Modeling fluid flow through irregular scaffolds for perfusion bioreactors

Abstract

Direct perfusion of 3D tissue engineered constructs is known to enhance osteogenesis, which can be partly attributed to enhanced nutrient and waste transport. In addition flow mediated shear stresses are known to upregulate osteogenic differentiation and mineralization. A quantification of the hydrodynamic environment is therefore crucial to interpret and compare results of in vitro bioreactor experiments. This study aims to deal with the pitfalls of numerical model preparation of highly complex 3D bone scaffold structures and aims to provide more accurate wall shear stress (WSS) estimates. microCT imaging techniques were used to reconstruct the geometry of both a titanium (Ti) and a hydroxyapatite scaffold, starting from 430 images with a resolution of 8 microm. To tackle the tradeoff between model size and mesh resolution we selected two concentric regions of interest (cubes with a volume of 1 and 3.375 mm(3), respectively) for both scaffolds. A flow guidance in front of the real inlet surface of the scaffold was designed to mimic realistic inlet conditions. With a flow rate of 0.04 mL/min perfused through a 5 mm diameter scaffold at an inlet velocity of 33.95 microm/s we obtained average WSSs of 1.10 and 1.46 mPa for the 1 mm(3) and the 3.375 mm(3) model of the hydroxyapatite scaffold compared to 1.40 and 1.95 mPa for the 1 mm(3) model and the 3.375 mm(3) model of the Ti scaffold, showing the important influence of the scaffold micro-architecture heterogeneity and the proximity of boundaries. To assess that influence we selected cubic portions, of which the WSS data were analyzed, with the same size and the same location within both 1 and 3.375 mm(3) cubic models. Varying the size of the inner portions simultaneously in both model selections gives a quantification of the sensitivity to boundary neighborhood. This methodology allows to get more insight in the complex concept of tissue engineering and will likely help to understand and eventually improve the fluid-mechanical aspects.

Model‐based cell number quantification using online single‐oxygen sensor data for tissue engineering perfusion bioreactors

“…The design of the dynamic perfusion flow condition is critical and will have to be adapted to the specific needs for every bioreactor setup, for example, depending on the O 2 consumption rate of the cells, scaffold design, or the expected number of cells (Cioffi et al, 2008;Maes et al, 2009;McCoy et al, 2012). The high flow rate in the step design is fairly unimportant regarding the measurements and will most conveniently be the functional flow rate that is used for the cell culture system.…”

Influence of flow rate and scaffold pore size on cell behavior during mechanical stimulation in a flow perfusion bioreactor

“…Calculation of the  within systems allows comparisons to be made on a single representative scale. In this study we successfully used established FVM techniques Jungreuthmayer et al, 2009a;Maes et al, 2009;Raimondi et al, 2006;Sandino et al, 2008), to characterise the shear stress distribution and  values within CT imaged CG scaffolds of differing mean pore sizes under different flow-rates. Pore size was found to have no effect on the average shear stress, maximum shear stress or the shear stress distribution for scaffolds having a constant porosity when subjected to the same flow-rate (Figure 3).…”

Biomimetic three-dimensional microenvironment for controlling stem cell fate

“…Computational models have been developed to characterize the engineering microenvironment as well as dynamic change in cellular activities. The flow-related parameters, such as oxygen, soluble factor concentration and shear stress, can be characterized by computational fluid dynamics, which reveal the local flow information in the microenvironment in a complex geometry [90][91][92][93][94]. The dynamic nature of the cellular activities can be described by cellular automata models.…”