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1. Introduction of tendon injury and repair with the advantage of an
in vivo physiological context. However, their translational
Tendons are fibrous connective tissues that link muscles to relevance is limited by interspecies differences in tendon
bones and facilitate the transmission of mechanical loads. structure, gene expression (e.g., lack of MMP1 in rodents),
1,2
As a mechanosensitive structure of the musculoskeletal and biomechanics. These discrepancies hinder accurate
system, it serves an essential function in transmitting the modeling of human tendinopathy. Nevertheless, animal
force produced by muscle contraction to bones, enabling models remain essential for studying systemic responses
movement and maintaining posture. Tendons exhibit high and evaluating surgical or regenerative interventions. Thus,
tensile strength and elasticity owing to their structure tendon organoids and animal models should be seen as
that is rich in extracellular matrix (ECM), enabling them complementary tools—organoids offer human-specific
to withstand considerable mechanical loads. However, insights, while animal models provide a whole-organism
3
tendons are susceptible to injuries, and tendon injuries are context essential for translational research. 9,10
the most common disorder in the musculoskeletal system.
The annual incidence in primary care settings is 4–7/1,000 In recent years, organoid technology has made
people, with a prevalence of 1–3% in the general population remarkable progress in multifaceted fields, including
and 7% among manual laborers. The most affected age neuroscience, gastroenterology, and hepatology. For
group is 42–54 years. Aging is a significant risk factor for example, brain organoids have been proven effective in
4
tendinopathy, as tendons undergo degenerative changes studying neurodevelopmental disorders, while intestinal
over time, leading to an increased susceptibility to injury. and liver organoids have become invaluable tools for
5
For example, the rotator cuff, a prevalent tendon injury, investigating disease mechanisms, drug screening, and
has an incidence of 9.7% in patients under 20 years old, personalized medicine. 11
but increases to 62% in patients aged 80 or older. Tendon Although organoid technology has been widely applied
6
injuries encompass a spectrum from tendinopathy—a in various fields, its use in tendon research remains in the
chronic degenerative condition typically managed non- early stages. Tendon organoids offer a promising approach
surgically—to complete ruptures that often require surgical to addressing the biomechanical complexity of tendon
repair. The majority of studies and applications of tendon tissues, potentially serving as a novel platform for studying
organoids have focused on tendinopathy, aiming to address tendon biology, modeling injuries and diseases, and testing
the limited efficacy of conservative treatments. While regenerative therapies.
surgical intervention is indispensable in full-thickness
tendon tears, non-surgical modalities for tendinopathy However, replicating the unique mechanical and
still face limitations in restoring native tendon structure biochemical environment of tendons presents significant
and function. This highlights the need for organoid-based challenges. Unlike other organs, such as the liver or
regenerative approaches beyond in vitro modeling and drug intestines, tendons exhibit distinctive characteristics,
screening, reinforcing their potential translational value in including highly organized collagen fibers, low cellular
clinical therapy. density, and a complex ECM. These features make in vitro
reconstruction of functional tendon tissue particularly
Current treatment options mainly focus on autografts
and allografts. However, the property of donor scarcity and difficult. Key research questions include identifying
optimal cell sources, determining appropriate biochemical
the potential for immune rejection for allografts limit its signals, and applying mechanical stimuli. In addition,
application. In addition, the suboptimal functional recovery scaffold materials and biofabrication techniques play a
of both treatments demonstrates the poor prognosis of crucial role in mimicking tendon structure and mechanical
patients. Despite advancements in surgical techniques, properties. 12
7
completely restoring tendon structure and function
remains elusive. Therefore, tissue engineering has emerged Recent advancements have addressed some of these
as a promising field for addressing these limitations. Among challenges. Notable progress includes the development
two-dimensional (2D) or three-dimensional (3D) tissue of high-performance scaffolds, the application of 3D
engineering, tendon-like organoids provide a simulation of bioprinting, and the use of bioreactors to simulate
tendons in vitro, structurally and functionally, contributing physiological mechanical conditions. Moreover,
to regenerative medicine with high biocompatibility. 8 interdisciplinary contributions from biomechanics, materials

Current preclinical studies on tendon pathology science, and cell biology have further propelled research in
13
primarily rely on 2D cultures and animal models. Although this field.
2D systems provide controlled environments, they fail to This review provides a comprehensive overview of
replicate the complex 3D architecture and ECM interactions recent progress in tendon organoid research, emphasizing
of native tendon tissue (e.g., lack of ECM). Animal key technical aspects and their clinical and translational
models, on the other hand, enable in vivo investigation potential. The discussion will cover strategies for

Volume 1 Issue 3 (2025) 2 doi: 10.36922/OR025170016