Overcoming hypoxia in 3D culture systems for tissue engineering of bone in vitro using an automated, oxygen-triggered feedback loop.

Tissue engineering is an attractive approach to heal bony defects. However, three-dimensional cell-scaffold constructs display uneven oxygen supply resulting in inhomogeneous tissue quality. We assessed different strategies to improve oxygen supply in vitro. Scaffolds with differing inner surface were seeded with preosteoblastic cells and cultivated either statically or in perfusion bioreactors. Oxygen concentration and pH were measured in the center of the scaffolds. An inductive feedback mechanism was build to increase bioreactor pump speed according to the oxygen concentrations measured within the scaffolds. While pH remained stable, oxygen concentration decreased significantly under static conditions within the cell-seeded scaffolds. Reducing the scaffolds' inner surface as well as increasing perfusion speeds in bioreactors resulted in improved oxygen supply. We conclude that improving oxygen supply to three dimensional culture systems for bone tissue engineering is feasible in an automated manner. Culture conditions have to be adapted to each cell-scaffold system individually.