We present an integrated experimental–computational
mechanobiology model of chondrogenesis. The
response of human articular chondrocytes to culture medium
perfusion, versus perfusion associated with cyclic pressurisation,
versus non-perfused culture, was compared in a pellet
culture model, and multiphysic computation was used
to quantify oxygen transport and flow dynamics in the various
culture conditions. At 2 weeks of culture, the measured
cell metabolic activity and the matrix content in
collagen type II and aggrecan were greatest in the perfused+
pressurised pellets. The main effects of perfusion
alone, relative to static controls, were to suppress collagen
type I and GAG contents, which were greatest in
the non-perfused pellets. All pellets showed a peripheral
layer of proliferating cells, which was thickest in the perfused
pellets, and most pellets showed internal gradients
in cell density and matrix composition. In perfused pellets,
the computed lowest oxygen concentration was 0.075mM
(7.5% tension), the maximal oxygen flux was
477.5 nmol/m2/s and the maximal fluid shear stress, acting
on the pellet surface, was 1.8mPa (0.018 dyn/cm2). In the
non-perfused pellets, the lowest oxygen concentration was
0.003mM (0.3% tension) and the maximal oxygen flux was
102.4nmol/m2/s.Alocal correlationwas observed, between
the gradients in pellet properties obtained from histology,
and the oxygen fields calculated with multiphysic simulation.
Our results showup-regulation of hyalinematrix protein
production by human chondrocytes in response to perfusion
associated with cyclic pressurisation. These results could be
favourably exploited in tissue engineering applications