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Design Criteria for Generating Physiologically Relevant In Vitro Models in Bioreactors

Research Center "E. Piaggio", University of Pisa, largo Lucio Lazzarino 1, 56122 Pisa, Italy
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Processes 2014, 2(3), 548-569;
Received: 21 May 2014 / Revised: 17 June 2014 / Accepted: 2 July 2014 / Published: 25 July 2014
(This article belongs to the Special Issue Design of Bioreactor Systems for Tissue Engineering)
PDF [4367 KB, uploaded 25 July 2014]


In this paper, we discuss the basic design requirements for the development of physiologically meaningful in vitro systems comprising cells, scaffolds and bioreactors, through a bottom up approach. Very simple micro- and milli-fluidic geometries are first used to illustrate the concepts, followed by a real device case-study. At each step, the fluidic and mass transport parameters in biological tissue design are considered, starting from basic questions such as the minimum number of cells and cell density required to represent a physiological system and the conditions necessary to ensure an adequate nutrient supply to tissues. At the next level, we consider the use of three-dimensional scaffolds, which are employed both for regenerative medicine applications and for the study of cells in environments which better recapitulate the physiological milieu. Here, the driving need is the rate of oxygen supply which must be maintained at an appropriate level to ensure cell viability throughout the thickness of a scaffold. Scaffold and bioreactor design are both critical in defining the oxygen profile in a cell construct and are considered together. We also discuss the oxygen-shear stress trade-off by considering the levels of mechanical stress required for hepatocytes, which are the limiting cell type in a multi-organ model. Similar considerations are also made for glucose consumption in cell constructs. Finally, the allometric approach for generating multi-tissue systemic models using bioreactors is described. View Full-Text
Keywords: bioreactors; milli-fluidics; in vitro models bioreactors; milli-fluidics; in vitro models

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This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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Mattei, G.; Giusti, S.; Ahluwalia, A. Design Criteria for Generating Physiologically Relevant In Vitro Models in Bioreactors. Processes 2014, 2, 548-569.

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