METHOD OF USING AN ANTI-GROWTH MATRIX AS A BARRIER FOR CELL ATTACHMENT AND OSTEO-INDUCTIVE FACTORS

• US 20090036988A1
• Filed: 08/03/2007
• Published: 02/05/2009
• Est. Priority Date: 08/03/2007
• Status: Active Grant

• Current Assignee: Warsaw Orthopedic Incorporated (Medtronic Plc)
• Original Assignee: Warsaw Orthopedic Incorporated (Medtronic Plc)
• Inventors: PECKHAM, STEVEN M.
• Granted Patent: US 8,092,541 B2
• Time in Patent Office: Days
• US Class Current: 623/17.160
• CPC Class Codes: A61B 17/56 Surgical instruments or methods for treatment of bones or joints; Devices specially adapted therefor
• CPC Class Codes: A61B 2017/564 Methods for bone or joint treatment
• CPC Class Codes: A61F 2/28 Bones joints A61F2/30
• CPC Class Codes: A61F 2/30756 Cartilage endoprostheses A61F2/3603 takes precedence
• CPC Class Codes: A61F 2/442 Intervertebral or spinal discs, e.g. resilient non-disc-shaped intervertebral inflatable pockets A61F2/441; non-disc-shaped intervertebral fusion implants A61F2/4455
• CPC Class Codes: A61F 2/4455 for the fusion of spinal bodies, e.g. intervertebral fusion of adjacent spinal bodies, e.g. fusion cages intervertebral discs A61F2/442
• CPC Class Codes: A61F 2002/009 for hindering or preventing attachment of biological tissue of bone tissue onto implantable joints A61F2002/30932
• CPC Class Codes: A61F 2002/2835 Bone graft implants for filling a bony defect or an endoprosthesis cavity, e.g. by synthetic material or biological material
• CPC Class Codes: A61F 2002/30062 (bio)absorbable, biodegradable, bioerodable, (bio)resorbable, resorptive
• CPC Class Codes: A61F 2002/30932 for retarding or preventing ingrowth of bone tissue
• CPC Class Codes: A61F 2002/4435 Support means or repair of the natural disc wall, i.e. annulus, e.g. using plates, membranes or meshes
• CPC Class Codes: A61F 2210/0004 bioabsorbable
• CPC Class Codes: A61F 2310/00365 Proteins; Polypeptides; Degradation products thereof
• CPC Class Codes: A61L 2300/414 Growth factors
• CPC Class Codes: A61L 2430/38 for reconstruction of the spine, vertebrae or intervertebral discs
• CPC Class Codes: A61L 27/52 Hydrogels or hydrocolloids
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: A61L 31/145 Hydrogels or hydrocolloids
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence

Abstract

The present invention generally relates to a method of using a matrix as a barrier for unwanted cell attachment and bone formation in unwanted areas of the human body during implant procedures. More specifically, a growth-inhibiting matrix may be used to prevent migration of osteo-inductive agents or bone tissue from an intervertebral disc space through the outer bands of annulus fibrosis that abuts the spinal tissue, canal, and other surrounding areas.

Claims

1. A method for repairing an intervertebral disc comprising:

forming a hole in an annulus fibrosis;

removing damaged annulus fibrosis or nucleus pulposus material from an intervertebral disc space of an intervertebral disc;

inserting an interbody fusion device into the intervertebral disc space; and

closing the hole formed in the annulus fibrosis at least in part by delivering a growth-inhibiting matrix in or about the hole, the growth-inhibiting matrix adapted to prevent tissue or growth agents associated with the implant from migrating into areas outside the intervertebral disc space.

2. The method of claim 1, wherein the hole in the annulus fibrosis extends from the outer bands of the annulus fibrosis of the intervertebral disc into the areas in or about the nucleus pulposus located near the center of the intervertebral disc space.

3. The method of claim 1 wherein the matrix cures in vivo.

4. The method of claim 1, wherein the matrix is further adapted to inhibit attachment of tissue cells onto or into inner surfaces of the growth-inhibiting matrix exposed to the intervertebral disc space.

5. The method of claim 1 wherein the matrix is adapted to inhibit migration of osteo-inductive agents associated with the intervertebral implant into areas outside the intervertebral disc space.

6. The method of claim 1 wherein the growth agents associated with the implant comprise at least one osteogenic agent selected from the group consisting of BMP (bone morphogenetic protein), BMP-2 (bone morphogenetic protein), bFGF (basic fibroblast growth factor), IGF-1 (insulin-like growth factor), PDGF (platelet-derived growth factor), rhBMP (human recombinant bone morphogenetic protein), TGF-β

1 (transforming growth factor beta

     1), VEGF (vascular endothelial growth factor), GDf (growth and differentiation factor), and any combinations thereof.

7. The method of claim 1, wherein the matrix comprises at least one osteogenic inhibitory agent selected from the group consisting of anti-BMP, anti-BMP-2, anti-bFGF, anti-IGF-1, anti-PDGF, anti-rhBMP, anti-TGF-β

1, anti-VEGF, anti-GDF, and any combinations thereof.

8. The method of claim 1, wherein the matrix is adapted to prevent cells or osteogenic factors from migrating into areas outside the intervertebral disc space.

9. The method of claim 8 wherein the matrix is fluid-permeable.

10. The method of claim 1, wherein the matrix is made from an anti-adhesion gel that is capable of curing in vivo.

11. The method of claim 10, wherein the anti-adhesion gel is selected from the group consisting of hyaluronic acid, carboxy methyl cellulose, gelatin, hydrogel, collagen gel, synthetic polymer formulation, and combinations thereof.

12. The method of claim 1, wherein the matrix further comprises an effective amount of at least one bioactive molecule capable of inhibiting cell attachment to a surface of the matrix that is exposed to the intervertebral disc implant or annulus fibrosis that is located in the disc space.

13. The method of claim 12, wherein the bioactive molecule capable of inhibiting cell attachment is an anionic polymer or polysaccharide.

14. The method of claim 1, wherein the matrix is delivered by injection into or about the hole in the annulus fibrosis.

15. The method of claim 1, wherein the matrix is bioresorbable within about 2 to 6 weeks.

16. The method of claim 15, wherein the bioresorbable matrix is selected from the group consisting of resorbable hydrogel, resorbable polymer composition, resorbable copolymer composition, resorbable polyion complex, fibrin, collagen, gelatin, alginate, hyaluronate, solubilized basement membrane preparation (MATRIGEL™

), Polyglycolide (PGA), glycolide-lactide copolymers (PGLA), polylactides (PLA), poly-L-lactide (PLLA), poly-D,L-lactide (PDLLA), ethylene oxide block copolymers with PLA, ethylene oxide block copolymers with propylene oxide chains, and any combination thereof.

17. The method of claim 1, wherein the tissue is bone tissue.

18. A kit comprising:

i. a composition capable of providing a growth-inhibiting matrix; and

ii. a delivery device.

19. The kit of claim 18 wherein the delivery device is selected from the group consisting of a syringe, needle, cannula, catheter, pump, and any combinations thereof.

20. The kit of claim 18 further comprising an effective amount of an osteogenic inhibitory agent.

21. The kit of claim 18 further comprising an effective amount of a bioactive molecule capable of preventing cell attachment to the growth-inhibiting matrix.

22. The kit of claim 18 further comprising an implant.

23. The kit of claim 22 wherein the implant is an interbody fusion device.

24. The kit of claim 18 further comprising an effective amount of a bioactive molecule capable of inducing cell growth, cell migration, or cell attachment.

25. A method for preventing unwanted tissue growth associated with an implant or growth agent, the method comprising:

disposing an implant, an effective amount of a growth agent, or both into a first region in which growth of a selected tissue type is desired; and

disposing a matrix between the first region and a second region in which growth of the selected tissue type is not desired, the matrix adapted to prevent the selected tissue type or growth agent from migrating between the first and second regions.

26. The method of claim 25 wherein the matrix cures in vivo.

27. The method of claim 25, wherein the matrix is further adapted to inhibit attachment of cells of the selected tissue type onto or into the matrix.

28. The method of claim 27, wherein the matrix further comprises an effective amount of at least one bioactive molecule capable of inhibiting cell attachment of cells of the selected tissue type to a surface of the matrix that is exposed to the first region.

29. The method of claim 28, wherein the bioactive molecule capable of inhibiting cell attachment is an anionic polymer or polysaccharide.

30. The method of claim 25 wherein the growth agent is selected from the group consisting of BMP (bone morphogenetic protein), BMP-2 (bone morphogenetic protein), bFGF (basic fibroblast growth factor), IGF-1 (insulin-like growth factor), PDGF (platelet-derived growth factor), rhBMP (human recombinant bone morphogenetic protein), TGF-β

1 (transforming growth factor beta

     1), VEGF (vascular endothelial growth factor), GDF (growth and differentiation factor), and any combinations thereof.

31. The method of claim 25, wherein the matrix comprises at least one osteogenic inhibitory agent selected from the group consisting of anti-BMP, anti-BMP-2, anti-bFGF, anti-IGF-1, anti-PDGF, anti-rhBMP, anti-TGF-β

1, anti-VEGF, anti-GDF, and any combinations thereof.

32. The method of claim 25 wherein the matrix is fluid-permeable.

33. The method of claim 25, wherein the matrix is made from an anti-adhesion gel that is capable of curing in vivo.

34. The method of claim 33, wherein the anti-adhesion gel is selected from the group consisting of hyaluronic acid, carboxy methyl cellulose, gelatin, hydrogel, collagen gel, synthetic polymer formulation, and combinations thereof.

35. The method of claim 25, wherein the matrix is disposed by injection.

36. The method of claim 25, wherein the matrix is bioresorbable within about 2 to 6 weeks.

37. The method of claim 36, wherein the bioresorbable matrix is selected from the group consisting of resorbable hydrogel, resorbable polymer composition, resorbable copolymer composition, resorbable polyion complex, fibrin, collagen, gelatin, alginate, hyaluronate, solubilized basement membrane preparation sold under the trademark MATRIGEL, Polyglycolide (PGA), glycolide-lactide copolymers (PGLA), polylactides (PLA), poly-L-lactide (PLLA), poly-D,L-lactide (PDLLA), ethylene oxide block copolymers with PLA, ethylene oxide block copolymers with propylene oxide chains, and any combination thereof.

38. The method of claim 25, wherein the selected tissue type is bone tissue.