  Despite numerous advances in the field of tissue engineering and regenerative
medicine, monitoring the formation of tissue regeneration and its metabolic
variations during culture is still a challenge and mostly limited to bulk
volumetric assays. Here, a simple method of adding capsules based optical
sensors in cell seeded 3D scaffolds is presented and the potential of these
sensors to monitor the pH changes in space and time during cell growth is
demonstrated. It is shown that the pH decreased over time in the 3D scaffolds,
with a more prominent decrease at the edges of the scaffolds. Moreover, the pH
change is higher in 3D scaffolds compared to monolayered 2D cell cultures. The
results suggest that this system, composed by capsules based optical sensors
and 3D scaffolds with predefined geometry and pore architecture network, can be
a suitable platform for monitoring pH variations during 3D cell growth and
tissue formation. This is particularly relevant for the investigation of 3D
cellular microenvironment alterations occurring both during physiological
processes, such as tissue regeneration, and pathological processes, such as
cancer evolution.
