Understanding the Influence of Local Physical Stimuli on Chondrocyte Behavior

Investigating the mechanobiology of chondrocytes is challenging due to the complex micromechanical environment of cartilage tissue. The innate zonal differences and poroelastic properties of the tissue combined with its heterogeneous composition create spatial- and temporal-dependent cell behavior, which further complicates the investigation. Despite the numerous challenges, understanding the mechanobiology of chondrocytes is crucial for developing strategies for treating cartilage related diseases as chondrocytes are the only cell type within the tissue. The effort to understand chondrocyte behavior under various mechanical stimuli has been ongoing over the last 50 years. Early studies examined global biosynthetic behavior under unidirectional mechanical stimulus. With the technological development in high-speed confocal imaging techniques, recent studies have focused on investigating real-time individual and collective cell responses to multiple / combined modes of mechanical stimuli. Such efforts have led to tremendous advances in understanding the influence of local physical stimuli on chondrocyte behavior. In addition, we highlight the wide variety of experimental techniques, spanning from static to impact loading, and analysis techniques, from biochemical assays to machine learning, that have been utilized to study chondrocyte behavior. Finally, we review the progression of hypotheses about chondrocyte mechanobiology and provide a perspective on the future outlook of chondrocyte mechanobiology.