Experimental and numerical investigations of fluid flow in bioreactors for optimized in vitro stem cell loading in xenografts

Abstract

In tissue engineering and regenerative medicine mesenchymal stem cells (MSC) are widely used to replace and restore the function of dysfunctional or missing tissue. Recent studies have shown significant enhancements of the in vivo healing process following dentofacial bone augmentation procedures employing stem cell-loaded xenografts. We conducted experimental and numerical investigations in perfusion flow bioreactor-xenograft-systems to identify flow conditions as well as bioreactor design features that allow for homogeneous MSC-distribution in Geistlich Bio- Oss Block xenografts. Pressure gradient - velocity characteristics and flow distributions were investigated experimentally and numerically for two bioreactor designs at steady-state flow conditions with Reynolds numbers (Re) ranging from 0.01 ≤ Re ≤ 0.32. Distilled water at 20°C with a dynamic viscosity of 1.002 mPa∙s and a density of 998 kg/m3 was used. The geometry of the xenograft utilized in three-dimensional computational fluid dynamics (CFD) simulation was obtained by means of micro-computed tomography (μCT) at an isotropic spatial resolution of 9.5 μm. The permeability values calculated from the experimental data are in good accordance with the numerical results. The investigations showed that the increase of the inflow- and outflow-area diameter, as well as the decrease of the volumetric flow rate, result in a decreasing heterogeneity of the flow distribution within the xenograft. The calculated wall shear stress rates in the three-dimensional (3D) scaffold range from 1∙10-12Pa ≤ τ ≤ 0.2 Pa. Experimentally validated CFD simulations introduced in this study provide an applicable tool to assess optimal flow conditions for homogeneous MSC distribution in bioreactor-xenograft-systems.

Keywords

• bone graft
• bone augmentation
• perfusion flow bioreactor
• computational fluid dynamics
• stem cell