Collagen hydrogel tube microbioreactors for cell and tissue manufacturing.

The large-scale production of mammalian cells, particularly stem cells for clinical applications, remains challenging with existing cell culture technologies such as two-dimensional cell culture flasks or three-dimensional stirred tank bioreactors. Current methods have issues such as excessive cell aggregation and significant shear stress-induced cell death, resulting in low cell yield, unacceptable batch-to-batch variation, high production costs, and difficulties in scaling up. We hypothesize that creating a cell-friendly microenvironment that has efficient mass transport and minimized shear stress can enhance cell culture efficiency. In this study, we developed a novel hydrogel tube microbioreactor using collagen proteins (ColTubes) to test this hypothesis. First, we designed an innovative micro-extruder for fabricating ColTubes loaded with cells. Our results show that collagen proteins form a dense and robust nanofiber network capable of shielding cells from hydrodynamic stress while maintaining cell mass below 400