Cartilage repair methods

• US 20070128155A1
• Filed: 12/07/2006
• Published: 06/07/2007
• Est. Priority Date: 12/07/2005
• Status: Active Grant

• Current Assignee: Isto Technologies Ii LLC
• Original Assignee: ISTO Technologies, Inc. (Isto Biologics, Inc.)
• Inventors: Seyedin, Mitchell, Matava, Matthew
• Granted Patent: US 8,444,968 B2
• Time in Patent Office: Days
• US Class Current: 424/78.370
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/765 Polymers containing oxygen
• CPC Class Codes: A61K 35/28 Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61L 2430/06 for cartilage reconstruction, e.g. meniscus
• CPC Class Codes: A61L 27/18 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 27/20 Polysaccharides
• CPC Class Codes: A61L 27/26 Mixtures of macromolecular compounds
• 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 27/3843 Connective tissue
• CPC Class Codes: A61L 27/48 with macromolecular fillers
• CPC Class Codes: C08L 5/08 Chitin; Chondroitin sulfate; Hyaluronic acid; Derivatives thereof
• CPC Class Codes: C08L 67/04 Polyesters derived from hydroxycarboxylic acids, e.g. lactones C08L67/06 takes precedence

Abstract

The present application discloses methods for repairing hyaline cartilage defects. The methods comprise a combination of introducing autologous bone mesenchymal stem cells to a joint, and applying to the joint a membrane comprising a polyester entangled with a polysaccharide. In some aspects, the bone mesenchymal stem cells are mesenchymal stem cells originating in bone underlying the joint. In these aspects, contact between the joint and the mesenchymal stem cells can be effected by introducing apertures through the bone using standard surgical techniques such as microfracture, abrasion, or drilling. Cartilage which forms in response to application of these methods is hyaline cartilage rather than fibrocartilage.

Claims

1. A method for repairing a hyaline cartilage defect in a mammalian joint, the method comprising:

infiltrating the joint with autologous mesenchymal stem cells; and

applying to the joint a membrane comprising a polyester entangled with a polysaccharide.

2. A method for repairing a hyaline cartilage defect in accordance with claim 1, wherein the autologous mesenchymal stem cells are autologous bone mesenchymal stem cells originating in a bone marrow cavity underlying the joint.

3. A method for repairing a hyaline cartilage defect in accordance with claim 2, wherein the infiltrating the joint with autologous mesenchymal stem cells comprises introducing at least one aperture into the bone underlying the joint, wherein the at least one aperture is sufficiently large to make possible migration of the autologous bone mesenchymal stem cells from the bone marrow cavity to the joint.

4. A method for repairing a hyaline cartilage defect in accordance with claim 1, wherein the mammal is a human patient in need of treatment.

5. A method for repairing a hyaline cartilage defect in accordance with claim 1, wherein the repairing a hyaline cartilage defect comprises repairing a full-thickness chondral defect.

6. A method for repairing a hyaline cartilage defect in accordance with claim 3, wherein the introducing at least one aperture into bone underlying the joint comprises abrading, microfracturing or drilling the bone.

7. A method for repairing a hyaline cartilage defect in accordance with claim 6, wherein the abrading comprises performing abrasion arthroplasty.

8. A method for repairing a hyaline cartilage defect in accordance with claim 3, wherein the introducing at least one aperture into bone underlying the joint comprises microfracturing the bone.

9. A method for repairing a hyaline cartilage defect in accordance with claim 1, wherein the membrane has a thickness of at least about 0.5 mm up to about 3 mm.

10. A method for repairing a hyaline cartilage defect in accordance with claim 3, wherein the applying a membrane precedes the introducing at least one aperture into bone underlying the joint.

11. A method for repairing a hyaline cartilage defect in accordance with claim 3, wherein the introducing at least one aperture into bone underlying the joint precedes the applying a membrane.

12. A method for repairing a hyaline cartilage defect in accordance with claim 1, wherein the polyester is selected from the group consisting of polylactic acid, polyglycolic acid, and a co-polymer comprising polylactic acid and polyglycolic acid.

13. A method for repairing a hyaline cartilage defect in accordance with claim 1, wherein the polyester is a co-polymer comprising polylactic acid and polyglycolic acid.

14. A method for repairing a hyaline cartilage defect in accordance with claim 13, wherein the polylactic acid and the polyglycolic acid are in a weight ratio of from about 5:

1 to about 2;

1.

15. A method for repairing a hyaline cartilage defect in accordance with claim 14, wherein the polylactic acid and the polyglycolic acid are in a weight ratio of about 3:

1.

16. A method for repairing a hyaline cartilage defect in accordance with claim 1, wherein the polysaccharide is selected from the group consisting of hyaluronic acid, chondroitin sulfate, dermatan sulfate, keratan sulfate, heparan, heparan sulfate, dextran, dextran sulfate, alginate, and a combination thereof.

17. A method for repairing a hyaline cartilage defect in accordance with claim 1, wherein the polysaccharide is hyaluronic acid.

18. A method for repairing a hyaline cartilage defect in accordance with claim 1, wherein the polyester and the polysaccharide are in a weight ratio of from 99:

1 to 1;

99.

19. A method for repairing a hyaline cartilage defect in accordance with claim 1, wherein the polyester and the polysaccharide are in a weight ratio of from about 9:

1 to about 1;

9.

20. A method for repairing a hyaline cartilage defect in accordance with claim 1, further comprising securing the membrane to the joint.

21. A method for repairing a hyaline cartilage defect in accordance with claim 20, wherein the securing the membrane to the joint comprises attaching at least one fastener to the membrane and the joint.

22. A method for repairing a hyaline cartilage defect in accordance with claim 21, wherein the at least one fastener is selected from the group consisting of a biocompatible glue, a suture, a tissue weld, a dart, a staple, a screw, and a tack.

23. A method for repairing a hyaline cartilage defect in accordance with claim 22, wherein the biocompatible glue is a fibrin glue.

24. A method for repairing a hyaline cartilage defect in accordance with claim 1, wherein the membrane further comprises at least one growth factor selected from the group consisting of a TGF-β

, a bone morphogenetic protein, a growth differentiation factor, ADMP-1, a fibroblast growth factor, a hedgehog protein, an insulin-like growth factor, a platelet-derived growth factor, an interleukin, a colony-stimulating factor, and an activin.

25. A method for repairing a hyaline cartilage defect in accordance with claim 1, wherein the membrane further comprises at least one collagen.

26. A method for repairing a full-thickness chondral defect in a joint of a patient in need of treatment, the method comprising:

microfracturing bone underlying the joint;

applying to the joint a membrane comprising a polyester co-polymer comprising polylactic acid and polyglycolic acid in a weight ratio of from about 5;

1 to about 2;

1, wherein the polyester is entangled with hyaluronic acid, and wherein the membrane has a thickness of at least about 0.5 mm up to about 3 mm; and

anchoring the membrane to the joint.

27. A method in accordance with claim 26, wherein the joint is a knee joint.

28. A method in accordance with claim 26, wherein the microfracturing precedes the applying a membrane.

29. A method in accordance with claim 26, wherein the applying a membrane precedes the microfracturing.

30. A method in accordance with claim 26, wherein the anchoring the membrane to the joint comprises applying at least one fastener which secures the membrane to the joint, wherein the at least one fastener is selected from the group consisting of a biocompatible glue, a suture, a tissue weld, a dart, a staple, a screw, and a tack.

31. A method for repairing a full-thickness chondral defect in a joint of a patient in need of treatment, the method comprising:

introducing at least one aperture through bone underlying the joint, wherein the at least one aperture makes possible migration to the joint of mesenchymal stem cells comprised by a marrow cavity of the bone;

applying to the joint a membrane comprising hyaluronic acid entangled with a polyester co-polymer comprising polylactic acid and polyglycolic acid in a weight ratio of from about 5;

1 to about 2;

1, wherein the membrane has a thickness of at least about 0.5 mm up to about 3 mm; and

securing the membrane to the joint.

32. A method in accordance with claim 31, wherein the introducing at least one aperture precedes the applying a membrane.

33. A method in accordance with claim 31, wherein the applying a membrane precedes the introducing at least one aperture.

34. A method for repairing a hyaline cartilage defect in accordance with claim 31, wherein the securing the membrane to the joint comprises applying at least one fastener to the membrane and the joint, wherein the at least one fastener is selected from the group consisting of a biocompatible glue, a suture, a tissue weld, a dart, a staple, a screw, and a tack.