Physiological and cell biological aspects of perfusion culture technique employed to generate differentiated tissues for long term biomaterial testing and tissue engineering

Optimal results in biomaterial testing and tissue engineering under in vitr o conditions can only be expected when the tissue generated resembles the o riginal tissue as closely as possible. However, most of the presently used stagnant cell culture models do not produce the necessary degree of cellula r differentiation, since important morphological, physiological, and bioche mical characteristics disappear. while atypical features arise. To reach a high degree of cellular differentiation and to optimize the cellular enviro nment, an advanced culture technology allowing the regulation of differenti ation on different cellular levels was developed. By the use of tissue carr iers, a variety of biomaterials or individually selected scaffolds could be tested for optimal tissue development. The tissue carriers are to be place d in perfusion culture containers, which are constantly supplied with fresh medium to avoid an accumulation of harmful metabolic products. The perfusi on of medium creates a constant microenvironment with serum-containing or s erum-free media. By this technique, tissues could be used for biomaterial o r scaffold testing either in a proliferative or in a postmitotic phase, as is observed during natural development. The present paper summarizes techni cal developments, physiological parameters, cell biological reactions, and theoretical considerations for an optimal tissue development in the field o f perfusion culture.