Formable and settable polymer bone composite and method of production thereof

• US 7,291,345 B2
• Filed: 12/12/2003
• Issued: 11/06/2007
• Est. Priority Date: 12/12/2002
• Status: Active Grant

• Current Assignee: Warsaw Orthopedic Incorporated (Medtronic Plc)
• Original Assignee: Osteotech Incorporated (Medtronic Plc)
• Inventors: Winterbottom, John, Kaes, David
• Primary Examiner(s): Davis; Ruth A.
• Application Number:
  US10/735,135
• Publication Number:
  US 20050008672A1
• Time in Patent Office: 1,425 Days
• Field of Search: 424/400, 424/422, 424/423, 424/93.1, 424/600, 435/325, 435/372, 435/395
• US Class Current: 424/400
• 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 composite osteoimplant, comprising:

a polymer, wherein the polymer is selected from the group consisting of starch poly(caprolactone), poly(caprolactone), poly(l-lactide), poly(dl-lactide-co-glycolide), poly(l-lactide-co-dl-lactide), enantiomers of the above, co-polymers of the above, and mixtures of the above; and

bone-derived particles;

wherein the composite is formable during implantation or immediately prior to implantation and is settable under suitable conditions; and

wherein the composite is not formable at about 37°

C., and wherein the composite becomes formable when heated to a temperature greater than about 40°

C.

2. The osteoimplant of claim 1, wherein the composite becomes formable when heated to a temperature greater than about 45°

C.

3. The osteoimplant of claim 2, wherein the composite becomes formable when heated to a temperature greater than about 50°

C.

4. The osteoimplant of claim 3, wherein the composite becomes formable when heated to a temperature greater than about 55°

C.

5. The osteoimplant of claim 4, wherein the composite becomes formable when heated to a temperature greater than about 60°

C.

6. The osteoimplant of claim 5, wherein the composite becomes formable when heated to a temperature greater than about 70°

C.

7. The osteoimplant of claim 6, wherein the composite becomes formable when heated to a temperature greater than about 80°

C.

8. The osteoimplant of claim 7, wherein the composite becomes formable when heated to a temperature greater than about 90°

C.

9. The osteoimplant of claim 1, wherein the composite is set by increasing the cross-link density of the polymer component.

10. The osteoimplant of claim 1, wherein the composite further comprises a monomer, the composite becoming set when the monomer is covalently incorporated into the polymer.

11. The osteoimplant of claim 1, wherein the composite further comprises at least one member selected from the group consisting of bone marrow, biomolecules, small molecules, bioactive agents, calcium phosphate, calcium carbonate, and cells.

12. The osteoimplant of claim 1, wherein the composite further comprises at least one member of nucleic acid vectors, mesenchymal stem cells, osteoblasts, osteoclasts, and fibroblasts.

13. The osteoimplant of claim 12, wherein the nucleic acid vector, when introduced into a cell, increases the cell'"'"'s production of bone morphogenetic proteins.

14. The osteoimplant of claim 1, wherein the osteoimplant is capable of being irrigated following implantation without substantially changing its shape.

15. The osteoimplant of claim 1, wherein the bone-derived particles are selected from the group consisting of nondemineralized bone particles, partially demineralized bone particles, superficially demineralized bone particles, fully demineralized bone particles and mixtures thereof.

16. The osteoimplant of claim 1, wherein the bone-derived particles are obtained from a member of the group consisting of cortical bone, cancellous bone, cortico-cancellous bone, and mixtures thereof.

17. The osteoimplant of claim 1, wherein the bone-derived particles are obtained from a member of the group consisting of autogenous bone, allogenic bone, xenogeneic bone, transgenic bone, and mixtures thereof.

18. The osteoimplant of claim 1, wherein the bone-derived particles are about 10% to about 99% by weight of the composite.

19. The osteoimplant of claim 18, wherein the bone-derived particles are about 25% to about 50% by weight of the composite.

20. The osteoimplant of claim 1, wherein a surface of the bone-derived particles is modified with at least one member selected from the group consisting of biomolecules, small molecules, bioactive agents, non-biologically active materials, and any combination of the above.

21. The osteoimplant of claim 20, wherein the member is linked to the surface by a coupling agent.

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

23. The osteoimplant of claim 1, wherein collagen fibers at the surface of the bone-derived particles are exposed.

24. The osteoimplant of claim 23, wherein the exposed collagen fibers are partially or fully separated from one another.

25. The osteoimplant of claim 23, wherein the exposed collagen fibers are derivatized with a moiety selected from the group consisting of biomolecules, small molecules, bioactive agents, non-biologically active materials, and any combination of the above.

26. The osteoimplant of claim 1, wherein the polymer comprises poly(caprolactone).

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

28. The osteoimplant of claim 1, wherein the osteoimplant has a shape selected from the group consisting of 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, and hyperbolic paraboloid.

29. The osteoimplant of claim 1, wherein the osteoimplant comprises a plurality of pieces of composite, wherein the pieces are joined together.

30. The osteoimplant of claim 29, wherein the pieces are joined together with a member selected from the group consisting of adhesives, mechanical fasteners, ultrasonic bonding, and any combination of the above.

31. The osteoimplant of claim 1, wherein the composite is adapted and constructed to be formed in a mold.

32. The osteoimplant of claim 1, wherein the distribution of bone-derived particles within the composite is not uniform with respect to a member of the group consisting of volume fraction, size, density, shape, size distribution, and any combination of the above.

33. The osteoimplant 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.

34. The osteoimplant 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-derived particles in a second portion of the composite.