Microengineering the Synovial Membrane Microenvironment in Rheumatoid Arthritis Research

Rheumatoid arthritis (RA) is a slow-progressive inflammatory autoimmune disorder characterized by synovial inflammation, hyperplasia, and joint degradation, leading to joint destruction and poor patients’ quality of life. Numerous in vitro RA models have been developed to elucidate disease mechanisms and identify therapeutic targets; however, most fail to fully recapitulate the in vivo synovial microenvironment, including the cellular heterogeneity, biomechanical stress, and dynamic cell-matrix interactions, limiting their translational relevance. This translational gap underscores the need for advanced 3D microengineered platforms that integrate patient-specific cells, biomechanical elements, and real-time biosensing to bridge in vitro findings to clinical outcomes. Recent progress in microengineering has enabled the development of systems that closely mimic the physiological and pathological conditions of the RA synovial membrane in vitro. This review highlights recent progress in microengineered synovial models and their applications in elucidating RA pathogenesis and seeking therapeutic interventions. We also introduce persisting technical and biological challenges, and emerging trajectories for innovation within this rapidly advancing discipline.