Organ-on-Chip: Revolutionizing Osteoarthritis Research and Beyond

Developmental Bioengineering group - University of Twente
Carolina Serrano Larrea

Have you ever felt the familiar ache in your knees, the stiffness that makes every movement a chore? If so, you're not alone. Osteoarthritis (OA), a degenerative joint disease that affects millions of people worldwide, is a silent menace that can steal away our mobility and quality of life. Conventional animal models have long been the mainstay of OA research, but their limitations have hampered our understanding of this complex disease. However, a groundbreaking technology known as "Organ-on-Chip" is now emerging as a game-changer in the realm of OA research. These tiny laboratories, often the size of a microchip, offer a more realistic and humanized model for studying OA, paving the way for breakthroughs in research and treatment.

What is Organ-on-Chip?
Imagine miniaturized devices that accurately replicate the intricate structures and functions of human organs. That's the essence of Organ-on-Chip, miniature platforms that harness the power of microfluidics to create highly controlled and customizable microenvironments. These tiny laboratories, often the size of a microchip, mimic the complex interactions between different cell types and their surrounding environment, providing a more realistic and physiologically relevant model for studying diseases.  In the context of OA, this means designing a chip that mimics the intricate microenvironment of joints. These chips incorporate living cells and provide a dynamic platform for studying disease progression, drug responses, and potential treatments with unparalleled precision. [1-4]

Organ-on-Chips are a promising solution to finally end animal testing
Conventional animal models, while historically integral to OA research, suffer from inherent limitations due to disparities in physiology and anatomy between humans and animals. Organ-on-Chip addresses this gap by employing human cells and tissues, providing a more accurate and direct model for studying OA pathophysiology and assessing potential therapies. Beyond scientific benefits, Organ-on-Chip technology responds to escalating ethical concerns related to animal research, offering a more precise and efficient means of studying diseases, thereby reducing reliance on controversial animal experimentation. Additionally, Organ-on-Chip technology enhances drug discovery, enabling realistic screening of therapeutic compounds and expediting the translation of research into clinical applications while minimizing ethical concerns associated with animal testing. [1-4]

Relevance of Organ-on-Chips to study Osteoarthritis
Unlike traditional cell culture models,  the real magic of Organ-on-Chip lies in their exceptional ability to be customized to simulate the physiological conditions of joints. Researchers can precisely control the physical and biochemical factors that influence cell behavior, mimicking the specific aspects of OA, such as cartilage degeneration, joint inflammation, or the effects of mechanical loading. This level of control is unparalleled in conventional animal models, enabling researchers to probe the underlying mechanisms of OA with unprecedented precision. The miniaturized nature of Organ-on-Chip makes them highly scalable, allowing for the generation of large numbers of tissues simultaneously. This opens up the exciting possibility of high-throughput drug screening, where a multitude of potential therapeutics can be evaluated in parallel, accelerating the discovery of novel therapies for OA and other diseases. [1-4]

The potential applications of Organ-on-Chip in OA research are vast. 

Researchers are already using these miniature platforms to [1-4]:
• Identify the molecular mechanisms of cartilage degeneration .
• Evaluate the effects of different therapeutic agents, including cell therapy, gene editing, and drug delivery systems.
• Understand the role of the immune system in OA development and progression.
• Investigate the impact of lifestyle factors such as obesity, nutrition, and exercise on OA risk.

Future Prospects: A Paradigm Shift in Biomedical Research
Figure 2: Schematic of a knee joint-on-chip platform [4]

The potential impact of Organ-on-Chip technology extends beyond the laboratory. With more precise models, researchers can unravel the underlying mechanisms of OA, paving the way for targeted therapies and personalized medicine. Patients may benefit from treatments tailored to their specific genetic makeup and disease characteristics, ushering in a new era of more effective and individualized healthcare.
Collaborations between engineers, biologists, and clinicians are crucial in advancing Organ-on-Chip technology for OA research. By combining expertise from various fields, scientists can enhance the fidelity of these microdevices, ensuring that they accurately replicate the complexity of joint tissues and the interplay between different cell types. Such interdisciplinary collaborations are pivotal in overcoming the challenges inherent in modeling a multifaceted disease like OA.

Conclusion
In conclusion, Organ-on-Chip technology represents a groundbreaking approach to OA research, offering a realistic and dynamic platform for studying disease mechanisms and developing targeted therapies. As advancements in this field continue, the potential for transformative breakthroughs in understanding and treating OA is vast. By combining cutting-edge technology with collaborative efforts across disciplines, we stand at the forefront of a new era in musculoskeletal research that holds immense promise for improving the lives of those affected by OA.

Call to Action
The field of Organ-on-Chip is rapidly advancing, and the opportunities for scientific discovery are vast. I encourage researchers, clinicians, and the general public to stay informed about this exciting technology and its potential to revolutionize our understanding of disease and usher in a new era of personalized medicine. Together, we can harness the power of Organ-on-Chip to improve human health and well-being.
To learn more about our research I invite you to visit the Developmental Bioengineering Group website and to check out our latest publications about Organ-on-Chip and Osteoarthritis research.

References:
[1] Alberto Paggi, C.; Hendriks, J.; Karperien, M.; Gac, S.L. Emulating the Chondrocyte Microenvironment Using Multi-Directional Mechanical Stimulation in a Cartilage-on-Chip. Lab Chip 2022, 22, 1815–1828.
[2] Paggi, C.A., Teixeira, L.M., Le Gac, S. et al. Joint-on-chip platforms: entering a new era of in vitro models for arthritis. Nat Rev Rheumatol 18, 217–231 (2022).
[3] L. Banh, K.K. Cheung, M.W.Y. Chan, E.W.K. Young, S. Viswanathan. Advances in organ-on-a-chip systems for modelling joint tissue and osteoarthritic diseases. Osteoarthritis Cartilage, 30 (2022), pp. 1050-1061
[4] Piluso S, Li Y, Abinzano F, Levato R, Moreira Teixeira L, Karperien M, Leijten J, van Weeren R, Malda J. Mimicking the Articular Joint with In Vitro Models. Trends Biotechnol. 2019 Oct;37(10):1063-1077.