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

Abstract

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.

Effect of interface mechanical discontinuities on scaffold‐cartilage integration

“…FE models have been used to quantify the micro‐mechanical environment of chondrocytes within mechanically loaded tissue, and from the nucleus to the pericellular and extracellular matrix . By mimicking the biphasic characteristics of articular cartilage, an analysis of the fluid flow around the cell and through the matrix is possible . For the current study, the bFEM developed was used to quantify tissue mechanics across a range of loading and peripheral confinement conditions, to parallel the physical bioreactor model.…”

“…40 By mimicking the biphasic characteristics of articular cartilage, an analysis of the fluid flow around the cell and through the matrix is possible. 12 For the current study, the bFEM developed was used to quantify tissue mechanics across a range of loading and peripheral confinement conditions, to parallel the physical bioreactor model.…”

“…Bioreactor models offer the opportunity to stimulate the scaffold‐cartilage interface response with controlled loads. Computational approaches such as finite element (FE) models are capable of quantifying the stresses, strains, and fluid flow within mechanically loaded tissue and scaffolds . By applying FE models to the analysis of bioreactor studies, an opportunity to relate mechanical conditions to cell response arises.…”

Biological and Mechanical Predictors of Meniscus Function: Basic Science to Clinical Translation

“…Computational models of bioreactor systems allow for quantification through tissue stresses and strains in response to controlled loads . The more closely the model replicates the fluid flow, and anisotropy of the tissue, the more the results will help to explain the biological response of the resident cells . Models created to mimic whole joints have been used to study the effect of knee variables on joint mechanics for both intact and partially meniscectomized knees .…”

Musculoskeletal mechanobiology: A new era for MechanoMedicine

“…This special issue begins with several outstanding reviews that provide updates on the significance of mechanobiology in musculoskeletal research involving cartilage, tendon, muscle and bone, [1][2][3][4][5][6][7][8][9][10] and that span topics from the role of candidate mechanosensors and chemical mediators, 1,5,9,10 in vitro and in vivo models of tissue injury and repair, 3,4 and supporting technologies. 6,7 The majority of original articles following the review papers are related to the mechanobiology of bone and cartilage, [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23] tissues whose physical regulation have traditionally garnered intensive research focus, followed by complementary research papers in areas of growing prominence: Ligaments, intervertebral discs, and stem cells. [24][25][26][27][28] From this Special Issue in Musculoskeletal Mechanobiology, it is clear that it has become technically possible to trace the impact of mechanics from individual molecules to an entire organism.…”