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human embryonic muscle development. Researchers have cartilage organoids by introducing pro-inflammatory
constructed new skeletal muscle organoid models using cytokines, such as IL-1β. Organoids not only simulate
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hPSCs and observed the construction of the models by the pathological processes of OA, such as chondrocyte
monitoring gene expression, myocyte formation, and death, inflammatory responses, and degradation of
changes in contractile force. Furthermore, Yin et al. the ECM but also allow for dynamic monitoring and
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used hPSCs to construct the first self-organizing hNMSO, quantitative analysis of the inflammatory responses and
achieving spatial self-organization of nerves, muscles, and ECM degradation during the inflammatory process.
bones through a co-development strategy, revealing the key Nevertheless, research and evaluation methods in OA
role of skeletal support in skeletal muscle development. animal models are predominantly confined to imaging, gait
analysis, and histological staining, which inherently limit
4.3. Organoids for the disease models quantitative analysis and impede real-time monitoring
While animal models have played an important role in bone of disease progression. In addition, Occhetta et al.
disease research, significant differences in pathological developed a “cartilage-on-a-chip” model that simulates
processes exist due to species differences, leading to the mechanical factors in OA pathogenesis by applying
many effective treatments in animal experiments failing compressive forces, thereby inducing a shift in cartilage
to achieve the same results in clinical applications. MSK from homeostasis to catabolism and hypertrophy.
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organoids, built using patients’ cells, can highly simulate Compared to the complex biomechanical loading in vivo,
the cellular composition, tissue structure, and physiological cartilage organoids engineered through “cartilage-on-a-
functions of the human MSK system, providing a platform chip” not only deliver hyperphysiological compression
closer to the real human environment for disease research. to cartilage but also enable systematic investigation into
This high degree of human simulation enables researchers mechanical alterations throughout OA pathogenesis.
to precisely observe the disease development process When investigating the relationship between tissues/organs
in vitro and investigate the interactions between cells and and biomechanics, OoC platforms and bioreactors exhibit
changes in signaling pathways, offering strong support for exceptional capabilities. For example, Iordachescu et al.
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the analysis of disease etiology and pathogenesis. utilized a microgravity bioreactor to simulate reduced
MSK organoids have wide applications in simulating mechanical stimulation, constructing an osteoporotic
diseases, including trauma, inflammation, neoplasms, and organoid model in vitro. This model enables the study of
hereditary disorders. First, MSK organoids can simulate the OP and bone remodeling processes. Organoids can also
complex pathological process of fracture healing, including be utilized to simulate the pathological processes of RA
inflammatory response, new bone formation, and bone and investigate the interactions between synovial tissue
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remodeling. Research by Price et al. successfully and immune cells. For example, co-culturing cartilage
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converted mouse muscle precursor cells into idSCs using organoids with synovial cells can mimic the inflammatory
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an organoid culture system. These idSCs exhibit robust self- responses observed in the joints of RA patients. For
renewal capacity and myogenic potential in vitro. In injury immune-mediated inflammatory diseases, specialized
models, idSCs effectively fuse into myofibers, replenish animal models or complex modeling approaches are
the satellite cell niche, and support muscle regeneration typically required, whereas organoids offer simpler, more
through matching freshly isolated satellite cells. Compared stable construction and significantly higher success rates
to in vivo trauma models, organoids, relatively isolated than in vivo models.
microenvironments, enable precise control over injury Moreover, MSK organoids can be utilized to model both
magnitude and frequency, while circumventing stress tumors and hereditary diseases. However, modeling animal
responses and mortality risks associated with repeated tumors poses several challenges: (i) significant biological
animal injuries. In addition, when investigating cellular disparities exist between animal and human tumors;
composition and behavioral changes in the MSK system (ii) constructing primary tumor models is technically
post-trauma, in vivo models often involve multiple demanding; (iii) tumor models exhibit poor stability and
cell types with mutual interference. Hence, researchers reproducibility; and (iv) stringent animal ethics regulations
engineered osteo-callus organoids incorporating and oversight impose limitations. MSK organoids, with
hydrogel microspheres encapsulated with BMSCs, which advantages including: (i) high-fidelity recapitulation of
effectively model the cellular composition and dynamics human tumor microenvironments; (ii) enhanced model
of endochondral ossification following long bone injury. 136 robustness and reproducibility; (iii) capability for real-time
Second, MSK organoids play an important role in monitoring and long-term culture; and (iv) absence of
simulating inflammatory diseases such as OA and RA. For ethical constraints, are increasingly favored for establishing
instance, researchers have successfully induced OA-like animal tumor models, superseding animal models as the
inflammatory responses and cartilage degeneration in preferred approach for tumor modeling. The raw materials

Volume 1 Issue 3 (2025) 14 doi: 10.36922/OR025280024