Degradable cage coated with mineral layers for spinal interbody fusion

• US 9,439,948 B2
• Filed: 10/29/2007
• Issued: 09/13/2016
• Est. Priority Date: 10/30/2006
• Status: Active Grant

• Current Assignee: Board of Regents of the University of Michigan (University of Michigan), Wisconsin Alumni Research Foundation (University of Wisconsin System)
• Original Assignee: Board of Regents of the University of Michigan (University of Michigan), Wisconsin Alumni Research Foundation (University of Wisconsin System)
• Inventors: Lin, Chia-Ying, LaMarca, Frank, Murphy, William L., Hollister, Scott J.
• Primary Examiner(s): Merene, Jan Christopher
• Assistant Examiner(s): MAHMUD, ATIYA S
• Application Number:
  US11/927,322
• Publication Number:
  US 20080215093A1
• Time in Patent Office: 3,242 Days
• Field of Search: 623 1711- 1716, 623/23.76, 606/87, 606/88
• US Class Current: 1/1
• CPC Class Codes: A61B 17/7059 Cortical plates A61B17/7007, A61B17/7058 take precedence
• 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 2002/30011 differing in porosity
• CPC Class Codes: A61F 2002/30032 differing in absorbability or resorbability, i.e. in absorption or resorption time
• CPC Class Codes: A61F 2002/30056 differing in radiographic density
• CPC Class Codes: A61F 2002/30062 (bio)absorbable, biodegradable, bioerodable, (bio)resorbable, resorptive
• CPC Class Codes: A61F 2002/3008 radio-opaque, e.g. radio-opaque markers
• CPC Class Codes: A61F 2002/30303 polypod-shaped
• CPC Class Codes: A61F 2002/30578 having apertures, e.g. for receiving fixation screws
• CPC Class Codes: A61F 2002/30785 parallel
• CPC Class Codes: A61F 2002/30789 perpendicular with respect to each other
• CPC Class Codes: A61F 2002/30838 Microstructures
• CPC Class Codes: A61F 2002/30878 with non-sharp protrusions, for instance contacting the bone for anchoring, e.g. keels, pegs, pins, posts, shanks, stems, struts
• CPC Class Codes: A61F 2002/30884 Fins or wings, e.g. longitudinal wings for preventing rotation within the bone cavity
• CPC Class Codes: A61F 2002/30892 parallel
• CPC Class Codes: A61F 2002/30899 Protrusions pierced with apertures
• CPC Class Codes: A61F 2002/4485 comprising three or more adjacent spinal implants
• CPC Class Codes: A61F 2210/0004 bioabsorbable
• CPC Class Codes: A61F 2310/00017 Iron- or Fe-based alloys, e.g. stainless steel
• CPC Class Codes: A61F 2310/00023 Titanium or titanium-based alloys, e.g. Ti-Ni alloys
• CPC Class Codes: A61F 2310/00029 : Cobalt-based alloys, e.g. Co-Cr alloys or Vitallium
• CPC Class Codes: A61F 2310/00089 : Zirconium or Zr-based alloys
• CPC Class Codes: A61F 2310/00113 : Silver or Ag-based alloys
• CPC Class Codes: A61F 2310/00131 : Tantalum or Ta-based alloys
• CPC Class Codes: A61F 2310/00149 : Platinum or Pt-based alloys
• CPC Class Codes: A61F 2310/00155 : Gold or Au-based alloys
• CPC Class Codes: A61F 2310/00293 : containing a phosphorus-containing compound, e.g. apatite
• CPC Class Codes: A61F 2310/00796 : Coating or prosthesis-covering structure made of a phosphorus-containing compound, e.g. hydroxy(l)apatite
• CPC Class Codes: A61F 2310/0097 : Coating or prosthesis-covering structure made of pharmaceutical products, e.g. antibiotics
• CPC Class Codes: A61F 2310/00976 : Coating or prosthesis-covering structure made of proteins or of polypeptides, e.g. of bone morphogenic proteins BMP or of transforming growth factors TGF
• CPC Class Codes: A61K 38/1825 : Fibroblast growth factor [FGF]
• CPC Class Codes: A61K 38/1841 : Transforming growth factor [TGF]
• CPC Class Codes: A61K 38/1858 : Platelet-derived growth factor [PDGF]
• CPC Class Codes: A61K 38/1875 : Bone morphogenic factor; Osteogenins; Osteogenic factor; Bone-inducing factor
• CPC Class Codes: A61K 38/30 : Insulin-like growth factors, i.e. somatomedins, e.g. IGF-1, IGF-2 insulin-like growth factor binding protein A61K38/1754

Abstract

A cage for facilitating fusion of bones, such as vertebrae, or fusion of adjacent bone surfaces is disclosed. In one form, the cage includes a plurality of spaced apart walls comprising a biodegradable polymeric material (e.g., polycaprolactone); an osteoconductive mineral coating (e.g., a calcium compound) on at least a portion of the walls; and a bioactive agent (e.g., a bone morphogenetic protein) associated with the polymeric material and/or the coating. The bioactive agent is present in amount that induces ossification between the bones or adjacent bone surfaces. The cage may also include a fixation plate connected to at least one of the walls.

Claims

1. A cage for facilitating fusion of adjacent bones or fusion of adjacent bone surfaces, the cage comprising:

a central section having a longitudinal proximal portion and a longitudinal distal portion;

a first wall, having a first height, a first length, and a first width, wherein each of the first length and the first height is greater than the first width, wherein the first length of the first wall extends transversely from the central section, and wherein the first height of the first wall extends between the longitudinal proximal portion and the longitudinal distal portion of the central section;

a second wall, having a second height, a second length, and a second width, wherein each of the second length and the second height is greater than the second width, wherein the second length of the second wall extends transversely from the central section, and wherein the second height of the second wall extends between the longitudinal proximal portion and the longitudinal distal portion of the central section; and

a third wall, having a third height, a third length, and a third width, wherein each of the third length and the third height is greater than the third width, wherein the third length of the third wall extends transversely from the central section, wherein the third height of the third wall extends between the longitudinal proximal portion and the longitudinal distal portion of the central section, wherein the third wall has a first side and a second side separated by the third width, wherein the third wall is positioned between the first wall and the second wall, and wherein the first side of the third wall faces the first wall and the second side of the third wall faces the second wall, wherein each of the first wall and the second wall comprises an end portion distal to the central section, wherein the end portion of the first wall and the end portion of the second wall avoid contact with the third wall,

wherein the central section, the first wall, the second wall, and the third wall comprise a designed porous microstructure and the designed porous microstructure further comprises a biocompatible material selected from at least one of a polymeric material, a metallic material, a ceramic material, or a mixture thereof;

an osteoconductive mineral coating on at least a portion of the designed porous microstructure, the osteoconductive mineral coating comprising a plurality of layers, wherein each of the layers has a distinct dissolution profile;

a bioactive agent associated with at least one of the biocompatible material or the osteoconductive mineral coating, wherein the bioactive agent being present in an amount that induces ossification between the adjacent bones or the adjacent bone surfaces; and

a fixation plate extending from the central section.

2. The cage of claim 1, wherein at least one of the first wall, the second wall, and the third wall is coupled to the central section at a respective proximal side of the at least one of the first wall, the second wall, and the third wall.

3. The cage of claim 2, wherein at least two adjacent of the first wall, the second wall, and the third wall are not coupled to each other at a respective distal side of each of the at least two adjacent of the first wall, the second wall, and the third wall.

4. The cage of claim 1, wherein at least two of the first wall, the second wall, and the third wall comprise projections extending perpendicularly therefrom.

5. The cage of claim 4, wherein the at least two of the first wall, the second wall, and the third wall are coupled to each other by the projections.

6. The cage of claim 1, wherein the fixation plate extends from the longitudinal proximal portion of the central section.

7. The cage of claim 6, wherein the fixation plate extends orthogonally to at least one of the first wall, the second wall, and the third wall.

8. The cage of claim 1 wherein:

the osteoconductive mineral coating comprises a plurality of discrete mineral islands.

9. The cage of claim 1 wherein:

the osteoconductive mineral coating comprises a substantially homogeneous mineral coating.

10. The cage of claim 1 wherein:

the bioactive agent is selected from bone morphogenetic proteins, demineralized bone matrix, bone marrow aspirate, transforming growth factors, fibroblast growth factor, insulin-like growth factor, platelet derived growth factor, vascular endothelial growth factor, growth and development factor-5, platelet rich plasma, and mixtures thereof.

11. The cage of claim 1 wherein:

the bioactive agent is selected from bone morphogenetic proteins.

12. The cage of claim 1 wherein:

the osteoconductive mineral coating comprises a calcium compound.

13. The cage of claim 1 wherein:

the osteoconductive mineral coating is selected from hydroxyapatite, calcium-deficient carbonate-containing hydroxyapatite, tricalcium phosphate, amorphous calcium phosphate, octacalcium phosphate, dicalcium phosphate, calcium phosphate, and mixtures thereof.

14. The cage of claim 1 wherein:

the biocompatible material comprises polycaprolactone.

15. The cage of claim 1, wherein the biocompatible material comprises polycaprolactone, and wherein the fixation plate comprises polycaprolactone.

16. The cage of claim 1 wherein:

the bones are adjacent vertebrae.

17. The cage of claim 1, wherein at least one of the first wall, the second wall, and the third wall is perpendicular to the fixation plate.

18. The cage of claim 1, wherein the first wall, the second wall, and the third wall are not connected via another wall or cage element.

19. The cage of claim 1, wherein the fixation plate is positioned transverse to at least one of the first wall, the second wall, and the third wall.

20. A cage for facilitating fusion of adjacent bones or fusion of adjacent bone surfaces, the cage comprising:

a central section having a longitudinal proximal portion and a longitudinal distal portion;

a first wall, having a first height, a first length, and a first width, wherein each of the first length and the first height is greater than the first width, wherein the first length of the first wall extends transversely from the central section, and wherein the first height of the first wall extends between the longitudinal proximal portion and the longitudinal distal portion of the central section;

a second wall, having a second height, a second length, and a second width, wherein each of the second length and the second height is greater than the second width, wherein the second length of the second wall extends transversely from the central section, and wherein the second height of the second wall extends between the longitudinal proximal portion and the longitudinal distal portion of the central section; and

a third wall, having a third height, a third length, and a third width, wherein each of the third length and the third height is greater than the third width, wherein the third length of the third wall extends transversely from the central section, wherein the third height of the third wall extends between the longitudinal proximal portion and the longitudinal distal portion of the central section, wherein the third wall has a first side and a second side separated by the third width, wherein the third wall is positioned between the first wall and the second wall, and wherein the first side of the third wall faces the first wall and the second side of the third wall faces the second wall, wherein each of the first wall and the second wall comprises an end portion distal to the central section, wherein the end portion of the first wall and the end portion of the second wall avoid contact with the third wall,

wherein the central section, the first wall, the second wall, and the third wall comprise a designed porous microstructure, and the designed porous microstructure further comprises a biocompatible material selected from at least one of a polymeric material, a metallic material, a ceramic material, or a mixture thereof;

an osteoconductive mineral coating on at least a portion of the designed porous microstructure, wherein the osteoconductive mineral coating comprises a plurality of layers including a calcium compound, at least two of the layers having a different concentration of a bioactive agent associated with the calcium compound such that release rate of the bioactive agent varies as the layers dissolve in physiological fluid;

wherein each of the plurality of layers comprises a distinct dissolution profile;

a bioactive agent associated with at least one of the biocompatible material or the osteoconductive mineral coating, wherein the bioactive agent being present in an amount that induces ossification between the adjacent bones or the adjacent bone surfaces; and

a fixation plate extending from the central section.

21. A cage for facilitating fusion of adjacent bones or fusion of adjacent bone surfaces, the cage comprising:

a central section having a longitudinal proximal portion and a longitudinal distal portion;

a first wall, having a first height, a first length, and a first width, wherein each of the first length and the first height is greater than the first width, wherein the first length of the first wall extends transversely from the central section, and wherein the first height of the first wall extends between the longitudinal proximal portion and the longitudinal distal portion of the central section;

a second wall, having a second height, a second length, and a second width, wherein each of the second length and the second height is greater than the second width, wherein the second length of the second wall extends transversely from the central section, and wherein the second height of the second wall extends between the longitudinal proximal portion and the longitudinal distal portion of the central section; and

a third wall, having a third height, a third length, and a third width, wherein each of the third length and the third height is greater than the third width, wherein the third length of the third wall extends transversely from the central section, wherein the third height of the third wall extends between the longitudinal proximal portion and the longitudinal distal portion of the central section, wherein the third wall has a first side and a second side separated by the third width, wherein the third wall is positioned between the first wall and the second wall, and wherein the first side of the third wall faces the first wall and the second side of the third wall faces the second wall, wherein each of the first wall and the second wall comprises an end portion distal to the central section, wherein the end portion of the first wall and the end portion of the second wall avoid contact with the third wall,

wherein the central section, the first wall, the second wall, and the third wall comprise a designed porous microstructure, and the designed porous microstructure further comprises a biocompatible material selected from at least one of a polymeric material, a metallic material, a ceramic material, or a mixture thereof;

an osteoconductive mineral coating on at least a portion of the designed porous microstructure, wherein the osteoconductive mineral coating comprises a plurality of layers including a calcium compound, at least two of the layers having a different calcium compound associated with a bioactive agent such that release rate of the bioactive agent varies as the layers dissolve in physiological fluid;

wherein each of the plurality of layers comprises a distinct dissolution profile;

a bioactive agent associated with at least one of the biocompatible material or the osteoconductive mineral coating, wherein the bioactive agent being present in an amount that induces ossification between the adjacent bones or the adjacent bone surfaces; and

a fixation plate extending from the central section.

22. A cage for facilitating fusion of adjacent bones or fusion of adjacent bone surfaces, the cage comprising:

a central section, having a longitudinal proximal portion and a longitudinal distal portion;

a first wall, having a first height, a first length, and a first width, wherein each of the first length and the first height is greater than the first width, wherein the first length of the first wall extends transversely from the central section, and wherein the first height of the first wall extends between the longitudinal proximal portion and the longitudinal distal portion of the central section;

a second wall, having a second height, a second length, and a second width, wherein each of the second length and the second height is greater than the second width, wherein the second length of the second wall extends transversely from the central section, and wherein the second height of the second wall extends between the longitudinal proximal portion and the longitudinal distal portion of the central section; and

a third wall, having a third height, a third length, and a third width, wherein each of the third length and the third height is greater than the third width, wherein the third length of the third wall extends transversely from the central section, wherein the third height of the third wall extends between the longitudinal proximal portion and the longitudinal distal portion of the central section, wherein the third wall has a first side and a second side separated by the third width, wherein the third wall is positioned between the first wall and the second wall, and, wherein the first side of the third wall faces the first wall and the second side of the third wall faces the second wall, wherein each of the first wall and the second wall comprises an end portion distal to the central section, wherein the end portion of the first wall and the end portion of the second wall avoid contact with the third wall,

wherein the central section, the first wall, the second wall, and the third wall comprise a designed porous microstructure, and the designed porous microstructure further comprises a biocompatible material selected from at least one of a polymeric material, a metallic material, a ceramic material, or a mixture thereof;

an osteoconductive mineral coating on at least a portion of the designed porous microstructure, wherein the osteoconductive mineral coating comprises a plurality of layers including a calcium compound, at least two of the layers having a different bioactive agent associated with the calcium compound such that release rate of the bioactive agent varies as the layers dissolve in physiological fluid;

wherein each of the plurality of layers comprises a distinct dissolution profile;

a bioactive agent associated with at least one of the biocompatible material or the osteoconductive mineral coating, wherein the bioactive agent being present in an amount that induces ossification between the adjacent bones or the adjacent bone surfaces; and

a fixation plate extending from the central section.

23. A cage for facilitating fusion of vertebrae, the cage comprising:

a fixation plate;

a central section having a longitudinal proximal portion and a longitudinal distal portion;

a first wall, having a first height, a first length, and a first width, wherein each of the first length and the first height is greater than the first width, wherein the first length of the first wall extends transversely from the central section, and wherein the first height of the first wall extends between the longitudinal proximal portion and the longitudinal distal portion of the central section;

a second wall, having a second height, a second length, and a second width, wherein each of the second length and the second height is greater than the second width, wherein the second length of the second wall extends transversely from the central section, and wherein the second height of the second wall extends between the longitudinal proximal portion and the longitudinal distal portion of the central section; and

a third wall, having a third height, a third length, and a third width, wherein each of the third length and the third height is greater than the third width, wherein the third length of the third wall extends transversely from the central section, wherein the third height of the third wall extends between the longitudinal proximal portion and the longitudinal distal portion of the central section, wherein the third wall has a first side and a second side separated by the third width, wherein the third wall is positioned between the first wall and the second wall, and wherein the first side of the third wall faces the first wall and the second side of the third wall faces the second wall, wherein each of the first wall and the second wall comprises an end portion distal to the central section, wherein the end portion of the first wall and the end portion of the second wall avoid contact with the third wall, wherein the fixation plate extending from the central section;

an osteoconductive mineral coating on at least a portion of at least one of the walls, the osteoconductive mineral coating comprising a plurality of layers, wherein each of the layers has a distinct dissolution profile; and

a bioactive agent associated with at least one of a polymeric material or the osteoconductive mineral coating, wherein the bioactive agent being present in amount that induces ossification between the vertebrae.

24. The cage of claim 23 wherein:

the polymeric material is porous polycaprolactone.

25. The cage of claim 23 wherein:

the bioactive agent is selected from bone morphogenetic proteins.

26. The cage of claim 23 wherein:

the osteoconductive mineral coating comprises a calcium compound.

27. The cage of claim 23, wherein the fixation plate comprises the polymeric material.

28. The cage of claim 23 wherein:

at least one of the first wall, the second wall, and the third wall comprises a projection extending transversely therefrom.

29. The cage of claim 23 further comprising:

at least one marking including a tracer that provides enhanced visibility via a medical imaging device.

30. The cage of claim 23 wherein:

the cage includes a region of no material or radiolucent material such that the region forms an imaging window for enhanced visibility through the imaging window via a medical imaging device.

31. A cage for facilitating fusion of vertebrae, the cage comprising:

a fixation plate;

a central section having a longitudinal proximal portion and a longitudinal distal portion;

a first wall, having a first height, a first length, and a first width, wherein each of the first length and the first height is greater than the first width, wherein the first length of the first wall extends transversely from the central section, and wherein the first height of the first wall extends between the longitudinal proximal portion and the longitudinal distal portion of the central section;

a second wall, having a second height, a second length, and a second width, wherein each of the second length and the second height is greater than the second width, wherein the second length of the second wall extends transversely from the central section, and wherein the second height of the second wall extends between the longitudinal proximal portion and the longitudinal distal portion of the central section; and

a third wall, having a third height, a third length, and a third width, wherein each of the third length and the third height is greater than the third width, wherein the third length of the third wall extends transversely from the central section, wherein the third height of the third wall extends between the longitudinal proximal portion and the longitudinal distal portion of the central section, wherein the third wall has a first side and a second side separated by the third width, wherein the third wall is positioned between the first wall and the second wall, and wherein the first side of the third wall faces the first wall and the second side of the third wall faces the second wall, wherein each of the first wall and the second wall comprises an end portion distal to the central section, wherein the end portion of the first wall and the end portion of the second wall avoid contact with the third wall, wherein the fixation plate extending from the central section;

an osteoconductive mineral coating on at least a portion of at least one of the walls, wherein the osteoconductive mineral coating comprises a plurality of layers including a calcium compound,

a bioactive agent associated with a polymeric material and/or the mineral coating, the bioactive agent being present in an amount that induces ossification between the vertebrae;

wherein at least two of the layers have a different concentration of the bioactive agent associated with the calcium compound such that release rate of the bioactive agent varies as the layers dissolve in physiological fluid;

wherein each of the plurality of layers comprises a distinct dissolution profile.

32. The cage of claim 31 wherein:

the calcium compound is selected from hydroxyapatite, calcium-deficient carbonate-containing hydroxyapatite, tricalcium phosphate, amorphous calcium phosphate, octacalcium phosphate, dicalcium phosphate, calcium phosphate, and mixtures thereof, and

the bioactive agent is selected from bone morphogenetic proteins.