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 method of preparing a bone void filler composition, the method comprising:
combining particles of a porous, osteoconductive material with a solution of a polypeptide to form a slurry; and
adding to the slurry a second polymer under conditions such that the polypeptide crosslinks with the second polymer to form a continuous matrix having the particles of the osteoconductive material dispersed therein;
wherein before said adding step, at least a portion of the pores in the particles of the osteoconductive material have a biocompatible material adsorbed therein.
2. The method according to claim 1 , wherein the biocompatible material adsorbed in the pores of the osteoconductive particles comprises the polypeptide used to form the slurry.
3. The method according to claim 1 , wherein the second polymer is a polysaccharide.
4. The method according to claim 1 , wherein the second polymer is a synthetic polymer.
5. The method according to claim 1 , wherein the second polymer is at least partially solubilized prior to said adding step.
6. The method according to claim 1 , further comprising adding a scaffolding reagent or an osteoinductive material to the composition.
7. The method according to claim 6 , comprising adding a scaffolding reagent selected from the group consisting of polar amino acids, divalent cation chelators, and combinations thereof.
8. The method according to claim 6 , comprising adding bone marrow aspirates as the osteoinductive material.
9. The method according to claim 1 , wherein the polypeptide comprises gelatin.
10. The method 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, corallin, and combinations thereof.
11. The method according to claim 1 , comprising combining the particles of the porous, osteoconductive material, the polypeptide, and the second polymer such that the particles and the continuous matrix are present in a dry weight ratio of about 90:10 to about 50:50.
12. The method according to claim 1 , further comprising dehydrating the composition.