Injectable porous bone graft materials

• US 20020193883A1
• Filed: 01/25/2002
• Published: 12/19/2002
• Est. Priority Date: 01/25/2001
• Status: Abandoned Application

• Current Assignee: Regeneration Technologies Incorporated (Surgalign Holdings, Inc.)
• Original Assignee: Regeneration Technologies Incorporated (Surgalign Holdings, Inc.)
• Inventors: Wironen, John F.
• Application Number:
  US10/056,217
• Publication Number:
  US 20020193883A1
• Time in Patent Office: Days
• US Class Current: 623/23.56
• 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 2002/30011 differing in porosity
• CPC Class Codes: A61F 2002/30062 (bio)absorbable, biodegradable, bioerodable, (bio)resorbable, resorptive
• CPC Class Codes: A61F 2002/30968 Sintering
• CPC Class Codes: A61F 2210/0004 bioabsorbable
• CPC Class Codes: A61F 2250/0023 differing in porosity
• CPC Class Codes: A61F 2310/00293 containing a phosphorus-containing compound, e.g. apatite
• CPC Class Codes: A61F 2310/00329 Glasses, e.g. bioglass
• CPC Class Codes: A61L 2300/252 Polypeptides, proteins, e.g. glycoproteins, lipoproteins, cytokines
• CPC Class Codes: A61L 2300/414 Growth factors
• CPC Class Codes: A61L 2300/43 Hormones, e.g. dexamethasone
• CPC Class Codes: A61L 2400/06 Flowable or injectable implant compositions
• CPC Class Codes: A61L 2430/02 for reconstruction of bones; weight-bearing implants
• CPC Class Codes: A61L 27/10 Ceramics or glasses
• CPC Class Codes: A61L 27/12 Phosphorus-containing materials, e.g. apatite
• CPC Class Codes: A61L 27/50 Materials characterised by their function or physical properties , e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: A61L 27/56 Porous materials, e.g. foams or sponges

Abstract

A bone-like implant capable of increasing its porosity in situ comprising at least one bone-like compound with at least one hydrophobic carrier, or a degradable component. The bone-like implant includes its manufacture and methods of use. One aspect of the bone-like implant is to provide a method of repairing a bone defect or related injuries. The bone-like implant includes several embodiments capable of increasing its porosity in situ.

Claims

1. An injectable bone-like implant capable of increasing its porosity in situ comprising at least one bone-like compound and a hydrophobic carrier.

2. The injectable bone-like implant according to claim 1, wherein said bone-like compound is capable of aqueous sintering or curing.

3. The injectable bone-like implant according to claim 1, wherein said at least one bone-like compound is tricalcium phosphate, dicalcium phosphate, or monocalcium phosphate, potassium phosphate, calcium sulphate, hydroxyapatite, bioactive glass or combinations thereof.

4. The injectable bone-like implant according to claim 1, wherein said bone-like implant further comprises at least one of osteogenic, vasogenic, neorogenic, or like growth factors, hormone, or protein.

5. The injectable bone-like implant according to claim 4, wherein said at least one osteogenic factor or protein is selected from the group consisting of platelet derived growth factors (PDGF), transforming growth factors (TGF-.beta.), insulin-like growth factors (IGF'"'"'s), fibroblast growth factors (FGF'"'"'s), epidermal growth factor (EGF), human endothelial cell growth factor (ECGF), granulocyte macrophage colony stimulating factor (GM-CSF), nerve growth factor (NGF), vascular endothelial growth factor (VEGF), cartilage derived morphogenetic protein (CDMP), bone morphogenetic proteins (BMP'"'"'s), and combinations of the foregoing

6. The injectable bone-like implant according to claim 4, wherein one or more said osteogenic protein is selected from the group consisting of OP-1, OP-2, BMP2, BMP3, BMP4, BMP9, DPP, Vg-1, 60A, and Vgr-1, including naturally sourced and recombinant derivatives of the foregoing.

7. The injectable bone-like implant according to claim 1, wherein said bone-like implant further comprises demineralized bone matrix.

8. The injectable bone-like implant according to claim 1, wherein said hydrophobic carrier is squalene, hydrophobic proteins, lipids, amphophyllic proteins, glycoproteins, polyesters, polyanhydrides, polyamines, nylons, or combinations thereof.

9. The injectable bone-like implant according to claim 1, wherein said hydrophobic carrier comprises a wax-like low molecular weight biodegradable polymers selected from the group consisting of polyglycolic acid, a copolymer of polycaprolactone and polyglycolic acid, or other polyesters, polyanhydrides, polyamines, nylons, or any combinations thereof.

10. The injectable bone-like implant according to claim 1, further comprising an aqueous component.

11. The injectable bone-like implant according to claim 10, wherein said aqueous component is water, saline, blood, or the like, or any combination thereof.

13. The method according to claim 12, wherein said at least one bone-like compound is tricalcium phosphate, dicalcium phosphate, or monocalcium phosphate, potassium phosphate, calcium sulphate, hydroxyapatite, bioactive glass or combinations thereof.

14. The method according to claim 12, wherein said bone-like implant further comprises at least one of osteogenic, vasogenic, neorogenic, or like growth factors, hormone, or protein.

15. The method according to claim 14, wherein said at least one osteogenic factor or protein is selected from the group consisting of platelet derived growth factors (PDGF), transforming growth factors (TGF-.beta.), insulin-like growth factors (IGF'"'"'s), fibroblast growth factors (FGF'"'"'s), epidermal growth factor (EGF), human endothelial cell growth factor (ECGF), granulocyte macrophage colony stimulating factor (GM-CSF), nerve growth factor (NGF), vascular endothelial growth factor (VEGF), cartilage derived morphogenetic protein (CDMP), bone morphogenetic proteins (BMP'"'"'s), and combinations of the foregoing.

16. The method according to claim 14, wherein one or more said osteogenic protein is selected from the group consisting of OP-1, OP-2, BMP2, BMP3, BMP4, BMP9, DPP, Vg-1, 60A, and Vgr-1, including naturally sourced and recombinant derivatives of the foregoing.

17. The method according to claim 12, wherein said method comprises adding demineralized bone matrix to said bone-like compound.

18. The method according to claim 12, wherein said hydrophobic carrier is squalene, hydrophobic proteins, lipids, amphophyllic proteins, glycoproteins, polyesters, polyanhydrides, polyamines, nylons, or combinations thereof.

19. The method according to claim 12, wherein said hydrophobic carrier comprises a wax-like low molecular weight biodegradable polymers selected from the group consisting of polyglycolic acid, a copolymer of polycprolactone and polyglycolic acid, or other polyesters, polyanhydrides, polyamines, nylons, or any combinations thereof.

20. The method according to claim 12, further comprises an aqueous component.

21. The method according to claim 20, wherein said aqueous component is water, saline, blood, or the like, or any combination thereof.

22. The method according to claim 12, wherein said step of mixing at least one bone-like compound in a hydrophobic carrier further comprises the step of:

providing said at least one bone-like compound in a dried powdered form, and reconstituting said dried bone-like compound with said hydrophobic carrier.

25. The injectable bone-like implant according to claim 24, wherein said at least one bone-like compound is tricalcium phosphate, dicalcium phosphate, or monocalcium phosphate, potassium phosphate, calcium sulphate, hydroxyapatite, bioactive glass or combinations thereof.

26. The injectable bone-like implant according to claim 24, wherein said bone-like implant further comprises at least one of osteogenic, vasogenic, neorogenic, or like growth factors, hormone, or protein.

27. The injectable bone-like implant according to claim 26, wherein said at least one osteogenic factor or protein is selected from the group consisting of platelet derived growth factors (PDGF), transforming growth factors (TGF-.beta.), insulin-like growth factors (IGF'"'"'s), fibroblast growth factors (FGF'"'"'s), epidermal growth factor (EGF), human endothelial cell growth factor (ECGF), granulocyte macrophage colony stimulating factor (GM-CSF), nerve growth factor (NGF), vascular endothelial growth factor (VEGF), cartilage derived morphogenetic protein (CDMP), bone morphogenetic proteins (BMP'"'"'s), and combinations of the foregoing.

28. The injectable bone-like implant according to claim 26, wherein one or more said osteogenic protein is selected from the group consisting of OP-1, OP-2, BMP2, BMP3, BMP4, BMP9, DPP, Vg-1, 60A, and Vgr-1, including naturally sourced and recombinant derivatives of the foregoing.

29. The injectable bone-like implant according to claim 24, wherein said bone-like implant further comprises demineralized bone matrix.

30. The injectable bone-like implant according to claim 24, wherein said at least one degradable component is gelatin, polyglycolic acid and other polyhydroxypolyesters, cross-linked albumin, collagen, proteins, polysaccharides, glycoproteins, or any combination thereof.

31. The injectable bone-like implant according to claim 24, wherein said at least one degradable component a degradable gas-producing compound and an effective amount of an acid.

32. The injectable bone-like implant according to claim 31, wherein said degradable gas-producing compound is sodium bicarbonate, calcium bicarbonate, or the like, or any combination thereof.

33. The injectable bone-like implant according to claim 31, wherein said acid is citric acid, formic acid, acetic phosphoric acids, or HCl.

34. The injectable bone like implant according to claim 31, wherein said degradable gas-producing component is hydrogen peroxide and peroxidase.

36. The method according to claim 35, wherein said at least one bone-like compound is tricalcium phosphate, dicalcium phosphate, or monocalcium phosphate, potassium phosphate, calcium sulphate, hydroxyapatite, bioactive glass or combinations thereof.

37. The method according to claim 35 wherein said bone-like implant further comprises at least one of osteogenic, vasogenic, neorogenic, or like growth factors, hormone, or protein.

38. The method according to claim 37, wherein said at least one osteogenic factor or protein is selected from the group consisting of platelet derived growth factors (PDGF), transforming growth factors (TGF-.beta.), insulin-like growth factors (IGF'"'"'s), fibroblast growth factors (FGF'"'"'s), epidermal growth factor (EGF), human endothelial cell growth factor (ECGF), granulocyte macrophage colony stimulating factor (GM-CSF), nerve growth factor (NGF), vascular endothelial growth factor (VEGF), cartilage derived morphogenetic protein (CDMP), bone morphogenetic proteins (BMP'"'"'s), and combinations of the foregoing.

39. The method according to claim 37, wherein one or more said osteogenic protein is selected from the group consisting of OP-1, OP-2, BMP2, BMP3, BMP4, BMP9, DPP, Vg-1, 60A, and Vgr-1, including naturally sourced and recombinant derivatives of the foregoing.

40. The method according to claim 35, wherein said method comprises adding demineralized bone matrix to said bone-like compound.

41. The method according to claim 35, wherein said at least one degradable component is gelatin, polyglycolic acid and other polyhydroxypolyesters, cross-linked albumin, collagen, proteins, polysaccharides, glycoproteins, or any combination thereof.

42. The method according to claim 35, further comprising an aqueous component.

43. The method according to claim 42, wherein said aqueous component is water, saline, blood, or the like, or any combination thereof.

44. The method according to claim 35, wherein said at least one degradable component comprises a degradable gas-producing compound and an effective amount of an acid.

45. The method according to claim 44, wherein said degradable gas-producing compound is sodium bicarbonate, calcium bicarbonate, or the like, or any combination thereof.

46. The method according to claim 44, wherein said acid is citric acid, formic acid, acetic phosphoric acids, or HCl.

47. The method according to claim 44, wherein said degradable gas-producing component is hydrogen peroxide and peroxidase.

49. The method according to claim 48, wherein said at least one bone-like compound is tricalcium phosphate, dicalcium phosphate, or monocalcium phosphate, potassium phosphate, calcium sulphate, hydroxyapatite, bioactive glass or combinations thereof.

50. The method according to claim 48, wherein said bone-like implant further comprises at least one of osteogenic, vasogenic, neorogenic, or like growth factors, hormone, or protein.

51. The method according to claim 50, wherein said at least one osteogenic factor or protein is selected from the group consisting of platelet derived growth factors (PDGF), transforming growth factors (TGF-.beta.), insulin-like growth factors (IGF'"'"'s), fibroblast growth factors (FGF'"'"'s), epidermal growth factor (EGF), human endothelial cell growth factor (ECGF), granulocyte macrophage colony stimulating factor (GM-CSF), nerve growth factor (NGF), vascular endothelial growth factor (VEGF), cartilage derived morphogenetic protein (CDMP), bone morphogenetic proteins (BMP'"'"'s), and combinations of the foregoing.

52. The method according to claim 50, wherein one or more said osteogenic protein is selected from the group consisting of OP-1, OP-2, BMP2, BMP3, BMP4, BMP9, DPP, Vg-1, 60A, and Vgr-1, including naturally sourced and recombinant derivatives of the foregoing.

53. The method according to claim 48, wherein said method comprises adding demineralized bone matrix to said bone-like compound.

54. The method according to claim 48, wherein said aqueous component is water, saline, blood, or the like, or any combination thereof.

55. The method according to claim 48, wherein said at least one degradable component comprises a degradable gas-producing compound and an effective amount of an acid.

56. The method according to claim 55, wherein said degradable gas-producing compound is sodium bicarbonate, calcium bicarbonate, or the like, or any combination thereof.

57. The method according to claim 55, wherein said acid is citric acid, formic acid, acetic phosphoric acids, or HCl.

58. The method according to claims 55, wherein said degradable gas-producing component is hydrogen peroxide and peroxidase.

12. A method of producing an injectable bone-like implant, wherein said implant is capable of increasing its porosity in situ, said method comprising the steps of:

mixing at least one bone-like compound in a hydrophobic carrier; and

concurrently or subsequent to said mixing step, combining said at least one bone-like compound and said hydrophobic carrier with an aqueous phase to form a combined mixture.

23. A method of repairing a bone defect and injury comprising the steps of:

mixing at least one bone-like compound in a hydrophobic carrier;

concurrently or subsequent to said mixing step, combining said at least one bone-like compound and said hydrophobic carrier with an aqueous phase to form a combined mixture; and

administering an amount of said combined mixture in a patient at a site of need;

wherein said combined mixture sets up in situ, thereby leaving a porous bone-like implant at the site of need.

24. An injectable bone-like implant capable of increasing its porosity in situ comprising at least one bone-like compound and at least one degradable component.

35. A method of producing an injectable bone-like implant, wherein said implant is capable of increasing its porosity in situ, said method comprising the steps of:

mixing at least one bone-like compound in a degradable component; and

concurrently or subsequent to said mixing step, combining said at least one bone-like compound and said degradable component with an aqueous phase to form a combined mixture.

48. A method of repairing a bone defect and injury comprising the steps of:

mixing at least one bone-like compound with at least one degradable component;

combining said at least one bone-like compound and at least one degradable substance with an aqueous phase to form a combined mixture; and

administering an amount of said combined mixture in a patient at a site of need;

wherein said combined mixture sets up in situ, thereby leaving a porous bone-like implant at the site of need.