Multiscale Strain Transfer in Cartilage.

The transfer of stress and strain signals between the extracellular matrix (ECM) and cells is crucial for biochemical and biomechanical cues that are required for tissue morphogenesis, differentiation, growth, and homeostasis. In cartilage tissue, the heterogeneity in spatial variation of ECM molecules leads to a depth-dependent non-uniform strain transfer and alters the magnitude of forces sensed by cells in articular and fibrocartilage, influencing chondrocyte metabolism and biochemical response. It is not fully established how these nonuniform forces ultimately influence cartilage health, maintenance, and integrity. To comprehend tissue remodelling in health and disease, it is fundamental to investigate how these forces, the ECM, and cells interrelate. However, not much is known about the relationship between applied mechanical stimulus and resulting spatial variations in magnitude and sense of mechanical stimuli within the chondrocyte's microenvironment. Investigating multiscale strain transfer and hierarchical structure-function relationships in cartilage is key to unravelling how cells receive signals and how they are transformed into biosynthetic responses. Therefore, this article first reviews different cartilage types and chondrocyte mechanosensing. Following this, multiscale strain transfer through cartilage tissue and the involvement of individual ECM components are discussed. Finally, insights to further understand multiscale strain transfer in cartilage are outlined.