Formable and settable polymer bone composite and methods of production thereof

• US 9,308,292 B2
• Filed: 11/05/2007
• Issued: 04/12/2016
• Est. Priority Date: 12/12/2002
• Status: Active Grant

• Current Assignee: Warsaw Orthopedic Incorporated (Medtronic Plc)
• Original Assignee: Warsaw Orthopedic Incorporated (Medtronic Plc)
• Inventors: Winterbottom, John, Kaes, David
• Primary Examiner(s): DAVIS, RUTH A
• Application Number:
  US11/934,980
• Publication Number:
  US 20080063684A1
• Time in Patent Office: 3,081 Days
• Field of Search: 424/400, 424/422
• US Class Current: 1/1
• CPC Class Codes: A61L 24/00 Surgical adhesives or cements; Adhesives for colostomy devices
• CPC Class Codes: A61L 2430/02 for reconstruction of bones; weight-bearing implants
• CPC Class Codes: A61L 27/3608 Bone, e.g. demineralised bone matrix [DBM], bone powder
• CPC Class Codes: A61L 27/365 Bones
• CPC Class Codes: A61L 27/3683 subjected to a specific treatment prior to implantation, e.g. decellularising, demineralising, grinding, cellular disruption/non-collagenous protein removal, anti-calcification, crosslinking, supercritical fluid extraction, enzyme treatment
• CPC Class Codes: A61L 27/3834 Cells able to produce different cell types, e.g. hematopoietic stem cells, mesenchymal stem cells, marrow stromal cells, embryonic stem cells
• CPC Class Codes: A61L 27/3847 Bones
• 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 27/446 with other specific inorganic fillers other than those covered by A61L27/443 or A61L27/46
• CPC Class Codes: A61L 27/46 with phosphorus-containing inorganic fillers
• CPC Class Codes: C08L 67/04 Polyesters derived from hydroxycarboxylic acids, e.g. lactones C08L67/06 takes precedence

Abstract

A composite osteoimplant. The osteoimplant includes a polymer and bone-derived particles. The composite is adapted and constructed to be formable during or immediately prior to implantation and to be set after final surgical placement.

Claims

1. A method of preparing an osteoimplant, comprising:

forming a composite comprising bone-derived particles and a polymer into a predetermined shape, the composite being manipulated into the predetermined shape at a temperature greater than about 40°

C., the polymer comprising starch poly(caprolactone), poly(caprolactone), poly(l-lactide), poly(dl-lactide-co-glycolide), poly(l-lactide-co-dl-lactide), enantiomers thereof, copolymers thereof, and/or mixtures thereof, wherein the bone-derived particles are about 50% to about 75% by weight of the composite and the bone-derived particles have a size between about 50 μ

m and about 1 mm; and

causing the polymer to set.

2. The method of claim 1, further comprising combining the composite with autogenous tissue.

3. The method of claim 1, wherein the predetermined shape is that of a wound site in a bone and the step of forming comprises packing the wound site with the composite.

4. The method of claim 1, wherein the step of causing comprises allowing the composite to cool to ambient temperature.

5. The method of claim 4, wherein the step of causing comprises allowing the composite to cool to body temperature.

6. The method of claim 1, wherein the step of causing comprises increasing the cross-link density of the polymer.

7. The method of claim 1, further comprising adding a mechanical fastener to the osteoimplant, wherein the step of forming comprises forming the composite to retain the mechanical fastener after the step of causing.

8. The method of claim 1, wherein the composite further comprises at least one member selected from the group consisting of bone marrow, a biomolecule, a small molecule, a bioactive molecule, calcium phosphate, calcium carbonate, and cells.

9. The method of claim 8, wherein the composite further comprises at least one member selected from the group consisting of nucleic acid vectors, mesenchymal stem cells, osteoblasts, osteoclasts, and fibroblasts.

10. The method of claim 9, wherein the nucleic acid vector, when introduced into a cell, increases the cell'"'"'s production of bone morphogenetic proteins.

11. The method of claim 1, wherein the polymer is selected from the group consisting of biodegradable, non-biodegradable, co-polymers of biodegradable polymers, co-polymers of non-biodegradable polymers, and co-polymers of biodegradable and nonbiodegradable polymers.

12. The method of claim 1, wherein the bone derived particles and the polymer are linked with a coupling agent.

13. The method of claim 1, wherein the predetermined shape is selected from the group consisting of a bone, a section of a bone, sheet, plate, particle, sphere, hemisphere strand, coiled strand, capillary network, film, fiber, mesh, disk, cone, portion of a cone, pin, screw, tube, cup, tooth, tooth root, strut, wedge, portion of wedge, cylinder, threaded cylinder, rod, hinge, rivet, anchor, spheroid, ellipsoid, oblate spheroid, prolate ellipsoid, or hyperbolic paraboloid.

14. The method of claim 1, further comprising forming at least a second composite, causing the polymer in the second composite to set, and joining the composites together to form an osteoimplant.

15. The method of claim 1, further comprising machining the composite into a shape, wherein the step of machining is performed before the step of forming, after the step of forming, before the step of causing, after the step of causing, or any combination of the above.

16. The method of claim 1, further comprising combining bone-derived particles and a polymer to form the composite.

17. The method of claim 16, wherein the step of combining comprises at least one member selected from the group consisting of pressing a mixture of polymer and bone-derived particles, hand mixing bone-derived particles into formable polymer, solvent casting a polymer and bone-derived particles, injection molding, extrusion forming, pressing a coating of bone-derived particles into a sheet of polymer, and combining the polymer with a solvent.

18. The method of claim 1, wherein the step of forming comprises at least one member selected from the group consisting of shaping the composite in a mold and arranging the composite in a tissue site.

19. The method of claim 1, wherein at least a portion of the bone-derived particles in the composite are elongate, and wherein an arrangement of bone-derived particles in the composite is isotropic or anisotropic.

20. The method of claim 1, wherein at least a portion of the bone-derived particles in the composite are elongate, and wherein a relative alignment of bone-derived particles in a first portion of the composite is different than the relative alignment of bone particles in a second portion of the composite.

21. The method of claim 1, wherein at least a portion of the bone-derived particles are covalently linked to one another.

22. The method of claim 1, wherein the composite further comprises poly(ethylene glycol).