Patent ID: 8367410

Claim:
A method for producing a three-dimensional tissue-engineered construct comprising: inoculating a three-dimensional substrate with a cell-gel suspension containing mammalian cells, thereby forming a cell-seeded construct; subjecting the cell-seeded construct to alternating flow perfusion through the construct immediately after the inoculating; supplying the cell-seeded construct with nutritive medium; cultivating the cell-seeded construct under conditions of direct medium perfusion, wherein the direct medium perfusion perfuses nutritive medium through the construct and provides substantially uniform cell density throughout the cell-seeded construct at depths greater than about 100 microns up to about 5 mm, except in regions shielded from medium flow; and, during cultivation, submitting the cells within the cell-seeded construct to a biomimetic electrical stimulation, the cultivating of the cell-seeded construct and biomimetic electrical stimulation extending for a time period to form a three-dimensional cell structure exhibiting structural and functional characteristics of a native tissue.