Cardiac tissue engineering: effects of bioreactor flow environment on tissue constructs

The limited ability of cardiac muscle to regenerate after injury and the small number of organs available for transplantation motivate studies aimed at curative treatment options. Tissue engineering based on the integrated use of cells on biomaterial scaffolds in bioreactors may offer cardiac grafts suitable for surgical attachment to the myocardium or for basic research. In one of the current approaches, neonatal rat cardiomyocytes are combined with collagen sponges, gels or polyglycolic acid scaffolds (PGA). Cultivations performed in dishes, static or mixed flasks or rotating bioreactors yield constructs with a thin (100-200 mu m) peripheral layer of tissue expressing markers of cardiac differentiation and able to propagate electrical signals. The non-uniform cell distribution is a result of oxygen diffusional limitations within the constructs. Cultivations with perfusion of culture medium through the construct enhance the convective-diffusive oxygen supply and yield 1-2mm thick constructs with physiologically high and spatially uniform distribution of viable cells expressing cardiac markers. We review here a series of studies we conducted using cells seeded on three-dimensional scaffolds and cultured in several different bioreactors, to demonstrate that the bioreactor flow environment can have substantial effects on structural and functional properties of cardiac constructs. (c) 2006 Society of Chemical Industry.