Cartilage repair methods

• US 8,444,968 B2
• Filed: 12/07/2006
• Issued: 05/21/2013
• 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 S., Matava, Matthew
• Primary Examiner(s): Hanley, Susan
• Assistant Examiner(s): NGUYEN, NGHI V
• Application Number:
  US11/635,265
• Publication Number:
  US 20070128155A1
• Time in Patent Office: 2,357 Days
• Field of Search: 424/93.7
• US Class Current: 424/93.7
• 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 full-thickness chondral defect of a joint of a patient in need of treatment, the method comprising:

a) microfracturing bone underlying the joint;

b) applying to the joint a membrane, wherein the membrane comprises a polyester polymer entangled with a hyaluronate polymer, at a weight ratio of polyester polymer to hyaluronate polymer of between 9;

1 and 1;

9, wherein the entanglement of the polymers is produced by forming an emulsified mixture of the polyester polymer in a first solvent and the hyaluronate polymer in a second solvent, adding the emulsified mixture to a mold, freezing the emulsified mixture in the mold, removing solvent from the resultant frozen mixture by vacuum, wherein the membrane has a thickness of at least 0.5 mm up to 3 mm; and

c) anchoring the membrane to the joint.

2. The method in accordance with claim 1, for repairing a full-thickness chondral defect in a knee joint, an elbow joint, or a shoulder joint, wherein said microfracturing, applying and anchoring steps are carried out on the defective joint.

3. The method in accordance with claim 1, wherein the polyester polymers comprise a co-polymer comprising polylactic acid and polyglycolic acid.

4. The method in accordance with claim 2, wherein the polylactic acid and the polyglycolic acid are in a weight ratio of about 5:

1 to about 2;

1.

5. The method in accordance with claim 1, 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.

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

a) 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;

b) applying to the joint a membrane, wherein the membrane comprises a polyester polymer entangled with a hyaluronate polymer, at a weight ratio of polyester polymer to hyaluronate polymer of between 9;

1 and 1;

9, wherein the entanglement of the polymers is produced by forming an emulsified mixture of the polyester polymer in a first solvent and the hyaluronate polymer in a second solvent, adding the emulsified mixture to a mold, freezing the emulsified mixture in the mold, removing solvent from the resultant frozen mixture by vacuum, wherein the membrane has a thickness of at least 0.5 mm up to 3 mm; and

c) securing the membrane to the joint.

7. The method in accordance with claim 6, wherein the polyester polymers comprise a co-polymer comprising polylactic acid and polyglycolic acid.

8. The method in accordance with claim 7, wherein the polylactic acid and the polyglycolic acid are in a weight ratio of about 5:

1 to about 2;

1.

9. The method for repairing a hyaline cartilage defect in accordance with claim 6, 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.