In vitro growth of tissues suitable to the formation of bone and bone forming tissue formed thereby

• US 20070105222A1
• Filed: 09/11/2006
• Published: 05/10/2007
• Est. Priority Date: 05/01/2003
• Status: Active Grant

• Current Assignee: LifeNet Health, Inc.
• Original Assignee: LifeNet Health, Inc.
• Inventors: Wolfinbarger, Lloyd, Qin, Xiaofei
• Granted Patent: US 9,080,141 B2
• Time in Patent Office: Days
• US Class Current: 435/373
• CPC Class Codes: A61L 2430/02 for reconstruction of bones; weight-bearing implants
• CPC Class Codes: A61L 27/3608 Bone, e.g. demineralised bone matrix [DBM], bone powder
• CPC Class Codes: A61L 27/3683 subjected to a specific treatment prior to implantation, e.g. decellularising, demineralising, grinding, cellular disruption/non-collagenous protein removal, anti-calcification, crosslinking, supercritical fluid extraction, enzyme treatment
• CPC Class Codes: C12M 21/08 for producing artificial tissue or for ex-vivo cultivation of tissue prostheses A61F2/00, grafts A61L27/00
• CPC Class Codes: C12M 25/14 Scaffolds; Matrices in general C12N5/0068
• CPC Class Codes: C12M 29/16 Hollow fibers hollow fiber modules in general B01D63/02
• CPC Class Codes: C12M 35/02 Electrical or electromagnetic means, e.g. for electroporation or for cell fusion
• CPC Class Codes: C12M 35/04 Mechanical means, e.g. sonic waves, stretching forces, pressure or shear stimuli
• CPC Class Codes: C12N 5/0654 Osteocytes, Osteoblasts, Odontocytes; Bones, Teeth

Abstract

The present invention is directed to a device for the growth of new bone or bone-like tissue under in vitro cell culture conditions.

Claims

1. A device for the growth of new bone or bone-like tissue under in vitro cell culture conditions comprising a bioreactor, wherein the bioreactor comprises an inlet port to receive nutrient solutions into the bioreactor, an outlet port to remove nutrient solutions from the bioreactor, sample injection ports, and an inlet port and outlet port for the bioreactor to cyclically receive negative pressure and positive pressure, optionally including hollow fibers for the delivery of nutrients and removal of wastes, wherein the bioreactor is capable of applying mechanical and electrical stimuli to the formed or forming new bone.

2. The device of claim 1, wherein the bioreactor comprises an outer nondeformable chamber and in inner deformable chamber.

3. The device of claim 2, wherein the inlet and outlet ports to receive and remove nutrient solutions permit the flow of nutrient solutions through the inner deformable chamber.

4. The device of claim 2, wherein the inlet and outlet ports to receive and remove nutrient solutions permit the flow of nutrient solutions to contact the hollow fibers in the inner deformable chamber.

5. The device of claim 2, wherein the inlet and outlet ports to receive and remove nutrient solutions permit the flow of nutrient solutions through the outer nondeformable chamber.

6. The device of claim 2, wherein the inner deformable chamber receives samples through the sample injection port.

7. The device of claim 2, wherein the negative and positive pressure is received in the volume between the outer nondeformable chamber and the inner deformable chamber through the inlet and outlet ports.

8. The device of claim 4, wherein a first endplate receives the inlet port for the delivery of nutrients solution and a second endplate receive the outlet port for the removal of nutrients solution.

9. The device of claim 8, wherein the first and second endplate secure the ends of the outer nondeformable chamber of the bioreactor.

10. The device of claim 8, wherein the first and second endplate secure the ends of the inner deformable chamber of the bioreactor.

11. The device of claim 1, further comprising hollow fibers.

12. The device of claim 11, wherein the hollow fibers are round and tubular.

13. The device of claim 11, wherein the hollow fibers are in the form of concentric rings.

14. The device of claim 11, wherein the hollow fibers are made of a resorbable or non-resorbable membrane.

15. The device of claim 14, wherein the hollow fibers comprise polydioxanone, polylactide, polyglactin, polyglycolic acid, polylactic acid, polyglycolic acid/trimethylene carbonate, cellulose, methylcellulose, cellulosic polymers, cellulose ester, regenerated cellulose, pluronic, collagen, elastin, or a combination thereof.

16. The device of claim 11, wherein the hollow fibers include pores of specified diameter that extend from the inside to the outside of the wall of the hollow fiber.

17. The device of claim 16, wherein the pores have a diameter of about 2 kiloDaltons to about 50 kiloDaltons.

18. The device of claim 17, wherein the pores have diameter of about 5 kiloDaltons to about 25 kiloDaltons.

19. The device of claim 17, wherein the pores have a diameter of about 2 kiloDaltons to about 15 kiloDaltons.

20. The device of claim 2, wherein the inner deformable chamber comprises a deformable wall comprising a flexible permeable barrier.

21. The device of claim 20, wherein the flexible permeable barrier comprises a resorbable or non-resorbable membrane.

22. The device of claim 21, wherein the membrane comprises polydioxanone, polylactide, polyglactin, polyglycolic acid, polylactic acid, polyglycolic acid/trimethylene carbonate, cellulose, methylcellulose, cellulosic polymers, cellulose ester, regenerated cellulose, pluronic, collagen, elastin, or a combination thereof.

23. The device of claim 20, wherein the inner deformable chamber further comprises a fine mesh.

24. The device of claim 23, wherein the fine mesh comprises sterilizable materials.

25. The device of claim 24, wherein the fine mesh comprises stainless steel, titanium, plastic polymer, nylon polymer, braided collagen, silk polymer, or a combination thereof.

26. The device of claim 23, wherein the fine mesh has a pore size range of between about 0.1 to about 10 mm.

27. The device of claim 26, wherein the fine mesh has a pore size range of between about 1 mm and about 5 mm.

28. The device of claim 23, wherein the fine mesh is contacted to the inner surface of the flexible permeable barrier.

29. The device of claim 23, wherein the fine mesh is contacted to the outer surface of the flexible permeable barrier.

30. The device of claim 23, wherein fine mesh contacts the inner surface of the flexible permeable barrier and the outer surface of the flexible permeable barrier.

31. The device of claim 11, wherein the hollow fibers have an average inside diameter of between about 0.5 to about 1.0 millimeter range.

32. The device of claim 31, wherein the hollow fibers are present in the amount of between about 10 to about 400.

33. The device of claim 32, wherein the bioreactor has an inside diameter of about 2 centimeters.

34. The device of claim 31, wherein the hollow fibers are present in an amount of between about 100 to about 4000.

35. The device of claim 34, wherein the bioreactor has an inside diameter of about 5 centimeters.

36. The device of claim 11, wherein the hollow fibers are present as concentric rings of double wall dialysis tubing of average inside diameter of 0.5 to 1.0 millimeter range.

37. The device of claim 36, wherein the hollow fibers are present in an amount of between about 5 to about 15.

38. The device of claim 37, wherein the bioreactor has an inside diameter of about 5 centimeters.

39. The device of claim 36, wherein the hollow fibers are present in an amount of between about 2 to about 10.

40. The device of claim 39, wherein the bioreactor has an inside diameter of about 2 centimeters.

41. The device of claim 20, wherein the deformable wall is sterilizable.

42. The device of claim 20, wherein the deformable wall has tensile properties rendering it deformable under negative and positive pressures between about 10 and 30 mmHg.

43. The device of claim 20, wherein the deformable wall conducts an electrical current.

44. The device of claim 23, wherein the fine mesh conducts an electrical current.

45-91. -91. (canceled)