A Computational Tool for the Upscaling of Regular Scaffolds During In Vitro Perfusion Culture

Inhomogeneous and uncontrolled cellular and tissue responses in bone tissue engineering constructs, as a result of heterogeneous oxygen delivery throughout the scaffold volume, is one of the hurdles hampering clinical transfer of cell-scaffold combinations. This study presents an accurate and computationally efficient one-dimensional model that predicts the oxygen distribution for a regular cell-seeded scaffold in a perfusion bioreactor and the maximum (i.e., critical) scaffold length (L-max) as a function of given oxygen constraints. After validation against computational fluid dynamics models, the one-dimensional model was applied to calculate L-max in the perfusion direction, to ensure appropriate oxygen levels throughout the bone tissue engineering construct during in vitro culture. Both cell-related (cell density and oxygen consumption rate) and bioreactor-related (oxygen constraints and flow rate) culture parameters were varied. Results demonstrated the substantial influence of the culture parameters on L-max. In conclusion, the presented computational tool was able to predict oxygen distribution and maximum scaffold length for regular cell-seeded scaffold. It can be used to design perfusion experiments wherein quantitative knowledge on both oxygen and flow characteristics is needed.