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is relatively scarce, the underlying mechanism studies and chip. This model aims to serve as a drug screening model
LGG’s modulation of inflammatory responses provide a for OA, which promotes the progress of drug treatment.
theoretical basis for its application in treating OA. 34,35 For Traditional in vivo animal models (such as mouse, rat,
instance, Cho et al. demonstrated that oral administration and rabbit OA models) have played a crucial role in OA
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of LGG not only improves intestinal damage and research by simulating the overall disease progression
inflammation but also reduces the severity of pain and and systemic responses. However, these models have
cartilage destruction in an OA rat model. Moreover, recent several limitations, including interspecies physiological
research indicates that LGG-EVs can serve as carriers of differences, long experimental durations, high costs,
bioactive molecules, directly participating in the regulation and ethical concerns. In contrast, cartilage-on-a-chip
of intraarticular inflammation and promoting cartilage models offer higher physiological relevance, throughput,
cell repair. This emerging therapeutic strategy offers new and reproducibility while reducing the need for animal
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possibilities for non-pharmaceutical treatments of OA. experiments. However, current cartilage-on-a-chip models
Given the proven effectiveness of oral LGG, the potential remain relatively simple, particularly lacking in the ability
of LGG-EVs represents a novel and promising strategy for to simulate systemic inflammatory responses and multi-
treating OA. Therefore, we used OA-like cartilage-on-chip organ interactions. Future studies could combine cartilage
to verify whether LGG-EVs can effectively treat OA. chips with other organ-on-a-chip models, such as synovial
Through the validation of the drug screening capability or bone chips, to develop more intricate multi-organ
of the cartilage-on-chip, we selected the potential biological system models. This approach would offer a more holistic
medicine, LGG-EVs, to treat the inflammation model and simulation of the systemic impacts of OA, including
verify its potential therapeutic effects on OA. To mimic inflammatory responses, drug metabolism, and immune
the primary intraarticular drug administration in clinical reactions. This integration would not only improve the
trials, it was incorporated into the growth medium for biological accuracy of disease models but also allow for
perfusion (Figure 6A). The characterization of LGG- a deeper understanding of how multi-organ interactions
EVs indicates that they have a typical saucer-like shape influence the onset and progression of OA, providing a
(Figure 6B and C). DLS analysis indicates that their average reliable platform for evaluating combination therapies. At
particle size is 178 ± 3 nm, with a particle size range of the same time, organ-on-a-chip models hold significant
30–200 nm, observed from the TEM results. Histological potential in personalized medicine, especially in studies
staining results indicated that LGG-EVs could significantly targeting patient-specific OA phenotypes. OA manifests
improve the inflammatory response, which was validated differently across individuals, with variations in cartilage
by the Western blot results (Figure 6D and E). We then degradation mechanisms and inflammatory responses.
measured the gene expression levels of selected biomarkers By adjusting environmental conditions and pathogenesis,
related to joint health and degeneration, finding that LGG- specific OA organ-on-a-chip models can be rapidly
EVs led to a statistically significant upregulation of cartilage constructed for drug screening, enabling precise prediction
formation genes (including COL II and SOX9). Moreover, of treatment outcomes, optimizing drug selection and
the gene expression levels of degenerative markers MMP13 dosing, and promoting the application of personalized
and Adamts5 were notably reduced (Figure 6F). medicine in OA therapy. In summary, organ-on-a-chip
These results collectively indicate that LGG-EVs have models offer immense potential in OA drug prediction,
a certain therapeutic effect on OA. However, to establish combination therapy evaluation, and personalized
LGG-EVs as a viable clinical drug, further studies are medicine, providing new directions for the development of
warranted. future therapeutic strategies.
Organ-on-a-chip technology represents a significant
4. Discussion innovation in biological modeling and has demonstrated
OA is a common degenerative joint disease that affects substantial promise in cartilage research. For instance, Paggi
millions of people worldwide. Although various et al. verified that appropriate stimulation in a cartilage-
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pharmacological and non-pharmacological therapies are on-chip can emulate the chondrocyte microenvironment
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available to alleviate symptoms, most treatments provide in vitro. Similarly, Lin et al. designed a biphasic
only temporary relief and have minimal effect on disease organ-on-a-chip that exhibited an OA-like phenotype after
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progression. Therefore, there is an urgent need to develop treatment with IL-1β. This model not only demonstrated
pharmaceuticals capable of altering the progression of active physiological crosstalk between bone and cartilage
diseases. However, existing models fail to accurately but also served as a potential drug screening platform. In
predict the outcomes of clinical trials. Consequently, we our study, we utilized GelMA hydrogel for the 3D culture of
have designed and developed a micro-joint model based primary chondrocytes, coupled with a microfluidic system,
on organ-on-a-chip technology, termed cartilage-on- to develop a specialized cartilage chip and further introduced

Volume 1 Issue 1 (2025) 14 doi: 10.36922/or.8461