Composition and process for bone growth and repair

• US 8,690,874 B2
• Filed: 08/03/2010
• Issued: 04/08/2014
• Est. Priority Date: 12/22/2000
• Status: Expired due to Fees

• Current Assignee: Zimmer Orthobiologics, Inc. (Zimmer Biomet Holdings, Inc.)
• Original Assignee: Zimmer Orthobiologics, Inc. (Zimmer Biomet Holdings, Inc.)
• Inventors: Thorne, Kevin J.
• Primary Examiner(s): LEITH, PATRICIA A
• Application Number:
  US12/849,414
• Publication Number:
  US 20110165199A1
• Time in Patent Office: 1,344 Days
• Field of Search: 424/423, 424/426, 623/16.11, 606/53, 606/60, 606/86, 523/114, 523/115
• US Class Current: 606/53
• CPC Class Codes: A61K 38/1875 Bone morphogenic factor; Osteogenins; Osteogenic factor; Bone-inducing factor
• CPC Class Codes: A61L 2430/02 for reconstruction of bones; weight-bearing implants
• CPC Class Codes: A61L 27/12 Phosphorus-containing materials, e.g. apatite
• CPC Class Codes: A61L 27/22 Polypeptides or derivatives thereof , e.g. degradation products
• CPC Class Codes: A61L 27/227 Other specific proteins or polypeptides not covered by A61L27/222, A61L27/225 or A61L27/24
• CPC Class Codes: A61L 27/24 Collagen
• CPC Class Codes: A61L 27/3608 Bone, e.g. demineralised bone matrix [DBM], bone powder
• CPC Class Codes: A61L 27/3616 Blood, e.g. platelet-rich plasma
• CPC Class Codes: A61L 27/46 with phosphorus-containing inorganic fillers
• CPC Class Codes: A61P 19/00 Drugs for skeletal disorders
• CPC Class Codes: A61P 19/08 for bone diseases, e.g. rachitism, Paget's disease
• CPC Class Codes: C08L 89/06 derived from leather or skin , e.g. gelatin

Abstract

A composition for the induction of bone growth is disclosed. The composition includes a substrate, bone growth protein, and sources of calcium and phosphate. The composition is acidic which promotes high activity of the bone growth protein. The calcium and phosphate sources can be provided as an acidic calcium phosphate salt. Also disclosed are methods of the making the composition and methods of using it.

Claims

1. A bone graft composition comprising:

particles of dehydrothermally cross-linked substrate including about 25 wt. % to about 40 wt. % bovine Type I dehydrothermally cross-linked dermal collagen and about 60 wt. % to about 75 wt. % calcium hydrogen phosphate, wherein the particles were prepared from a lyophilized composition of collagen and calcium hydrogen phosphate; and

a fluid selected from the group consisting of bone marrow aspirate, whole blood or combinations thereof,

wherein the composition comprises about 2 to about 150 parts by weight of fluid.

2. The bone graft composition of claim 1 wherein the substrate comprises an acidic buffering potential when combined with the fluid.

3. The bone graft composition of claim 2 wherein the acidic buffering potential is between about pH 2 and about pH 5.

4. The bone graft composition of claim 1 wherein the substrate comprises calcium hydrogen phosphate in the form of particles which are about 125 microns to about 5000 microns in average size.

5. The bone graft composition of claim 1 wherein the lyophilized composition comprises a porosity of about 95% to about 98%.

6. The bone graft composition of claim 1 wherein the lyophilized composition is a sponge.

7. The bone graft composition of claim 1 wherein the average particle size is about 125 microns to about 300 microns.

8. The bone graft composition of claim 1 wherein the composition further comprises an acidic calcium phosphate other than calcium hydrogen phosphate.

9. The bone graft composition of claim 8 wherein the acidic calcium phosphate mineral comprises monocalcium phosphate.

10. The bone graft composition of claim 8 wherein the composition comprises about 2 parts by weight to about 15 parts by weight of an acidic calcium phosphate mineral other than calcium hydrogen phosphate.

11. The bone graft composition of claim 1 wherein the composition further comprises a second collagen other than bovine Type I dermal collagen.

12. The bone graft composition of claim 11 wherein the second collagen comprises a soluble collagen.

13. The bone graft composition of claim 11 wherein the composition comprises 1 part by weight to about 20 parts by weight of collagen other than bovine Type I dermal collagen.

14. The bone graft composition of claim 11 wherein the composition comprises about 85 parts by volume to about 95 parts by volume of the substrate and about 5 parts by volume to about 15 parts by volume of the second collagen.

15. The bone graft composition of claim 11 wherein the composition comprises about 3 parts by weight to about 10 parts by weight of the substrate;

about 1 part by weight to about 20 parts by weight of collagen other than bovine Type I dermal collagen; and

about 2 parts by weight to about 15 parts by weight of an acidic calcium phosphate mineral other than calcium hydrogen phosphate.

16. The bone graft composition of claim 1 wherein the composition is in the form of a putty.

17. The bone graft composition of claim 16, wherein a volume ratio of the fluid to a dry substrate volume is 0.6:

1.

18. The bone graft composition of claim 16 wherein a volume ratio of the fluid to a dry substrate volume is 1.3:

1.

19. The bone graft composition of claim 1 wherein the composition is in the form of a paste.

20. The bone graft composition of claim 1 wherein the fluid further comprises a fluid selected from the group consisting of platelet-rich-plasma, serum, saline, water, PBS, cell culture media or combinations thereof.