Abstract: A bioreactor is described comprising: at least one cartridge having disposed therein at least one collagen substrate comprised of a collagen sponge layer and a nonporous to cells, semipermeable collagen layer; a substrate support that retains the collagen substrate within the cartridge; a first compartment between the collagen sponge layer and the inner surface of the first side of the cartridge casing and a second compartment between the nonporous to cells, semipermeable collagen layer and the inner surface of the second side of the cartridge casing; inlet and outlet means for transferring a first medium and a first cell type to the first compartment and inlet and outlet means for transferring a second medium and a second cell type to the second compartment.