Organic tissues in rotating bioreactors: fluid-mechanical aspects, dynamic growth models and morphological evolution

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Abstract

This analysis deals with advances in tissue engineering models and computational methods as well as with novel results on the relative importance of ‘controlling forces’ in the growth of organic constructs. The attention is focused in particular on the Rotary Culture System since this technique has proven to be the most practical solution to provide a suitable culture environment supporting 3-D tissue assemblies. From a numerical point of view, the growing biological specimen gives rise to a moving boundary problem. A ‘Volume of Fraction’ Method is specifically and carefully developed according to the complex properties and mechanisms of organic tissue growth and in particular taking into account the sensitivity of the construct/liquid interface to the effect of the fluid-dynamic shear stress (it induces changes in the tissue metabolism and function eliciting a physiologic response from the biological cells). The paper uses available data to introduce a set of growth models. The surface conditions are coupled to the transfer of mass and momentum at the specimen/culture-medium interface and lead to the introduction of a group of differential equations for the nutrient concentration around the sample and for the evolution of the tissue mass displacement. The models then are used to show how the proposed surface kinetic laws can predict (through sophisticated numerical simulations) many of the known characteristics of biological tissues grown using the rotating-wall perfused vessel bioreactors. This procedure provides validation of the models and associated numerical method and at the same time gives insights into the mechanisms of the phenomena. The interplay between the increasing size of the tissue and the structure of the convective field is investigated. It is shown that this interaction is essential in determining the time-evolution of the tissue shape. The size of the growing specimen plays a ‘critical role’ for the intensity of convection and the related shear stresses. Convective effects, in turn, are found to impact growth rates, tissue size and morphology as well as the mechanisms driving growth. The method exhibits novel capabilities to predict and elucidate experimental observations and to identify cause-and-effect relationships.
Original languageEnglish
Pages (from-to)518-532
Number of pages15
JournalBiotechnology and Bioengineering
Volume84
Issue number5
DOIs
Publication statusPublished - 24 Sep 2003

Keywords

  • tissue engineering
  • rotating vessel
  • growth kinetics
  • fluid motion
  • mathematical models
  • moving boundary method
  • morphology evolution
  • growth models
  • convective effects

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