Tissue scaffold having aligned fibrils and artificial tissue comprising the same

• US 7,338,517 B2
• Filed: 06/04/2004
• Issued: 03/04/2008
• Est. Priority Date: 06/04/2003
• Status: Active Grant

• Current Assignee: University of South Carolina
• Original Assignee: University of South Carolina
• Inventors: Goldsmith, Edie C., Gore, C. Michael, Goodwin, Richard L., Yost, Michael J., Terracio, Louis
• Primary Examiner(s): Saucier; Sandra E.
• Assistant Examiner(s): DRISCOLL, LORA E BARNHART
• Application Number:
  US10/861,664
• Publication Number:
  US 20050009178A1
• Time in Patent Office: 1,369 Days
• Field of Search: None
• US Class Current: 623/1.1
• CPC Class Codes: B29C 48/09 Articles with cross-sections having partially or fully enclosed cavities, e.g. pipes or channels
• CPC Class Codes: B29C 48/33 with parts rotatable relative to each other
• CPC Class Codes: C12M 21/08 for producing artificial tissue or for ex-vivo cultivation of tissue prostheses A61F2/00, grafts A61L27/00
• CPC Class Codes: C12M 25/14 Scaffolds; Matrices in general C12N5/0068

Abstract

A tubular tissue scaffold is described which comprises a tube having a wall, wherein the wall includes biopolymer fibrils that are aligned in a helical pattern around the longitudinal axis of the tube where the pitch of the helical pattern changes with the radial position in the tube wall. The scaffold is capable of directing the morphological pattern of attached and growing cells to form a helical pattern around the tube walls. Additionally, an apparatus for producing such a tubular tissue scaffold is disclosed, the apparatus comprising a biopolymer gel dispersion feed pump that is operably connected to a tube-forming device having an exit port, where the tube-forming device is capable of producing a tube from the gel dispersion while providing an angular shear force across the wall of the tube, and a liquid bath located to receive the tubular tissue scaffold from the tube-forming device. A method for producing the tubular tissue scaffolds is also disclosed. Also, artificial tissue comprising living cells attached to a tubular tissue scaffold as described herein is disclosed. Methods for using the artificial tissue are also disclosed.

Claims

1. A tubular tissue scaffold comprising a tube having a wall, wherein the wall includes biopolymer fibrils that are aligned in a helical pattern around the longitudinal axis of the tube, wherein the pitch of the helical pattern changes wherein the pitch of the helical pattern of the biopolymer fibrils changes from a right-hand pitch or a left-hand pitch at the luminal surface to a pitch of the opposite direction at the outside surface of the tube wall through the thickness of the tube wall, wherein the tube is substantially free of discrete layers.

2. The tubular tissue scaffold according to claim 1, wherein the pitch of the helical pattern of the biopolymer fibrils at the luminal surface of the tube is different from the pitch of the helical pattern of the biopolymer fibrils at the outer surface of the tube.

3. The tubular tissue scaffold according to claim 1, wherein the biopolymer is selected from the group consisting of collagen, fibronectin, laminin, elastin, fibrin, proteoglycans, hyaluronan, and combinations thereof.

4. The tubular tissue scaffold according to claim 3, wherein the collagen is selected from the group consisting of type I collagen, type II collagen, type Ill collagen, type V collagen, type Xl collagen, and combinations thereof.

5. The tubular tissue scaffold according to claim 4, wherein the collagen is selected from the group consisting of type I collagen, type Ill collagen, and combinations thereof.

6. The tubular tissue scaffold according to claim 5, wherein the collagen is type I collagen.

7. The tubular tissue scaffold according to claim 1, wherein the tissue scaffold comprises a tube having an outside diameter, a luminal diameter, and a wall thickness.

8. The tubular tissue scaffold according to claim 7, wherein the outside diameter is between about 0.1 millimeter and about 100 millimeters.

9. The tubular tissue scaffold according to claim 8, wherein the outside diameter is between about 1 millimeter and about 10 millimeters.

10. The tubular tissue scaffold according to claim 7, wherein the wall thickness is between about 0.1 millimeters and about 5 millimeters.

11. The tubular tissue scaffold according to claim 7, wherein the wall thickness is between about 0.1 millimeters and about 1 millimeter.

12. The tubular tissue scaffold according to claim 1, wherein the pitch of the helical pattern of the biopolymer fibrils at the luminal surface is between about 0 degrees and about 89 degrees and the pitch of the helical pattern of the biopolymer fibrils at the outer surface is between about 0 degrees and about 89 degrees, and wherein the pitch of the helical pattern of the fibrils at the luminal surface is different from the pitch of the fibrils at the outer surface.

13. The tubular tissue scaffold according to claim 1, wherein the pitch of the helical pattern of the biopolymer fibrils at the luminal surface is between about 18 degrees and about 62 degrees and the pitch of the helical pattern of the bio polymer fibrils at the outer surface is between about 18 degrees and about 62 degrees.

14. The tubular tissue scaffold according to claim 1, wherein the pitch of the helical pattern of the biopolymer fibrils at the luminal surface is between about 26 degrees and about 60 degrees and the pitch of the helical pattern of the biopolymer fibrils at the outer surface is between about 26 degrees and about 60 degrees.

15. The tubular tissue scaffold according to claim 1, wherein the pitch of the helical pattern of the biopolymer fibrils at the luminal wall and the outside wall of the tube are roughly equal in degrees but opposite in direction.

16. The tubular tissue scaffold according to claim 1, wherein the tube wall of the scaffold has pores.

17. The tubular tissue scaffold according to claim 16, wherein the average diameter of the pores is between about 1 micron and about 20 microns.

18. The tubular scaffold according to claim 16, wherein the average diameter of the pores is between about 2 microns and about 10 microns.

19. The tubular tissue scaffold according to claim 1, wherein the tubular tissue scaffold has a luminal surface and an outer surface and, wherein the luminal surface and the outer surface supports cell attachment and growth.

20. The tubular tissue scaffold according to claim 1, wherein the tissue scaffold directs the morphology of attached cells to align along the helical pattern of the biopolymer fibrils and express a phenotype like that found in the same cells in vivo.

21. The tubular tissue scaffold according to claim 1, wherein the tube has been split longitudinally and opened into a sheet.

22. The tubular tissue scaffold according to claim 21, wherein the sheet is coated with an additional layer of biopolymer fibrils, wherein the biopolymer fibrils polymerize and are oriented in the direction in which they are applied.

23. The tubular tissue scaffold according to claim 1, wherein the tubular tissue scaffold is treated with UV radiation.

24. The tubular tissue scaffold according to claim 23, wherein the UV radiation comprises a wavelength that is from about 250 to about 280 nm and an energy density of from about 100 to about 1000 μ

w/cm².

25. The tubular tissue scaffold according to claim 1, wherein the tubular tissue scaffold has a burst pressure of at least about 100 mm Hg.

26. The tubular tissue scaffold according to claim 25, wherein the tubular tissue scaffold has a burst pressure of at least about 250 mm Hg.

27. An artificial tissue comprising living cells attached to a tubular tissue scaffold that comprises a tube having a wall, wherein the wall includes biopolymer fibrils that are aligned in a helical pattern around the longitudinal axis of the tube, wherein the pitch of the helical pattern changes from a right-hand pitch or a left-hand pitch at the luminal surface to a pitch of the opposite direction at the outside surface of the tube wall through the thickness of the tube wall, wherein the tube is substantially free of discrete layers.

28. The artificial tissue according to claim 27, wherein the biopolymer is selected from the group consisting of collagen, fibronectin, laminin, elastin, fibrin, proteoglycans, hyaluronan, and combinations thereof.

29. The artificial tissue according to claim 28, wherein the collagen is selected from the group consisting of type I collagen, type II collagen, type Ill collagen, type V collagen, type Xl collagen, and combinations thereof.

30. The artificial tissue according to claim 29, wherein the collagen is type I collagen.

31. The artificial tissue according to claim 27, wherein the tissue scaffold comprises a tube having an outside diameter, a luminal diameter, and a wall thickness.

32. The artificial tissue according to claim 31, wherein the outside diameter of the tubular tissue scaffold is between about 0.1 millimeter and about 100 millimeters.

33. The artificial tissue according to claim 31, wherein the outside diameter of the tubular tissue scaffold is between about 1 millimeters and about 10 millimeters.

34. The artificial tissue according to claim 31, wherein the wall thickness of the tubular tissue scaffold is between about 0.1 millimeters and about 3 millimeters.

35. The artificial tissue according to claim 31, wherein the wall thickness of the tubular tissue scaffold is between about 0.5 millimeters and about 1 millimeter.

36. The artificial tissue according to claim 27, wherein the pitch of the helical pattern of the biopolymer fibrils of the tubular tissue scaffold at the luminal surface is between about 0 degrees and about 89 degrees and the pitch of the helical pattern of the biopolymer fibrils at the outer surface is between about 0 degrees and about 89 degrees, and wherein the pitch of the helical pattern of the fibrils at the luminal surface is different from the pitch of the fibrils at the outer surface.

37. The artificial tissue according to claim 27, wherein the pitch of the helical pattern of the biopolymer fibrils at the luminal surface of the tubular tissue scaffold is between about 18 degrees and about 62 degrees and the pitch of the helical pattern of the biopolymer fibrils at the outer surface of the tubular tissue scaffold is between about 18 degrees and about 62 degrees.

38. The artificial tissue according to claim 27, wherein the pitch of the helical pattern of the biopolymer fibrils at the luminal surface of the tubular tissue scaffold is between about 26 degrees and about 60 degrees and the pitch of the helical pattern of the biopolymer fibrils at the outer surface of the tubular tissue scaffold is between about 26 degrees and about 60 degrees.

39. The artificial tissue according to claim 27, wherein the pitch of the helical pattern of the biopolymer fibrils of the tubular tissue scaffold at the luminal wall and the outside wall of the tube are roughly equal in degrees but opposite in direction.

40. The artificial tissue according to claim 27, wherein the tube wall of the scaffold has pores.

41. The artificial tissue according to claim 40, wherein the number average diameter of the pores is between about 1 micron and about 20 microns.

42. The artificial tissue according to claim 27, wherein the living cells are attached to the luminal and outer surfaces of the tubular tissue scaffold.

43. The artificial tissue according to claim 27, wherein the living cells align along the helical pattern of the biopolymer fibrils.

44. The artificial tissue according to claim 27, wherein the living cells are selected from the group consisting of myocyte precursor cells, cardiac myocytes, skeletal myocytes, satellite cells, fibroblasts, cardiac fibroblasts, chondrocytes, osteoblasts, endothelial cells, epithelial cells, embryonic stem cells, hematopoetic stem cells, neuronal cells, mesenchymal stem cells, anchorage-dependent cell precursors, and combinations thereof.

45. The artificial tissue according to claim 27, wherein the living cells establish intercellular and extracellular connections.

46. The artificial tissue according to claim 27, wherein the living cells are contractile.

47. The artificial tissue according to claim 46, wherein the contractile cells are cardiac myocytes.

48. The artificial tissue according to claim 47, wherein the cardiac myocytes contract synchronously along the helical pattern of the biopolymer, resulting in a wringing action of the tubular tissue scaffold.

49. The artificial tissue according to claim 27, wherein the living cells are attached to two or more tubular tissue scaffolds.

50. The artificial tissue according to claim 49, wherein the tubular tissue scaffolds are in the form of concentric tubes.

51. The artificial tissue according to claim 49, wherein the living cells attached to individual tubular tissue scaffolds are of different cell types.

52. The artificial tissue according to claim 27, wherein the tubular artificial tissue has been split longitudinally and opened into a sheet.

53. The artificial tissue according to claim 27, wherein the tubular tissue scaffold is treated with a growth factor prior to attaching the living cells to the tissue scaffold.

54. The artificial tissue according to claim 53, wherein the growth factor is selected from the group consisting of vascular endothelial growth factor, epidermal growth factor, fibroblast growth factor, erythropoietin, hematopoietic cell growth factor, platelet-derived growth factor, nerve growth factor, transforming growth factor α

, bone morphogenic protein, transforming growth factor β

, and combinations thereof.

55. The artificial tissue according to claim 53, wherein the growth factor is selected from the group consisting of vascular endothelial growth factor, platelet-derived growth factor, nerve growth factor, and combinations thereof.

56. The artificial tissue according to claim 53, wherein the tubular tissue scaffold is treated with UV radiation prior to being treated with the growth factor.

57. The artificial tissue according to claim 56, wherein the UV radiation comprises a wavelength of 254 nm and an energy density of 500 μ

w/cm².