Bone graft composition
A particle comprising hydroxyapatite, β-tricalcium phosphate, α-tricalcium phosphate, and/or bioactive glass is provided. The particle can be useful in bone graft compositions further comprising a carrier. The composition can include a quadphasic particle having hydroxyapatite, β-tricalcium phosphate, α-tricalcium phosphate, bioactive glass, and a carrier. The particle can have a size in the range of 50 microns to 2.5 mm. A method of repairing a bone defect is also provided. The method can include a step of applying the bone graft composition to a subject having the bone defect, such as a spinal bone defect. The subject receiving the bone graft composition can be a mammal, namely a human, pet, or domestic animal.
1 . A sintered particle comprising one or more particles each of hydroxyapatite, β-tricalcium phosphate, α-tricalcium phosphate, and bioactive glass, wherein the one or more particles each of hydroxyapatite β-tricalcium phosphate, α-tricalcium phosphate, and bioactive glass are sintered together to form a unitary particle; wherein the particle has a particle size of about 50 microns to about 2.5 mm, and wherein the sintered particle comprises:
about 40 wt. % to about 60 wt. % hydroxyapatite;
about 30 wt. % to about 50 wt. % β-tricalcium phosphate;
about 2.5 wt. % to about 25 wt. % α-tricalcium phosphate; and
about 5 wt. % to about 20 wt. % bioactive glass.
2 . The particle of claim 1 ;
wherein the particle size of the hydroxyapatite ranges from about 2 μm to about 20 μm;
wherein the particle size of the β-tricalcium phosphate ranges from about 2 μm to about 20 μm;
wherein the particle size of the α-tricalcium phosphate ranges from about 50 μm to about 100 μm; and
wherein the particle size of the bioactive glass ranges from about 20 μm to about 90 μm.
3 . A bone graft composition comprising a plurality of sintered particles wherein each sintered particle comprises one or more particles each of hydroxyapatite, β-tricalcium phosphate, α-tricalcium phosphate, and bioactive glass sintered together to form a unitary particle; and a carrier, wherein the unitary particle comprises:
about 40 wt. % to about 60 wt. % hydroxyapatite;
about 30 wt. % to about 50 wt. % β-tricalcium phosphate;
about 2.5 wt. % to about 25 wt. % α-tricalcium phosphate; and
about 5 wt. % to about 20 wt. % bioactive glass.
4 . The bone graft composition of claim 3 , further comprising additional hydroxyapatite particles having a particle size in the range of about 50 nm to about 100 μm.
5 . The bone graft composition of claim 3 , wherein the carrier comprises a bioresorbable polymer.
6 . The bone graft composition of claim 5 wherein the carrier comprises polyethylene glycol (PEG) or methylcellulose.
7 . The bone graft composition of claim 6 , wherein the polyethylene glycol (PEG) comprises a PEG having a molecular weight in a range of about 500 grams/mole to about 3000 grams/mole.
8 . The bone graft composition of claim 7 , wherein the polyethylene glycol (PEG) comprises a PEG having a molecular weight in a range of about 1500 grams/mole to about 2500 grams/mole.
9 . The bone graft composition of claim 6 , wherein the composition comprises between about 30 wt % and about 50 wt % methylcellulose.
10 . The bone graft composition of claim 3 , wherein the carrier comprises glycerol.
11 . The bone graft composition of claim 3 , wherein the particles comprise about 30 wt. % to about 70 wt. % of the composition.
12 . The bone graft composition of claim 3 , wherein the carrier comprises about 40 wt. % to about 60 wt. % of the composition.
13 . The bone graft composition of claim 4 , wherein the average particle size of each sintered particle is in a range of about 50 microns to about 1 millimeter.
14 . The bone graft composition of claim 13 , wherein the average particle size of each sintered particle is in a range of about 250 microns to about 1 millimeter.
15 . The bone graft composition of claim 3 , wherein the bone graft composition exhibits a quadphasic resorption profile.
16 . The bone graft composition of claim 3 , wherein the unitary particle comprises a surface texturing.
17 . The bone graft composition of claim 16 , wherein the surface texturing is osteoconductive.
18 . The bone graft composition of claim 16 , wherein the surface texturing comprises nano, micro or sub-micron hydroxyapatite.
19 . The bone graft composition of claim 3 , further comprising demineralized bone matrix.
20 . The bone graft composition of claim 19 , comprising about 10% to about 90% by weight of demineralized bone matrix.
21 . The bone graft composition of claim 20 , comprising about 20% to about 80% by weight of demineralized bone matrix.
22 . The bone graft composition of claim 21 , comprising about 40% to about 60% by weight of demineralized bone matrix.
23 . The bone graft composition of claim 19 , comprising about 15% to about 45% by volume of demineralized bone matrix.
24 . The bone graft composition of claim 19 , comprising about 10% to about 50% by volume of demineralized bone matrix.
25 . The bone graft composition of claim 3 , wherein the carrier comprises an embedded substrate of hydroxyapatite particles,
wherein the hydroxyapatite particles comprise micro-hydroxyapatite particles, submicron-hydroxyapatite particles, and/or nano-hydroxyapatite particles.
26 . The bone graft composition of claim 25 , wherein the hydroxyapatite particles of the embedded substrate have a size from about 20 nm to about 100 μm.
27 . The bone graft composition of claim 26 , wherein the hydroxyapatite particles of the embedded substrate have a size from about 20 nm to about 50 μm.
28 . The bone graft composition of claim 27 , wherein the hydroxyapatite particles of the embedded substrate have a size from about 5 μm to about 35 μm.
29 . The bone graft composition of claim 28 , comprising about 40 wt. % to about 55 wt. % of the embedded hydroxyapatite substrate.
30 . A prefilled cartridge for a delivery device, wherein the prefilled cartridge contains the bone graft composition of any one of claims 3-29 .
31 . A method of preparing the particle of claim 1 comprising admixing the one or more particles of hydroxyapatite, the one or more particles of β-tricalcium phosphate, the one or more particles of α-tricalcium phosphate, and the one or more particles of bioactive glass; sintering the admixed particles at a temperature from about 500° C. to about 1700° C. to obtain sintered particles; and adjusting the size of sintered particles to be in the range of 50 microns to about 2.5 mm.
32 . A method of repairing a bone defect, comprising applying the bone graft composition of any one of claims 3-29 to a subject having the bone defect and in need of repair of the bone defect.
33 . The method of claim 32 , wherein the subject is a mammal, or a primate mammal, or a non-human primate mammal, or a human, or wherein the mammal is a canine or dog, a feline or domestic house cat, a bovine or a cow or a bull, an ovine or a sheep or ewe, a porcine or a pig or a sow or a gilt or a boar, an equine or a horse, a cumulus or a camel, or a caprinae or a goat.
34 . The method of claim 32 , wherein the bone defect is a spinal bone defect.
35 . A kit comprising the bone graft composition as claimed in claim 3 and a delivery device for administering the bone graft composition to a subject having a bone defect; and optionally instructions for use.
36 . The kit of claim 35 , further comprising an additional implantation device.
37 . The kit of claim 36 , wherein the additional implantation device is a 3D printed cage.
38 . The kit of claim 36 , wherein the additional implantation device is a loading case.
39 . The bone graft composition of claim 4 , wherein the additional hydroxyapatite particles are present in an amount of about 40 wt. % to about 55 wt. %.