Tailoring human joint-on-a-chip: from biological principles, materials, to disease modeling

Joint-on-a-chip (JoC) is a miniaturized <i>in vitro</i> model based on microfluidics and tissue engineering, aiming to provide revelational platform to study joint physiology and pathology for personalized medicine. Engineering biomimetic JoC necessitates recreating the physiological architecture and biomechanical environment, while incorporating systemic risk factors involved in pathogenesis. In this review, we aim to provide an overview manual to bridge the gap between engineers, biologists, and clinicians. We start with joint biology to the basic characteristics of JoC and summarize the important designing factors. We categorize materials used in chip fabrication and highlight how recent advances in material science, integrated with established microfabrication techniques have enabled the development of advanced chips. Existing joint-on-a-chip platforms enable targeted investigation and high-fidelity modeling of disease-specific analysis through deliberately simplified, reductionist tissue interaction systems. We anticipate that the future development of joint-on-a-chip models will hinge on addressing cell co-culture, automated control, and real-time monitoring. Successfully tackling these challenges will greatly accelerate the application of JoC in foundational research, drug discovery, and personalized medicine.