Preparation for repairing cartilage tissue, especially articular cartilage defects

• US 20070148242A1
• Filed: 02/23/2004
• Published: 06/28/2007
• Est. Priority Date: 02/26/2003
• Status: Active Grant

• Current Assignee: Zimmer Orthobiologics, Inc. (Zimmer Biomet Holdings, Inc.)
• Original Assignee: Zimmer Orthobiologics, Inc. (Zimmer Biomet Holdings, Inc.)
• Inventors: Bittmann, Peter, Wagner, Philipp, Frenz, Martin, Vilei, Simona
• Granted Patent: US 8,173,162 B2
• Time in Patent Office: Days
• US Class Current: 424/484
• 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 2/30767 Special external or bone-contacting surface, e.g. coating for improving bone ingrowth
• CPC Class Codes: A61F 2/30965 Reinforcing the prosthesis by embedding particles or fibres during moulding or dipping
• CPC Class Codes: A61F 2/3872 Meniscus for implantation between the natural bone surfaces
• CPC Class Codes: A61F 2002/30004 the prosthesis being made from materials having different values of a given property at different locations within the same prosthesis
• CPC Class Codes: A61F 2002/30006 differing in density or specific weight
• CPC Class Codes: A61F 2002/30062 (bio)absorbable, biodegradable, bioerodable, (bio)resorbable, resorptive
• CPC Class Codes: A61F 2002/30131 horseshoe- or crescent- or C-shaped or U-shaped
• CPC Class Codes: A61F 2002/30224 cylindrical
• CPC Class Codes: A61F 2002/30225 Flat cylinders, i.e. discs
• CPC Class Codes: A61F 2002/30235 tubular, e.g. sleeves
• CPC Class Codes: A61F 2002/3092 having an open-celled or open-pored structure
• CPC Class Codes: A61F 2210/0004 bioabsorbable
• CPC Class Codes: A61F 2230/0013 Horseshoe-shaped, e.g. crescent-shaped, C-shaped, U-shaped
• CPC Class Codes: A61F 2230/0069 cylindrical
• CPC Class Codes: A61F 2250/0014 having different values of a given property or geometrical feature, e.g. mechanical property or material property, at different locations within the same prosthesis
• CPC Class Codes: A61F 2250/0015 differing in density or specific weight
• CPC Class Codes: A61F 2310/00293 containing a phosphorus-containing compound, e.g. apatite
• CPC Class Codes: A61F 2310/00365 Proteins; Polypeptides; Degradation products thereof
• CPC Class Codes: A61L 2430/06 : for cartilage reconstruction, e.g. meniscus
• CPC Class Codes: A61L 27/3608 : Bone, e.g. demineralised bone matrix [DBM], bone powder
• CPC Class Codes: A61L 27/3612 : Cartilage, synovial fluid
• CPC Class Codes: A61L 27/3654 : Cartilage, e.g. meniscus
• CPC Class Codes: A61L 27/3817 : Cartilage-forming cells, e.g. pre-chondrocytes
• CPC Class Codes: A61L 27/3852 : Cartilage, e.g. meniscus
• CPC Class Codes: A61L 27/56 : Porous materials, e.g. foams or sponges
• CPC Class Codes: A61P 19/00 : Drugs for skeletal disorders

Abstract

The invention relates to preparations which are suitable for repairing enchondral or osteochondral defects (4) by means of implantation, said preparations comprising a cartilage element (A) and optionally a bone element (B) which is connected to the cartilage element (A). The cartilage element (A) can already contain cells during the implantation or is populated after the implantation with cells migrating from surrounding tissue. The aim of the invention is to better equip the cartilage element (A) of one such preparation for integration into the surrounding tissue and/or for an easy-to-achieve, primary stability. To this end, said cartilage element is not homogeneously embodied but has different characteristics in a peripheral and/or basal region (2, 3) to those in a central region (3). Said differing characteristics (A) relate to the structure and/or composition of the matrix used and/or to the cells established in the matrix, and are in no way used to prevent the migration of cells into the preparation from the surrounding tissue.

Claims

1. Preparation for repairing cartilage tissue, said preparation comprising a cartilage part that comprises a homogenous open-porous matrix suitable for being populated with cells, characterized in that a peripheral region and/or a basal region of the cartilage part has characteristics differing from characteristics of a central region of the cartilage part wherein said characteristics relate to the inclusion of a different factor, a factor acting differently over time, different concentrations of a factor, cells having different degrees of differentiation and/or cells having different phenotypic potential.

2. Preparation according to claim 1, characterized in that the matrix of the cartilage part is populated with cells and that the cells in the central region are in a state of higher differentiation than the cells in the peripheral and/or basal region.

3. Preparation according to claim 2, characterized in that the cells in the central region are chondrocytes or cells in a state of differentiation close to the state of differentiation of chondrocytes, and that the cells in the peripheral and/or basal region are stem cells.

4. Preparation according to claim 1, characterized in that the matrix of the cartilage part is populated with cells, wherein a cell density in the central region is greater than the cell density in the basal region.

5. Preparation according to claim 1, characterized in that the matrix of the cartilage part is populated with cells in vitro.

6. Preparation according to claim 1, characterized in that the concentration of the factor refers to its immediately active form.

7. Preparation according to claim 6, characterized in that in the peripheral and/or basal region contain a factor promoting cell propagation, said factors being absent from the central region.

8. Preparation according to claim 6, characterized in that the central region contains an immediately-acting factor that promotes cell differentiation to chondrocytes, said factor being absent from the peripheral and/or basal region or being contained therein in a form with a delayed effect.

9. Preparation according to claim 1, characterized in that the matrix of the cartilage part contains an inhibitor or antisense in its peripheral and/or basal region, said inhibitor or antisense being absent from the central region.

10. Preparation according to claim 9, characterized in that the matrix of the cartilage part contains in the peripheral and/or basal region an inflammation inhibitor, protease inhibitor, and/or apoptosis inhibitor, said inflammation inhibitor, protease inhibitor, and/or apoptosis inhibitor being absent from the central region.

11. Preparation according to claim 1, characterized in that the concentration of the factor in the central region is zero.

12. Preparation according to claim 3, characterized in that the stem cells are pluripotent.

13. Preparation according to claim 1, characterized in that the matrix of the cartilage part in the peripheral and/or basal region contains a bonding agent which is missing from the central region.

14. Preparation according to claim 1, characterized in that the matrix of the cartilage part contains an in situ activatable bonding agent in its peripheral and/or basal region, said in situ activatable bonding agent being absent from its central region.

15. Preparation according to claim 14, characterized in that the in situ activatable bonding agent comprises a mixture of an albumin adhesive with indocyanine green.

16. Preparation according to claim 1, characterized in that it is suitable for repairing a defective enchondral site in articular cartilage.

17. Preparation according to claim 1, characterized in that it comprises a bone part.

18. Preparation according to claim 1, characterized in that it is suitable for repairing a meniscus.

19. Preparation according to claim 1, characterized in that the characteristics relate to the inclusion of a different factor in the matrix.

20. Preparation according to claim 1, characterized in that the characteristics relate to a factor acting differently over time in the matrix.

21. Preparation according to claim 1, characterized in that the characteristics relate to different concentrations of a factor in the matrix.

22. Preparation according to claim 1, characterized in that the characteristics relate to cells having different degrees of differentiation in the matrix.

23. Preparation according to claim 1, characterized in that the characteristics relate to cells having different phenotypic potential in the matrix.

24. Preparation according to claim 1, characterized in that the matrix of the cartilage element (A) is populated with cells and that the cells in the basal region are of a different phenotypic potential than are the cells in the central and/or peripheral region.

25. Preparation according to claim 24, characterized in that the cells in the basal region have an osteogenic potential and the cells in the central and/or peripheral region have a chondrogenic potential.

26. Preparation according to claim 21, characterized in that it is suitable for repairing a defective osteochondral site in joint cartilage.

53. Preparation according to claim 7, characterized in that it is suitable for repairing a defective chondral site in joint cartilage.

27. Preparation for repairing cartilage tissue, said preparation comprising a cartilage element, having a open-porous matrix suitable for populating with cells, characterized in that a peripheral region and/or a basal region of the cartilage element has characteristics differing from a central region of the cartilage element, wherein the aforementioned characteristics relate to the inclusion of a different factor, a factor acting differently over time, and/or different concentrations of a factor in the matrix.

28. Preparation according to claim 27, characterized in that the characteristics relate to the inclusion of a different factor in the matrix.

29. Preparation according to claim 27, characterized in that the characteristics relate to a factor acting differently over time in the matrix.

30. Preparation according to claim 27, characterized in that the characteristics relate to different concentrations of a factor in the matrix.

31. Preparation according to claim 27, characterized in that a peripheral region and/or a basal region of the cartilage element includes cells having a degree of differentiation differing from the degree of differentiation of cells in the central region.

32. Preparation according to claim 27, characterized in that a central region and/or a peripheral region of the cartilage element includes cells having a different phenotypic potential than that of cells in the basal region.

33. Preparation according to claim 27, characterized in that the matrix of the cartilage element is populated with cells and that the cells in the central region are more differentiated than are the cells in the peripheral and/or basal region.

34. Preparation according to claim 33, characterized in that the cells in the central region are chondrocytes or cells with a degree of differentiation close to that of chondrocytes, and that the cells in the peripheral and/or basal region are stem cells.

35. Preparation according to claim 27, characterized in that the cells in the basal region have an osteogenic potential and the cells in the central and/or peripheral region have a chondrogenic potential.

36. Preparation according to claim 27, characterized in that the matrix of the cartilage element is populated with cells, wherein the cell density in the central region is greater than the cell density in the basal region.

37. Preparation according to claim 27, characterized in that the matrix of the cartilage element is populated with cells in vitro.

38. Preparation according to claim 27, characterized in that the concentration of the factor refers to its immediately active form.

39. Preparation according to claim 27, characterized in that the peripheral and/or basal region contains a factor promoting cell propagation, which is missing from the central region.

40. Preparation according to claim 27, characterized in that the peripheral and/or basal region contains a factor promoting cell propagation, which is at a lower concentration in the central region.

41. Preparation according to claim 27, characterized in that in the central region, an immediately acting factor is present that promotes cell differentiation with respect to chondrocytes and that is missing from the peripheral and/or basal region or is contained in a form with a delayed effect.

42. Preparation according to claim 27, characterized in that in the central region, an immediately acting factor is present that promotes cell differentiation with respect to chondrocytes and that is at a lower concentration in the peripheral and/or basal region.

43. Preparation according to claim 27, characterized in that the matrix of the cartilage element contains an inhibitor or antisense in its peripheral and/or basal region, which is missing from the central region.

44. Preparation according to claim 27, characterized in that the matrix of the cartilage element contains an inhibitor or antisense in its peripheral and/or basal region, which is at a lower concentration in the central region.

45. Preparation according to claim 27, characterized in that the matrix of the cartilage element in the peripheral and/or basal region contains an inflammation inhibitor, a protease inhibitor, and/or an apoptosis inhibitor, which is missing from the central region.

46. Preparation according to claim 27, characterized in that the matrix of the cartilage element in the peripheral and/or basal region contains an inflammation inhibitor, a protease inhibitor, and/or an apoptosis inhibitor, which is at a lower concentration in the central region.

47. Preparation according to claim 27, characterized in that the concentration of the factor in the central region is zero.

48. Preparation according to claim 34, characterized in that the stem cells are pluripotent.

49. Preparation according to claim 27, characterized in that the matrix of the cartilage element in the peripheral and/or basal region contains a bonding agent which is missing from the central region.

50. Preparation according to claim 27, characterized in that the matrix of the cartilage element contains an in situ activatable connecting element in its peripheral and/or basal region, which is missing from its central region.

51. Preparation according to claim 50, characterized in that the in situ activatable connecting element comprises an admixture of albumin adhesive and indocyanine green.

52. Preparation according to claim 27, characterized in that the peripheral and/or basal region has a greater porosity and/or pores of greater size than the central region.

54. Preparation according to claim 27, characterized in that it has a bone element.

55. Preparation according to claim 54, characterized in that it is suitable for repairing a defective osteochondral site in joint cartilage.

56. Preparation according to claim 27, characterized in that it is suitable for repairing a meniscus.