Composite tissue-engineered intervertebral disc with self-assembled annular alignment

• US 9,044,335 B2
• Filed: 05/05/2010
• Issued: 06/02/2015
• Est. Priority Date: 05/05/2009
• Status: Active Grant

• Current Assignee: Cornell University
• Original Assignee: Cornell University
• Inventors: Bonassar, Lawrence J., Hartl, Roger, Bowles, Robert D., Gebhard, Harry H.
• Primary Examiner(s): GITOMER, RALPH J
• Application Number:
  US13/319,025
• Publication Number:
  US 20130079881A1
• Time in Patent Office: 1,854 Days
• Field of Search: 623/17.16, 623/17.11, 435/366
• US Class Current: 1/1
• 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 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 2002/444 for replacing the nucleus pulposus
• CPC Class Codes: A61F 2002/4445 Means for culturing intervertebral disc tissue
• CPC Class Codes: A61F 2002/445 Intervertebral disc tissue harvest sites
• CPC Class Codes: A61K 35/32 Bones; Osteocytes; Osteoblasts; Tendons; Tenocytes; Teeth; Odontoblasts; Cartilage; Chondrocytes; Synovial membrane
• CPC Class Codes: A61L 2430/38 for reconstruction of the spine, vertebrae or intervertebral discs
• CPC Class Codes: A61L 27/20 Polysaccharides
• CPC Class Codes: A61L 27/22 Polypeptides or derivatives thereof , e.g. degradation products
• CPC Class Codes: A61L 27/24 Collagen
• CPC Class Codes: A61L 27/3658 Intervertebral discs mechanical aspects and structures of intervertebral discs A61F2/442
• CPC Class Codes: A61L 27/3691 characterised by physical conditions of the treatment, e.g. applying a compressive force to the composition, pressure cycles, ultrasonic/sonication or microwave treatment, lyophilisation
• CPC Class Codes: A61L 27/3817 Cartilage-forming cells, e.g. pre-chondrocytes
• CPC Class Codes: A61L 27/3856 Intervertebral discs mechanical aspects and structures of intervertebral discs A61F2/442
• CPC Class Codes: A61L 27/3886 comprising two or more cell types
• CPC Class Codes: A61L 27/44 having a macromolecular matrix
• CPC Class Codes: A61L 27/52 Hydrogels or hydrocolloids
• CPC Class Codes: C08L 5/04 Alginic acid; Derivatives thereof

Abstract

The present invention relates to a tissue-engineered intervertebral disc (IVD) suitable for total disc replacement in a mammal and methods of fabrication. The IVD comprises a nucleus pulposus structure comprising a first population of living cells that secrete a hydrophilic protein and an annulus fibrosis structure surrounding and in contact with the nucleus pulposus structure, the annulus fibrosis structure comprising a second population of living cells and type I collagen. The collagen fibrils in the annulus fibrosis structure are circumferentially aligned around the nucleus pulposus region due to cell-mediated contraction in the annulus fibrosis structure. Also disclosed are methods of fabricating tissue-engineered intervertebral discs.

Claims

1. A tissue-engineered intervertebral disc (IVD) suitable for total disc replacement in a mammal, said IVD comprising:

a nucleus pulposus structure comprising a first population of living cells that secrete a hydrophilic protein and

an annulus fibrosis structure surrounding and in contact with the nucleus pulposus structure, the annulus fibrosis structure comprising a second population of living cells and type I collagen, wherein collagen fibrils in the annulus fibrosis structure are circumferentially aligned around the nucleus pulposus region due to cell-mediated contraction in the annulus fibrosis structure.

2. The tissue-engineered IVD according to claim 1, wherein the nucleus pulposus structure comprises an alginate gel.

3. The tissue-engineered IVD according to claim 2, wherein the alginate gel comprises about 0.5% to about 10% (w/v) alginate.

4. The tissue-engineered IVD according to claim 1, wherein the first population of cells are present in a concentration of about 1×

10⁶ cells/ml to about 50×

10⁶ cells/ml.

5. The tissue-engineered IVD according to claim 1, wherein the first population of cells secrete proteoglycan.

6. The tissue-engineered IVD according to claim 1, wherein the first population of cells comprise nucleus pulposus cells.

7. The tissue-engineered IVD according to claim 6, wherein the nucleus pulposus cells are isolated from one or more of the following sources:

ovine, murine, lapine, porcine, canine, bovine, simian, or human.

8. The tissue-engineered IVD according to claim 1, wherein the nucleus pulposus structure further comprises type II collagen.

9. The tissue-engineered IVD according to claim 1, wherein the nucleus pulposus has an isotropic structure.

10. The tissue-engineered IVD according to claim 1, wherein the second population of cells comprises annulus fibrosus cells.

11. The tissue-engineered IVD according to claim 10, wherein the annulus fibrosus cells are isolated from one or more of the following sources:

ovine, murine, lapine, porcine, canine, bovine, simian, or human.

12. The tissue-engineered IVD according to claim 1, wherein the second population of cells are present in a concentration of about 0.1-5.0×

10⁶ cells/ml.

13. The tissue-engineered IVD according to claim 1, wherein the annulus fibrosus structure comprises type I collagen at a concentration of about 1 mg/ml to about 30 mg/ml.

14. The tissue-engineered IVD according to claim 1, wherein the annulus fibrosus has an anisotropic structure.

15. The tissue-engineered IVD according to claim 1, wherein the IVD is permeable to allow nutrient transport to developing tissue.

16. The tissue-engineered IVD according to claim 1, wherein the mammal is selected from a mouse, rat, guinea pig, rabbit, dog, cat, pig, sheep, cow, horse, monkey, or human.