Process Simulation in a Mechatronic Bioreactor Device with Speed‐Regulated Motors for Growing of Three‐Dimensional Cell Cultures

Abstract

Tissue engineering is a new scientific research field that allows the establishment of tissue equivalents rising from isolated cells in combination with biocompatible materials and cultivation in more or less sophisticated bioreactor systems. Such systems gave the unique opportunity to perform in vitro investigations of transcription and translation, cell growth, biochemistry and mechanics of healthy normal organs as well as those affected by malignant tumors, infections, and immune deficiency under controlled conditions. In rotating vessel bioreactors under microgravity and defined medium content, cells proliferate, stay abundant to each other, and form three-dimensional structures, assigned as spheroids. Such spheroids might be grown on microcarriers. A wide spectrum of different cell culture experiments involving normal and transformed human cells indicates that: in the rotating bioreactor system miniPERM no complete lack of gravity could be reached; a great part of the seeded cell material does not proliferate at the beginning; and the appearance of bigger spheroids is rather random. We describe the acquisition of spheroids from HD-MY-Z and Neuro-2A tumor cells. Spheroids of 100 and more cells were obtained from HD-MY-Z and Neuro-2A cells. Interestingly, chronic myeloid leukemia LAMA-84 cells did not form any cell clumps and they kept a completely undifferentiated phenotype despite their semiadherent manner of growth under conventional conditions. A detailed theoretical and virtual simulation study of the influence of every component of gravitation, inertia, and hydrodynamic force fields was performed. Therefore, a new concept for mechatronic bioreactor device with active electronic control was developed and virtually tested.