of
iPSCs TGF-β1, Ascorbic Matrigel 75 multi-tissue units represents a promising approach to
Acid, BMP2, GDF5 achieving good rotator cuff repair.
Chondrocytes 411D-250 medium Hydrogel 76 Rotator cuff organoids, integrating skeletal muscle,
Notes: CTCC-Y002 is a commercial chondrogenic differentiation tendon, cartilage, and bone structures, are one of the
medium, whereas 411D-250 is a commercial chondrogenic types of bone-tendon-muscle multitissue structures that
differentiation medium. may meet the needs of rotator cuff repair. However, given
Abbreviations: BMP2: Bone morphogenetic protein 2; BMSCs: Bone its complexity, strategies for the development of rotator
marrow mesenchymal stem cells; GDF5: Growth differentiation factor cuff organoids are not yet mature. In the following, we
5; IGF-1: Insulin-like growth factor 1; iPSCs: Induced pluripotent
stem cells; RGD: Arginine-glycine-aspartic acid; SF: Silk fibroin; will introduce the construction methodology for rotator
TGF-β3: Transforming growth factor beta 3. cuff organoids from three critical dimensions: cell source,

Figure 5. Construction and applications of cartilage organoids. Created in BioRender. Shi, Q. (2025) https://BioRender.com/1c8ds9y.
Abbreviations: BMP2: Bone morphogenetic protein 2; BMSCs: Bone marrow mesenchymal stem cells; IGF-1: Insulin-like growth factor 1; iPSCs: Induced
pluripotent stem cells; PDCs: Periosteum-derived cells; TGF-β1: Transforming growth factor beta 1.

Volume 1 Issue 3 (2025) 9 doi: 10.36922/OR025320025