Guided development and support of hydrogel-cell compositions

• US 6,171,610 B1
• Filed: 11/25/1998
• Issued: 01/09/2001
• Est. Priority Date: 04/24/1998
• Status: Expired due to Term

• Current Assignee: Children's Medical Center Corporation, Vbi Technologies, LLC
• Original Assignee: Children's Medical Center Corporation, University Of Massachusetts
• Inventors: Vacanti, Martin P., Vacanti, Charles A., Vacanti, Joseph P.
• Primary Examiner(s): AZPURU, CARLOS A
• Application Number:
  US09/200,033
• Time in Patent Office: 776 Days
• Field of Search: 424/426, 623/12, 623/16
• US Class Current: 424/426
• CPC Class Codes: A61F 2/28 Bones joints A61F2/30
• CPC Class Codes: A61F 2/30756 Cartilage endoprostheses A61F2/3603 takes precedence
• CPC Class Codes: A61F 2002/30062 (bio)absorbable, biodegradable, bioerodable, (bio)resorbable, resorptive
• CPC Class Codes: A61F 2002/30199 Three-dimensional shapes
• CPC Class Codes: A61F 2210/0004 bioabsorbable
• CPC Class Codes: A61F 2230/0063 Three-dimensional shapes
• CPC Class Codes: A61F 2310/00293 containing a phosphorus-containing compound, e.g. apatite
• CPC Class Codes: A61L 27/12 Phosphorus-containing materials, e.g. apatite
• CPC Class Codes: A61L 27/18 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 27/3821 Bone-forming cells, e.g. osteoblasts, osteocytes, osteoprogenitor cells
• CPC Class Codes: A61L 27/383 Nerve cells, e.g. dendritic cells, Schwann cells
• CPC Class Codes: A61L 27/3843 Connective tissue
• CPC Class Codes: A61L 27/3878 Nerve tissue, brain, spinal cord, nerves, dura mater
• CPC Class Codes: A61L 27/52 Hydrogels or hydrocolloids
• CPC Class Codes: A61L 27/56 Porous materials, e.g. foams or sponges
• CPC Class Codes: A61L 27/58 Materials at least partially resorbable by the body
• CPC Class Codes: C08L 67/00 Compositions of polyesters obtained by reactions forming a carboxylic ester link in the main chain of polyester-amides C08L77/12; of polyester-imides C08L79/08; Compositions of derivatives of such polymers
• CPC Class Codes: C08L 67/04 Polyesters derived from hydroxycarboxylic acids, e.g. lactones C08L67/06 takes precedence
• CPC Class Codes: C08L 73/02 Polyanhydrides
• CPC Class Codes: C12N 2533/30 Synthetic polymers thermoreactive polymers, e.g. PNIPAm, C12N2539/10
• CPC Class Codes: C12N 2533/40 : Polyhydroxyacids, e.g. polymers of glycolic or lactic acid (PGA, PLA, PLGA); Bioresorbable polymers
• CPC Class Codes: C12N 5/0068 : General culture methods using substrates for specific animal cell type C12N5/06

Abstract

The invention features a method for generating new tissue by obtaining a liquid hydrogel-cell composition including a hydrogel and tissue precursor cells; delivering the liquid hydrogel-cell composition into a permeable, biocompatible support structure; and allowing the liquid hydrogel-cell composition to solidify within the support structure and the tissue precursor cells to grow and generate new tissue. The invention also features a tissue forming structure including a permeable, biocompatible support structure having a predetermined shape that corresponds to the shape of desired tissue; and a hydrogel-cell composition at least partially filling the support structure, wherein the hydrogel-cell composition includes a hydrogel and tissue precursor cells. The new tissue forming structure can be used in new methods to generate various tissues (e.g., to treat defective tissue) including new bone, cartilage, and nervous tissue such as spinal cord tissue. The invention also new isolated nervous system stem cells.

Claims

1. A method for generating new tissue, the method comprising:

obtaining a liquid hydrogel-cell composition comprising a hydrogel and tissue precursor cells;

delivering the liquid hydrogel-cell composition into a permeable, biocompatible support structure; and

allowing the liquid hydrogel-cell composition to solidify within the support structure and the tissue precursor cells to grow and generate new tissue that can engraft to tissue outside the support structure, and

wherein the tissue precursor cells are selected from the group consisting of central nervous system neural stem cells, autonomic nervous system neural stem cells, peripheral nervous system neural stem cells, neuroendocrine stem cells, and cartilage forming cells.

2. The method of claim 1, wherein the delivered liquid hydrogel-cell composition is injected into the support structure.

3. The method of claim 1, further comprising implanting the support structure into an animal.

4. The method of claim 3, wherein the hydrogel-cell composition is delivered after the support structure is implanted into an animal.

5. The method of claim 1, wherein the support structure comprises a ceramic material.

6. The method of claim 1, wherein the support structure is shaped in the form of desired tissue.

7. The method of claim 6, wherein the support structure is shaped in the form of articular cartilage adjacent a joint, a bone, a portion of a bone, or a bone defect.

8. The method of claim 6, wherein the support structure is shaped in the form of a cylinder having the diameter of the spinal cord of a mammal to be treated.

9. The method of claim 1, wherein the support structure is biodegradable.

10. The method of claim 1, wherein the support structure comprises a sponge or foam.

11. The method of claim 1, wherein the support structure is compressible.

12. The method of claim 1, wherein the support structure comprises a mesh of fibers.

13. The method of claim 1, wherein the support structure is rigid.

14. The method of claim 1, wherein the support structure is formed from polyanhydride, polyorthoester, polyglycolic acid, polylactic acid, or polyglactin.

15. The method of claim 1, wherein the support structure comprises porous hydroxyapatite.

16. The method of claim 1, wherein the hydrogel is selected from the group consisting of polysaccharides, proteins, polyphosphazenes, poly(oxyethylene)-poly(oxypropylene) block polymers, poly(oxyethylene)-poly(oxypropylene) block polymers of ethylene diamine, poly(acrylic acids), poly(methacrylic acids), copolymers of acrylic acid and methacrylic acid, poly(vinyl acetate), and sulfonated polymers.

17. The method of claim 1, wherein the tissue precursor cells are selected from the group consisting of central nervous system neural stem cells, autonomic nervous system neural stem cells, and peripheral nervous system neural stem cells.

18. The method of claim 1, wherein the tissue precursor cells are selected from the group consisting of brain stem cells and spinal cord stem cells.

19. The method of claim 1, wherein the tissue precursor cells are neuroendocrine stem cells.

20. The method of claim 1, wherein the tissue precursor cells are selected from the group consisting of bladder, small intestine, lung, heart, kidney, and liver autonomic neural stem cells.

48. The method of claim 1, wherein the tissue precursor cells are cartilage-forming cells.

50. The method of claim 1, wherein the tissue precursor cells are central nervous system neural stem cells.

51. The method of claim 1, wherein the tissue precursor cells are autonomic nervous system neural stem cells.

52. The method of claim 1, wherein the tissue precursor cells are peripheral nervous system neural stem cells.

21. A tissue forming structure comprising:

a permeable, biocompatible support structure having a predetermined shape that corresponds to the shape of desired tissue; and

a hydrogel-cell composition at least partially filling the support structure, wherein the hydrogel-cell composition comprises a hydrogel and tissue precursor cells, and wherein the support structure is sufficiently permeable to permit the tissue precursor cells to grow and generate new tissue that can engraft to tissue outside the support structure, and

wherein the tissue precursor cells are selected from the group consisting of central nervous system neural stem cells, autonomic nervous system neural stem cells, peripheral nervous system neural stem cells, neuroendocrine stem cells, and cartilage forming cells.

22. The tissue forming structure of claim 21, wherein the hydrogel-cell composition is a solidified suspension of hydrogel supporting dispersed tissue precursor cells.

23. The tissue forming structure of claim 21, wherein the support structure comprises a ceramic material.

24. The tissue forming structure of claim 21, wherein the support structure is biodegradable.

25. The tissue forming structure of claim 21, wherein the support structure comprises a sponge or foam.

26. The tissue forming structure of claim 21, wherein the support structure is compressible.

27. The tissue forming structure of claim 21, wherein the support structure comprises a mesh of polymeric fibers.

28. The tissue forming structure of claim 21, wherein the support structure comprises a mesh of polyglycolic acid fibers and polylactic acid.

29. The tissue forming structure of claim 21, wherein the support structure is formed from polyanhydride, polyorthoester, polyglycolic acid, polylactic acid, or polyglactin.

30. The tissue forming structure of claim 21, wherein the support structure comprises porous hydroxyapatite.

31. The tissue forming structure of claim 21, wherein the support structure comprises metal.

32. The tissue forming structure of claim 21, wherein the support structure is rigid.

33. The tissue forming structure of claim 21, wherein the hydrogel is selected from the group consisting of polysaccharides, proteins, polyphosphazenes, poly(oxyethylene)-poly(oxypropylene) block polymers, poly(oxyethylene)-poly(oxypropylene) block polymers of ethylene diamine, poly(acrylic acids), poly(methacrylic acids), copolymers of acrylic acid and methacrylic acid, poly(vinyl acetate), and sulfonated polymers.

34. The tissue forming structure of claim 21, wherein the tissue precursor cells are selected from the group consisting of central nervous system neural stem cells, autonomic nervous system neural stem cells, and peripheral nervous system neural stem cells.

35. The tissue forming structure of claim 21, wherein the tissue precursor cells are selected from the group consisting of brain stem cells and spinal cord stem cells.

36. The tissue forming structure of claim 21, wherein the tissue precursor cells are neuroendocrine stem cells.

37. The tissue forming structure of claim 21, wherein the tissue precursor cells are selected from the group consisting of bladder, small intestine, lung, heart, kidney, and liver autonomic neural stem cells.

38. A tissue forming structure of claim 22, wherein the cells are bone forming cells and the support structure comprises porous hydroxyapatite.

49. The structure of claim 21, wherein the tissue precursor cells are cartilage-forming cells.

53. The tissue forming structure of claim 21, wherein the tissue precursor cells are central nervous system neural stem cells.

54. The tissue forming structure of claim 21, wherein the tissue precursor cells are autonomic nervous system neural stem cells.

55. The tissue forming structure of claim 21, wherein the tissue precursor cells are peripheral nervous system neural stem cells.

39. A method of treating defective nervous tissue, the method comprising

locating the physical boundaries of the defective tissue;

removing the defective tissue to create a cavity and exposing healthy nervous tissue at the surfaces of the cavity;

loading a hydrogel-neural stem cell composition into a support structure in the general size and shape of the cavity, wherein the neural stem cells are selected to differentiate into the healthy nervous tissue; and

implanting the support structure into the cavity, thereby treating the defective nervous tissue.

40. The method of claim 39, wherein the defective nervous tissue is central nervous system tissue.

41. The method of claim 39, wherein the defective nervous tissue is in the brain.

42. The method of claim 39, wherein the defective nervous tissue is autonomic nervous system tissue.

43. The method of claim 39, wherein the defective nervous tissue is neuroendocrine tissue.

44. The method of claim 39, wherein the neural stem cells are isolated from the healthy nervous tissue.

45. The method of claim 39, wherein a spacer is implanted into the cavity temporarily, and is then replaced with the support structure.

46. The method of claim 39, wherein the hydrogel-neural stem cell composition is loaded into the support structure after the structure is implanted into the cavity.

47. A method of claim 39, wherein the defective nervous tissue is in the spinal cord, the method comprising

locating the physical boundaries of the defective spinal cord tissue;

removing the defective tissue to create a cavity and exposing healthy spinal cord tissue at the surfaces of the cavity;

loading a hydrogel-spinal cord stem cell composition into a support structure in the general size and shape of the spinal cord cavity; and

implanting the support structure into the spinal cord cavity, thereby treating the defective spinal cord tissue.

56. The method of claim 39, wherein the defective nervous tissue is peripheral nervous system tissue.

57. The method of claim 39, wherein the hydrogel-neural stem cell. composition is loaded into the support structure after the structure has been implanted.

58. The method of claim 47, wherein the hydrogel-spinal cord stem cell composition is loaded into the support structure after the structure has been implanted.