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therapeutic strategies. However, despite its advantages biological environments. Our team is also committed to
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in simulating the cartilage environment, this technology developing novel hydrogels, such as DNA-GelMA. This
has limitations, particularly the lack of mechanical load composite material not only improves the spatial structure
and joint-specific factors, which significantly influence of the scaffold but also enhances its biological functionality,
chondrocyte behavior. In vivo, cartilage is subjected to both potentially making the organ-on-a-chip model more
compressive and shear stresses, but current chip models physiologically relevant. In the future, by simulating
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typically simulate only shear stress, limiting the replication realistic biological environments, we can evaluate the
of biomechanical stimuli and affecting the accuracy of performance and biocompatibility of new hydrogels. The
cellular behavior and pathological processes. 34,35 Moreover, cartilage chip we designed could function as a platform for
in vivo, cartilage interacts closely with subchondral bone, screening new materials, thereby driving the advancement
synovium, and synovial fluid. Chondrocytes interact with and application of scaffold materials in tissue engineering
matrix proteins, immune cells, and other cell types, and and regenerative medicine.
they are regulated by cytokines and hormones. 36,37 Existing The scalability of microfluidic systems for high-
microfluidic cartilage models are often simplified and fail to throughput drug screening is a crucial research focus,
fully replicate these interactions, reducing their biological particularly with respect to enhancing experimental
relevance and accuracy when studying joint diseases such efficiency, accuracy, and the ability to accommodate diverse
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as OA. Future research should address these gaps by experimental conditions. Microfluidic technology allows
more accurately simulating the joint environment, thereby precise control of fluid flow in small volumes and enables
enhancing the potential applications of cartilage models parallel processing of multiple experiments through
in disease research, drug screening, and regenerative microchannel designs, which makes microfluidic chips
medicine. highly promising for high-throughput screening. Current

In organ-on-a-chip technology, scaffold materials are experiments are based on single-chip systems, but in future
essential for mimicking the functions of in vivo tissues and expansions for high-throughput drug screening, we are
organs, providing physical support for cell growth, and considering the integration of parallel chip processing
simulating the physiological and biomechanical properties and automation systems. For example, some microfluidic
of tissues. Scaffold materials are generally classified into systems integrate arrays of microchips, allowing hundreds
three categories: natural hydrogels, synthetic hydrogels, of experiments to be conducted simultaneously in a single
and composite materials, each of which offers distinct device. Through custom-designed integrated circuits,
advantages due to differences in their origin, physical such as multi-channel or array chips, the system can even
properties, and applications. Natural hydrogels, such as be scaled to the thousands, enabling a broader range
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GelMA, hyaluronic acid (HA), and alginate, are widely used of drug screening. However, scaling up the system for
due to their excellent biocompatibility and biodegradability. broader applications presents several challenges. First,
For example, HA, owing to its natural origin and good the complexity of chip integration increases, especially
biocompatibility, is frequently used to simulate cartilage in coordinating the operation of multiple chips and
and synovial fluid environments. However, its mechanical controlling reaction conditions. Second, system costs must
properties are relatively soft, which may not be sufficient be controlled, particularly in large-scale screenings, where
to support high-strength cellular growth. In contrast, reducing manufacturing costs while ensuring accuracy is a
GelMA offers higher mechanical stability, making it key issue. In addition, balancing throughput and accuracy,
suitable for simulating tissues such as cartilage while adapting to diverse screening needs, and enhancing data
maintaining biocompatibility comparable to HA. processing and analysis capabilities are all critical aspects
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Synthetic hydrogels, such as polyethylene glycol (PEG) that must be addressed during system expansion. Finally, the
and polyacrylamide (PAAm), allow for precise control over stability and long-term reliability of the chips are essential
their physicochemical properties (e.g., mechanical strength for the sustained operation of the system. In summary, the
and degradation rate). However, these materials generally scalability of microfluidic systems for drug screening relies
lack the biocompatibility of natural proteins, and thus, on technical innovations in chip integration, cost control,
chemical modifications are often required to enhance cell accuracy, adaptability to screening requirements, data
adhesion and growth. GelMA, in particular, effectively processing, and stability. 42,43 Addressing these challenges
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replicates the structure of the native ECM, making it widely will advance the widespread application of microfluidic
applicable in tissue models such as cartilage and bone. For technology in drug screening.
these reasons, GelMA is considered an ideal material choice Drug screening is one of the key functions of organ-on-
for organ-on-a-chip technology. Composite hydrogels, chip technology. To validate the drug screening capability
which combine natural and synthetic materials, aim to of the designed cartilage chip, this study evaluated three
leverage the advantages of both, allowing for more complex different types of therapeutic approaches: DS, HC-030031,

Volume 1 Issue 1 (2025) 16 doi: 10.36922/or.8461