Journal Article

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

Florea, Cristina, Orozco, Gustavo A., Julkunen, Petro, Eskelinen, Atte S. A., Tanska, Petri, Korhonen, Rami K., Grodzinsky, Alan J.

2020

Overview

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 (p<0.01). Combined biochemical and biomechanical degradation is found near the free surfaces and especially near the lesion, and the corresponding bulk FCD loss agrees with experiments. We suggest that the presence of lesions plays a role in cytokine diffusion-driven degradation, and also predisposes cartilage for further biomechanical degradation. Models considering both these cartilage degradation pathways concomitantly are promising in silico tools for predicting disease progression, recognizing lesions at high risk, simulating treatments, and ultimately optimizing treatments to postpone the development of PTOA.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Animals / Applied physics / Arthritis / Biodegradation / Bioengineering / Biology and Life Sciences / Biomechanics / Biomedical materials / Biophysics / Cartilage / Cartilage - injuries / Cartilage - metabolism / Cartilage diseases / Charge density / Collagen / Complications and side effects / Computer applications / Computer engineering / Computer science / Computer simulation / Cytokines / Cytokines - metabolism / Degradation / Depletion / Electrical engineering / Experiments / Finite element method / Free surfaces / Funding / Gene expression / Homeostasis / Humans / Inflammation / Inflammation Mediators - metabolism / Injuries / Interleukin / Interleukin 1 / Interleukins / Lesions / Mathematical models / Mechanical engineering / Mechanical properties / Medicine and Health Sciences / Observations / Osteoarthritis / Physical Sciences / Physiological aspects / Proteoglycans / Quality of life / Research and Analysis Methods / Shear strain / Software / Stress, Mechanical / Supervision / Tissues