Joint-on-a-Chip: The Future of Preclinical Modelling of Joint Diseases.

Joint diseases, including osteoarthritis (OA) and rheumatoid arthritis (RA), are leading causes of disability worldwide and pose a major socioeconomic burden. Effective treatments remain limited, partly due to difficulties in understanding and replicating complex joint structures as well as the dynamic interactions among multiple tissues and immune components. Traditional in vitro and animal models are restricted in their ability to accurately simulate the human joint microenvironment, limiting their predictive value for drug discovery and therapeutic development. Joint-on-a-Chip (JOC) is emerging as a powerful platform for studying joint diseases, providing a physiologically relevant microenvironment on a microfluidic chip that integrates key joint tissues, such as cartilage, subchondral bone, synovium, and adipose tissue, along with mechanical and biochemical cues. This review provides a comprehensive analysis of current JOC models, highlighting their key features, advantages, and limitations. We discuss advances in model features, chip manufacturing, and microenvironment regulation, including mechanical and biological stimulation that improve JOC fabrication and functionality. We also critically analyse the challenges of JOC designs, including the ability to faithfully mimic joint dynamics, immune interactions, and long-term tissue viability. Finally, we outline future directions for enhancing JOC platforms to advance drug discovery, personalised medicine, and regenerative therapies for joint diseases.