Methods of tissue repair and compositions therefor

• US 8,512,730 B2
• Filed: 06/07/2006
• Issued: 08/20/2013
• 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
• Primary Examiner(s): Azpuru, Carlos
• Assistant Examiner(s): HAGOPIAN, CASEY SHEA
• Application Number:
  US11/448,701
• Publication Number:
  US 20060228391A1
• Time in Patent Office: 2,631 Days
• Field of Search: None
• US Class Current: 424/423
• 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 method of promoting tissue growth at a tissue site in need of tissue growth in a mammal in need thereof, the method comprising injecting an injectable tissue matrix composition at the site, wherein the injectable matrix composition comprises polyester polymers entangled with hyaluronic acid polymers by a process comprising 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; and

(iii) pouring the emulsified mixture of the two polymers into a mold, (iv) successively removing the organic solvent and water from the mold to form a solid matrix comprising the polyester polymers entangled with the hyaluronic acid polymers;

(v) granulating the solid matrix to form matrix granules; and

(vi) combining the matrix granules with an aqueous liquid solution comprising hyaluronic acid to form a paste or a viscous liquid capable of injection at the tissue site.

2. The method of claim 1, wherein the matrix composition comprises a paste.

3. The method of claim 1, wherein the matrix composition comprises a viscous liquid.

4. The method of claim 1, wherein the mammal is a human in need of treatment.

5. The method of claim 1, wherein the site in need of tissue growth comprises bone and periosteal tissue.

6. The method of claim 1, wherein the tissue growth comprises facial contour augmentation.

7. The method of claim 1, wherein the matrix further comprises at least one therapeutic agent.

8. The method of claim 7, wherein the at least one therapeutic agent is selected from the group consisting of an anti-infective agent, a pain medication, an analgesic, an anti-inflammatory agent, and an immunosuppressive agent.

9. The method of claim 1, wherein the site in need of tissue growth comprises bone and a periodontal ligament.

10. The method of claim 1, wherein the site in need of tissue growth comprises bone and cartilage.

11. The method of claim 1, wherein the site in need of tissue growth comprises bone and hyaline cartilage.

12. The method of claim 11 wherein the hyaline cartilage is costal cartilage.

13. The method of claim 1, wherein the site in need of tissue growth comprises bone and fibrous cartilage.

14. The method of claim 13 wherein the fibrous cartilage is meniscus cartilage.

15. The method of claim 1, wherein the polyester polymers and hyaluronic acid polymers are combined at a weight ratio of polyester polymers to hyaluronic polymers of between 9:

1 and 1;

9.

16. The method of claim 1, wherein the matrix composition 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.

17. The method of claim 1, wherein the site in need of tissue growth is selected from the group consisting of bone tissue, cartilage tissue, tendon tissue, ligament tissue, vascular tissue, dermal tissue, periodontal tissue, intervertebral disc tissue, hyaline cartilage, fibrous cartilage, elastic cartilage, a nerve tunnel or a combination thereof.