Mimicking biophysical stimuli within bone tumor microenvironment.

In vivo, cells reside in a complex environment regulating their fate and function. Most of this complexity is lacking in standard in vitro models, leading to readouts falling short of predicting the actual in vivo situation. The use of engineering tools, combined with deep biological knowledge, leads to the development and use of bioreactors providing biologically sound niches. Such bioreactors offer new tools for biological research, and are now also entering the field of cancer research. Here we present the development and validation of a modular bioreactor system providing: (i) high throughput analyses, (ii) a range of biological conditions, (iii) high degree of control, and (iv) application of physiological stimuli to the cultured samples. The bioreactor was used to engineer a three-dimensional (3D) tissue model of cancer, where the effects of mechanical stimulation on the tumor phenotype were evaluated. Mechanical stimuli applied to the engineered tumor model activated the mechanotransduction machinery and resulted in measurable changes of mRNA levels towards a more aggressive tumor phenotype.