Moldable bone graft compositions
The present disclosure relates to compositions useful in synthetic bone graft applications. Particularly, the disclosure teaches moldable bone graft compositions, methods of making the compositions, and methods of utilizing the same.
1. A moldable bone graft composition, comprising:
a) one or more bioresorbable polymers;
b) biphasic calcium phosphate particles comprising hydroxyapatite and tricalcium phosphate; and
c) a bioactive glass component,
wherein said biphasic calcium phosphate particles and said bioactive glass together comprise about 10-70% by weight of the moldable bone graft composition.
2. The moldable bone graft composition of claim 1 , wherein the bioactive glass component comprises about 1-40% by weight of the moldable bone graft composition.
3. The moldable bone graft composition of claim 1 , wherein the one or more bioresorbable polymers comprise a polyalkylene oxide polymer having at least one of the following: a molecular weight of about 500-1500 grams/mole; a specific gravity of about 1.0-1.3 (at 25° C.); a viscosity of about 10-40 cSt (at 210° C.); or a melting temperature of about 38-50° C.
4. The moldable bone graft composition of claim 1 , wherein the biphasic calcium phosphate particles comprise about 20-60% hydroxyapatite and about 40-80% tricalcium phosphate.
5. The moldable bone graft composition of claim 1 , wherein the biphasic calcium phosphate particles have interconnected macro- and microporosity.
6. The moldable bone graft composition of claim 1 , wherein about 30-90% of the biphasic calcium phosphate particles have a particle size of about 1000-2000 μm; about 10-70% of the biphasic calcium phosphate particles have a particle size of about 425-1000 μm, about 10-50% of the biphasic calcium phosphate particles have a particle size of about 710-1000 μm; and about 1-30% of the biphasic calcium phosphate particles have a particle size of about 425-710 μm.
7. The moldable bone graft composition of claim 1 , wherein the bioactive glass comprises 45S5 bioactive glass.
8. The moldable bone graft composition of claim 1 , wherein the bioactive glass is in the form of particles having a particle size of about 1-600 μm.
9. The moldable bone graft composition of claim 1 , wherein the bioactive glass is in the form of particles having a particle size of about 1-425 μm.
10. The moldable bone graft composition of claim 1 , wherein at least 80% of the bioactive glass is in the form of particles having a particle size of about 212-425 μm.
11. The moldable bone graft composition of claim 1 , wherein the bioactive glass is in the form of irregular granules.
12. The moldable bone graft composition of claim 1 , wherein the bioactive glass is in the form of approximately spherical particles.
13. The moldable bone graft composition of claim 1 , wherein the bioactive glass is in the form of fibers.
14. The moldable bone graft composition of claim 1 , wherein about 60-90% of the biphasic calcium phosphate particles and bioactive glass together are in the form of particles having a particle size of about 425-2000 μm, and about 10-40% of the particles have a particle size of about 1-425 μm.
15. A single use moldable bone graft composition of claim 1 , having a mass of about 1.5-30 grams.
16. A single use moldable bone graft composition of claim 1 , having a volume of about 1-20 cc.
17. The moldable bone graft composition of claim 1 , having a density of about 1.2-1.8 g/cc.
18. The moldable bone graft composition of claim 1 , in the form of a cylinder.
19. The moldable bone graft composition of claim 18 , wherein said composition has a crush resistance force of less than about 20 lbf.
20. The moldable bone graft composition of claim 1 , wherein said composition can be molded into any desired shape without loss of homogeneity.
21. The moldable bone graft composition of claim 1 , having a cubical shape.
22. A syringe applicator filled with the moldable bone graft composition of claim 1 .
23. The syringe applicator of claim 22 , wherein the force required to eject the moldable bone graft composition from the syringe applicator is less than 20 lbf.
24. The moldable bone graft composition of claim 1 , further comprising: a melt skin layer disposed on the outer surface of the composition, wherein the melt skin layer comprises the bioresorbable polymer.
25. The moldable bone graft composition of claim 1 , wherein the bioresorbable polymer dissolves in PBS at 37° C. at a rate of about 0.01-0.20 grams/minute.
26. The moldable bone graft composition of claim 1 , wherein the bioresorbable polymer dissolves in PBS at 37° C. in about 60-600 minutes.
27. The moldable bone graft composition of claim 1 , wherein the bioresorbable polymer dissolves in PBS at 37° C. in less than 60 minutes.
28. The moldable bone graft composition of claim 1 , wherein the composition is supplied with, or used in conjunction with, allograft tissue.
29. The moldable bone graft composition of claim 1 , wherein the moldable bone graft composition forms a hydroxyapatite surface layer in simulated body fluid.
30. The moldable bone graft composition of claim 1 , wherein the moldable bone graft composition stimulates mesenchymal stem cell differentiation in a cell culture assay.
31. The moldable bone graft composition of claim 1 , wherein the moldable bone graft composition stimulates osteoblast cell proliferation in a cell culture assay.
32. The moldable bone graft composition of claim 1 , wherein the moldable bone graft composition demonstrates an antimicrobial efficacy according to methods based on USP <51>.
33. The moldable bone graft composition of claim 1 , wherein the moldable bone graft composition stimulates mesenchymal stem cell differentiation and osteoblast cell proliferation in a cell culture assay and demonstrates an antimicrobial effect.
34. The moldable bone graft composition of claim 1 , wherein the moldable bone graft composition provides a spine fusion rate of greater than or equal to 50% in a New Zealand white rabbit spine fusion model.
35. A method for repairing a bone defect, comprising: applying the moldable bone graft composition of claim 1 to a bone defect in a patient in need thereof.
36. The method of claim 35 , wherein the bone defect is a spinal bone defect.
37. The method of claim 35 , wherein the bone defect is in the posterolateral gutter of a vertebral body.
38. The moldable bone graft composition of claim 1 , wherein the composition is supplied with, or used in conjunction with, xenograft tissue.
39. The moldable bone graft composition of claim 1 , wherein the moldable bone graft composition is osteoinductive.