ENGINEERED OSTEOCHONDRAL CONSTRUCT FOR TREATMENT OF ARTICULAR CARTILAGE DEFECTS

• US 20100241228A1
• Filed: 01/29/2010
• Published: 09/23/2010
• Est. Priority Date: 07/07/2006
• Status: Abandoned Application

• Current Assignee: Musculoskeletal Transplant Foundation
• Original Assignee: Musculoskeletal Transplant Foundation
• Inventors: von Versen, Rudiger Walter Arthur, Syring, Carina
• Application Number:
  US12/696,366
• Publication Number:
  US 20100241228A1
• Time in Patent Office: Days
• US Class Current: 623/14.120
• 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: A61K 35/32 Bones; Osteocytes; Osteoblasts; Tendons; Tenocytes; Teeth; Odontoblasts; Cartilage; Chondrocytes; Synovial membrane
• 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 27/3654 Cartilage, e.g. meniscus
• 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: A61L 27/3817 Cartilage-forming cells, e.g. pre-chondrocytes
• CPC Class Codes: A61L 27/3852 Cartilage, e.g. meniscus
• CPC Class Codes: A61L 27/3895 using specific culture conditions, e.g. stimulating differentiation of stem cells, pulsatile flow conditions
• CPC Class Codes: C12N 2533/18 Calcium salts, e.g. apatite, Mineral components from bones, teeth, shells
• CPC Class Codes: C12N 5/0655 Chondrocytes; Cartilage

Abstract

An implant for articular cartilage repair includes (1) a three-dimensional body formed of cancellous bone having a demineralized section that contains bone morphogenetic proteins (BMP'"'"'s) that are released by the demineralization but retained in the body, and (2) a cartilage layer formed on a surface of the demineralized section. The cartilage layer is formed by a method including the steps of (a) isolating chondrocytes from articular cartilage of a donor; (b) cultivating the isolated chondrocytes in a medium; (c) adding the cultivated chondrocytes to the demineralized section of the body, whereby the cultivated chondrocytes are stimulated by the BMP'"'"'s retained in the body; and (d) incubating the cultivated chondrocytes to form a plurality of layers of chondrocytes on the demineralized section, wherein the plurality of layers of chondrocytes forms the cartilage layer.

Claims

1. An implant for articular cartilage repair, comprising a three-dimensional body formed of cancellous bone and having a demineralized section, the demineralized section containing bone morphogenetic proteins (BMP'"'"'s) that are released by the demineralization but retained in said body, and a cartilage layer formed on a surface of the demineralized section, said cartilage layer being formed by a method including the steps of:

(a) isolating chondrocytes from articular cartilage of a donor;

(b) cultivating the isolated chondrocytes in a medium;

(c) adding the cultivated chondrocytes to the demineralized section of said body, whereby the cultivated chondrocytes are stimulated by the BMP'"'"'s retained in said body; and

(d) incubating the cultivated chondrocytes to form a plurality of layers of chondrocytes on the demineralized section, wherein the plurality of layers of chondrocytes forms said cartilage layer.

2. The implant as claimed in claim 1, wherein the plurality of layers of chondrocytes includes four layers.

3. The implant as claimed in claim 1, wherein the chondrocytes are allograft chondrocytes.

4. The implant as claimed in claim 3, wherein the donor is less than 50 years of age.

5. The implant as claimed in claim 3, wherein the donor is alive.

6. The implant as claimed in claim 3, wherein the donor is deceased.

7. The implant as claimed in claim 1, wherein the chondrocytes are autograft chondrocytes.

8. The implant as claimed in claim 1, wherein said body is formed of allograft cancellous bone.

9. The implant as claimed in claim 1, wherein step (b) includes placing the surface of the demineralized section in a culture vessel and preparing the surface of the demineralized section for cell seeding.

10. The implant as claimed in claim 1, wherein step (d) is performed until said cartilage layer has a thickness in a range of from 2 mm to 5 mm.

11. The implant as claimed in claim 1, wherein said body includes pores having a size that represents a multiple of the cell volume of a chondrocyte.

12. The implant as claimed in claim 1, wherein step (d) is performed for a period of at least 40 days.

13. The implant as claimed in claim 1, wherein the cell density of the chondrocytes in said cartilage layer is about 10 million cells per cm³.

14. The implant as claimed in claim 1, wherein all of said body is demineralized.

15. The implant as claimed in claim 1, wherein the demineralized section has a depth of approximately 2 mm.

16. The implant as claimed in claim 15, wherein said body includes a mineralized section and a boundary layer formed between the demineralized section and the mineralized section, the boundary layer having a thickness of about 50 microns.

17. The implant as claimed in claim 1, wherein said body includes pores having a size that ranges from 10 to 100 microns.

18. The implant as claimed in claim 1, wherein step (b) includes expanding the chondrocytes in a two-dimensional culture until the chondrocytes show a dedifferentiated fibroblast-like phenotype.

19. The implant as claimed in claim 1, wherein step (d) is performed until said cartilage layer has a thickness of approximately 2.0 mm.

20. A construct for repairing an articular cartilage defect, said construct comprising a body entirely formed from substantially demineralized bone.

21. The construct as claimed in claim 20, wherein said body contains bone morphogenetic proteins (BMPs).

22. The construct as claimed in claim 20, wherein said body is porous.

23. The construct as claimed in claim 22, wherein said body includes pores having a size that represents a multiple of the cell volume of a chondrocyte.

24. The construct as claimed in claim 22, wherein said pores have a size that ranges from 10 to 100 microns.

25. The construct as claimed in claim 20, wherein said body is sterile.

26. The construct as claimed in claim 20, wherein said body is spongy.

27. The construct as claimed in claim 20, wherein said body is formed from allograft bone.

28. The construct as claimed in claim 20, wherein said body has at least one surface which contains chondrocytes.

29. The construct as claimed in claim 28, wherein said chondrocytes are allograft chondrocytes.

30. The construct as claimed in claim 28, wherein said chondrocytes have a cell density that ranges from about 0.2 million to about 10 million cells per cm³.

31. The construct as claimed in claim 28, wherein said chondrocytes cover the entirety of said at least one surface of said body.

32. The construct as claimed in claim 31, further comprising an extracellular matrix that surrounds said chondrocytes.

33. The construct as claimed in claim 31, further comprising at least one cartilage layer overlying said at least one surface.

34. The construct as claimed in claim 33, wherein said cartilage layer has a thickness of approximately 2 millimeters.

35. The A construct as claimed in claim 33, wherein said at least one cartilage layer has a cell density that ranges from about 0.2 million to about 10 million cells per cm³.

36. The construct as claimed in claim 31, further comprising a multiplicity of cartilage layers overlying said at least one surface of said body.

37. The construct as claimed in claim 36, wherein said multiplicity of cartilage layers has a thickness of approximately 2 millimeters.