Abstract
In vitro tissue engineering is investigated as a potential source of functional tissue constructs for cartilage repair, as well as a model system for controlled studies of cartilage development and function. Among the different kinds of devices for the cultivation of 3D cartilage cell colonies, we consider here polymeric scaffold-based perfusion bioreactors, where an interstitial fluid supplies nutrients and oxygen to the growing biomass. At the same time, the fluid-induced shear acts as a physiologically relevant stimulus for the metabolic activity of cells, provided that the shear stress level is appropriately tuned. In this complex environment, mathematical and computational modeling can help in the optimal design of the bioreactor configuration. In this perspective, we propose a computational model for the simulation of the biomass growth, under given inlet and geometrical conditions, where nutrient concentration, fluid dynamic field and cell growth are consistently coupled. The biomass growth model is calibrated with respect to the shear stress dependence on experimental data using a simplified short-time analysis in which the nutrient concentration and the fluid-induced shear stress are assumed constant in time and uniform in space. Volume averaging techniques are used to derive effective parameters that allow to upscale the microscopic structural properties to the macroscopic level. The biomass growth predictions obtained in this way are significant for long times of culture.
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The Author RS was partly supported by the GNCS–INdAM Research Funding Program 2010 “Modelli Computazionali per Problemi Multifisica/Multiscala in Presenza di Bio-Interfacce”. The Author PC was supported by the Italian Research Funding Program PRIN 2007 “Modellistica numerica per il calcolo scientifico ed applicazioni avanzate”. The Author PZ was supported by the European Research Council Advanced Grant “Mathcard, Mathematical Modelling and Simulation of the Cardiovascular System”, Project ERC-2008-AdG 227058. The Author MTR was partly supported by the Italian Institute of Technology (IIT), Genoa, Italy.
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Sacco, R., Causin, P., Zunino, P. et al. A multiphysics/multiscale 2D numerical simulation of scaffold-based cartilage regeneration under interstitial perfusion in a bioreactor. Biomech Model Mechanobiol 10, 577–589 (2011). https://doi.org/10.1007/s10237-010-0257-z
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DOI: https://doi.org/10.1007/s10237-010-0257-z