Effects of mixing intensity on tissue-engineered cartilage

Mechanical forces regulate the structure and function of many tissues in vi ve; recent results indicate that the mechanical environment can decisively influence the development of engineered tissues cultured in vitro. To inves tigate the effects of the hydrodynamic environment on tissue-engineered car tilage, primary bovine calf chondrocytes were seeded on fibrous polyglycoli c acid meshes and cultured in spinner flasks either statically or at one of nine different turbulent mixing intensities. In medium from unmixed flasks , CO2 accumulated and O-2, was depleted, whereas in medium from mixed flask s the concentrations of both gases approached their equilibrium values. Rel ative to constructs exposed to nonmixed conditions, constructs exposed to m ixing contained higher fractions of collagen, synthesized and released more GAG, but contained lower fractions of GAG. Across the wide range of mixing intensities investigated, the presence or absence of mixing, but not the i ntensity of the mixing, was the primary determinant of the GAG and collagen content in the constructs. The all-or-none nature of these responses may p rovide insight into the mechanism(s) by which engineered cartilage perceive s changes in its hydrodynamic environment and responds by modifying extrace llular matrix production and release. 2001 John Wiley & Sons, Inc.