Macro‐scale topology optimization for controlling internal shear stress in a porous scaffold bioreactor

Abstract

Shear stress is an important physical factor that regulates proliferation, migration and morphogenesis. In particular, the homeostasis of blood vessels is dependent on shear stress. To mimic this process ex vivo, efforts have been made to seed scaffolds with vascular and other cell types in the presence of growth factors and under pulsatile flow conditions. However, the resulting bioreactors lack information on shear stress and flow distributions within the scaffold.Consequently, it is difficult to interpret the effects of shear stress on cell function. Such knowledge would enable researchers to improve upon cell culture protocols. Recent work has focused on optimizing the microstructural parameters of the scaffold to fine tune the shear stress.In this study, we have adopted a different approach whereby flows are redirected throughout the bioreactor along channels patterned in the porous scaffold to yield shear stress distributions that are optimized for uniformity centered on a target value. A topology optimization algorithm coupled to computational fluid dynamics simulations was devised to this end. The channel topology in the porous scaffold was varied using a combination of genetic algorithm and fuzzy logic. The method is validated by experiments using magnetic resonance imaging (MRI) readouts of the flow field.

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

“…The scaffold was imaged using a microCT (Scanco40, Scanco, CH); this 3D volume, 16 µm voxel size, was then used to feed the scaffold macro‐ and micro‐architecture into the LBE model. It is very possible that electron micrograph scans may yield higher resolution scaffold features on the nanoscale not picked up in the computed tomography (CT) scan data (e.g., Youssef et al, 2012) but given that the average pore size is 20 times larger than the CT resolution it is assumed that the CT data are well representative and non‐permeable. In a second case study, to follow, the PLLA scaffold was cleaved in silico into a regular cube of side L = 4 mm and then inserted into a square cross‐section flow guide with an inlet and outlet manifold both of length L in order to measure scaffold flow properties alone (Fig.…”

“…The PLLA scaffold boundary derives from microCT scans, as previously used, inserted in to the LBE model via the marker cell method (Porter et al, 2005; Voronov et al, 2010; Youssef et al, 2012). For the cases shown in the Results Section, unidirectional flow is impulsively started at t = 0 and allowed to run to either steady state or a typical seeding time in order to explore the models findings and behavior.…”

“…Perfusion bioreactors are often simulated using generalized assumptions and simplifications; while these simpler models provide quick answers, they are limited to a maximum number of species and more over only provide an approximation of the operational parameters (Cioffi et al, 2006; Hidalgo‐Bastida et al, 2012; Okkels et al, 2011; Raimondi et al, 2006). Recently, new models for tissue engineering transport phenomena have been based in the lattice Boltzmann equation (LBE) technique, which is suited to parallel computation, multi‐scaling and to simple handling of complex boundary shaped scaffolds (Hussein et al, 2008; Moaty Sayed et al, 2010; Porter et al, 2005; Voronov et al, 2010; Youssef et al, 2012). LBE differs from conventional forms of computational fluid dynamics (CFD) by solving flow and CD at a micro‐scale.…”

“…In a second example, accurate solutions of the NS and CD equations have been obtained from CFD calculations. These works have addressed transport in small volumes of a prototype porous medium comprised of idealized spherical voids and cylindrical channels, or 1 mm 3 sections of irregular scaffolds with fictitiously smoothed surfaces (Boschetti et al, 2006; Maes et al, 2009), or 2D approximations of the real systems (Youssef et al, 2012). There is an increased interest towards modeling of flows in larger, more representative, scaffold samples.…”

Shear-resistant hydrogels to control permeability of porous tubular scaffolds in vascular tissue engineering

“…As drawbacks, these scaffolds impair VSMC infiltration, making the re-cellularization process hard and time-dispersive [19]. Moreover, decellularized biological tissues do not overcome the availability issue, while synthetic scaffolds offer favorable advantages, as higher reproducibility and both controlled microstructure [24] and degradation rate [25,26]. On one hand, porous scaffolds able to promote VSMCs colonization from the external side towards the lumen are required [27,28].…”