Method for repair and reconstruction of ruptured ligaments or tendons and for treatment of ligament and tendon injuries

• US 20070162121A1
• Filed: 01/12/2007
• Published: 07/12/2007
• Est. Priority Date: 01/12/2006
• Status: Active Grant

• Current Assignee: Histogenics Corporation (Ocugen, Inc.)
• Original Assignee: Histogenics Corporation (Ocugen, Inc.)
• Inventors: Smith, Robert, Kusanagi, Akihiko, Tarrant, Laurence
• Granted Patent: US 8,070,810 B2
• Time in Patent Office: Days
• US Class Current: 623/13.120
• CPC Class Codes: A61B 17/00491 Surgical glue applicators surgical adhesives A61L24/00; two-component delivery syringes A61M5/19
• CPC Class Codes: A61B 17/1146 of tendons
• CPC Class Codes: A61B 2017/1132 End-to-end connections
• CPC Class Codes: A61F 2/08 Muscles; Tendons; Ligaments sutures A61B17/04
• CPC Class Codes: A61L 2430/10 for reconstruction of tendons or ligaments
• CPC Class Codes: A61L 27/3804 characterised by specific cells or progenitors thereof, e.g. fibroblasts, connective tissue cells, kidney cells
• CPC Class Codes: A61L 27/386 Ligaments, tendons
• CPC Class Codes: Y10S 623/908 Bone

Abstract

A method and a means for repair and reconstruction of ruptured ligaments and tendons by in vivo or ex vivo repair and reconstruction surgical procedures. The method comprises providing a biodegradable sleeve placed around the frayed edges of an injured ligament or tendon for protecting the ligament or tendon injury with a protective shield. A composition comprising a biodegradable tissue adhesive applied on top of, around and/or between the frayed edges of the injured ligament.

Claims

1. A method for repair and reconstruction of injured ligaments and tendons comprising steps of:

(a) fabricating a protective sleeve or a composite of the protective sleeve with a support matrix;

(b) selecting a biologically acceptable biodegradable tissue adhesive having a sufficiently fast setting time to set the tissue adhesive in from about 30 seconds to about ten minutes to have a sufficient strength to hold frayed edges of a ruptured ligament or tendon together for a time needed for healing said injured ligament or tendon;

(c) surgically attaching one end of the protective sleeve or said composite to the uninjured portion of ligament or tendon, or to the bone where the uninjured healthy ligament or tendon is attached;

(d) surgically juxtaposing the frayed edges of the ruptured ligament or tendon to a close proximity of each other;

(e) applying said tissue adhesive to a top of, around or in between said juxtaposed edges of step (d) thereby attaching said edges together and sealing an area around and between said edges with said adhesive;

(f) extending said protective sleeve or said composite over and covering a sealed area of step (e) with said protective sleeve or said composite;

(g) attaching a second end of said protective sleeve or said composite to an uninjured portion of the ligament or tendon or to a bone where the other end of the uninjured ligament is attached, or to a muscle where the uninjured tendon is attached; and

(h) stabilizing a site of the injury for a time needed for the injury to heal.

2. The method of claim 1 wherein said protective sleeve or said composite is fabricated as a sheet, mesh, strands, fibers, net, fibrous sheet, fibrous mesh, fibrous netting, or from a knitted sheath comprising individual strands of yarn.

3. The method of claim 2 wherein said protective sleeve or said composite is fabricated from a biodegradable silk, a porous collagen matrix, a derivatized polymer, a bundle of yarn strands comprising one to several fibers of polymer or silk.

4. The method of claim 2 wherein a material used for fabrication of said protective sleeve or said composite is selected from the group consisting of Type I collagen, Type II collagen, Type IV collagen, gelatin, agarose, collagen containing proteoglycan, glycosaminoglycan or glycoprotein, polymer of aromatic organic acid, fibronectin, laminin, bioactive peptide growth factor, cytokine, elastin, fibrin, synthetic polymeric fibers made of polylactic, polyglycolic or polyamino acid, polycaprolactone, polyamino acid, polypeptide gel, copolymer thereof and a combination thereof.

5. The method of claim 2 wherein a material used for fabrication of a support matrix of said composite is a sol, gel, sol-gel or thermo-reversible hydrogel.

6. The method of claim 1 wherein said supporting matrix of said composite is incorporated with, have embedded into or is seeded exogenously added cells.

7. The method of claim 6 wherein said cells are fibroblasts, tenocytes, their progenitor cells, mesenchymal cells, embryonic cells or stem cells.

8. The method of claim 7 wherein said cells are adhered to a surface of said support matrix or are adhered to a collagenous scaffold and said scaffold is incorporated into said support matrix of said composite or into said protective sleeve.

9. The method of claim 7 additionally comprising growth hormones, modulators of cell growth or pharmaceutical agents.

10. The method of claim 7 wherein said cells are autologous fibroblasts or autologous tenocytes.

11. The method of claim 1 wherein said tissue adhesive is a biologically acceptable polymer having a polymerization setting time between about one and about five minutes.

12. The method of claim 11 wherein said tissue adhesive is selected from the group consisting of a hydrogel, derivatized polyethylene glycol (PEG), protein, albumin, albumin cross-linked with a collagen compound, derivatized polyethylene glycol (PEG) cross-linked with a collagen compound, tetra-hydrosuccinimidyl, tetra-thiol derivatized PEG, a combination thereof, two-part polymer composition that rapidly form a matrix where at least one of the compounds is polyamino acid, polysaccharide, polyalkylene oxide, polyethylene glycol, polyethylene glycol cross-linked with methylated collagen, collagen, fibrin-based adhesive, a copolymer of polyethylene glycol and polylactide, polyglycolide, polyhydroxybutyrate and a polymer of an aromatic organic amino acid, a copolymer thereof, and a combination thereof.

13. The method of claim 12 wherein the tissue adhesive material is polyethylene glycol cross-linked with methylated collagen.

14. The method of claim 12 wherein said adhesive is polyhydroxybutyrate.

15. A device for repair and reconstruction of injured ligament or tendon comprising a protective sleeve or a composite of the protective sleeve with a support matrix fabricated from a biologically acceptable biodegradable material.

16. The device of the claim 15 wherein said supporting matrix of said composite is incorporated with, have embedded into or is seeded with exogenously added cells, wherein said cells are fibroblasts, tenocytes, fibroblast progenitors, tenocyte progenitors, mesenchymal cells, embryonic cells or stem cells.

17. The device of claim 15 wherein said protective sleeve or said composite is flexible and contractible.

18. The device of claim 17 wherein said flexible and contractible protective sleeve or composite, when extended, compresses frayed edges of an injured ligament or tendon juxtaposed together and covered with a tissue adhesive able to hold said frayed edges together for a time needed for healing said injured ligament or tendon.

19. The device of claim 18 wherein said protective sleeve or said composite protects said frayed edges for a time needed for healing said injury.

20. A composition suitable for repair and reconstruction of ruptured ligament or tendon comprising a biologically acceptable biodegradable adhesive selected from the group consisting of a hydrogel, derivatized polyethylene glycol (PEG), protein, albumin, albumin cross-linked with a collagen compound, derivatized polyethylene glycol (PEG) cross-linked with a collagen compound, tetra-hydrosuccinimidyl, tetra-thiol derivatized PEG, a combination thereof, two-part polymer composition that rapidly form a matrix where at least one of the compounds is polyamino acid, polysaccharide, polyalkylene oxide, polyethylene glycol, polyethylene glycol cross-linked with methylated collagen, collagen alone, fibrin-based adhesive, a copolymer of polyethylene glycol and polylactide, polyglycolide, polyhydroxybutyrate, a polymer of an aromatic organic amino acid, copolymer thereof and a combination thereof.