COMPRESSED BONE COMPOSITION AND METHODS OF USE THEREOF

• US 20160256607A1
• Filed: 10/09/2014
• Published: 09/08/2016
• Est. Priority Date: 10/09/2013
• Status: Active Grant

• Current Assignee: LifeNet Health, Inc.
• Original Assignee: LifeNet Health, Inc.
• Inventors: Francis, Michael, Rodriguez, Rudy, Kemper, Nathan
• Granted Patent: US 10,780,196 B2
• Time in Patent Office: Days
• US Class Current: 1/1
• CPC Class Codes: A61F 2/28 Bones joints A61F2/30
• 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 2002/2828 Femoral head
• 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 27/3834 Cells able to produce different cell types, e.g. hematopoietic stem cells, mesenchymal stem cells, marrow stromal cells, embryonic stem cells
• CPC Class Codes: A61L 27/502 Plasticizers
• CPC Class Codes: A61L 27/56 Porous materials, e.g. foams or sponges
• CPC Class Codes: B28B 1/007 by freezing the material
• CPC Class Codes: B28B 17/02 Conditioning the material prior to shaping for mixtures containing clay or cement B28C
• CPC Class Codes: B33Y 80/00 Products made by additive manufacturing

Abstract

The present disclosure relates to compressed bone compositions, bone implants, and variants thereof. The present disclosure also relates to methods of preparing compressed bone compositions, bone implants, and variants thereof. The present disclosure also relates to methods of using the bone compositions, bone implants and variants thereof.

Claims

1. A method for preparing a compressed bone composition, comprising:

loading bone particles into a mold with a predetermined shape,

applying pressure between about 0.1 and 30 MPa to the bone particles, and

freeze drying the compressed bone particles to create the compressed bone composition.

2. The method according to claim 1, wherein the pressure is from about 0.1 MPa to about 6 MPa.

3. The method according to claim 1, wherein the pressure is between 100 psi and 1000 psi.

4. The method according to claim 1, wherein said predetermined shape comprises grooves.

5. The method according to claim 1, wherein the compressed bone composition retains its integrity in liquid for at least 5-30 minutes.

6. The method according to claim 1, wherein the pressure is applied at room temperature.

7. The method according to claim 1, wherein the compressed bone composition does not comprise a binder or a chemical cross-linker.

8. The method according to claim 1, wherein said bone particles comprise bone fiber, bone powder, or a mixture of bone fiber and bone powder.

9. The method according to claim 1, wherein said bone particles are from cortical bone, cancellous bone, cortical cancellous bone, or a mixture of cortical and cancellous bone.

10. The method according to claim 1, further comprising demineralizing the bone particles prior to applying the pressure.

11. The method according to claim 1, further comprising cleaning the bone particles prior to applying the pressure.

12. The method according to claim 11, wherein said cleaning comprising incubating the bone particles with an antibiotic, a detergent, an alcohol, and/or a H₂O₂.

13. The method according to claim 11, wherein said cleaning comprising using the Allowash®

process.

14. The method according to claim 1, further comprising sterilizing the compressed bone composition.

15. The method according to claim 14, wherein the bone particles are sterilized by gamma or e-beam Irradiation, ethylene oxide, or critical CO₂.

16. The method according to claim 1, further comprising treating the compressed bone composition with a plasticizer composition.

17. The method according to claim 16, wherein said plasticizer composition comprises one or more plasticizers selected from the group consisting of glycerol, adonitol, sorbitol, ribitol, galactitol, D-galactose, 1,3-dihydroxypropanol, ethylene glycol, triethylene glycol, propylene glycol, glucose, sucrose, mannitol, xylitol, meso-erythritol, adipic acid, proline, hydroxyproline, polyol, and a fatty acid.

18. The method according to claim 1, wherein said bone particles are obtained from a human, a cow, a pig, a dog, a horse, a goat, or a sheep.

19. A bone implant prepared by the method according to claim 1, wherein the structure comprises grooves.

20. The bone implant according to claim 19, wherein said bone particle is from a human, a cow, a pig, a dog, a horse, a goat, or a sheep.

21. The bone implant according to claim 19, wherein said bone particles comprise bone fiber, bone powder, or a mixture of bone fiber and bone powder.

22. The bone implant according to claim 19, wherein said bone particles are demineralized.

23. The bone Implant according to claim 19, wherein said bone particles have an average residual calcium content of 0.01-8 wt %.

24. The bone implant according to claim 19, wherein said bone particles have an average residual calcium content of 0.01-4 wt %.

25. The bone implant according to claim 19, wherein said bone particles are from cortical bone, cancellous bone, cortical cancellous bone, or a mixture of cortical and cancellous bone.

26. The bone implant according to claim 19, wherein said bone implant further comprises at least one cell and/or at least one bioactive factor.

27. The bone implant according to claim 19, wherein said bone implant has a higher density at the groove areas compared to rest of the structure.

28. The bone implant according to claim 19, wherein the density of the bone implant is between about 0.24 and 0.35 g/cm³.

29. The bone implant according to claim 19, wherein said bone particles have a median diameter of about 10-1,000 microns, a median length of about 0.5-100 mm, and a median thickness of about 10-1000 microns.

30. The bone implant according to claim 19, wherein said bone implant does not comprise a binder or a chemical cross-linker.

31. A bone composition comprising bone fibers, wherein the bone fibers comprise microfibers having an average width (W) of less than about 5 μ

m and an average length (L);

W ratio of greater than about 2.

32. The bone composition of claim 31, wherein the average L:

W ratio is greater than about 5.

33. The bone composition of claim 31, wherein the average L:

W ratio is greater than about 7.

34. The bone composition of claim 31, wherein the average L:

W ratio is in a range from 2 to 30.

35. The bone composition of claim 31, wherein the average L:

W ratio is in a range from 5 to 8.

36. The bone composition of claim 31, wherein the W of the microfibers is less than about 2 μ

m.

37. The bone composition of claim 31, wherein the W of the microfibers is less than about 1 μ

m.

38. The bone composition of claim 31, wherein the L of the microfibers is less than about 12 μ

m.

39. The bone composition of claim 31, wherein the L of the microfibers is less than about 7 μ

m.

40. The bone composition of claim 31, wherein the bone compositions are prepared by applying pressure to bone fibers.

41. The bone composition of claim 31, wherein the bone composition is wet and the mode of the pore sizes of the wet bone composition is in a range from 25 to 250 μ

m.

42. The bone composition of claim 41, wherein the mode of pore sizes of the wet bone composition at equilibrium does not have a bimodal distribution.

43. The bone composition of claim 31, wherein when the bone composition is wet, the mean of the pore sizes of the wet bone composition is in a range from 20 to 100 μ

m.

44. The bone composition of claim 43, wherein the mean of pore sizes of the wet bone composition at equilibrium is less than 30 μ

m or more than 65 μ

m.

45. A method of making a bone implant for an individual, the method comprising:

loading bone composition into a mold that is based upon three dimensional (3D) measurements taken from a bone structure of the individual for the implant, wherein the bone composition comprises microfibers having an average length (L);

average width (W) ratio greater than about 2;

applying pressure of between about 0.1 and 30 MPa to the bone composition to fit the mold; and

freeze drying the compressed bone composition to make the bone implant.

46. The method of claim 45, wherein the mold is constructed with 3-D printing.

47. The method of claim 45, wherein the individual is a human, a dog, a pig, a cow, a cat or a horse.

48. The method of claim 45, wherein the individual is a human.

49. The method of claim 45, wherein the bone structure is a segmental defect without load bearing.

50. The method of claim 45, wherein the bone structure is selected from a group consisting of a femoral head, a femur trochanter, a skull flap, and mandible.

51. The method of claim 45, wherein the mold comprises a groove.

55. The method of claim 45, further comprising applying the bone Implant to a prosthesis.

56. The method of claim 55, wherein the prosthesis comprises a metal or a synthetic material.

52. A method of promoting osteoinductivity, osteoconductivity, chondroinductivity, chondroconductivity, or ligament/tendon differentiation or growth of cells, comprising contacting cells with a bone composition comprising bone fibers, wherein the bone fibers comprise microfibers having an average width (W) of less than about 5 μ

m and an average length (L);

W ratio of greater than about 2.

53. The method of claim 52, wherein the cells are progenitor cells or adult stem cells.

54. The method of claim 53, wherein the progenitor cells or the adult stem cells are derived from placenta, bone marrow, adipose tissue, blood vessel, amniotic fluid, synovial fluid, synovial membrane, pericardium, periosteum, dura, peripheral blood, umbilical blood, menstrual blood, baby teeth, nucleus pulposus, brain, skin, hair follicle, Intestinal crypt, neural tissue, or muscle.