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Adult-stem-cell-seeded scaffolds have been found to differentiate along the osteoblastic lineage under flow in perfusion bioreactors. This study aimed to investigate the behavior of cells seeded and cultured on scaffolds with different internal architectures under perfusion with static cultures serving as controls. For this, rat mesenchymal stem cells were cultured on poly(L-lactic acid) scaffolds made by solvent casting/particulate leaching or spunbonding. These two methods created geometrically different scaffold architectures, porous foams and nonwoven fibrous meshes. The flow field and the shear stresses within the scaffolds were also characterized in detail with flow simulations based on the lattice Boltzmann method. The porosity (∼85%) and the surface-area-to-solid-volume ratio were approximately equal for both types of scaffolds. High-resolution microcomputed tomography was used to obtain the three-dimensional (3D) internal structure of the scaffolds to be used as the computational domain in the simulations. For both scaffold architectures, flow perfusion cultures demonstrated 4-6 times higher cellularities after 8 days and ∼4 times higher alkaline phosphatase activity for the same culture period. Although scaffold architecture did not appear to create significant differences in average shear or shear stress distributions, the proliferation and differentiation of cells seemed to be affected, especially after 4 days of culturing, where the cellularity in dynamically cultured nonwoven fibers was 3 times higher than the dynamically cultured foams. Dynamically cultured nonwoven fibers also had more than 4 times higher alkaline phosphatase activity than dynamically cultured foams. Interestingly, these differences diminished between dynamically cultured scaffolds after 8 days of culturing.

Previous observations of cytocompatibility and calcification on the PEEK biomaterial could be carried through to this new porous form of the PEEK biomaterial. This helps porous PEEK to potentially offer more design options for implant devices requiring reduced modulus and/or increased tissue ingrowth aspects at the surface.

The present study combines chemical and mechanical stimuli to modulate the osteogenic differentiation of mesenchymal stem cells (MSCs). Arg-Gly-Asp (RGD) peptides incorporated into biomaterials have been shown to upregulate MSC osteoblastic differentiation. However, these effects have been assessed under static culture conditions, while it has been reported that flow perfusion also has an enhancing effect on MSC osteoblastic differentiation. It is clear that there is a need to combine RGD modification of biomaterials with mechanical stimulation of MSCs via flow perfusion and evaluate its effects on MSC differentiation down the osteogenic lineage. In this study, the effect of different levels of RGD modification of poly(L-lactic acid) scaffolds on MSC osteogenesis was evaluated under conditions of flow perfusion. It was found that there is a synergistic enhancement of different osteogenic markers, due to the combination of flow perfusion and RGD surface modification when compared to their individual effects. Furthermore, under conditions of flow perfusion, there is an RGD surface concentration optimal for differentiation, and it is flow rate-dependent. This report underlines the significance of incorporating combined biomimesis via biochemical and mechanical microenvironments that modulate in vivo cell behaviour and tissue function for more efficient tissue-engineering strategies.

SUMMARYMass transfer in the presence of chemical reactions for flows through porous media is of interest to many disciplines. The Lattice Boltzmann method (LBM) is particularly attractive in such cases due to the ease with which it handles complicated boundary conditions. However, useful Lagrangian information (such as solute survival distance, effective diffusivity, collision frequency) is challenging to obtain from the LBM. In this paper, we present a straightforward and efficient Lagrangian methodology (Lagrangian scalar tracking, LST) for performing solute transport simulations in the presence of heterogeneous, first-order, irreversible reactions, based on a velocity field obtained from LBM. The hybrid LST/LBM technique tracks passive mass markers that have two contributions to their movement: convective (obtained through interpolation of a previously obtained velocity field) and Brownian. Various Schmidt number solutes and different solute release modes can be modeled with a single solvent flow field using this method. Moreover, the mass markers can have a range of reaction rate coefficients. This allows for the exploration of the whole spectrum of first-order heterogeneous reaction rates with just a single simulation. In order to show the applicability of the LST/LBM scheme, results from a case study are presented in which the consumption of oxygen and/or nutrients within a porous bone tissue engineering scaffold is modeled under flow perfusion culturing conditions. Although the reactive LST methodology described in this paper compliments the LBM, it can also be used with any other flow simulation that can generate the velocity field.