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Figure 3. The diverse applications of tendon organoids. At the center, a schematic representation and electron microscopy images of tendon organoids
provide an overview of their structure. The top left panel illustrates regenerative medicine, where tendon organoids are transplanted into injured tendons
to promote healing and tissue regeneration. The top right panel is about disease modeling, where inflammatory tendons exhibit elevated levels of specific
inflammatory factors, TNF-α, IL-1β, and MMPs. By introducing these factors into tendon organoid cultures, researchers can simulate pathological
conditions, enabling in vitro exploration of inflammation mechanisms and signaling pathways. The bottom left panel shows a comparison between
traditional methods and organoid-based approaches in terms of drug testing. Conventional models, including 2D cultures and animal studies, often
suffer from low relevance to human biology, ethical concerns, and high costs. In contrast, organoid-based methods involve isolating patient-derived
tendon cells, inducing them into organoids, and utilizing them for high-throughput drug screening. This strategy enhances relevance, eliminates ethical
issues, and enables personalized medicine by identifying the most effective treatment for each patient. The bottom right panel demonstrates biomechanics
research, where tendon organoids are subjected to tensile force using a stretch bioreactor to investigate optimal biomechanical conditions for growth and
repair. The findings inform rehabilitation strategies, ensuring that controlled mechanical stimulation—such as appropriate exercise—enhances tendon
recovery. Created with Adobe Photoshop Yixi Wu, Zi Yin (2025) https://imgur.la/images/2025/09/09/figure3.jpg.
Abbreviations: 2D: Two-dimensional; HTS: High-throughput screening; IL-1β: Interleukin-1 beta; MMPs: Matrix metalloproteinases; TNF-α: Tumor
necrosis factor-alpha; TSPCs: Tendon stem/progenitor cells.

application. They provide a versatile platform for refining complicating repair. By providing a controlled research
regenerative therapies while offering a more effective and environment, tendon organoids enable the investigation
personalized solution for tendon repair. of these pathological processes and their underlying
mechanisms. 175
5.2. Disease modeling
Emerging evidence suggests that tendinopathy
Tendon organoids serve as a powerful in vitro platform for comprises distinct subtypes, each with unique pathological
studying various tendon disorders, including tendinopathy, characteristics. This distinction underscores the need for
rotator cuff injuries, Achilles tendon ruptures, and subtype-specific models to enhance understanding of
chronic tendon degeneration. These conditions often disease mechanisms and treatment responses. Tendon
result from overuse, aging, or systemic diseases, such organoids offer a versatile alternative to in vivo models,
as diabetes, which compromise tendon structure and enabling the precise replication of different disease
function. Tendinopathy, for example, is characterized by states. Pathological conditions in tendon organoids can
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chronic inflammation, matrix degradation, and collagen be recreated by modulating biochemical, mechanical, and
disorganization, leading to pain and reduced mobility. cellular factors. Inflammatory and catabolic environments
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Similarly, chronic rotator cuff tears involve progressive are simulated by introducing key cytokines and
collagen breakdown and cellular senescence, further enzymes, such as tumor necrosis factor-alpha (TNF-α),

Volume 1 Issue 3 (2025) 14 doi: 10.36922/OR025170016