Implantable collagen devices and related methods and systems of making same
View Patent ↗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.
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.