Matrix made of polyester polymers entangled with hyaluronic polymers useful for supporting tissue repair

• US 8,192,759 B2
• Filed: 07/11/2005
• Issued: 06/05/2012
• Est. Priority Date: 07/12/2004
• Status: Active Grant

• Current Assignee: Isto Technologies Ii LLC
• Original Assignee: ISTO Technologies, Inc. (Isto Biologics, Inc.)
• Inventors: Seyedin, Mitchell S., Spiro, Robert
• Primary Examiner(s): Azpuru, Carlos
• Assistant Examiner(s): HAGOPIAN, CASEY SHEA
• Application Number:
  US11/179,425
• Publication Number:
  US 20060008530A1
• Time in Patent Office: 2,521 Days
• Field of Search: None
• US Class Current: 424/484
• CPC Class Codes: A61K 31/727 Heparin; Heparan
• CPC Class Codes: A61K 31/728 Hyaluronic acid
• CPC Class Codes: A61K 31/737 Sulfated polysaccharides, e.g. chondroitin sulfate, dermatan sulfate A61K31/727 takes precedence
• CPC Class Codes: A61K 38/1875 Bone morphogenic factor; Osteogenins; Osteogenic factor; Bone-inducing factor
• CPC Class Codes: A61K 38/39 Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin, cold insoluble globulin [CIG]
• CPC Class Codes: A61L 27/26 Mixtures of macromolecular compounds
• CPC Class Codes: C08L 5/00 Compositions of polysaccharides or of their derivatives not provided for in groups C08L1/00 or C08L3/00
• CPC Class Codes: C08L 67/04 Polyesters derived from hydroxycarboxylic acids, e.g. lactones C08L67/06 takes precedence

Abstract

The present application discloses matrix compositions to support the repair of tissue defects such as an osteochondral injury. A matrix described herein comprises a polyester polymer entangled with a polysaccharide polymer. Also disclosed are methods of preparing a matrix, and methods of using a matrix in the repair of tissue. In certain configurations, a matrix can comprise a polyester cross-linked with a polysaccharide, which can be an oxidized polysaccharide. In some configurations, a matrix can further comprise one or more additional components, such as a growth factor.

Claims

1. A matrix for supporting repair of bone or cartilage comprising polyester polymers entangled with hyaluronic acid polymers, said matrix being formed by the steps of:

(i) dissolving polyester polymers in an organic solvent;

(ii) blending the polyester polymers with hyaluronic acid polymers contained in an aqueous medium to form an emulsified mixture;

(iii) pouring the emulsified mixture of the two polymers into a mold, and

(iv) successively removing the organic solvent and water from the mold;

wherein said matrix is characterized by (i) retention of pore structure and shape when hydrated and (ii) the ability to support the growth of cells in vivo or ex vivo.

2. A matrix in accordance with claim 1, wherein the polyester polymers are selected from the group consisting of polylactic acid, polyglycolic acid, and a co-polymer comprising polylactic acid and polyglycolic acid.

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

4. A matrix in accordance with claim 3, wherein the polylactic acid and the polyglycolic acid are in a weight ratio of about 5:

1 to about 2;

1.

5. A matrix in accordance with claim 4, wherein the weight ratio of polylactic acid to polyglycolic acid is about 3:

1.

6. A matrix in accordance with claim 1, wherein the hyaluronic acid polymers are oxidized.

7. A matrix in accordance with claim 1, wherein the hyaluronic acid polymers are covalently crosslinked.

8. A matrix in accordance with claim 1, wherein the polyester polymers and the hyaluronic acid polymers are in a weight ratio of from 99:

1 to 1;

99.

9. A matrix in accordance with claim 8, wherein the polyester polymers comprise a co-polymer comprising polylactic acid and polyglycolic acid, wherein the weight ratio of the co-polymer to the hyaluronic acid polymers is from about 9:

1 to about 1;

9.

10. A matrix in accordance with claim 1, further comprising at least one growth factor.

11. A matrix in accordance with claim 10, wherein the at least one growth factor is 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.

12. A matrix in accordance with claim 10, wherein the at least one growth factor is a bone morphogenetic protein.

13. A matrix in accordance with claim 1, further comprising at least one collagen.