Influence of the pericellular and extracellular matrix structural properties on chondrocyte mechanics.

Understanding the mechanical factors that drive the biological responses of chondrocytes is central to our interpretation of the cascade of events that lead to osteoarthritic changes in articular cartilage. Chondrocyte mechanics is complicated by changes in tissue properties that can occur as osteoarthritis (OA) progresses and by the interaction between macro-scale, tissue level, properties, and micro-scale pericellular matrix (PCM) and local extracellular matrix (ECM) properties, both of which cannot be easily studied using in vitro systems. Our objective was to study the influence of macro- and micro-scale OA-associated structural changes on chondrocyte strains. We developed a multi-scale finite element model of articular cartilage subjected to unconfined loading, for the following three conditions: (i) normal articular cartilage, (ii) OA cartilage (where macro and micro-scale changes in collagen content, matrix modulus, and permeability were modeled), and (iii) early-stage OA cartilage (where only micro-scale changes in matrix modulus were modeled). In the macro-scale model, we found that a depth-dependent strain field was induced in both healthy and OA cartilage and that the middle and superficial zones of OA cartilage had increased tensile and compressive strains. At the micro-scale, chondrocyte shear strains were sensitive to PCM and local ECM properties. In the early-OA model, micro-scale spatial softening of PCM and ECM resulted in a substantial increase (30%) of chondrocyte shear strain, even with no structural changes in macro-scale tissue properties. Our study provides evidence that micromechanical changes at the cellular level may affect chondrocyte activities before macro-scale degradations at the tissue level become apparent. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:721-729, 2018.