Mechanobiological model for simulation of injured cartilage degradation via pro-inflammatory cytokines and mechanical stimulus

Abstract

Post-traumatic osteoarthritis (PTOA) is associated with cartilage degradation, ultimately leading to disability and decrease of quality of life. Two key mechanisms have been suggested to occur in PTOA: tissue inflammation and abnormal biomechanical loading. Both mechanisms have been suggested to result in loss of cartilage proteoglycans, the source of tissue fixed charge density (FCD). In order to predict the simultaneous effect of these degrading mechanisms on FCD content, a computational model has been developed. We simulated spatial and temporal changes of FCD content in injured cartilage using a novel finite element model that incorporates (1) diffusion of the pro-inflammatory cytokine interleukin-1 into tissue, and (2) the effect of excessive levels of shear strain near chondral defects during physiologically relevant loading. Cytokine-induced biochemical cartilage explant degradation occurs near the sides, top, and lesion, consistent with the literature. In turn, biomechanically-driven FCD loss is predicted near the lesion, in accordance with experimental findings: regions near lesions showed significantly more FCD depletion compared to regions away from lesions (pin silico tools for predicting disease progression, recognizing lesions at high risk, simulating treatments, and ultimately optimizing treatments to postpone the development of PTOA. Post-traumatic osteoarthritis is a musculoskeletal disorder where inflammatory processes and abnormal joint loading predispose articular cartilage to degradation after a mechanical injury. Since inflamed and injured cartilage cannot be reversed back to healthy state, prevention of osteoarthritis progression is advisable, a prestigious goal where computational models could serve as tools. The current literature is short of computational models combining both biochemical and biomechanical aspects of osteoarthritis. Thus, here we implemented inflammation of living cartilage tissue followed by biochemical perturbations of tissue homeostasis and shear strain-induced biomechanical degradation in novel cell-to-tissue-level finite element models. The models presented in this paper and enriched by our experimental findings/previous literature provide profound new mechanobiological insights and predictions about cartilage degradation in injured and inflamed tissue under physiologically relevant mechanical loading. We suggest that mechanobiological computational models could be applied as in silico analysis tools that provide clinicians information of the personalized progression of post-traumatic osteoarthritis and decision-making guidance for treatment of the disease.