Cultured tissue and bioreactor systems and methods for production thereof
The present disclosure relates to cultured tissue, methods for production of the cultured tissue, and a bioreactor system for production of the cultured tissue. In some embodiments, the production of the cultured tissue may involve, at a first bioreactor, feeding a fiber scaffold into a chamber containing culture media, seeding the chamber with precursor cells, and allowing the precursor cells to proliferate and differentiate on a surface of the fiber scaffold. At downstream bioreactors, the production of the cultured tissue may further involve twisting a plurality of the cell-laden fibers to provide a cell-laden yarn, and weaving or knitting the cell-laden yarn into a three-dimensional (3D) structure. In some embodiments, the cultured tissue may be whole muscle cultured meat composed of muscle cell-laden fibers and fat cell-laden fibers. The whole muscle cultured meat may have a structural organization and hierarchy that mimics natural skeletal muscle tissue.
1 . A system for the production of cultured tissue, comprising:
a first bioreactor including
an internal chamber containing culture medium,
a fiber inlet for feeding a fiber scaffold into the internal chamber, and
a cell inlet for feeding precursor cells into the internal chamber, wherein the precursor cells proliferate and differentiate on a surface of the fiber scaffold in the culture medium to provide a cell-laden fiber composed of cells attached to the fiber scaffold, and
an outlet through which the cell-laden fiber emerges from the first bioreactor, wherein the cell-laden fiber is used in the production of the cultured tissue.
2 . The system of claim 1 , further comprising a second bioreactor downstream of the first bioreactor and configured to combine and twist the cell-laden fibers emerging from one or more of the first bioreactors to provide a cell-laden yarn.
3 . The system of claim 2 , wherein the second bioreactor includes wheels attached to each end of the cell-laden fibers which rotate at a rotation rate to twist the cell-laden fibers.
4 . The system of claim 2 , further comprising a third bioreactor downstream of the second bioreactor and configured to weave or knit the cell-laden yarn into a three-dimensional (3D) structure.
5 . The system of claim 2 , further comprising a third bioreactor configured to weave or knit the cell-laden yarn from the second bioreactor into a two-dimensional (2D) sheet.
6 . The system of claim 5 , wherein the third bioreactor is further configured to build the 2D sheet into a three-dimensional (3D) structure.
7 . The system of claim 6 , wherein the 2D sheet or the 3D structure provides the cultured tissue.
8 . The system of claim 7 , wherein the cell-laden fiber includes muscle cells, fat cells, or a combination thereof.
9 . The system of claim 8 , wherein the cell-laden fibers of the cultured tissue include muscle cell-laden fibers, fat cell-laden fibers, or a combination of muscle cell-laden fibers and fat cell-laden fibers.
10 . The system of claim 9 , wherein the first bioreactor, the second bioreactor, and the third bioreactor are configured to operate automatically and continuously to produce the cultured tissue.
11 . The system of claim 10 , further comprising one or more computer controllers in communication with the first bioreactor, the second bioreactor, and the third bioreactor for automating the operation of the first bioreactor, the second bioreactor, and the third bioreactor.
12 . The system of claim 11 , wherein the cells are cultured in a culture media to at least 75% confluence in the first bioreactor.
13 . The system of claim 12 , wherein a concentration of growth factors in the culture media decreases from a proximal end to a distal end of the first bioreactor.
14 . The system of claim 1 , wherein the cultured tissue is cultured meat for consumption.
15 . The system of claim 1 , wherein the cells are engineered to produce vital nutrients.
16 . The system of claim 1 , wherein the fiber scaffold is edible.
17 . The system of claim 11 , wherein the one or more computer controllers are configured to control one or more of a time frame for proliferation and differentiation of the precursor cells at the first bioreactor, a degree of twisting of the cell-laden fibers at the second bioreactor, a rotation rate of the wheels of the second bioreactor, a composition of the cultured tissue, a size of the cultured tissue, a cell density of the cultured tissue, a packing density of the cultured tissue, and a ratio of muscle cell-laden fibers and fat cell-laden fibers in the cultured tissue.
18 . The system of claim 1 , wherein the cells include tetracycline responsive promoters for expression of myogenic or adipogenic genes, and wherein the culture medium includes tetracycline.
19 . The system of claim 1 , wherein the cultured tissue is composed of muscle cell-laden fibers, fat cell-laden fibers, or a combination of muscle cell-laden fibers and fat cell-laden fibers.
20 . The system of claim 1 wherein the fiber scaffold is composed of a material selected from the group consisting of collagen, silk, chitosan, wheat gluten, cellulose, zein, starch, soy protein, fungal mycelia, and combinations thereof.