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and is mainly thought to be caused by both injury and types and scaffolds, following a top-down pathway. 17,18 Since
degeneration. For the treatment of rotator cuff injuries, its inception, organoid technology has greatly influenced
8,9
1,8
there are mainly surgical and non-surgical methods. Non- the drug screening process and the study of pathological
surgical treatments—including pharmacologic interventions mechanisms. Following the pioneering generation of
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such as non-steroidal anti-inflammatory drugs—can intestinal organoids by Sato et al. in 2009, this technology
alleviate the symptoms but fail to stop the progression of the has been widely used in virtually all major tissues. Organoid
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disease, whereas surgical treatments such as direct suture protocols such as thalamus, liver, heart, kidney, and
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21
9
have been widely used for rotator cuff tears. Liu et al. also intestines have been established, which have been applied
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10
11
developed the parachute suture technique for massive rotator in disease modeling, drug screening, regenerative medicine,
cuff tears and to reduce postoperative re-tear rates. However, and other fields. Despite their relatively recent advent,
these methods fail to alter the biological progression of the musculoskeletal system organoids have undergone rapid
tendon. Moreover, some patients present with postoperative evolution, marked by the continuous emergence of organoids
healing failures and the potential for re-tears. Therefore, modeling bone, muscle, joint, and other tissues, which
9
conventional therapeutic approaches for rotator cuff demonstrate immense potential in research and treatment
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injuries demonstrate suboptimal clinical outcomes. In of musculoskeletal system diseases. Rotator cuff organoids
recent years, rotator cuff tissue engineering strategies have are miniature functional models generated in vitro from
become an important direction in the treatment of rotator stem cells through three-dimensional (3D) culture, induced
cuff injuries, including platelet-rich plasma (PRP), growth differentiation, and self-organization to simulate key rotator
12
factors, stem cells, 1,13,14 and exosomes. Despite the advances cuff structures, specifically the tendon-bone interface. The
2
2
achieved, restoration of the injured rotator cuff remains a application of organoid technology to RCI research can
considerable clinical challenge. As an emerging technology, provide a robust platform that can recapitulate the disease-
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organoids have significant potential to be used as a platform specific microenvironments in vitro, accelerate progress of
for studying the mechanisms of RCI and exploring novel RCI research, and offer hope for solving the difficulties and
effective therapeutic measures. bottlenecks faced in the current therapeutic paradigms.
Organoids are in vitro cultured 3D tissue structures In this paper, we systematically outline the construction
originating from stem or progenitor cells that can mimic strategies of skeletal muscle organoids, tendon organoids,
the cellular composition, spatial structure, and even bone organoids, and cartilage organoids and discuss the
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physiological functions of natural organs (Figure 1). application pathways of these organoids (Table 1). On
Organoid models are regarded as a novel and high- this basis, we further propose construction strategies for
performing strategy, being applied to disease modeling, rotator cuff organoids, analyze their applications in disease
drug discovery, regenerative repair, and beyond. In contrast pathogenesis research and therapy development, and
to engineered tissues, organoids are self-assembled models address prevailing technical and translational challenges.
that utilize cells’ self-organization potential to form 2. Musculoskeletal system organoids
aggregates and tissue-like arrangements, representing
a bottom-up approach. Conversely, engineered tissues As 3D cell clusters cultured in vitro that can mimic
involve the construction of structures with relevant cell the structure and function of natural tissues, organoid

Figure 1. Comparison of key characteristics between organoids, 2D cell cultures, and animal models. 25-27 Created in BioRender. Shi, Q. (2025) https://
BioRender.com/7k2i76x.

Volume 1 Issue 3 (2025) 2 doi: 10.36922/OR025320025