Continuous matrix with osteoconductive particles dispersed therein, method of forming thereof, and method of regenerating bone therewith

• US 8,940,317 B2
• Filed: 12/20/2012
• Issued: 01/27/2015
• Est. Priority Date: 12/23/2011
• Status: Active Grant

• Current Assignee: Xtant Medical Holdings, Inc. (OrbiMed Advisors LLC (China))
• Original Assignee: Pioneer Surgical Technology Incorporated (Surgalign Holdings, Inc.)
• Inventors: Lamberti, Francis Vincent, Hill, Ronald Stewart, MacMillan, Adam, Ahn, Edward, Schlossberg, Brian, Capistron, Stephen, Lloyd, William H.
• Primary Examiner(s): AZPURU, CARLOS A
• Application Number:
  US13/722,237
• Publication Number:
  US 20130195928A1
• Time in Patent Office: 768 Days
• US Class Current: 424/426
• CPC Class Codes: A61K 9/0024 Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L
• CPC Class Codes: A61L 2300/112 Phosphorus-containing compounds, e.g. phosphates, phosphonates
• CPC Class Codes: A61L 2400/06 Flowable or injectable implant compositions
• CPC Class Codes: A61L 2430/02 for reconstruction of bones; weight-bearing implants
• CPC Class Codes: A61L 27/22 Polypeptides or derivatives thereof , e.g. degradation products
• CPC Class Codes: A61L 27/40 Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
• CPC Class Codes: A61L 27/46 with phosphorus-containing inorganic fillers
• CPC Class Codes: A61L 27/48 with macromolecular fillers
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: A61L 27/56 Porous materials, e.g. foams or sponges
• CPC Class Codes: A61L 27/58 Materials at least partially resorbable by the body
• CPC Class Codes: C08L 5/02 Dextran; Derivatives thereof
• CPC Class Codes: C08L 89/00 Compositions of proteins; Compositions of derivatives thereof foodstuff preparations A23J3/00

Abstract

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.

Claims

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.