Mechanical Drivers of Glycosaminoglycan Content Changes in Intact and Damaged Human Cartilage

Abstract

Articular cartilage undergoes significant degeneration during osteoarthritis, currently lacking effective treatments. This study explores mechanical influences on cartilage health using a novel finite element-based mechanoregulatory model, predicting combined degenerative and regenerative responses to mechanical loading. Calibrated and validated through one-week longitudinal ex vivo experiments on intact and damaged cartilage samples, the model underscores the roles of maximum shear strain, fluid velocity, and dissipated energy in driving changes in cartilage glycosaminoglycan (GAG) content. It delineates the distinct regenerative contributions of fluid velocity and dissipated energy, alongside the degenerative contribution of maximum shear strain, to GAG adaptation in both intact and damaged cartilage under physiological mechanical loading. Remarkably, the model predicts increased GAG production even in damaged cartilage, consistent with our in vitro experimental findings. Beyond advancing our understanding of mechanical loadings role in cartilage homeostasis, our model aligns with contemporary ambitions by exploring the potential of in silico trials to optimize mechanical loading in degenerative joint disease, fostering personalized rehabilitation.