A modular culture system for the generation of multiple specialized tissues.

Numerous factors influence cell functions and tissue development in culture. A modular culture system has been developed to allow the control of many of these important environmental parameters. Optimal adhesion of cells is obtained by selecting an individual biomaterial. Selected specimens are mounted in a tissue carrier in order to protect it against damage during handling and after seeding cells, the carriers can be used in a series of compatible perfusion culture containers. This technique allows the simple bathing of growing tissue under continuous medium transport and the exposure of epithelia to a gradient with different fluids at the luminal and basal sides. A further container is made of transparent material to observe microscopically the developing tissue. In addition, a special model features a flexible silicone lid to apply force to mimic the mechanical load required for developing connective and muscular tissue. Perfusion culture of stem/progenitor cells at the interface of an artificial interstitium made by a polyester fleece results in the spatial development of tubules. During long term culture over weeks the growing tissue is continuously exposed to fresh nutrition and respiratory gas. The medium is transported in a constant flow or in pulses, preventing unstirred layers of fluid. A variety of applications of this modular system, described in this paper, demonstrates that the biological profile of cells and tissues can be strongly improved when perfusion culture with a permanent provision of fresh medium is applied.