In-Vitro Models for Osteoarthritis Drug Development: Past, Present, and Future Directions

Abstract

Abstract

Osteoarthritis (OA) poses a global health challenge, impacting millions of patients with debilitating symptoms. Despite available symptom-alleviating treatments, a lack of long-term treatments persists. No Disease-Modifying OA Drugs (DMOADs) have demonstrated efficacy in OA patients, partly due to an incomplete understanding of OA pathogenesis and heterogeneity, hindering the identification of a universal therapeutic target. This review emphasizes the need for predictive preclinical in vitro models to expedite pharmaceutical agent development and enhance drug response prediction in humans. This review outlines recent advancements in in vitro models for OA modeling and drug development, encompassing 2D and 3D cell cultures, explant models, scaffold-free and scaffold-based models, and microphysiological systems, including tissue- and organ-on-a-chip and joint-systems. Emphasis is placed on modelsfeaturing multi-joint tissue cultures facilitating crosstalk, mimicking OA inflammation, applying mechanical stimulation, and incorporating immune cells.

Microphysiological systems, such as Organ-on-a-Chip (OoC) and Joint-on-a-Chip (JoC), emerge as promising tools for drug development, accurately recapitulating organ-level physiology and pathophysiology. This enhances predictive accuracy for drug safety and efficacy and positions them as potential platforms for personalized medicine. This article concludes by outlining challenges and opportunities for future advancements in in vitro disease modeling. It contributes to the ongoing dialogue on improving preclinical models for a more effective and targeted approach to OA drug development.