In silico multi‐scale model of transport and dynamic seeding in a bone tissue engineering perfusion bioreactor

Computer simulations can potentially be used to design, predict, and inform properties for tissue engineering perfusion bioreactors. In this work, we investigate the flow properties that result from a particular poly‐L‐lactide porous scaffold and a particular choice of perfusion bioreactor vessel design used in bone tissue engineering. We also propose a model to investigate the dynamic seeding properties such as the homogeneity (or lack of) of the cellular distribution within the scaffold of the perfusion bioreactor: a pre‐requisite for the subsequent successful uniform growth of a viable bone tissue engineered construct. Flows inside geometrically complex scaffolds have been investigated previously and results shown at these pore scales. Here, it is our aim to show accurately that through the use of modern high performance computers that the bioreactor device scale that encloses a scaffold can affect the flows and stresses within the pores throughout the scaffold which has implications for bioreactor design, control, and use. Central to this work is that the boundary conditions are derived from micro computed tomography scans of both a device chamber and scaffold in order to avoid generalizations and uncertainties. Dynamic seeding methods have also been shown to provide certain advantages over static seeding methods. We propose here a novel coupled model for dynamic seeding accounting for flow, species mass transport and cell advection‐diffusion‐attachment tuned for bone tissue engineering. The model highlights the timescale differences between different species suggesting that traditional homogeneous porous flow models of transport must be applied with caution to perfusion bioreactors. Our in silico data illustrate the extent to which these experiments have the potential to contribute to future design and development of large‐scale bioreactors. Biotechnol. Bioeng. 2013; 110: 1221–1230. © 2012 Wiley Periodicals, Inc.

[1]  T. N. Stevenson,et al.  Fluid Mechanics , 2021, Nature.

[2]  C P Chen,et al.  Enhancement of cell growth in tissue‐engineering constructs under direct perfusion: Modeling and simulation , 2007, Biotechnology and bioengineering.

[3]  Robert E Guldberg,et al.  Effects of medium perfusion rate on cell-seeded three-dimensional bone constructs in vitro. , 2003, Tissue engineering.

[4]  D. Wendt,et al.  Oscillating perfusion of cell suspensions through three‐dimensional scaffolds enhances cell seeding efficiency and uniformity , 2003, Biotechnology and bioengineering.

[5]  On the lattice Boltzmann method simulation of a two-phase flow bioreactor for artificially grown cartilage cells. , 2008, Journal of biomechanics.

[6]  Martin Dufva,et al.  Optimal Homogenization of Perfusion Flows in Microfluidic Bio-Reactors: A Numerical Study , 2009, PloS one.

[7]  Nicola Elvassore,et al.  Mathematical Modeling of Three-Dimensional Cell Cultures in Perfusion Bioreactors , 2006 .

[8]  Josep A Planell,et al.  Computational modelling of the mechanical environment of osteogenesis within a polylactic acid-calcium phosphate glass scaffold. , 2009, Biomaterials.

[9]  F. Boschetti,et al.  Prediction of the micro-fluid dynamic environment imposed to three-dimensional engineered cell systems in bioreactors. , 2006, Journal of biomechanics.

[10]  S. Moestrup,et al.  Receptors. Models for binding, trafficking, and signalling: Edited by D.A. Lauffenburger and J.J. Linderman. IRL Press; Oxford, 1996. x+365 pp. £22.95 (pb) , 1996 .

[11]  Margherita Cioffi,et al.  The effect of hydrodynamic shear on 3D engineered chondrocyte systems subject to direct perfusion. , 2006, Biorheology.

[12]  M. Loosdrecht,et al.  Three‐dimensional simulations of biofilm growth in porous media , 2009 .

[13]  L. A. Hidalgo-Bastida,et al.  Mesenchymal stem cells, osteoblasts and extracellular matrix proteins: enhancing cell adhesion and differentiation for bone tissue engineering. , 2010, Tissue engineering. Part B, Reviews.

[14]  Shiyi Chen,et al.  Simulation of Cavity Flow by the Lattice Boltzmann Method , 1994, comp-gas/9401003.

[15]  Vassilios I Sikavitsas,et al.  Computational modeling of flow-induced shear stresses within 3D salt-leached porous scaffolds imaged via micro-CT. , 2010, Journal of biomechanics.

[16]  W. T. Grandy,et al.  Kinetic theory : classical, quantum, and relativistic descriptions , 2003 .

[17]  M. Iruela-Arispe,et al.  Macro‐scale topology optimization for controlling internal shear stress in a porous scaffold bioreactor , 2011, Biotechnology and bioengineering.

[19]  Z. Koza,et al.  Tortuosity-porosity relation in porous media flow. , 2008, Physical review. E, Statistical, nonlinear, and soft matter physics.

[20]  R Pietrabissa,et al.  Computational modeling of combined cell population dynamics and oxygen transport in engineered tissue subject to interstitial perfusion , 2007, Computer methods in biomechanics and biomedical engineering.

[21]  T. Becker,et al.  An innovative lattice Boltzmann model for simulating Michaelis–Menten-based diffusion–advection kinetics and its application within a cartilage cell bioreactor , 2010, Biomechanics and modeling in mechanobiology.

[22]  G. I. Bell.  Models for the specific adhesion of cells to cells. , 1978, Science.

[23]  Elmar Heinzle,et al.  Measurement of oxygen uptake and carbon dioxide production rates ofmammalian cells using membrane mass spectrometry , 2004, Cytotechnology.

[24]  D. Birchall,et al.  Computational Fluid Dynamics , 2020, Radial Flow Turbocompressors.

[25]  Margherita Cioffi,et al.  An in silico bioreactor for simulating laboratory experiments in tissue engineering , 2008, Biomedical microdevices.

[26]  L. A. Hidalgo-Bastida,et al.  Modeling and design of optimal flow perfusion bioreactors for tissue engineering applications. , 2012, Biotechnology and bioengineering.

[27]  C. Please,et al.  Experimental characterization and computational modelling of two-dimensional cell spreading for skeletal regeneration , 2007, Journal of The Royal Society Interface.

[28]  D. Wendt,et al.  Uniform tissues engineered by seeding and culturing cells in 3D scaffolds under perfusion at defined oxygen tensions. , 2006, Biorheology.

[29]  J. Fisher,et al.  Bone tissue engineering bioreactors: dynamic culture and the influence of shear stress. , 2011, Bone.

[30]  Gabriele Dubini,et al.  Modeling evaluation of the fluid-dynamic microenvironment in tissue-engineered constructs: a micro-CT based model. , 2006, Biotechnology and bioengineering.

[31]  Rosemary Dyson,et al.  Mathematical modelling of fibre-enhanced perfusion inside a tissue-engineering bioreactor. , 2009, Journal of theoretical biology.

[32]  Roger Zauel,et al.  3-D computational modeling of media flow through scaffolds in a perfusion bioreactor. , 2005, Journal of biomechanics.

[33]  Sunil Wadhwa,et al.  Fluid Flow Induction of Cyclo‐Oxygenase 2 Gene Expression in Osteoblasts Is Dependent on an Extracellular Signal‐Regulated Kinase Signaling Pathway , 2002, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[34]  J. Boon.  The Lattice Boltzmann Equation for Fluid Dynamics and Beyond , 2003 .

[35]  F. Maes,et al.  Modeling fluid flow through irregular scaffolds for perfusion bioreactors , 2009, Biotechnology and bioengineering.