Finite Element Modeling of Fluid Dynamics, Oxygen Transport, and Cell Proliferation Inside 3D-Printed Scaffolds in a PerfusionBioreactor

Background and Aim: A major bottleneck in the 3D-bone tissueengineering field is the lack of efficient vascularization strategies sincea constant flow of oxygen and nutrients is needed to maintain viabilityand functionality of bone tissue constructs. Fluid dynamics and oxygenconcentration in 3D-printed scaffolds within perfusion bioreactorsare crucial for bone cell proliferation and distribution. We aimed todetermine the fluid dynamics, oxygen transfer, cell proliferation anddistribution in 3D-printed scaffolds inside perfusion bioreactors by finiteelementmodeling.Methods: M3T3-E1 osteoblasts were treated with pulsating fluid flow(PFF, frequency 1 Hz) for 1 h with low (0.8 Pa; low-PFF) or high peakshear stress (6.5 Pa; high-PFF), and nitric oxide production was measuredto validate the sensitivity of the cells to fluid shear stress. Fluid flow andoxygen transfer between scaffold-strands were simulated at three inletflow rates (0.4, 2, and 10 mL/min) for 5 days.Results: High-PFF more strongly stimulated nitric oxide production byosteoblasts compared to low-PFF. 3D-simulation demonstrated thatfluid velocity reached a maximum (100-2400 μm/s) between scaffoldstrandsdependent on inlet flow rate. Fluid shear stress (0.24-6 mPa) andwall shear stress (0.04-25 mPa) reached a maximum on scaffold-strandsurfaces. At all inlet flow rates, cell distribution was homogeneous, whilecell density increased due to sufficient oxygen transfer.Conclusion: We conclude that fluid dynamics inside 3D-printedscaffolds can be controlled by changing the inlet flow rate of a perfusionbioreactor. The oxygen concentration and cell proliferation appearhomogeneous independent of the inlet flow rate. Our findings providea quantitative insight into the fluid dynamics, oxygen transport, and cellproliferation and distribution within a 3D-printed scaffold containingcells in a perfusion bioreactor, which will have important implications forbone tissue engineering strategies using bioreactors, scaffolds, and cells.

کلیدواژه ها:

Finite element modeling ، Fluid dynamics ، Oxygen transfer ، Perfusion bioreactor ، Three-dimensional scaffold