DECORATING HYDROXYAPATITE BIOMATERIALS WITH MODULAR BIOLOGICALLY ACTIVE MOLECULES

• US 20110129611A1
• Filed: 12/01/2009
• Published: 06/02/2011
• Est. Priority Date: 12/01/2009
• Status: Active Grant

• Current Assignee: Wisconsin Alumni Research Foundation (University of Wisconsin System)
• Original Assignee: Wisconsin Alumni Research Foundation (University of Wisconsin System)
• Inventors: Graf, Ben K., Lee, Jae Sung, Markel, Mark D., Murphy, William L.
• Granted Patent: US 8,420,774 B2
• Time in Patent Office: Days
• US Class Current: 427/429
• CPC Class Codes: B05D 1/18 performed by dipping
• CPC Class Codes: B05D 1/28 performed by transfer from the surfaces of elements carrying the liquid or other fluent material, e.g. brushes, pads, rollers
• CPC Class Codes: C07K 14/50 Fibroblast growth factor [FGF]
• CPC Class Codes: C07K 14/51 Bone morphogenetic factor; Osteogenins; Osteogenic factor; Bone-inducing factor
• CPC Class Codes: C07K 14/52 Cytokines; Lymphokines; Interferons

Abstract

A modular peptide design strategy wherein the modular peptide has two functional units separated by a spacer portion is disclosed. More particularly, the design strategy combines a hydroxyapatite-binding portion and a biomolecule-derived portion. The modular peptides have improved non-covalent binding to the surface of the HA-based materials, and are capable of initiating osteogenesis, angiogenesis, and/or osteogenic differentiation.

Claims

1. A modular peptide for non-covalently binding to a surface of a biomaterial, the modular peptide comprising:

a hydroxyapatite-binding portion, a spacer portion, and a biomolecule-derived portion.

2. The modular peptide as set forth in claim 1 wherein the biomaterial is selected from the group consisting of hydoxyapatite and hydroxyapatite-based materials.

4. The modular peptide as set forth in claim 1 wherein the hydroxyapatite-binding portion comprises an amino acid sequence selected from the group consisting of SEQ ID NO:

1, SEQ ID NO;

2, SEQ ID NO;

3, SEQ ID NO;

4, SEQ ID NO;

5, and SEQ ID NO;

6.

6. The modular peptide as set forth in claim 1 wherein the spacer portion is an amino acid sequence capable of forming an α

-helix.

7. The modular peptide as set forth in claim 1 wherein the spacer portion is SEQ ID NO:

7.

10. The modular peptide as set forth in claim 1 wherein the biomolecule-derived portion is a growth factor capable of initiating at least one of osteogenesis, angiogenesis, and osteogenic differentiation.

12. The modular peptide as set forth in claim 10 wherein the growth factor comprises an amino acid sequence selected from the group consisting of SEQ ID NO:

8, SEQ ID NO;

9, SEQ ID NO;

10, and SEQ ID NO;

11.

15. The modular peptide as set forth in claim 1 having the sequence selected from the group consisting of SEQ ID NO:

12, SEQ ID NO;

13, SEQ ID NO;

14, SEQ ID NO;

15, SEQ ID NO;

16, SEQ ID NO;

17, and SEQ ID NO;

18.

3. (canceled)

5. (canceled)

8. (canceled)

9. (canceled)

11. (canceled)

13. (canceled)

14. (canceled)

16-21. -21. (canceled)

22. A method of coating a biomaterial with a modular peptide, the method comprising:

exposing a biomaterial to a phosphate buffered saline (PBS) solution comprising the modular peptide.

23. The method as set forth in claim 22 wherein the exposing a biomaterial to a PBS solution comprises a method selected from the group consisting of dip coating the biomaterial in the PBS solution, painting the biomaterial with the PBS solution, stamping the biomaterial with the PBS solution, spotting the biomaterial with the PBS solution, and brushing the biomaterial with the PBS solution.

24. The method as set forth in claim 22 wherein the biomaterial is exposed to the PBS solution under constant agitation.

25. The method as set forth in claim 24 wherein the biomaterial is exposed to the PBS solution for a period of from about two minutes to about 10 hours.

27. The method as set forth in claim 22 wherein the biomaterial is selected from the group consisting of hydroxyapatite and hydroxyapatite-based materials.

29. The method as set forth in claim 22 wherein the PBS solution comprises from about 100 μ

g to about 1500 μ

g modular peptide.

31. The method as set forth in claim 22 wherein the modular peptide comprises a hydroxyapatite-binding portion, a spacer portion, and a biomolecule-derived portion.

33. The method as set forth in claim 31 wherein the hydroxyapatite-binding portion comprises an amino acid sequence selected from the group consisting of SEQ ID NO:

1, SEQ ID NO;

2, SEQ ID NO;

3, SEQ ID NO;

4, SEQ ID NO;

5, and SEQ ID NO;

6.

35. The method as set forth in claim 31 wherein the spacer portion is an amino acid sequence capable of forming an α

-helix.

39. The method as set forth in claim 31 wherein the biomolecule-derived portion is a growth factor capable of initiating at least one of osteogenesis, angiogenesis, and osteogenic differentiation.

41. The method as set forth in claim 39 wherein the growth factor comprises an amino acid sequence selected from the group consisting of SEQ ID NO:

8, SEQ ID NO;

9, SEQ ID NO;

10, and SEQ ID NO;

11.

44. The method as set forth in claim 31 wherein the PBS solution comprises the modular peptide having the sequence selected from the group consisting of SEQ ID NO:

12, SEQ ID NO;

13, SEQ ID NO;

14, SEQ ID NO;

15, SEQ ID NO;

16, SEQ ID NO;

17, and SEQ ID NO;

18.

26. (canceled)

28. (canceled)

30. (canceled)

32. (canceled)

34. (canceled)

36. (canceled)

37. (canceled)

38. (canceled)

40. (canceled)

42. (canceled)

43. (canceled)

45-50. -50. (canceled)