ORIGINAL RESEARCH ARTICLE Open Access Noninvasive Oxygen Monitoring in Three-Dimensional Tissue Cultures Under Static and Dynamic Culture Conditions

We present a new method for noninvasive real-time oxygen measurement inside three-dimensional tissue-engi-neered cell constructs in static and dynamic culture settings in a laminar flow bioreactor. The OPAL system (op-tical oxygen measurement system) determines the oxygen-dependent phosphorescence lifetime of spherical microprobes and uses a two-frequency phase-modulation technique, which fades out the interference of back-ground fluorescence from the cell carrier and culture medium. Higher cell densities in the centrum of the scaf-folds correlated with lower values of oxygen concentration obtained with the OPAL system. When scaffolds were placed in the bioreactor, higher oxygen values were measured compared to statically cultured scaffolds in a Petri dish, which were significantly different at day 1–3 of culture. This technique allows the use of signal-weak mi-croprobes in biological environments and monitors the culture process inside a bioreactor. Key words: cell culture; extracellular matrix; hypoxia; stem cells; tissue engineerin