We present an integrated experimental–computationalmechanobiology model of chondrogenesis. Theresponse of human articular chondrocytes to culture mediumperfusion, versus perfusion associated with cyclic pressurisation,versus non-perfused culture, was compared in a pelletculture model, and multiphysic computation was usedto quantify oxygen transport and flow dynamics in the variousculture conditions. At 2 weeks of culture, the measuredcell metabolic activity and the matrix content incollagen type II and aggrecan were greatest in the perfused+pressurised pellets. The main effects of perfusionalone, relative to static controls, were to suppress collagentype I and GAG contents, which were greatest inthe non-perfused pellets. All pellets showed a peripherallayer of proliferating cells, which was thickest in the perfusedpellets, and most pellets showed internal gradientsin cell density and matrix composition. In perfused pellets,the computed lowest oxygen concentration was 0.075mM(7.5% tension), the maximal oxygen flux was477.5 nmol/m2/s and the maximal fluid shear stress, actingon the pellet surface, was 1.8mPa (0.018 dyn/cm2). In thenon-perfused pellets, the lowest oxygen concentration was0.003mM (0.3% tension) and the maximal oxygen flux was102.4nmol/m2/s.Alocal correlationwas observed, betweenthe gradients in pellet properties obtained from histology,and the oxygen fields calculated with multiphysic simulation.Our results showup-regulation of hyalinematrix proteinproduction by human chondrocytes in response to perfusionassociated with cyclic pressurisation. These results could befavourably exploited in tissue engineering applications.
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