Organ-on-chip bridging musculoskeletal disease modeling and precision therapeutic discovery

Musculoskeletal (MSK) disorders remain a leading cause of disability, yet effective disease-modifying therapies are limited by poor translational relevance of conventional models. Organ-on-chip (OoC) technologies have emerged as promising platforms for disease modeling and therapeutic discovery. This review highlights recent advances in patient-derived and induced pluripotent stem cell-based OoC systems, multicellular tissue engineering, biomechanical and immune integration, real-time sensing, and data-driven analytics that enhance physiological relevance and predictive capability. We further discuss automated high-throughput screening and machine learning approaches for scalable drug testing and personalized therapeutic prediction. Finally, we address challenges including reproducibility, vascularization, and standardization, and outline a future roadmap toward precision medicine through intelligent OoC platforms and patient-specific digital twins.