FJ. Influence of flow rate and scaffold pore size on cell behavior during mechanical stimulation in a flow perfusion bioreactor. Biotechnology and Bioengineering. 2012;109(6):1583-1594.-Use LicenceAttribution-Non-Commercial-ShareAlike 1.0 You are free:• to copy, distribute, display, and perform the work.• to make derivative works.
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AbstractMechanically stimulating cell-seeded scaffolds by flow-perfusion is one approach utilised for developing clinically applicable bone graft substitutes. A key challenge is determining the magnitude of stimuli to apply that enhances cell differentiation but minimises cell detachment from the scaffold. In this study we employed a combined computational modelling and experimental approach to examine how the scaffold mean pore size influences cell attachment morphology and subsequently impacts upon cell deformation and detachment when subjected to fluid-flow. Cell detachment from osteoblast-seeded collagen-GAG scaffolds was evaluated experimentally across a range of scaffold pore sizes subjected to different flow-rates and exposure times in a perfusion bioreactor. Cell detachment was found to be proportional to flow-rate and inversely proportional to pore size. Using this data, a theoretical model was derived that accurately predicted cell detachment as a function of mean shear stress, mean pore size and time. Computational modelling of cell deformation in response to fluid flow showed the percentage of cells exceeding a critical threshold of deformation correlated with cell detachment experimentally and the majority of these cells were of a bridging morphology (cells stretched across pores). These findings will help researchers optimise the mean pore size of scaffolds and perfusion bioreactor operating conditions to manage cell detachment when mechanically simulating cells via flow perfusion.