Three-dimensional (3D) in vitro culture is now a recognized technique to improve the performance and physiological relevance of immortalized and primary cells. 3D culture also increases proliferation rates in some cell types (e.g. mesenchymal stem cells, osteosarcoma cells, HUVECs, which puts extra demands on nutrient supply and waste removal. This issue can be addressed by the use of bioreactors, which circulate a large quantity of medium over or around the 3D culture and further improve cell proliferation and specific protein expression beyond that seen for static 3D cultures (e.g. dermal fibroblasts, cardiac cells, marrow stromal cells, osteogenic cells.