Continuous matrix with osteoconductive particles dispersed therein, method of forming thereof, and method of regenerating bone therewith
View Patent ↗The present disclosure provides compositions useful in regeneration of connective tissue, particularly bone. The compositions comprise a continuous matrix formed of a polypeptide crosslinked with a second polymer and further comprise particles of a porous, osteoconductive material dispersed in the continuous matrix. The composition can be provided in a dehydrated form. The disclosure further provides methods of preparing the composition in a clinically useful form, methods of using the composition in regenerating bone, and kits including the composition.
1. A composition comprising:
a continuous matrix formed of a polypeptide crosslinked with a second polymer; and
particles of a porous, osteoconductive material dispersed in the continuous matrix;
wherein the pores of the osteoconductive material have adsorbed therein a biocompatible material.
2. The composition according to claim 1 , wherein the second polymer is a polysaccharide.
3. The composition according to claim 2 , wherein the polysaccharide is dextran.
4. The composition according to claim 1 , wherein the second polymer is a synthetic polymer.
5. The composition according to claim 4 , wherein the synthetic polymer is a polyethylene glycol.
6. The composition according to claim 1 , wherein the polypeptide comprises gelatin.
7. The composition according to claim 1 , wherein the biocompatible material comprises a polypeptide.
8. The composition according to claim 7 , wherein the polypeptide comprises the same polypeptide that is crosslinked with the second polymer.
9. The composition according to claim 7 , wherein the polypeptide comprises a material that is different from the polypeptide that is crosslinked with the second polymer.
10. The composition according to claim 1 , wherein the porous, osteoconductive material is selected from the group consisting of calcium phosphate, calcium sulfate, calcium aluminate, alumina, zirconia, aluminum silicates, polypropylene fumarate, bioactive glass, porous titanium, porous nickel-titanium alloy, porous tantalum, sintered cobalt-chrome beads, autologous bone, allogenic bone, xenogenic bone, coralline, and combinations thereof.
11. The composition according to claim 10 , wherein the porous, osteoconductive material is hydroxyapatite.
12. The composition according to claim 1 , wherein the particles of the porous osteoconductive material comprise macropores, micropores, and nanopores.
13. The composition according to claim 1 , wherein the particles of the porous, osteoconductive material have an average diameter of about 1μm to about 3,000 μm.
14. The composition according to claim 1 , wherein the particles of the porous, osteoconductive material have a mean pore diameter (volume) of about 100 μm to about 450 μm.
15. The composition according to claim 1 , wherein the particles of the porous, osteoconductive material have a mean pore diameter (area) of about 20μm to about 60 μm.
16. The composition according to claim 1 , wherein the particles of the porous, osteoconductive material have a porosity of about 35% or greater.
17. The composition according to claim 1 , wherein the particles of the porous, osteoconductive material have a surface area of about 1m 2 /g or greater.
18. The composition according to claim 1 , wherein the particles of the porous, osteoconductive material are amorphous with interconnecting pores.
19. The composition according to claim 1 , wherein the composition further comprises one or more of a scaffolding reagent, a buffer, and an osteoinductive material.
20. The composition according to claim 19 , wherein the composition comprise a scaffolding reagent selected from the group consisting of polar amino acids, divalent cation chelators, and combinations thereof.
21. The composition according to claim 20 , wherein the composition comprises an osteoinductive material selected from the group consisting of bone morphogenetic proteins (BMPs), transforming growth factors (TGFs), fibroblast growth factors (FGFs), insulin-like growth factors (IGFs), platelet-derived growth factors (PDGFs), epidermal growth factors (EGFs), vascular endothelial growth factors (VEGFs), vascular permeability factors (VPFs), cell adhesion molecules (CAMs), platelet-rich plasma, natural or synthetic peptides, bone marrow aspirates, and combinations thereof.
22. The composition according to claim 1 , wherein the particles and the continuous matrix are present in a dry weight ratio of about 90:10 to about 50:50.
23. The composition according to claim 1 , wherein the composition is dehydrated.
24. A kit comprising:
one or more containers containing a composition comprising a continuous matrix formed of a polypeptide crosslinked with a second polymer and particles of a porous, osteoconductive material dispersed in the continuous matrix, wherein the pores of the osteoconductive material have adsorbed therein a biocompatible material; and
an instruction set directed to a health care provider describing steps for administering the composition to a bone void in an amount effective for regenerating bone in the void.
25. A composition comprising:
a continuous matrix formed of a polypeptide crosslinked with a second polymer; and
particles of a porous, osteoconductive material dispersed in the continuous matrix;
wherein the pores of the osteoconductive material have adsorbed therein a polypeptide that is the same polypeptide that is crosslinked with the second polymer.
26. A composition comprising:
a continuous matrix formed of a polypeptide crosslinked with a second polymer; and
particles of a porous, osteoconductive material dispersed in the continuous matrix;
wherein the pores of the osteoconductive material have adsorbed therein a biocompatible material, and one or more of the following conditions are met:
the particles of the porous, osteoconductive material have an average diameter of about 1μm to about 3,000 μm;
the particles of the porous, osteoconductive material have a mean pore diameter (volume) of about 100μm to about 450 μm;
the particles of the porous, osteoconductive material have a mean pore diameter (area) of about 20μm to about 60μm;
the particles of the porous, osteoconductive material have a porosity of about 35% or greater;
the particles of the porous, osteoconductive material have a surface area of about 1m 2 /g or greater;
the particles of the porous, osteoconductive material are amorphous with interconnecting pores;
the particles of the porous, osteoconductive material and the continuous matrix are present in a dry weight ratio of about 90:10 to about 50:50;
the composition is dehydrated.