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

Abstract

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.

Estimation of anisotropic permeability in trabecular bone based on microCT imaging and pore-scale fluid dynamics simulations

“…As discussed in Odsæter, while periodic boundary conditions are most suitable in many applications, numerical convergence may be affected by the choice of boundary conditions (Odsæter, 2013) . The velocity magnitudes obtained in our simulations correspond well to those found by Spencer et al in the range of 1.6 ⋅ 10  −5 to 3.2 ⋅ 10  −5   m/s (Spencer et al, 2013). …”

Prediction of cell growth rate over scaffold strands inside a perfusion bioreactor

“…For improvement, computational fluid dynamics has been recently used to obtain knowledge of the fluid velocity, shear stress and nutrient concentration distribution inside the tissue scaffolds (Porter et al 2005;Cioffi et al 2006;Chung et al 2007) as well as cell attachment (Spencer et al 2013). Cell growth rates and cell volume fractions have also been predicted and are in good qualitative agreement with the experimental data (Sacco et al 2011).…”

Modeling, simulations, and optimization of smooth muscle cell tissue engineering for the production of vascular grafts

“…Hence, the focus in this study is on a continuum transport model in a multiphase medium to represent a porous scaffold, with an additional growing cell phase and a permeating culture medium, where phase volume averaging has been applied (Gosman, Lekakou, Politis, Issa, & Looney, ; Lemon & King, ). The vast number of computational simulation studies in the literature, including recent ones, are dedicated to cartilage (Bandeiras & Completo, ; Y. Zhu et al, ) and bone tissue engineering (Bersini et al, ; Carlier et al, ; Guyot et al, ; Song et al, ; Song et al, ; Spencer, Hidalgo‐Bastida, Cartmell, Halliday, & Care, ; Zhao, Vaughan, & Mcnamara, ). To the best of our knowledge, no such modeling and computational simulation studies have been published for vascular tissue engineering despite a plethora of experimental studies in the literature, and as such the present paper breaks new ground.…”