Dynamics of diffusivity and pressure drop in flow‐through and parallel‐flow bioreactors during tissue regeneration

Abstract

In this study, transport characteristics in flow-through and parallel-flow bioreactors used in tissue engineering were simulated using computational fluid dynamics. To study nutrient distribution and consumption by smooth muscle cells colonizing the 100 mm diameter and 2-mm thick scaffold, effective diffusivity of glucose was experimentally determined using a two-chambered setup. Three different concentrations of chitosan-gelatin scaffolds were prepared by freezing at -80°C followed by lyophilization. Experiments were performed in both bioreactors to measure pressure drop at different flow rates. At low flow rates, experimental results were in agreement with the simulation results for both bioreactors. However, increase in flow rate beyond 5 mL/min in flow-through bioreactor showed channeling at the circumference resulting in lower pressure drop relative to simulation results. The Peclet number inside the scaffold indicated nutrient distribution within the flow-through bioreactor to be convection-dependent, whereas the parallel-flow bioreactor was diffusion-dependent. Three alternative design modifications to the parallel-flow were made by (i) introducing an additional inlet and an outlet, (ii) changing channel position, and (iii) changing the hold-up volume. Simulation studies were performed to assess the effect of scaffold thickness, cell densities, and permeability. These new designs improved nutrient distribution for 2 mm scaffolds; however, parallel-flow configuration was found to be unsuitable for scaffolds more than 4-mm thick, especially at low porosities as tissues regenerate. Furthermore, operable flow rate in flow-through bioreactors is constrained by the mechanical strength of the scaffold. In summary, this study showed limitations and differences between flow-through and parallel-flow bioreactors used in tissue engineering.

Modeling of porous scaffold deformation induced by medium perfusion

“…CG scaffolds were prepared following the procedure previously described . In brief, 2%–2% (wt/v) CG solution was prepared in 0.5 M acetic acid and 25 mL of the solution was poured in the wells.…”

“…Experiments were performed at flow rates from 5 to 25 mL/min using 10 cm diameter and 0.2 cm thick scaffolds (high aspect ratio) following the procedure described previously . In brief, a flow through bioreactor, which allows housing the 0.2 cm thick and 10 cm diameter scaffold was constructed in‐house using polycarbonate plastic.…”

Application of computational fluid dynamics in tissue engineering

“…We recently reported experimental validation of pressure drop across the porous structure, demonstrating the validity of the assumptions for freeze dried scaffolds (13,14). If electrospinning or rapid prototypic methods are used to generate the porous matrix scaffold, then fibrous architecture based hydraulic permeability has to be used.…”

“…The non-ideal fluid distribution is characterized using the residence time distribution (RTD). The RTD measures the amount of time different fluid molecules spend within the bioreactor (13,14), allowing for consumption by the cellular components. RTD is a measure of dispersal of a molecule in a flowing medium owing to the combined action of a velocity profile and molecular diffusion.…”

Applications of Computational Modelling and Simulation of Porous Medium in Tissue Engineering

“…Alternatively, Mackie-Meares relationship can be used to determine the effective diffusivity. An example of Mackie-Meares relationship [13] is…”