Tissue-engineered ligament

• US 6,737,053 B1
• Filed: 11/10/2000
• Issued: 05/18/2004
• Est. Priority Date: 11/12/1999
• Status: Expired due to Fees

• Current Assignee: National University of Singapore
• Original Assignee: National University of Singapore
• Inventors: Chan, Kwan-Ho, Goh, James Cho Hong
• Primary Examiner(s): Witz, Jean C.
• Application Number:
  US09/710,435
• Time in Patent Office: 1,285 Days
• Field of Search: 424/93.7, 623/11, 623/13, 623/11.1
• US Class Current: 424/93.7
• CPC Class Codes: A61F 2/08 Muscles; Tendons; Ligaments sutures A61B17/04

Abstract

An apparatus and method for the reconstruction of a previously torn ligament using a tissue-engineered ligament. The tissue-engineered ligament includes a scaffold of biocompatible material having at least one layer and forming a sheet. The scaffold is placed in a cultured medium for seeding with fibrocyte forming cells. The seeded scaffold is then placed in an incubator to increase the number of cells. The seeded scaffold is then formed into a slender structure suitable for implantation. The method of making a tissue-engineered ligament includes forming a scaffold of biocompatible material having at least one layer forming a sheet. Next, the scaffold sheet is seeded with fibrocyte forming cells. The method further includes increasing the number of cells on the seeded scaffold and forming a slender structure suitable for implantation from the scaffold.

Claims

1. An apparatus for reconstruction of a previously torn ligament, said apparatus comprising:

a scaffold of biocompatible material, the scaffold having at least one layer forming a scaffold sheet, and the scaffold sheet containing at least one slit;

means for seeding the scaffold sheet with fibrocyte forming cells to form a seeded scaffold;

means for increasing the number of the fibrocyte forming cells seeded on the scaffold to create a tissue-engineered scaffold; and

means for forming a slender structure from the tissue-engineered scaffold, the slender structure being a tissue-engineered ligament suitable for implantation into a patient for reconstruction of a ligament.

2. The apparatus of claim 1 wherein the scaffold sheet is bioabsorbable.

3. The apparatus of claim 1 wherein the scaffold sheet is porous.

4. The apparatus of claim 3 wherein the porous scaffold sheet forms at least one perforation.

5. The apparatus of claim 1 wherein the seeding means is a cultured medium containing the fibrocyte forming cells, the scaffold sheet being placed into the cultured medium for seeding with fibrocyte forming cells.

6. The apparatus of claim 1 wherein the fibrocyte forming cells increasing means is incubation of the scaffold sheet.

7. The apparatus of claim 1 wherein the slender structure forming means is a rolled tubular structure formed by rolling the scaffold sheet.

8. The apparatus of claim 1 wherein the slender structure forming means is an accordion structure formed by folding the scaffold sheet.

9. The apparatus of claim 1 wherein the slender structure forming means is a series of strips cut from the scaffold sheet and the series of scaffold strips are stacked on top of one another.

10. The apparatus of claim 1 wherein threads are molded into each end of the tissue-engineered ligament.

11. The apparatus of claim 1 wherein the scaffold sheet has an interlocking surface along a first section and a second section whereby portions of the first section and the second section interlock with corresponding portions of the first section and the second section when the slender structure is formed from the scaffold sheet.

12. The apparatus of claim 11 wherein the first interlocking section and the second interlocking section each contain a male pattern on one side and a female pattern on the opposite side.

13. The apparatus of claim 1 wherein the tissue-engineered ligament has opposed end margins connected by strips, the end margins having a greater thickness than the strips, wherein the configuration of the strips acts as scaffolding for the fibrocyte forming cells to grow therein.

14. The apparatus of claim 1 further comprising means for cyclic tensile loading prior to implantation.

15. The apparatus of claim 1 wherein the fibrocyte forming cells are mesenchymal stem cells.

16. The apparatus of claim 1 wherein the fibrocyte forming cells are fibroblast cells.

17. The apparatus of claim 1 wherein the fibrocyte forming cells increasing means includes implantation in a penultimate location of a patient'"'"'s body prior to implantation in a functional location.

18. The apparatus of claim 1 wherein the scaffold sheet includes one or more of the group comprising polyglycolic acid, polyactic acid, a mixture of PGA/PLA, chitin, collagen, autograft tissue, and allograft tissue.

19. The apparatus of claim 18 wherein the tissues are fascia lata.

20. The apparatus of claim 1 wherein the scaffold sheet is coated with a material to promote adhesion of the fibrocyte forming cells.

21. The apparatus of claim 20 wherein the coating material is collagen.

43. The apparatus of claim 1 wherein the apparatus further comprises:

means for attaching each end of the tissue-engineered ligament to implantation sites within a patient.

44. The apparatus of claim 1 wherein the apparatus further comprises:

means for forming microchannels in the scaffold sheet.

53. The apparatus of claim 43 wherein the means for attaching is an interference screw for fixation of the end of each ligament at the implantation site.

22. A method of making a tissue-engineered ligament, said method comprising:

forming a scaffold sheet of biocompatible material having at least one layer;

seeding the scaffold sheet with fibrocyte forming cells to form a seeded scaffold of at least one sheet;

increasing the number of the fibrocyte forming cells on the seeded scaffold to create a tissue-engineered scaffold; and

forming a slender structure from the tissue-engineered scaffold, the slender structure being a tissue-engineered ligament suitable for implantation into a patient for reconstruction of a ligament.

23. The method of claim 22 further comprising attaching each end of the tissue-engineered ligament to implantation sites within a patient.

24. The method of claim 22 wherein the scaffold is a single sheet.

25. The method of claim 22 wherein the scaffold is slit at least once, the slit is made in the direction of a first end of the scaffold to a second end of the scaffold, and the slit terminates prior to the first end and the second end.

26. The method of claim 22 wherein seeding the scaffold with fibrocyte forming cells includes placing the scaffold into a cultured medium containing the fibrocyte forming cells.

27. The method of claim 22 wherein increasing the number of fibrocyte cells includes incubating the scaffold sheet after seeding.

28. The method of claim 23 wherein increasing the number of fibrocyte cells further includes incubating the tissue-engineered ligament after forming the slender structure.

29. The method of claim 22 wherein increasing the number of fibrocyte cells includes incubating the tissue-engineered ligament after forming the slender structure.

30. The method of claim 22 wherein forming a slender structure includes rolling the scaffold sheet to form a rolled tubular structure.

31. The method of claim 22 wherein forming a slender structure includes folding the scaffold sheet to form an accordion structure.

32. The method of claim 22 wherein forming a slender structure includes cutting a series of strips from the scaffold sheet and stacking the series of strips on top of one another to form the slender structure.

33. The method of claim 23 wherein attaching each end of the ligament to implantation sites within a patient involves using an interference screw for fixation.

34. The method of claim 22 further comprising molding threads into each end of the tissue-engineered ligament for implantation.

35. The method of claim 22 further comprising providing interlocking surfaces on the scaffold sheet for locking the scaffold sheet into the tissue-engineered ligament when the method step of forming a slender structure is accomplished.

36. The method of claim 22, further comprising applying cyclic tensile loading of the seeded scaffold prior to implantation to increase the strength of the scaffold.

37. The method of claim 22 further comprising applying cyclic tensile loading of the slender structure prior to implantation to strengthen the tissue-engineered scaffold.

38. The method of claim 22 further comprising forming spaces within the slender structure to allow the fibrocyte forming cells to grow therein.

39. The method of claim 22 wherein increasing the number of fibrocyte forming cells further comprises implanting the seeded scaffold in a penultimate section of a patient'"'"'s body prior to implantation in a functional location.

40. The method of claim 22 wherein increasing the number of fibrocyte forming cells further comprises implanting the slender structure in a penultimate location of a patient'"'"'s body prior to implantation in a functional location.

41. The method of claim 22 further comprising coating the scaffold sheet with a material to promote adhesion of the fibrocyte forming cells.

42. The method of claim 22 further comprising genetically altering fibrocyte forming cells to increase production of fibrocyte cells.

45. The method of claim 22 further comprising forming microchannels in the scaffold sheet.

46. An apparatus for reconstruction of a previously torn ligament, said apparatus comprising:

a scaffold of biocompatible material, the scaffold having at least one layer forming a scaffold sheet;

means for seeding the scaffold sheet with fibrocyte forming cells to form a seeded scaffold;

means for increasing the number of the fibrocyte forming cells seeded on the scaffold to create a tissue-engineered scaffold; and

means for forming a slender structure from the tissue-engineered scaffold, the slender structure being a tissue-engineered ligament suitable for implantation into a patient for reconstruction of a ligament, and the tissue-engineered ligament having threads molded into each end thereof.

47. An apparatus for reconstruction of a previously torn ligament, said apparatus comprising:

a scaffold of biocompatible material, the scaffold having at least one layer forming a scaffold sheet;

means for seeding the scaffold sheet with fibrocyte forming cells to form a seeded scaffold;

means for increasing the number of the fibrocyte forming cells seeded on the scaffold to create a tissue-engineered scaffold; and

means for forming a slender structure from the tissue-engineered scaffold, the slender structure being a tissue-engineered ligament suitable for implantation into a patient for reconstruction of a ligament;

wherein the scaffold sheet has an interlocking surface along a first section and a second section whereby portions of the first section and the second section interlock with corresponding portions of the first section and the second section when the slender structure is formed from the scaffold sheet.

48. An apparatus for reconstruction of a previously torn ligament, said apparatus comprising:

a scaffold of biocompatible material, the scaffold having at least one layer forming a scaffold sheet;

means for seeding the scaffold sheet with fibrocyte forming cells to form a seeded scaffold;

means for increasing the number of the fibrocyte forming cells seeded on the scaffold to create a tissue-engineered scaffold; and

means for forming a slender structure from the tissue-engineered scaffold, the slender structure being a tissue-engineered ligament suitable for implantation into a patient for reconstruction of a ligament, and the tissue-engineered ligament having opposed end margins connected by strips, the end margins having a greater thickness than the strips, wherein the configuration of the strips acts as scaffolding for the fibrocyte forming cells to grow therein.

49. An apparatus for reconstruction of a previously torn ligament, said apparatus comprising:

a scaffold of biocompatible material, the scaffold having at least one layer forming a scaffold sheet;

means for seeding the scaffold sheet with fibrocyte forming cells to form a seeded scaffold;

means for increasing the number of the fibrocyte forming cells seeded on the scaffold to create a tissue-engineered scaffold;

means for forming a slender structure from the tissue-engineered scaffold, the slender structure being a tissue-engineered ligament suitable for implantation into a patient for reconstruction of a ligament; and

means for cyclic tensile loading prior to implantation.

50. An apparatus for reconstruction of a previously torn ligament, said apparatus comprising:

a scaffold of biocompatible material, the scaffold having at least one layer forming a scaffold sheet;

means for seeding the scaffold sheet with fibrocyte forming cells to form a seeded scaffold;

means for increasing the number of the fibrocyte forming cells seeded on the scaffold to create a tissue-engineered scaffold; and

means for forming a slender structure from the tissue-engineered scaffold, the slender structure being a tissue-engineered ligament suitable for implantation into a patient for reconstruction of a ligament;

wherein the fibrocyte forming cells increasing means includes implantation in a penultimate location of a patient'"'"'s body prior to implantation in a functional location.

51. An apparatus for reconstruction of a previously torn ligament, said apparatus comprising:

a scaffold of biocompatible material, the scaffold having at least one layer forming a scaffold sheet;

means for seeding the scaffold sheet with fibrocyte forming cells to form a seeded scaffold;

means for increasing the number of the fibrocyte forming cells seeded on the scaffold to create a tissue-engineered scaffold; and

means for forming a slender structure from the tissue-engineered scaffold, the slender structure being a tissue-engineered ligament suitable for implantation into a patient for reconstruction of a ligament;

wherein the scaffold sheet comprises fascia lata tissue.

52. An apparatus for reconstruction of a previously torn ligament, said apparatus comprising:

a scaffold of biocompatible material, the scaffold having at least one layer forming a scaffold sheet;

means for seeding the scaffold sheet with fibrocyte forming cells to form a seeded scaffold;

means for increasing the number of the fibrocyte forming cells seeded on the scaffold to create a tissue-engineered scaffold;

means for forming a slender structure from the tissue-engineered scaffold, the slender structure being a tissue-engineered ligament suitable for implantation into a patient for reconstruction of a ligament; and

means for forming microchannels in the scaffold sheet.