Engineering human synovial organoids as predictive ecosystems for disease modeling and therapeutic response in...

The synovium is a critical site for the initiation and persistence of inflammatory joint diseases, including rheumatoid arthritis (RA), osteoarthritis (OA), and gout. Conventional 2D cultures and animal models fail to recapitulate the multicellular organization, mechanical regulation, and inter-tissue communication that shape human joint pathology. Synovial organoids and related microphysiological systems address these gaps by reconstructing stromal, macrophage, vascular, and immune components within controllable human 3D environments. Here, we review advances in synovial organoid engineering, focusing on multicellular integration, mechanically active modeling, and modular coupling with joint tissues. We discuss how these systems reveal disease-relevant stromal-immune-vascular circuits, mechanobiological regulation, and synovium-tissue crosstalk across RA, OA, and gout. We further highlight their translational value for therapeutic testing and target prioritization, while outlining challenges in durable vascularization, complete immune organization, multiaxial mechanical control, and functional benchmarking. Together, these advances are transforming synovial models into tractable joint microecosystems for mechanistic and translational rheumatology.