Tissue matrix system

• US 8,580,289 B2
• Filed: 06/23/2011
• Issued: 11/12/2013
• 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., Gage, Gary B.
• Primary Examiner(s): Azpuru, Carlos
• Assistant Examiner(s): HAGOPIAN, CASEY SHEA
• Application Number:
  US13/167,537
• Publication Number:
  US 20110256095A1
• Time in Patent Office: 873 Days
• Field of Search: None
• US Class Current: 424/422
• 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 38/00 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 2400/06 Flowable or injectable implant compositions
• CPC Class Codes: A61L 27/26 Mixtures of macromolecular compounds
• CPC Class Codes: A61L 27/50 Materials characterised by their function or physical properties , e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
• CPC Class Codes: A61P 19/00 Drugs for skeletal disorders
• CPC Class Codes: A61P 19/04 for non-specific disorders of the connective tissue
• 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 injury to tendon tissue, ligament tissue, vascular tissue, dermal tissue, or muscle tissue. 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 or an anti-infective agent. In some configurations, a matrix can be a viscous fluid or a paste, while in other configurations a matrix can be comprised by a solid such as a plug, a granule or a membrane.

Claims

1. A matrix composition for supporting repair of a tissue comprising polyester polymers entangled with hyaluronic acid polymers, wherein the polyester polymers are selected from the group consisting of polylactic acid, polyglycolic acid, and a co-polymer consisting of polylactic acid and polyglycolic acid, said composition being formed by the steps of:

(i) dissolving the 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) freezing the emulsified mixture of the two polymers, and (iv) successively removing the organic solvent and water from the frozen mixture;

wherein said composition is characterized by (a) retention of pore structure when hydrated and (b) the ability to support the growth of cells in vivo or ex vivo.

2. The matrix of claim 1, wherein steps (iii) and (iv) comprise lyophilizing the emulsified mixture.

3. The matrix of claim 2, comprising granules formed from the lyophilized emulsified mixture.

4. The matrix of claim 3, wherein the granules are combined with an aqueous liquid to form a paste or viscous liquid capable of injection at a tissue site.

5. The matrix of claim 4, wherein the granules are mixed with an aqueous liquid selected from the group consisting of water, physiological saline, blood, serum, plasma, a hyaluronic acid solution and a protein solution.

6. The matrix of claim 5, wherein the aqueous liquid is a hyaluronic acid solution.

7. The matrix of claim 5, further comprising bone marrow aspirate.

8. The matrix of claim 4, further comprising at least one therapeutic agent.

9. The matrix of claim 8, wherein the at least one therapeutic agent is selected from the group consisting of an anti-infective agent, an analgesic agent, an anti-inflammatory agent, and an immunosuppressive agent.

10. The matrix of claim 1, wherein the polyester polymers are copolymers consisting of polylactic acid and polyglycolic acid.

11. The matrix of claim 10, wherein the polylactic acid and the polyglycolic acid are in a weight ratio of about 5:

1 to about 2;

1.

12. The matrix of claim 10, wherein the weight ratio of polylactic acid to polyglycolic acid is about 3:

1 to 5;

1.

13. The matrix of claim 1, wherein the hyaluronic acid polymers are oxidized.

14. The matrix of claim 1, wherein the hyaluronic acid polymers are covalently crosslinked.

15. The matrix of claim 1, wherein the polyester and the hyaluronic acid polymers are in a weight ratio of from 99:

1 to 1;

99.

16. The matrix of claim 1, wherein the polyester polymers are copolymers consisting of polylactic acid and polyglycolic acid, wherein the weight ratio of polylactic acid to polyglycolic acid in the co-polymer is from about 5:

1 to about 2;

1.

17. The matrix of claim 1, further comprising at least one growth factor.

18. The matrix of claim 17, 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.

19. The matrix of claim 18, wherein the at least one growth factor is a bone morphogenetic protein.

20. The matrix of claim 1, further comprising at least one collagen.