Polymer-ceramic-hydrogel composite scaffold for osteochondral repair

• US 20060036331A1
• Filed: 03/04/2005
• Published: 02/16/2006
• Est. Priority Date: 03/05/2004
• Status: Abandoned Application

• Current Assignee: Trustees Of Columbia University In The City Of New York (Columbia University)
• Original Assignee: Trustees Of Columbia University In The City Of New York (Columbia University)
• Inventors: Lu, Helen H., Hung, Clark T., Jiang, Jie, Ateshian, Gerard, Guo, X. Edward
• Application Number:
  US11/073,261
• Publication Number:
  US 20060036331A1
• Time in Patent Office: Days
• US Class Current: 623/23.510
• CPC Class Codes: A61F 2/30756 Cartilage endoprostheses A61F2/3603 takes precedence
• CPC Class Codes: A61F 2002/2817 Bone stimulation by chemical reactions or by osteogenic or biological products for enhancing ossification, e.g. by bone morphogenetic or morphogenic proteins [BMP] or by transforming growth factors [TGF]
• CPC Class Codes: A61F 2002/30062 (bio)absorbable, biodegradable, bioerodable, (bio)resorbable, resorptive
• CPC Class Codes: A61F 2002/30766 Scaffolds for cartilage ingrowth and regeneration
• CPC Class Codes: A61F 2002/30957 using a positive or a negative model, e.g. moulds
• CPC Class Codes: A61F 2210/0004 bioabsorbable
• CPC Class Codes: A61F 2310/00293 containing a phosphorus-containing compound, e.g. apatite
• CPC Class Codes: A61K 35/12 Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells vaccines or medicinal preparations containing antigens or antibodies A61K39/00
• CPC Class Codes: A61L 27/3817 Cartilage-forming cells, e.g. pre-chondrocytes
• CPC Class Codes: A61L 27/3821 Bone-forming cells, e.g. osteoblasts, osteocytes, osteoprogenitor cells
• CPC Class Codes: A61L 27/3839 characterised by the site of application in the body materials for artificial blood vessels A61L27/507; materials for use in artificial skin A61L27/60
• CPC Class Codes: A61L 27/3891 as distinct cell layers
• CPC Class Codes: C12N 2502/1311 Osteocytes, osteoblasts, odontoblasts
• CPC Class Codes: C12N 2502/1317 Chondrocytes
• CPC Class Codes: C12N 2533/14 Ceramic
• CPC Class Codes: C12N 2533/40 Polyhydroxyacids, e.g. polymers of glycolic or lactic acid (PGA, PLA, PLGA); Bioresorbable polymers
• CPC Class Codes: C12N 2533/72 Chitin, chitosan
• CPC Class Codes: C12N 2533/74 Alginate
• CPC Class Codes: C12N 2533/76 Agarose, agar-agar
• CPC Class Codes: C12N 5/0654 Osteocytes, Osteoblasts, Odontocytes; Bones, Teeth
• CPC Class Codes: C12N 5/0655 : Chondrocytes; Cartilage
• CPC Class Codes: C12N 5/0697 : Artificial constructs associating cells of different lineages, e.g. tissue equivalents blood vessels C12N5/0691

Abstract

This invention pertains to materials and methods relating to the biological fixation of one tissue type to another different tissue type, i.e., the fixation of cartilage to bone. A scaffold apparatus for osteochondral tissue engineering is described. The apparatus comprises regions of varying matrices which provide a functional interface between multiple tissue types. Further, a method for preparing the scaffold apparatus is provided. Methods for treating osteochondral tissue injury and cartilage degeneration using the scaffold apparatus are also described. In addition, a method for evaluating cell-mediated and scaffold-related parameters of development and maintenance of multiple tissue zones in vitro is described.

Claims

1. An apparatus for osteochondral tissue engineering, wherein said apparatus comprises regions of varying matrices which provide a functional interface between multiple tissue types, said regions comprising:

(a) a first region comprising a hydrogel;

(b) a second region adjoining the first region; and

(c) a third region adjoining the second region and comprising a porous scaffold.

2. The apparatus of claim 1, wherein the apparatus promotes growth and development of multiple tissue types.

3. The apparatus of claim 1, wherein the first region is seeded with cells for chondrogenesis, the third region is seeded with cells for osteogenesis, and the scaffold apparatus comprising the first region seeded with the cells for chondrogenesis, and the third region seeded with the cells for osteogenesis is maintained in an environment supporting migration of at least some of the cells for chondrogenesis into the second region and migration of at least some of the cells for osteogenesis into the second region.

4. The apparatus of claim 3, wherein the cells for chondrogenesis include chondrocytes.

5. The apparatus of claim 4, wherein the chondrocytes are selected from the group comprising surface zone chondrocytes, middle zone chondrocytes or deep zone chondrocytes.

6. The apparatus of claim 3, wherein the cells for chondrogenesis include stem cells.

7. The apparatus of claim 3, wherein the cells for osteogenesis include osteoblasts and/or osteoblast-like cells.

8. The apparatus of claim 3, wherein the cells for osteogenesis include stem cells.

9. The apparatus of claim 1, wherein the first region supports the growth and maintenance of cartilage tissue, the third region supports the growth and maintenance of bone tissue, and the second region functions as an osteochondral interfacial zone.

10. The apparatus of claim 3, wherein the first region is rich in glycosaminoglycan.

11. The apparatus of claim 1, one or more agents selected from a group comprising the following are introduced in said first region:

anti-infectives;

hormones, analgesics;

anti-inflammatory agents;

growth factors;

chemotherapeutic agents;

anti-rejection agents; and

RGD peptides.

12. The apparatus of claim 11, wherein the growth factor is Transforming Growth Factor-beta (TGF-beta).

13. The apparatus of claim 1, wherein the hydrogel of the first region is agarose hydrogel.

14. The apparatus of claim 1, wherein the second region supports the growth and maintenance of fibrocartilage.

15. The apparatus of claim 1, wherein the second region includes a combination of hydrogel and the porous scaffold.

16. The apparatus of claim 14, wherein the second region is rich in glycosaminoglycan and collagen.

17. The apparatus of claim 1, wherein one or more growth factors selected from the following are introduced into the second region:

Transforming Growth Factor-beta (TGF-beta), parathyroid hormone and insulin-derived growth factors (IGF).

18. The apparatus of claim 1, wherein the third region for supporting the growth and maintenance of bone tissue is seeded with at least one of osteoblasts, osteoblast-like cells and stem cells.

19. The apparatus of claim 1, wherein the third region includes a mineralized collagen matrix.

20. The apparatus of claim 1, wherein the third region contains at least one of osteogenic agents, osteogenic materials, osteoinductive agents, osteoinductive materials, osteoconductive agents, osteoconductive materials, growth factors and chemical factors.

21. The apparatus of claim 20, wherein the growth factors are selected from the group comprising Transforming Growth Factor-beta (TGF-beta), bone morphogenetic proteins, vascular endothelial growth factor, platelet-derived growth factor and insulin-derived growth factors (IGF).

22. The apparatus of claim 1, wherein the porous scaffold comprises a composite of polymer and ceramic.

23. The apparatus of claim 22, wherein the ceramic is bioactive glass.

24. The apparatus of claim 22, wherein the ceramic is calcium phosphatase.

25. The apparatus of claim 23, wherein the third region contains approximately 25% bioactive glass by weight.

26. The apparatus of claim 22, wherein a gradient of calcium phosphate concentrations appears across the first, second and third regions.

27. The apparatus of claim 26, wherein the gradient of calcium phosphate concentration is related to the percent of bioactive glass by weight in the third region

28. The apparatus of claim 26, wherein the calcium phosphate is selected from the group comprising tricalcium phosphate, hydroxyapatite and a combination thereof.

29. The apparatus of claim 22, wherein the polymer in the third region is selected from the group comprising aliphatic polyesters, poly(amino acids), copoly(ether-esters), polyalkylenes oxalates, polyamides, poly(iminocarbonates), polyorthoesters, polyoxaesters, polyamidoesters, poly(ε

-caprolactone)s, polyanhydrides, polyarylates, polyphosphazenes, polyhydroxyalkanoates, polysaccharides, and biopolymers, and a blend of two or more of the preceding polymers.

30. The apparatus of claim 29, wherein the polymer comprises at least one of the poly(lactide-co-glycolide), poly(lactide) and poly(glycolide).

31. The apparatus of claim 1, wherein the apparatus is biodegradable.

32. The apparatus of claim 1, wherein the apparatus is osteointegrative.

33. A method for treating osteochondral tissue injury in a subject comprising grafting the apparatus of claim 1 with a co-culture of two or more cells selected from the group comprising chondrocytes, osteoblasts, osteoblast-like cells and stem cells in the subject at the location of osteochondral injury.

34. The method of claim 33, wherein the osteochondral tissue injury is craniofacial tissue injury.

35. The method of claim 33, wherein the osteochondral tissue injury is musculoskeletal tissue injury.

36. The method of claim 33, wherein the chondrocytes are selected from the group comprising surface zone chondrocytes, middle zone chondrocytes and deep zone chondrocytes.

37. A method for treating cartilage degeneration in a subject comprising grafting the apparatus of claim 1 with a co-culture of two or more cells selected from the group comprising chondrocytes, osteoblasts, osteoblast-like cells and stem cells in the subject at the location of cartilage degeneration.

38. The method of claim 37, wherein the cartilage degeneration is caused by osteoarthritis.

39. The method of claim 37, wherein the chondrocytes are selected from the group comprising surface zone chondrocytes, middle zone chondrocytes and deep zone chondrocytes.

40. A method for evaluating cell-mediated and scaffold-related parameters of development and maintenance of multiple tissue zones in vitro comprising:

(a) co-culturing cells of different tissue on the apparatus of claim 1;

(b) after a suitable period of time, examining the development and maintenance of the cells on the apparatus.

41. The method of claim 40, wherein the cells of different tissues comprise two or more of the cells selected from the group comprising chondrocytes, osteoblasts, osteoblast-like cells and stem cells.

42. The method of claim 41, wherein the chondrocytes are selected from the group comprising surface zone chondrocytes, middle zone chondrocytes and deep zone chondrocytes.

43. The method of claim 40, wherein the cell-mediated and scaffold related parameters of development and maintenance comprise cell proliferation, alkaline phosphatase activity, glycosaminoglycan deposition, mineralization, cell viability, scaffold integration, cell morphology, phenotypic expression, and collagen production.

44. A method for preparing an apparatus for osteochondral tissue engineering, said method comprising the steps of:

(a) using a mold to form an apparatus comprising a first region comprising hydrogel, a second region adjoining said first region, and a third region adjoining said second region and comprising a porous scaffold;

(b) seeding said first region with one or more cells for chondrogenesis;

(c) seeding said third region with one or more cells for osteogenesis; and

(d) maintaining the apparatus comprising the first region seeded with the cells for chondrogenesis and the third region seeded with the cells for osteogenesis in an environment supporting migration of at least some of the cells for chondrogenesis into the second region and migration of at least some of the cells for osteogenesis into the second region.

45. The method of claim 44, wherein said cells for chondrogenesis include chondrocytes.

46. The method of claim 45, wherein the chondrocytes are selected from the group comprising surface zone chondrocytes, middle zone chondrocytes and deep zone chondrocytes.

47. The method of claim 44, wherein said cells for chondrogenesis include stem cells.

48. The method of claim 44, wherein the first region supports the growth and maintenance of cartilage tissue, the third region supports the growth and maintenance of bone tissue, and the second region functions as an osteochondral interfacial zone.

49. The method of claim 44, wherein said cells for osteogenesis include osteoblasts and/or osteoblast-like cells.

50. The method of claim 44, wherein said cells for osteogenesis include stem cells.

51. The method of claim 44, wherein the first region is rich in glycosaminoglycan.

52. The method of claim 44, further comprising the step of introducing in said first region one or more agents selected from a group comprising the following:

anti-infectives;

hormones;

analgesics;

anti-inflammatory agents;

growth factors;

chemotherapeutic agents;

anti-rejection agents; and

RGD peptides.

53. The method of claim 52, wherein the growth factor is Transforming Growth Factor-beta (TGF-beta).

54. The method of claim 44, wherein the hydrogel of the first region is agarose hydrogel.

55. The method of claim 44, wherein the second region supports the growth and maintenance of fibrocartilage.

56. The method of claim 44, wherein the second region includes a combination of hydrogel and the porous scaffold

57. The method of claim 55, wherein the second region is rich in glycosaminoglycan and collagen.

58. The method of claim 44, wherein one or more growth factors selected from the following are introduced into the second region:

Transforming Growth Factor-beta (TGF-beta), parathyroid hormone and insulin-derived growth factors (IGF).

59. The method of claim 44, wherein the third region includes a mineralized collagen matrix.

60. The method of claim 44, wherein the third region contains at least one of osteogenic agents, osteogenic materials, osteoinductive agents, osteoinductive materials, osteoconductive agents, osteoconductive materials, growth factors and chemical factors.

61. The method of claim 60, wherein the growth factors are selected from the group comprising Transforming Growth Factor-beta (TGF-beta), bone morphogenetic proteins, vascular endothelial growth factor, platelet-derived growth factor and insulin-derived growth factors (IGF).

62. The method of claim 44, wherein the porous scaffold comprises a composite of polymer and ceramic.

63. The method of claim 62, wherein the ceramic is bioactive glass.

64. The method of claim 62, wherein the ceramic is calcium phosphatase.

65. The method of claim 63, wherein the third region contains approximately 25% bioactive glass by weight.

66. The method of claim 62, wherein a gradient of calcium phosphate concentrations appear across said first, second and third regions.

67. The method of claim 66, wherein the gradient of calcium phosphate concentrations is related to the percent of bioactive glass by weight in the third region.

68. The method of claim 66, wherein the calcium phosphate is selected from the group comprising tricalcium phosphate, hydroxyapatite, and a combination thereof.

69. The method of claim 62, wherein the polymer in the third region is selected from the group comprising aliphatic polyesters, poly(amino acids), copoly(ether-esters), polyalkylenes oxalates, polyamides, poly(iminocarbonates), polyorthoesters, polyoxaesters, polyamidoesters, poly(ε

-caprolactone)s, polyanhydrides, polyarylates, polyphosphazenes, polyhydroxyalkanoates, polysaccharides, and biopolymers, and a blend of two or more of the preceding polymers.

70. The method of claim 69, wherein the polymer comprises at least one of poly(lactide-co-glycolide), poly(lactide) and poly(glycolide).

71. The method of claim 44, wherein the apparatus prepared though said method is biodegradable.

72. The method of claim 44, wherein the apparatus prepared through said method is osteoinductive.