Maxillofacial bone augmentation using rhPDGF-BB and a biocompatible matrix

• US 8,114,841 B2
• Filed: 11/17/2006
• Issued: 02/14/2012
• Est. Priority Date: 10/14/2004
• Status: Active Grant

• Current Assignee: Biomimetic Therapeutics LLC (Stryker Corporation)
• Original Assignee: Biomimetic Therapeutics Incorporated (Stryker Corporation)
• Inventors: Lynch, Samuel E., Nevins, Myron, Simion, Massimo
• Primary Examiner(s): FORD, ALLISON M
• Application Number:
  US11/601,376
• Publication Number:
  US 20070129807A1
• Time in Patent Office: 1,915 Days
• Field of Search: None
• US Class Current: 514/8.2
• CPC Class Codes: A61C 8/0006 Periodontal tissue or bone regeneration support means for endoprosthetic bone substitute or bone graft implants A61F2/2846
• CPC Class Codes: A61F 2/2803 for mandibular reconstruction temporo-mandibular joints A61F2/3099; bone plates for the jaw A61B17/8071
• CPC Class Codes: A61F 2/2846 Support means for bone substitute or for bone graft implants, e.g. membranes or plates for covering bone defects nets or sleeves applied to surface of endoprostheses A61F2/30907; bone plates A61B17/80; bone regeneration in dental surgery A61C8/0006
• 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 2002/30062 (bio)absorbable, biodegradable, bioerodable, (bio)resorbable, resorptive
• CPC Class Codes: A61F 2210/0004 bioabsorbable
• CPC Class Codes: A61F 2310/00293 containing a phosphorus-containing compound, e.g. apatite
• CPC Class Codes: A61L 2300/414 Growth factors
• 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 27/425 of phosphorus containing material, e.g. apatite
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: A61P 19/08 for bone diseases, e.g. rachitism, Paget's disease
• CPC Class Codes: A61P 19/10 for osteoporosis
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

The present invention provides effective new methods and materials for maxillofacial bone augmentation, particularly alveolar ridge augmentation, that are free of problems associated with prior art methods. In one embodiment, these materials include human recombinant platelet derived growth factor (rhPDGF-BB) and a biocompatible matrix. In another embodiment, these materials include rhPDGF-BB, a deproteinized bone block or calcium phosphate, and a bioresorbable membrane. The use of these materials in the present method is effective in regenerating maxillofacial bones and facilitating achievement of stable osseointegrated implants. The mandible and maxilla are preferred bones for augmentation, and enhancement of the alveolar ridge is a preferred embodiment of the present invention.

Claims

1. A method of enhancing bone augmentation in a subject comprising applying a composition consisting of a biocompatible matrix having incorporated therein a solution consisting of platelet derived growth factor (PDGF) in a buffer to a site for desired bone augmentation in the subject;

wherein the biocompatible matrix consists of collagen and a porous calcium phosphate;

wherein the calcium phosphate consists of particles in a range of about 75 micron to about 5000 micron in size;

wherein the calcium phosphate comprises interconnected pores; and

wherein the biocompatible matrix is flowable, moldable and/or extrudable.

2. The method of claim 1, wherein the calcium phosphate consists of particles in a range of about 100 microns to about 5000 microns in size.

3. The method of claim 1, wherein the calcium phosphate consists of particles in a range of about 100 microns to about 300 microns in size.

4. The method of claim 1, wherein the calcium phosphate consists of particles in a range of about 250 microns to about 1000 microns in size.

5. The method of claim 1, wherein the calcium phosphate consists of particles in a range of about 1000 microns to about 2000 microns in size.

6. The method of claim 1, wherein the calcium phosphate is resorbable such that the calcium phosphate is resorbed within one year of being implanted.

7. The method of claim 1, wherein the calcium phosphate has a porosity that facilitates osteoinduction, osteoconduction, or osteoinduction and osteoconduction.

8. The method of claim 1, wherein the calcium phosphate has macroporosity.

9. The method of claim 1, wherein the calcium phosphate has a porosity greater than 25%.

10. The method of claim 1, wherein the calcium phosphate has a porosity greater than 50%.

11. The method of claim 1, wherein the calcium phosphate is β

-tricalcium phosphate.

12. The method of claim 1, wherein the PDGF is recombinant PDGF.

13. The method of claim 12, wherein the recombinant PDGF comprises recombinant human PDGF-BB.

14. The method of claim 13, wherein the recombinant human PDGF-BB (rhPDGF-BB) comprises at least 65% intact rhPDGF-B.

15. The method of claim 1, wherein the solution consists of PDGF at a concentration in a range of about 0.01 mg/ml to about 10 mg/ml in a buffer.

16. The method of claim 1, wherein the solution consists of PDGF at a concentration in a range of about 0.05 mg/mL to about 5 mg/mL in a buffer.

17. The method of claim 1, wherein the solution consists of PDGF at a concentration in a range of about 0.1 mg/mL to about 1.0 mg/mL in a buffer.

18. The method of claim 1, wherein the solution consists of PDGF at a concentration of about 0.3 mg/mL in a buffer.

19. The method of claim 1, wherein the PDGF comprises PDGF-AA, PDGF-BB, PDGF-AB, PDGF-CC, PDGF-DD, or a derivative thereof.

20. The method of claim 1, wherein the PDGF comprises one or more fragments of the B chain, wherein the fragments are selected from the group consisting of:

the amino acid sequences 1-31 (SEQ ID NO;

     1), 1-32 (SEQ ID NO;

     2), 33-108 (SEQ ID NO;

     3), 33-109 (SEQ ID NO;

     4), and 1-108 (SEQ ID NO;

     5) of the B chain.

21. The method of claim 1, wherein the biocompatible matrix consists of collagen and a porous calcium phosphate, wherein the calcium phosphate consists of particles in a range of about 100 microns to about 5000 microns in size, wherein the calcium phosphate has a porosity greater than 25%, wherein the calcium phosphate is β

-tricalcium phosphate, wherein the PDGF comprises recombinant human PDGF-BB, and wherein the solution consists of PDGF at a concentration in a range of about 0.01 mg/ml to about 10 mg/ml in a buffer.

22. The method of claim 21, wherein the PDGF is present in the solution at a concentration of about 0.1 to about 1.0 mg/ml.

23. The method of claim 21, wherein the PDGF is present in the solution at a concentration of about 0.3 mg/ml.

24. The method of claim 21, wherein the calcium phosphate consists of particles in a range of about 100 microns to about 300 microns in size.

25. The method of claim 21, wherein the calcium phosphate consists of particles in a range of about 250 microns to about 1000 microns in size.

26. The method of claim 21, wherein the calcium phosphate consists of particles in a range of about 1000 microns to about 2000 microns in size.

27. The method of claim 21, wherein the calcium phosphate has a porosity that facilitates osteoinduction, osteoconduction, or osteoinduction and osteoconduction.

28. The method of claim 1, further comprising administering a bisphosphonate to the subject.

29. The method of claim 1, wherein the site is a maxillofacial site and a maxillofacial bone is augmented.

30. The method of claim 29, wherein the maxillofacial site is an alveolar ridge, a bone defect, a wall of the maxillary sinus, or an extraction socket.

31. The method of claim 29, wherein the maxillofacial site is located in a maxilla or a mandible.

32. The method of claim 1, wherein the subject is diabetic.

33. The method of claim 1, wherein the subject is an osteoporotic subject.

34. The method of claim 1, wherein the subject is a smoker.

35. The method of claim 1, wherein the subject is a steroid user.

36. The method of claim 1, wherein the method facilitates achievement of a stable osseointegrated implant.

37. The method of claim 1, wherein the method comprises repair of an extraction socket.

38. The method of claim 1, further comprising covering the composition with a bioresorbable membrane.

39. The method of claim 38, wherein the bioresorbable membrane comprises collagen.

40. The method of claim 38 or 39, wherein the bioresorbable membrane comprises PDGF.