Systems Used for Drug Testing

The importance of handling a large quantity of tissue constructs in parallel has already been addressed in Section 2.1. Most systems discussed so far do not fulfill this requirement; rather, they are mostly applicable for a specific tissue construct of a desired size, to provide a controlled environment, and to enable a continuous supply of nutrients and oxygen as well as the removal of metabolites. Some systems were successfully applied for in-vitro drug studies [45, 55, 67, 74, 75], but these proved mostly to be unsuitable for handling a magnitude of culture units in parallel, as the need for additional devices such as pumps, tubes, medium reservoirs and aeration units ballooned.

As an alternative, tissue culture units especially intended for HTS have been developed, and included the multicellular spheroid model [11, 77, 78], microelectrode arrays ("Biology on a Chip" [79-82]), the cultivation of organ slices [83], or multilayered post-confluent cell culture [84]. The specific features of these techniques are discussed at length in the following sections. Most of these techniques are well suited to the cultivation of small tissue constructs, and it could be shown that tissue-specific functions were maintained satisfactorily. The lack of environmental control is seen as the main drawback of these systems; for example, the exchange of medium occurs mostly in batch mode, which leads to a constantly changing environment. A continuous exchange of medium under controlled conditions, such as in bioreactors for tissue constructs, is seldom achieved. Hence, the future challenge will be to combine the advantages of both approaches - to have a "conventional" bioreactor design for tissue constructs on the one hand, and HTS-culture techniques for 3D-constructs on the other hand.

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