Design and performance of a bioreactor system for mechanically promoted three-dimensional tissue engineering.

There is currently considerable interest in increasing the response of mesenchymal cells to physical forces, and numerous loading devices have been used to increase the formation of skeletal tissue in vivo and in vitro. We have developed a bioreactor system to apply cyclic strains on three-dimensional specimens over a range of 0-20,000 mustrain. The piezoelectric-driven mechanism allows the precise adjustment and control over load-related deformations of tissue, as shown by finite-element calculations of deformation of a collagen gel under load. We present the design of the bioreactor and its performance in specimens of tissue containing activated osteoblasts and chondrocytes. Biaxial tissue straining at 2,000 mustrain led to a substantial increase in the number of both types of cell compared with unstimulated controls. The synthesis of cell-specific extracellular matrix proteins increased when physiological loads (2,000 mustrain) were applied in the bioreactor, whereas higher deformations (20,000 mustrain) resulted in a reduction in proliferation and differentiation of cells. The mechanisms whereby mechanical stimulation leads to a defined cell reaction are not known, but the application of physiological micromovements in extracorporeal tissue chambers is a promising approach to the formation of hard tissue.