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.