The Design of Cell Culture Systems and Bioreactors

The aim in designing any drug-testing bioreactor should be to adhere as much as possible to the architecture and homeostasis of the respective sub-organoid structure in man. Thus, the development of biomaterials and shapes that emulate the extracellular habitat and architecture are mandatory. Due to the fact that Nature miniaturizes these functionally self-reliant sub-organoids in the body (often to a volume of less than 1 mm ), bioreactors should employ this possibility with regard to decreased cell demand and ease of high throughput to the same scale. The development of appropriate microsensors to monitor and control such small cell culture spaces is necessary and ongoing. Currently, the major hurdles are:

(1) a lack of biomaterials that efficiently emulate the natural extracellular matrix;

(2) the biocompatible miniaturized cell culture spaces themselves; and (3) the automation and multiplication of such systems for high-throughput testing.

These hurdles apply to all types of bioreactor, and are not necessarily limited to the final testing devices themselves. In order to succeed in a drug-testing strategy of human micro-organoids in vitro, stem cell expansion devices may be essential for cell supply. Within such cell- and tissue-manufacturing devices, both intrinsic symmetrical division as well as intrinsic and environmental asymmetric division for the expansion and differentiation of the necessary cell populations to charge the drug-testing bioreactors are mandatory. In contrast to the drug-testing bioreactors where differentiated micro-organoids are kept alive, these devices must emulate the embryonal environment or somatic stem cell niches. An additional challenge here is to prevent the induction of irreversible molecular pathways by traumatic events in stem cell fate. Thus, it is essential that a proper environment is applied, not only for the formation of differentiated human micro-organoids but also for human stem cells directly after delivery of the primary material from the human donor.

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