Bone graft composites and methods of treating bone defects

• US 20080033572A1
• Filed: 08/03/2006
• Published: 02/07/2008
• Est. Priority Date: 08/03/2006
• Status: Abandoned Application

• Current Assignee: EBI LLC (Zimvie Incorporated)
• Original Assignee: EBI LP (Zimvie Incorporated)
• Inventors: D'Antonio, Paul, Simon, Joshua, Cripps, Benjamin T.
• Application Number:
  US11/498,341
• Publication Number:
  US 20080033572A1
• Time in Patent Office: Days
• US Class Current: 623/23.51
• CPC Class Codes: A61F 2/4601 for introducing bone substitute, for implanting bone graft implants or for compacting them in the bone cavity
• 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 2002/2835 Bone graft implants for filling a bony defect or an endoprosthesis cavity, e.g. by synthetic material or biological material
• CPC Class Codes: A61F 2002/2839 Bone plugs or bone graft dowels
• CPC Class Codes: A61F 2002/30224 cylindrical
• CPC Class Codes: A61F 2002/30677 Means for introducing or releasing pharmaceutical products, e.g. antibiotics, into the body
• CPC Class Codes: A61F 2002/4649 Bone graft or bone dowel harvest sites
• CPC Class Codes: A61F 2230/0069 cylindrical
• 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: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 35/32 Bones; Osteocytes; Osteoblasts; Tendons; Tenocytes; Teeth; Odontoblasts; Cartilage; Chondrocytes; Synovial membrane
• CPC Class Codes: A61K 38/39 Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin, cold insoluble globulin [CIG]
• 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 27/365 Bones
• CPC Class Codes: A61L 27/3804 characterised by specific cells or progenitors thereof, e.g. fibroblasts, connective tissue cells, kidney cells
• CPC Class Codes: A61L 27/46 with phosphorus-containing inorganic fillers
• CPC Class Codes: A61P 19/00 Drugs for skeletal disorders

Abstract

Bone graft compositions comprising demineralized bone matrix, calcium phosphate, collagen and bioinductive cellular solution. Methods to repair and heal defective and missing bone using the bone graft compositions are also described.

Claims

1. A bone graft composition, comprising:

demineralized bone matrix;

calcium phosphate;

collagen; and

bioinductive cellular solution.

2. A composition according to claim 1, wherein the demineralized bone matrix is demineralized, partially demineralized or superficially demineralized cortical, cancellous or cortico-cancellous bone.

3. The composition of claim 2, wherein the demineralized bone matrix is selected from the group consisting of bone chips, bone particles, bone morsels, ground bone, bone powders, and mixtures thereof.

4. A composition according to claim 1, wherein the calcium phosphate is selected from the group consisting of tricalcium phosphate, hydroxyapatite, tetra calcium phosphate, amorphous calcium phosphate, and mixtures thereof.

5. A composition according to claim 1, wherein the collagen carrier is selected from the group consisting of mammalian type I, type, II, type III, type IV, type IX, type X, type XI and type XII collagen, and mixtures thereof.

6. A composition according to claim 5, wherein, the collagen carrier is selected from the group consisting of mammalian type I, type II, type III, type IV collagens, and mixtures thereof.

7. A composition according to claim 1, wherein, the bioinductive cellular solution is selected from the group consisting of bone marrow aspirate, blood, adipose tissue liposuction aspirate, cultured cells, progenitor cells, stem cells, stromal cells, and mixtures thereof.

8. A composition according to claim 7, wherein the bioinductive cellular solution comprises autologous bone marrow aspirate.

9. A composition according to claim 7, wherein the bioconductive cellular solution comprises blood selected from the group consisting of autologous blood, autologous buffy coat cells, autologous plasma, allogeneic blood, allogeneic buffy coat cells, allogeneic plasma, and mixtures thereof.

10. A composition according to claim 7, wherein the bioconductive cellular solution comprises mesenchymal stem cells.

11. A composition according to claim 7, wherein the bioinductive cellular solution comprises one or more of physiological saline, physiological buffers and water.

12. A composition according to claim 1, comprising:

from about 55 to about 80 parts of demineralized bone matrix;

from about 1 to about 10 parts of calcium phosphate;

from about 15 to about 40 parts of collagen; and

from about 1 to about 5 parts of a bioinductive cellular solution.

13. A composition according to claim 1, comprising one or more bioactive factors selected from the group consisting of growth factors, structural proteins, cytokines, antibiotics, chemotherapeutics, serum proteins, and mixtures thereof.

18. An implant comprising a composition of claim 1, possessing the shape of a cylinder, wedge, plate, threaded cylinder, fibular wedge, femoral strut or tibial strut, said implant being capable of initially bearing loads upon implantation.

19. An implant according to claim 18, wherein the shaped composition is hardened ex vivo and implanted surgically.

20. An implant according to claim 18, wherein the shaped composition is infused with a bioinductive cellular solution prior to implantation into the patient.

14. A method for treating a bone defect site, said method comprising applying to the site of said defect a bone graft composition comprising demineralized bone matrix, calcium phosphate ceramic, collagen, and a bioinductive cellular solution.

15. A method according to claim 14, wherein said composition is admixed intraoperatively and implanted into said sites where defective osseous tissue has been removed from said site.

16. A method according to claim 15, wherein said composition is effective to induce bone formation in said defective osseous tissue.

17. A method according to claim 14, wherein said composition is implanted surgically into the site.

21. A method for implanting to a patient an orthopedic device having contact on at least one surface with bone, comprising:

applying to at least one surface of the orthopedic device a bone graft composition comprising demineralized bone matrix, calcium phosphate, collagen, and bioinductive cellular solution; and

implanting the orthopedic device into the patient.

22. A method according to claim 21, wherein the orthopedic device is adopted for use in arthroplasty, orthopedic distraction, or fixation, wherein the orthopedic device is to remain in permanent contact with the supporting bone.

23. A method of preparing a bone graft material comprising:

a) providing a matrix comprising;

demineralized bone;

calcium phosphate; and

collagen; and

b) mixing said matrix with a bioinductive cellular solution to yield a bone graft material containing bioinductive cells distributed within the bone graft material.

24. A method according to claim 23, wherein the demineralized bone matrix is demineralized, partially demineralized or superficially demineralized cortical, cancellous or cortico-cancellous bone.

25. A method according to claim 23, wherein the demineralized bone matrix is selected from the group consisting of bone chips, bone particles, bone morsels, ground bone and bone powders, and mixtures thereof.

26. A method according to claim 23, wherein the calcium phosphate is selected from the group consisting of tricalcium phosphate, hydroxyapatite, tetra calcium phosphate, poorly crystalline apatite and mixtures thereof.

27. A method according to claim 23, wherein the collagen carrier is selected from the group consisting of mammalian type I, type II, type III, type IV collagen, and mixtures thereof.

28. A method according to claim 23, wherein, the bioinductive cellular solution is selected from the group consisting of blood, bone marrow aspirate, adipose tissue liposuction aspirate, allogeneic stem cells, cultured human and/or animal stem and stromal cells, and mixtures thereof.

29. A method according to claim 28, wherein the bioinductive cellular solution comprises autologous bone marrow aspirate.

30. A method according to claim 23, wherein the bioinductive cells comprise mesenchymal stem cells.

31. A method according to claim 28, wherein the bioconductive cellular solution comprises blood selected from the group consisting of autologous blood, autologous buffy coat cells, autologous plasma, allogeneic blood, allogeneic buffy coat cells, allogeneic plasma, and mixtures thereof.

32. A method according to claim 28, wherein the bioconductive cellular solution comprises mesenchymal stem cells.

33. A method according to claim 28, wherein the bioinductive cellular solution comprises one or more of physiological saline, physiological buffers and water.

34. A kit, comprising:

a mixture comprising;

demineralized bone matrix;

calcium phosphate; and

collagen; and

instructions for preparing said mixture by admixture with bioactinductive cellular solution.

35. A kit according to claim 34, wherein the bioinductive cellular solution is selected from the group consisting of autologous bone marrow aspirate, autologous blood, autologous buffy coat cells, autologous plasma, autologous adipose tissue liposuction aspirate, allogeneic adipose tissue liposuction aspirate, allogeneic bone marrow aspirate, allogeneic blood, allogeneic buffy coat cells, allogeneic plasma, xenogeneic bone marrow aspirate, xenogeneic blood, xenogeneic adipose tissue aspirate, saline, and mixtures thereof.