CA2400826A1 - Methods and compositions for treating intervertebral disc degeneration - Google Patents

Methods and compositions for treating intervertebral disc degeneration Download PDF

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Publication number
CA2400826A1
CA2400826A1 CA002400826A CA2400826A CA2400826A1 CA 2400826 A1 CA2400826 A1 CA 2400826A1 CA 002400826 A CA002400826 A CA 002400826A CA 2400826 A CA2400826 A CA 2400826A CA 2400826 A1 CA2400826 A1 CA 2400826A1
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disc
injectable
cell growth
cells
matrix
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CA2400826C (en
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Jeffrey William Moehlenbruck
John Paul Ranieri
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Zimmer Orthobiologics Inc
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
    • A61L27/38—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix containing added animal cells
    • A61L27/3804—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix containing added animal cells characterised by specific cells or progenitors thereof, e.g. fibroblasts, connective tissue cells, kidney cells
    • A61L27/3834—Cells able to produce different cell types, e.g. hematopoietic stem cells, mesenchymal stem cells, marrow stromal cells, embryonic stem cells
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
    • A61L27/3604—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix characterised by the human or animal origin of the biological material, e.g. hair, fascia, fish scales, silk, shellac, pericardium, pleura, renal tissue, amniotic membrane, parenchymal tissue, fetal tissue, muscle tissue, fat tissue, enamel
    • A61L27/3612—Cartilage, synovial fluid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
    • A61L27/3641—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix characterised by the site of application in the body
    • A61L27/3645—Connective tissue
    • A61L27/3654—Cartilage, e.g. meniscus
    • A61L27/3658—Intervertebral discs
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
    • A61L27/3683—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
    • A61L27/3683—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix 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
    • A61L27/3687—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix 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 characterised by the use of chemical agents in the treatment, e.g. specific enzymes, detergents, capping agents, crosslinkers, anticalcification agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
    • A61L27/38—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix containing added animal cells
    • A61L27/3804—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix containing added animal cells characterised by specific cells or progenitors thereof, e.g. fibroblasts, connective tissue cells, kidney cells
    • A61L27/3817—Cartilage-forming cells, e.g. pre-chondrocytes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
    • A61L27/38—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix containing added animal cells
    • A61L27/3839—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix containing added animal cells characterised by the site of application in the body
    • A61L27/3843—Connective tissue
    • A61L27/3852—Cartilage, e.g. meniscus
    • A61L27/3856—Intervertebral discs
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
    • A61L27/38—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix containing added animal cells
    • A61L27/3895—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix containing added animal cells using specific culture conditions, e.g. stimulating differentiation of stem cells, pulsatile flow conditions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02—Prostheses implantable into the body
    • A61F2/30—Joints
    • A61F2/44—Joints for the spine, e.g. vertebrae, spinal discs
    • A61F2/442—Intervertebral or spinal discs, e.g. resilient
    • A61F2002/444—Intervertebral or spinal discs, e.g. resilient for replacing the nucleus pulposus
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2400/00—Materials characterised by their function or physical properties
    • A61L2400/06—Flowable or injectable implant compositions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2430/00—Materials or treatment for tissue regeneration
    • A61L2430/38—Materials or treatment for tissue regeneration for reconstruction of the spine, vertebrae or intervertebral discs

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Medicinal Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Dermatology (AREA)
  • Epidemiology (AREA)
  • Transplantation (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Botany (AREA)
  • Cell Biology (AREA)
  • Zoology (AREA)
  • Urology & Nephrology (AREA)
  • Molecular Biology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Vascular Medicine (AREA)
  • Developmental Biology & Embryology (AREA)
  • Organic Chemistry (AREA)
  • Rheumatology (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Hematology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Materials For Medical Uses (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Medicinal Preparation (AREA)

Abstract

A fluid matrix comprising cross-linked remodelable collagen from a donor vertebrate animal is useful for regener-ating hydrodynamic function in damaged intervertebral discs in vivo. The matrix may be injectable and may comprise cells and a plurality of purified cell growth factors. The matrix promotes cell growth and elaboration of proteoglycans to facilitate regeneration of native tissues. The collagen in the matrix may be cross-linked using photooxidative catalysis and visible light, and purified cell growth factors are preferably at least partly bone-derived.

Claims (59)

1. A matrix for treating a patient having degenerative disc disease, the matrix comprising an injectable fluid comprising digestion-resistant remodelable collagen, said collagen being cross-linked through photooxidative catalysis and irradiation by visible light; and a plurality of living cells dispersed within said injectable fluid to form an injectable cell matrix for treating degenerative disc disease, said cells having inherent capability to elaborate proteoglycans in vivo.
2. The injectable matrix of claim 1, further comprising a plurality of purified cell growth factors dispersed within said injectable cell matrix to form an injectable disc regeneration fluid, said living cells being responsive to said purified cell growth factors by increased elaboration of proteoglycans in vivo.
3. The matrix of claim 1 wherein said cells are chondrocytes.
4. The matrix of claim 1 wherein said cells are mesenchymal stem cells.
5. The matrix of claim 4 wherein said cells are human-derived.
6. The matrix of claim 1 wherein said collagen is cross-linked using methylene blue as a photooxidative catalyst.
7. The matrix of claim 1 wherein said cells are cultured in vitro to increase their response to said cell growth factors.
8. The injectable disc regeneration fluid of claim 2 wherein at least two of said plurality of cell growth factors are bone-derived.
9. An injectable disc regeneration fluid, comprising an injectable cell matrix according to claim 7; and a plurality of cell growth factors dispersed within said injectable cell matrix to form an injectable disc regeneration fluid, said living cells being responsive to said cell growth factors by increased elaboration of proteoglycans in vivo.
10. A method of treating a patient presenting with degenerative disc disease, the method comprising providing an injectable disc regeneration fluid according to claim 2; and injecting said injectable disc regeneration fluid into at least one of said patient's intervertebral discs to treat degenerative disc disease in said disc.
11. A method of continuing treatment of a patient presenting with degenerative disc disease, the method comprising treating the patient according to the method of claim 10; and injecting a plurality of cell growth factors into said at least one of said patient's intervertebral discs after completion of the method of claim 10 to continue treatment of a patient presenting with degenerative disc disease.
12. A patient having a history of degenerative disc disease, wherein the patient has been treated by the method of claim 11.
13. An intervertebral disc in vivo, said disc having been injected with injectable disc regeneration fluid according to claim 2.
14. A method of treating a patient presenting with signs of hydrodynamic intervertebral disc dysfunction, the method comprising diagnosing hydrodynamic disc dysfunction in at least one intervertebral disc of said patient;
testing said at least one intervertebral disc of said patient to establish cellular proteoglycan production within said at least one disc; and injecting a plurality of purified cell growth factors into said at least one disc to treat a patient presenting with signs of hydrodynamic intervertebral disc dysfunction.
15. The method of claim 14 wherein at least two of said plurality of cell growth factors are bone-derived.
16. An injectable cell growth medium for intervertebral disc regeneration, said medium comprising an injectable fluid comprising digestion-resistant remodelable collagen, said collagen being cross-linlced through photooxidative catalysis and irradiation by visible light; and a plurality of purified cell growth factors dispersed within said fluid to form an injectable cell growth medium.
17. The injectable cell growth medium of claim 16 wherein at least two of said plurality of cell growth factors are bone-derived.
18. An injectable disc regeneration fluid for intervertebral discs, the material comprising injectable cell growth medium according to claim 17; and cells responsive to said injectable cell growth medium through proteoglycan elaboration in vivo.
19. The disc regeneration fluid of claim 18 wherein said cells are chondrocytes.
20. The disc regeneration fluid of claim 18 wherein said cells are mesenchymal stem cells.
21. The disc regeneration fluid of claim 20 wherein said cells are human-derived.
22. The disc regeneration fluid of claim 20 wherein said cells are cultured in vitro to increase their response to said cell growth factors.
23. An injectable material for treating a patient for hydrodynamic disc dysfunction, the material made by a process comprising cross-linking collagen through photooxidative catalysis and irradiation by visible light;
purifying a plurality of bone-derived cell growth factors;
dispersing said purified bone-derived cell growth factors within said cross-linked collagen; and dispersing cells responsive to said purified plurality of bone-derived cell growth factors within said cross-linked collagen to form an injectable material for treating hydrodynamic disc dysfunction.
24. The injectable material of claim 23 wherein said cells are chondrocytes.
25. The injectable material of claim 23 wherein said cells are mesenchymal stem cells.
26. The injectable material of claim 24 wherein said cells are human-derived.
27. The injectable material of claim 24 wherein said cells are cultured in vitro to increase their response to said cell growth factors.
28. A method of hydrating an intervertebral disc annulus fibrosus in vivo, the method comprising testing said disc for cellular proteoglycan production within said disc; and injecting cell growth medium according to claim 16 into said disc to hydrate the annulus fibrosus.
29. A method of reducing susceptibility to herniation of an intervertebral disc in a patient having a history of intervertebral disc herniation, the method comprising testing said disc for cellular proteoglycan production within said disc; and injecting cell growth medium according to claim 16 into said disc to reduce susceptibility to herniation through hydration of the annulus fibrosus.
30. A method of increasing the height of a patient presenting with hydrodynamic disc dysfunction in at least one intervertebral disc, the method comprising testing said at least one disc for cellular proteoglycan production within said at least one disc; and injecting cell growth medium according to claim 16 into said at least one disc to increase the height of said patient by increasing intervertebral spacing through increased proteoglycan production in said at least one disc.
31. An injectable cell suspension for treating a patient having degenerative disc disease, the suspension comprising an injectable fluid comprising a plurality of purified cell growth factors;
and a plurality of living cells dispersed within said injectable fluid to form an injectable cell suspension for treating degenerative disc disease, said cells being responsive to said cell growth factors by increased elaboration of proteoglycans.
32. The injectable cell suspension of claim 31 wherein said cells are chondrocytes.
33. The injectable cell suspension of claim 31 wherein said cells are mesenchymal stem cells.
34. The injectable cell suspension of claim 33 wherein said cells are human-derived.
35. The injectable cell suspension of claim 31 wherein said cells are cultured in vitro to increase their response to said cell growth factors.
36. The injectable cell suspension of claim 31 wherein at least two of said plurality of cell growth factors are bone-derived.
37. A method of treating a patient presenting with degenerative disc disease, the method comprising providing an injectable cell growth medium according to claim 16; and injecting said injectable cell growth medium into at least one of said patient's intervertebral discs to treat degenerative disc disease in said disc.
38. A method of treating a patient presenting with hydrodynamic disc dysfunction, the method comprising providing an injectable material according to claim 23; and injecting said injectable material into at least one of said patient's intervertebral discs to treat hydrodynamic disc dysfunction in said disc.
39. A method of treating a patient presenting with degenerative disc disease, the method comprising providing an injectable cell suspension according to claim 31; and injecting said injectable cell suspension into at least one of said patient's intervertebral discs to treat degenerative disc disease in said disc.
40. A method of cross-linking collagen to make digestion-resistant remodelable cross-linked collagen, the method comprising providing a hydrogel comprising collagen;
containing said hydrogel within a semipermeable membrane, said membrane being substantially transparent to visible light and substantially permeable to at least one photooxidative catalyst;
transporting at least one photooxidative catalyst through said semipermeable membrane and into said hydrogel; and irradiating said hydrogel with visible light to cross-link said collagen.
41. The method of claim 40 comprising an additional step between said containing step and said transporting step, the additional step being submerging said hydrogel-containing semipermeable membrane in a high salt:high sucrose solution for about 24 to about 72 hours.
42. The method of claim 41 wherein said hydrogel comprises nucleus pulposus tissue.
43. The method of claim 42 wherein said transporting step occurs at a substantially constant hydrogel temperature of about 10°C.
44. Digestion-resistant remodelable cross-linked collagen made by the method of claim 43.
45. The method of claim 41 wherein said hydrogel comprises substantially Type II collagen.
46. The method of claim 43 wherein said semipermeable membrane comprises dialysis tubing having a molecular weight cutoff of about 3500 Daltons.
47. The method of claim 43 wherein said transporting step and said irradiating step are substantially simultaneous.
48. The method of claim 43 wherein said transporting step occurs while said semipermeable membrane containing said hydrogel is immersed in a solution comprising at least one photooxidative catalyst.
49. The method of claim 43 comprising an additional step after said irradiating step, the additional step being terminating said transporting step and said irradiating step when said collagen cross-linking is substantially complete.
50. The method of claim 49 comprising an additional step after said terminating step, the additional step being extracting said cross-linked collagen from said hydrogel.
51. The method of claim 43 wherein said at least one photooxidative catalyst comprises methylene blue.
52. A fluid matrix for treating intervertebral disc disease in a vertebrate, said fluid comprising nucleus pulposus tissue of a donor vertebrate.
53. The fluid matrix of claim 52 wherein said nucleus pulposus tissue is cross-linked.
54. The fluid matrix of claim 53 further comprising a growth factor.
55. The fluid matrix of claim 54 further comprising a plurality of living cells.
56. The fluid matrix of claim 55, wherein said plurality of living cells comprise chondrocytes.
57. The fluid matrix of claim 55, wherein said plurality of living cells comprise mesenchymal stem cells.
58. The fluid matrix of claim 55, wherein said plurality of living cells are human-derived.
59. The fluid matrix of claim 52, wherein said nucleus pulposus tissues are decellularized.
CA2400826A 2000-04-07 2001-04-09 Methods and compositions for treating intervertebral disc degeneration Expired - Fee Related CA2400826C (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US09/545,441 US6723335B1 (en) 2000-04-07 2000-04-07 Methods and compositions for treating intervertebral disc degeneration
US09/545,441 2000-04-07
PCT/US2001/011576 WO2001076654A1 (en) 2000-04-07 2001-04-09 Methods and compositions for treating intervertebral disc degeneration

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CA2400826A1 true CA2400826A1 (en) 2001-10-18
CA2400826C CA2400826C (en) 2010-02-23

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US (4) US6723335B1 (en)
EP (2) EP1707225A3 (en)
JP (1) JP2003530364A (en)
CA (1) CA2400826C (en)
DE (1) DE60120667T2 (en)
ES (1) ES2263612T3 (en)
WO (1) WO2001076654A1 (en)

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US7004970B2 (en) 1999-10-20 2006-02-28 Anulex Technologies, Inc. Methods and devices for spinal disc annulus reconstruction and repair
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WO2001076654A1 (en) 2001-10-18
US6723335B1 (en) 2004-04-20
US20050002909A1 (en) 2005-01-06
US7556649B2 (en) 2009-07-07
JP2003530364A (en) 2003-10-14
EP1272236A1 (en) 2003-01-08
CA2400826C (en) 2010-02-23
EP1272236B1 (en) 2006-06-14
EP1707225A2 (en) 2006-10-04
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US20100021439A1 (en) 2010-01-28
US20110256106A1 (en) 2011-10-20

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