Functional Synovium-Based 3D Models in the Context of Human Disease and Inflammation

The synovium plays a crucial role in joint function and is a primary site of pathology in inflammatory joint diseases, such as rheumatoid arthritis (RA). Immune-mediated inflammatory diseases (IMIDs), including RA, are becoming increasingly prevalent worldwide. However, the development of effective treatments remains hindered by the limitations of preclinical modeling techniques. Traditional methods, such as 2D in vitro monolayer cultures and animal models, often fail to replicate the complexity of human tissues. To address these challenges, tissue engineering (TE) and biofabrication strategies have emerged as promising alternatives. These approaches enable the creation of 3D in vitro models that better mimic physiological conditions. Techniques like 3D bioprinting allow researchers to replicate cellular interactions and the extracellular matrix, improving the accuracy of disease models. The application of 3D models in therapy development, drug screening, and personalized medicine has grown significantly. These platforms offer valuable insights into IMID pathophysiology by simulating relevant microenvironments. This review examines current synovium models used in IMID research and explores future directions in TE and 3D biofabrication. Additionally, the impact of inflammation on tissues and discuss the clinical potential of 3D disease models to address current disregarded aspects of coexistent diseases is highlighted.