Time-dependent computational model of post-traumatic osteoarthritis to estimate how mechanoinflammatory mechanisms impact cartilage aggrecan content

Degenerative musculoskeletal diseases like osteoarthritis can be initiated by joint injury. Injurious overloading-induced mechanical straining of articular cartilage and subsequent biological responses may trigger cartilage degradation. One early sign of degradation is loss of aggrecan content which is potentially accelerated near chondral lesions under physiological loading. Yet, the mechanoinflammatory mechanisms explaining time-dependent degradation in regions with disparate mechanical loading are unclear and challenging to assess with experiments alone. Here, we developed computational models unraveling potential mechanisms behind aggrecan content adaptation. Incorporating mechanical strain-driven cell damage and downstream proteolytic enzyme release, fluid flow-driven aggrecan depletion, and fluid pressure-stimulated regulation of aggrecan biosynthesis, the models agreed with experiments and exhibited 14%-points greater near-lesion aggrecan loss after 12 days of physiological loading compared to without loading. This significant advancement in mechanistic understanding incorporated into cartilage adaptation model can help in development and guidance of personalized therapies, such as rehabilitation protocols and tissue- engineered constructs.