Achievement of viable engineered tissues through in-vitro cultivation in bioreactor systems requires a thorough understanding of the complex interplay between mechanical forces and biochemical cues. Briefly, bioreactors have been employed to impart mechanical stimuli to support tissue growth and development. Continuous fluid-induced shear stress, for example, has been shown to influence morphology and properties of engineered cartilage.1 Fluid flow enhances mass transfer mechanisms and simultaneously provides mechanical stimuli across or through the construct to emulate shear forces that occur in the knee or other joints. Critical biochemical factors, such as growth factors, are secreted by cells2,3 and involved in cell-to-cell signaling. Guided by these molecules, cells can communicate with each other and work synergistically to accomplish a specific task. It has also been demonstrated that the pathways of certain growth factors, such as transforming growth factor-β (TGF-β) family and insulin-like growth factor-1 (IGF-1), are responsive to shear stress, resulting in enhanced cell and tissue activities, and their expression is also up-regulated by fluid-induced shear stress.4,5 This evidence suggests their involvement in mechanotransduction mechanisms. However, a combination of mechanical and biochemical stimuli results in a complex culture environment which is not yet fully characterized. The present study was designed to obtain an understanding of the combined effects of hydrodynamic forces and growth factors on cartilage regeneration by employing a custom-designed wavy-walled bioreactor1 (WWB) and by selecting IGF-1 and TGF-β1 as two model molecules. We hypothesized that bioprocessing conditions which optimize mechanical, biochemical and compositional properties of tissue-engineered cartilage can be achieved under hydrodynamic stimuli in combination with an appropriate use of IGF-1 or TGF-β.

This content is only available via PDF.
You do not currently have access to this content.