Implantable collagen devices and related methods and systems of making same

• US 8,986,378 B2
• Filed: 11/02/2012
• Issued: 03/24/2015
• Est. Priority Date: 11/02/2011
• Status: Active Grant

• Current Assignee: Mimedx Group Incorporated
• Original Assignee: Mimedx Group Incorporated
• Inventors: Koob, Thomas J.
• Primary Examiner(s): STEWART, JASON-DENNIS NEILKEN
• Application Number:
  US13/667,507
• Publication Number:
  US 20130105348A1
• Time in Patent Office: 872 Days
• Field of Search: 623/11.11, 623 1311- 132
• US Class Current: 623/13.11
• CPC Class Codes: A61F 2/0095 Packages or dispensers for prostheses or other implants for intraocular lenses A61F2/1691; for dental surgery A61C19/02
• CPC Class Codes: A61F 2/02 Prostheses implantable into the body closure means for urethra or rectum or for artificial body openings therefor A61F2/0004
• 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 27/24 Collagen
• 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: C12N 2506/1307 from adult fibroblasts
• CPC Class Codes: C12N 2506/1346 from mesenchymal stem cells
• CPC Class Codes: C12N 2527/00 Culture process characterised by the use of mechanical forces, e.g. strain, vibration
• CPC Class Codes: C12N 2533/54 Collagen; Gelatin
• CPC Class Codes: C12N 5/066 Tenocytes; Tendons, Ligaments

Abstract

The invention relates to implantable collagen devices made by seeding at least one elongate collagen construct, e.g., comprising at least one elongate synthetic collagen fiber with a plurality of cells and applying a strain and/or stress to the at least one elongate collagen fiber to induce the cells to differentiate into target phenotypes, e.g., tendon or ligament phenotype cells (and/or fibroblasts), typically with an extracellular matrix of collagen to organize into a tissue on the at least one collagen fiber.

Claims

1. An implantable collagen fiber construct, comprising:

a plurality of elongate collagen fibers; and

a plurality of cells attached to the elongate collagen fibers,

wherein ex vivo the cells comprise tendon or ligament phenotype cells and an extracellular matrix comprising collagen, wherein collagen is present in an amount greater than other extracellular matrix proteins.

2. The construct of claim 1, wherein the plurality of elongate collagen fibers are arranged as a construct body, and wherein the attached tendon or ligament phenotype cells and extracellular matrix comprising collagen are organized into tendon-like or ligament-like tissue that increases a volume of the construct body, measured dry, by between about 20-200% or that increases a thickness of the construct body by between 10%-200%.

3. The construct of claim 1, wherein the plurality of elongate collagen fibers are arranged as a construct body, and wherein the tendon or ligament phenotype cells and extracellular matrix of collagen extend over at least 50% of a length of the construct body shape about the elongate collagen fibers.

4. The construct of claim 1, wherein the fibers include tendon phenotype cells and at least 20% extracellular matrix of collagen by volume, dry.

5. The construct of claim 1, wherein the plurality of elongate collagen fibers are synthetic collagen fibers derived from soluble collagen and define a construct body with a shape, and wherein the construct includes tendon or ligament phenotype cells and extracellular matrix of collagen, in an amount between about 20% to 200% by volume of the construct body, dry.

6. The construct of claim 1, wherein the collagen fibers are synthetic collagen fibers that are cross-linked with NDGA, and wherein the tendon or ligament phenotype cells extend over at least a major portion of a surface area of each collagen fiber for at least 50% of an overall length of the collagen fibers.

7. The construct of claim 1, wherein the plurality of collagen fibers are wound, twisted, braided and/or woven together.

8. The construct of claim 1, wherein the implantable collagen fiber construct is a tendon or a ligament prosthesis, and wherein the collagen fiber construct has a tensile strength, stiffness, and dynamic flexibility that meets or exceeds that of a natural tissue the collagen construct is designed to mimic.

9. The construct of claim 1, wherein the cells are differentiated cells derived from cells selected from the group consisting of embryonic, neonatal or adult cells, pluripotent stem cells from any tissue source, mesenchymal stem cells, or combinations thereof.

10. The construct of claim 1, wherein the plurality of elongate collagen fibers are arranged in a construct body, and wherein the cells are organized into tendon-like or ligament-like tissue that increases a thickness of the construct body between 100%-200%.

11. The construct of claim 1, wherein the implantable collagen fiber construct is held in a package.

12. The construct of claim 11, wherein the package is flexible.

13. The construct of claim 11, wherein the package is sterile.

14. The construct of claim 11, wherein interior surfaces of the package are configured to inhibit cell adhesion to the interior surfaces of the package.

15. A medical material, comprising:

at least one elongate synthetic collagen fiber; and

a plurality of cells attached to the at least one elongate synthetic collagen fiber,

wherein ex vivo the cells comprise defined phenotype cells and an extracellular matrix comprising collagen, wherein collagen is present in an amount greater than other extracellular matrix proteins.

16. The material of claim 15, wherein the at least one collagen fiber includes the defined phenotype cells and the extracellular matrix comprising collagen that increases a volume of the fiber, measured dry, by between about 20-200%.

17. The material of claim 15, wherein the defined phenotype cells and extracellular matrix of collagen extend over at least 50% of a length and about at least a major portion of an outer surface of the at least one elongate collagen fiber.

18. The material of claim 15, wherein the at least one collagen fiber includes tendon phenotype cells and at least 20% extracellular matrix of collagen by volume, dry.

19. The material of claim 15, wherein the implantable collagen fiber construct is held in a package.

20. The material of claim 19, wherein the package is flexible.

21. The material of claim 19, wherein the package is sterile.

22. The material of claim 19, wherein interior surfaces of the package are configured to inhibit cell adhesion to the interior surfaces of the package.