Standard techniques for the analysis of biological tissues like immunohistochemical staining are typically invasive and
lead to mortification of cells. Non-invasive monitoring is an important element of regenerative medicine because
implants and components of implants should be 100% quality-checked with non-invasive and therefore also marker-free
methods. We report on a new bioreactor for the production of collagen scaffolds seeded with Mesenchymal Stem Cells
(MSCs). It contains a computer controlled mechanical activation and ultrasonic online monitoring and has been
constructed for the in situ determination of ultrasonic and rheological parameters.
During the cultivation period of about two weeks the scaffold is periodically compressed by two movable pistons for
improved differentiation of the MSCs. This periodic compression beneficially ensures the supply with nutrition even
inside the sample. During the physiological stimuli, rheological properties are measured by means of highly sensitive
load cells. In addition measurements of the speed of sound in the sample and in the culture medium, with frequencies up
to 16 MHz, are performed continuously. Therefore piezoceramic transducers are attached to the pistons and emit and
detect ultrasonic waves, travelling through the pistons, the sample and the culture medium. The time-of-flight (TOF) of
the ultrasonic signals is determined in real time with the aid of chirped excitation and correlation procedures with a
resolution of at least 10 ps. The implemented ultrasonic measurement scheme allows beside the speed of sound
measurements the detection of the distance between the pistons with a resolution better than 100 nm.
The developed monitoring delivers information on rigidity, fluid dynamics and velocity of sound in the sample and in the
culture medium. The hermetically sealed bioreactor with its life support system provides a biocompatible environment
for MSCs for long time cultivation.