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matrix material, and construction technique and strategy 3.1.1. BMSCs
(Figure 6).
As the first MSC population type discovered, BMSCs are
3.1. Cell sources mainly found in the bone marrow stroma, accounting for
about 0.001–0.01% of bone marrow mononuclear cells. 84,85
Cells are the basis of organoid construction. To successfully Owing to their technical accessibility and robust multilineage
construct a mature rotator cuff organoid that meets differentiation ability in vitro, BMSCs have been widely
the requirements, it is necessary to select suitable and validated for diverse applications such as tissue repair and
personalized cell sources, and then, with the assistance of regeneration, treatment of immune-related diseases,
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specific matrix materials, induce directional differentiation and drug delivery as well as gene therapy. In rotator
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of cells through cytokines combined with physical cuff organoid constructions, BMSCs are usually loaded
stimulation, to recapitulate the structure and function as into matrix materials along with cytokines to achieve the
well as the microenvironment of the natural rotator cuff. formation of tendon and bone and can be implanted along
Stem cells serve as a cornerstone in organoid construction with endothelial cells to improve vascularization. Liu et al.
89
88
due to their robust dual competencies in self-renewal and developed a tendon-fibrocartilage-bone composite bridging
multipotent differentiation. patch loaded with BMSCs cell sheets, and the complex was
MSCs are critical cellular building blocks for subsequently placed in a bioreactor for dynamic culture,
constructing rotator cuff organoids. As a type of adult which is expected to improve rotator cuff repair. Du et al.
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multipotent stem cell, MSCs, which exhibit strong self- used BMSC-loaded polydopamine-modified 3D-printed
renewal ability, multipotent differentiation potential, and polycaprolactone (PCL) scaffolds in combination with growth
immunomodulatory properties, are ubiquitously found factor-loaded liposomes for the repair of infraspinatus tendon
in bone marrow, adipose, mucous membrane, amniotic tears, showing therapeutic efficacy superior to that of direct
membranes, and other tissues, and can be induced to suture. In addition, with the aim of improving the rotator
differentiate to produce bone, cartilage, tendon, and cuff repair capacity of organoids, some researchers have used
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muscle tissues. Beyond this, they can also secrete matrix gene editing techniques to modify stem cells. For example,
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components such as osteocalcin and type II collagen. Liu et al. genetically modified BMSCs to overexpress Msx1,
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Owing to these properties, they are utilized in the which was subsequently embedded in the hydrogel scaffolds,
construction of musculoskeletal system organoids. In the and demonstrated formation of bone, cartilage, and collagen
fabrication of rotator cuff organoids, BMSCs and adipose- following implantation of the scaffolds into the tendon-bone
derived stem cells (ADSCs) are predominantly utilized. 14 interface.

Figure 6. Construction strategies and application prospects for rotator cuff organoids. This includes descriptions of cell sources, matrix materials, core
methodologies, and application prospects, such as anatomical structure simulation and regenerative repair. Created in BioRender. Shi, Q. (2025) https://
BioRender.com/s7ghtnr.
Abbreviations: ADSCs: Adipose-derived stem cells; BMSCs: Bone marrow mesenchymal stem cells; hAMSCs: Human amniotic membrane mesenchymal
stem cells; TDSCs: Tendon-derived stem cells.

Volume 1 Issue 3 (2025) 10 doi: 10.36922/OR025320025