A Novel Perfusion Bioreactor for 3D Cell Culture in Microgravity Conditions

Cell suspension culture methods based on the generation of microgravity environment are widely used in regenerative medicine for (1) the production of native-like three-dimensional (3D) cell aggregates and engineered tissues [1,2,3], for (2) low cost scalable cell expansion and long-term cell viability maintenance [4,5], and for (3) guiding differentiation of stem cells (SCs) [6]. The generation of a microgravity environment for 3D cell cultures, mimicking the native environment, promotes spatial freedom, cell growth, cell-cell interaction and improves mass transfer and cell exposure to nutrients. Nowadays, microgravity cell cultures are obtained by using stirred or rotating bioreactors, but both devices suffer from limitations: stirring bioreactors generate non-physiological shear stresses, which could damage cultured cells, interfere with SC pluripotency, and limit reproducibility of the culture process; rotating bioreactors are expensive devices due to the complex technological solutions adopted for obtaining rotation [5].