Overcoming the Dependence on Animal Models for Osteoarthritis Therapeutics – The Promises and Prospects of In Vitro Models

Abstract Osteoarthritis (OA) is a musculoskeletal disease characterized by progressive degeneration of osteochondral tissues. Current treatment is restricted to the reduction of pain and loss of function of the joint. To better comprehend the OA pathophysiological conditions, several models are employed, however; there is no consensus on a suitable model. In this review, different in vitro models being developed for possible therapeutic intervention of OA are outlined. Herein, various in vitro OA models starting from 2D model, co‐culture model, 3D models, dynamic culture model to advanced technologies‐based models such as 3D bioprinting, bioassembly, organoids, and organ‐on‐chip‐based models are discussed with their advantages and disadvantages. Besides, different growth factors, cytokines, and chemicals being utilized for induction of OA condition are reviewed in detail. Furthermore, there is focus on scrutinizing different molecular and possible therapeutic targets for better understanding the mechanisms and OA therapeutics. Finally, the underlying challenges associated with in vitro models are discussed followed by future prospective. Taken together, a comprehensive overview of in vitro OA models, factors to induce OA‐like conditions, and intricate molecular targets with the potential to develop personalized osteoarthritis therapeutics in the future with clinical translation is provided.