Next-generation osteoarthritis models: integrating biological, computational, and engineering approaches

Osteoarthritis (OA) is a complex degenerative joint disease with substantial global health implications, yet effective disease-modifying treatments remain elusive. This review explores next-generation models revolutionizing OA research, including microfluidic organ-on-a-chip (OOAC) platforms, organoid systems, computational modelling, finite element analysis (FEA), and artificial intelligence (AI). OOAC systems replicate joint microenvironments, integrating biomechanical stimulation and dynamic tissue interactions, thereby enabling precise investigations of inflammatory and degenerative processes. While organoid technologies capture cellular heterogeneity and self-organization, they primarily serve as static, multicellular models rather than dynamic biomechanical systems. FEA provides high-resolution, patient-specific simulations of joint mechanics and cartilage degeneration, offering insights into mechanical stress distribution and OA progression. Computational modelling and AI enhance predictive capabilities, facilitating precision medicine approaches and optimizing treatment strategies. Despite significant advancements, critical challenges remain, particularly regarding biological fidelity, cross-model integration, and clinical translation. Ensuring computer-based model validation against curated, high-quality datasets-including patient-derived biomechanical, imaging, and molecular data-is imperative for increasing accuracy and translatability. By improving early diagnosis, treatment personalization, and cost-effective therapeutic screening, these advanced technologies can inform healthcare policies, optimize resource allocation, and shape evidence-based guidelines for OA management. This review underscores the necessity of interdisciplinary collaboration to refine these advanced platforms, bridge the gap between preclinical and clinical research, and accelerate the development of patient-specific OA interventions while informing adequate healthcare policies.