Claims
- 1. A method for forming a target tissue substitute, comprising the steps:
(a) providing a scaffold comprising one or more layers of one or more arrays of microfibers, wherein one or more of the arrays of microfibers is designed to mimic the configuration of one or more structural elements in a target tissue; and (b) culturing cells on the scaffold to produce a target tissue substitute.
- 2. The method of claim 1, wherein the microfibers have a diameter between about 1 micrometer and about 20 micrometer.
- 3. The method of claim 1, wherein the microfibers have a diameter between about 1 micrometers and about 15 micrometers.
- 4. The method of claim 1, wherein the microfibers have a diameter between about 1 micrometer and about 6 micrometers.
- 5. The method of claim 1, wherein the spacing of adjacent microfibers in the array is between about 10 micrometers and 100 micrometers.
- 6. The method of claim 1, wherein the spacing of adjacent microfibers in the array is between about 30 micrometers and 70 micrometers.
- 7. The method of claim 1, wherein the spacing of adjacent microfibers in the array is between about 40 micrometers and 60 micrometers.
- 8. The method of claim 1, wherein the spacing of the layers of microfiber arrays is between about 10 micrometers and about 200 micrometers.
- 9. The method of claim 1, wherein the spacing of the layers of microfiber arrays is between about 60 micrometers and about 160 micrometers.
- 10. The method of claim 1, wherein the spacing of the layers of microfiber arrays is between about 80 micrometers and about 120 micrometers.
- 11. The method of claim 1, wherein the microfibers comprise a biodegradable polymer that gradually transfers load from the scaffold to the target tissue substitute.
- 12. The method of claim 11, wherein the biodegradable polymer is selected from the group consisting of a poly-L-lactic acid/polycaprolactone co-polymer, a poly-caprolactone/poly-caprolactone-co-glycolide/poly-hydroxybutyrate-co-hydroxyvalerate/urethane co-polymer, degradable polyurethane, and polyglycolic acid.
- 13. The method of claim 1, wherein the microfiber scaffold is coated with a cell adhesion-enhancing agent.
- 14. The method of claim 13, wherein the cell adhesion-enhancing agent is selected from the group consisting of collagen, laminin, and fibronectin.
- 15. The method of claim 1, wherein the cells are cultured on the microfiber scaffold in the presence of dynamic mechanical conditioning.
- 16. The method of claim 1, wherein the target tissue is an arterial blood vessel, wherein an array of microfibers is designed to mimic the configuration of elastin in the medial layer of an arterial blood vessel and wherein cells are cultured on the microfiber scaffold to form a blood vessel substitute.
- 17. The method of claim 16, wherein the cells comprise smooth muscle cells.
- 18. The method of claim 17, wherein the cells further comprise endothelial cells.
- 19. The method of claim 16, wherein the scaffold comprises between 2 and 25 layers.
- 20. The method of claim 16, wherein the blood vessel substitute comprises three layers and has a burst pressure of more than 1500 mm Hg after 2 weeks of culture in the absence of mechanical conditioning.
- 21. The method of claim 1, wherein the target tissue is a muscle tissue, wherein an array of microfibers is designed to mimic the configuration of muscle fibers in the muscle tissue, and wherein cells are cultured on the scaffold to form a muscle substitute.
- 22. The method of claim 21, wherein the target tissue is skeletal muscle.
- 23. The method of claim 21, wherein the target tissue is cardiac muscle.
- 24. The method of claim 21, wherein the cells comprise muscle cells.
- 25. The method of claim 24, wherein the cells further comprise fibroblasts.
- 26. The method of claim 21, wherein the scaffold comprises between 1 and 20 layers.
- 27. The method of claim 1, wherein the target tissue is esophagus tissue, wherein the scaffold comprises at least two layers of at least two arrays of microfibers, wherein a first array of microfibers is designed to mimic the configuration of muscle fibers in the circumferential layer in the muscularis externa of the esophagus, wherein a second array of microfibers is designed to mimic the configuration of muscle fibers in the longitudinal layer in the muscularis externa of the esophagus, and wherein cells are cultured on the scaffold to form an esophagus substitute.
- 28. The method of claim 27, wherein the cells comprise muscle cells.
- 29. The method of claim 1, wherein the target tissue is cartilage tissue, wherein one or more of the arrays of microfibers is designed to mimic the configuration of collagen fibers fibrous cartilage tissue, and wherein cells are cultured on the scaffold to form a cartilage substitute.
- 30. The method of claim 29, wherein the cells comprise chondrocytes.
- 31. The method of claim 30, wherein the cells further comprise fibroblasts.
- 32. The method of claim 1, wherein the target tissue is mitral heart valve tissue, wherein the scaffold comprises a plurality of arrays of microfibers, wherein the plurality of arrays of microfibers is designed to mimic the configuration of collagen fibers mitral heart valve, and wherein cells are cultured on the scaffold to form a mitral heart valve substitute.
- 33. The method of claim 32, wherein the cells comprise at least one of interstitial valvular cells, smooth muscle cells, and endothelial cells.
- 34. The method of claim 33, wherein the cells further comprise fibroblasts.
- 35. An implantable medical device, comprising a scaffold comprising one or more layers of one or more arrays of microfibers, wherein one or more of the arrays of microfibers is arranged to mimic the configuration of one or more structural elements in a target tissue.
- 36. The device of claim 35, wherein the microfibers have a diameter between about 1 micrometer and about 20 micrometer.
- 37. The device of claim 35, wherein the microfibers have a diameter between about 1 micrometer and about 15 micrometer.
- 38. The device of claim 35, wherein the microfibers have a diameter between about 1 micrometer and about 6 micrometer.
- 39. The device of claim 35, wherein the spacing of adjacent microfibers in the array is between about 10 micrometers and 100 micrometers.
- 40. The device of claim 35, wherein the spacing of adjacent microfibers in the array is between about 30 micrometers and 70 micrometers.
- 41. The device of claim 35, wherein the spacing of adjacent microfibers in the array is between about 40 micrometers and 60 micrometers.
- 42. The device of claim 35, wherein the spacing of the layers of microfiber arrays is between about 10 micrometers and about 200 micrometers.
- 43. The device of claim 35, wherein the spacing of the layers of microfiber arrays is between about 60 micrometers and about 160 micrometers.
- 44. The device of claim 35, wherein the spacing of the layers of microfiber arrays is between about 80 micrometers and about 120 micrometers.
- 45. The device of claim 35, wherein the microfiber scaffold is coated with a cell adhesion-enhancing agent.
- 46. The device of claim 45, wherein the cell adhesion-enhancing agent is selected from the group consisting of collagen, laminin, and fibronectin.
- 47. The device of claim 35 further comprising cells cultured on the scaffold to form a target tissue substitute.
- 48. The device of claim 47, wherein the microfibers comprise a biodegradable polymer that gradually transfers load from the scaffold to the target tissue substitute.
- 49. The device of claim 48, wherein the biodegradable polymer is selected from the group consisting of a poly-L-lactic acid/polycaprolactone co-polymer, a poly-caprolactone/poly-caprolactone-co-glycolide/poly-hydroxybutyrate-co-hydroxyvalerate/urethane co-polymer, degradable polyurethane, and polyglycolic acid.
- 50. The device of claim 35, wherein the target tissue is an arterial blood vessel, wherein an array of microfibers is arranged to mimic the configuration of elastin in the medial layer of an arterial blood vessel.
- 51. The device of claim 50, wherein the scaffold comprises between 2 and 25 layers.
- 52. The device of claim 50 further comprising cells cultured on the scaffold to form a blood vessel substitute.
- 53. The device of claim 52, wherein the cells comprise smooth muscle cells.
- 54. The device of claim 53, wherein the cells further comprise endothelial cells.
- 55. The device of claim 52, wherein the blood vessel substitute comprises three layers and has a burst pressure of more than 1500 mm Hg after 2 weeks of culture in the absence of mechanical conditioning.
- 56. The device of claim 35, wherein the target tissue is a muscle tissue, wherein an array of microfibers is arranged to mimic the configuration of muscle fibers in the muscle tissue.
- 57. The device of claim 56, wherein the muscle tissue is skeletal muscle tissue.
- 58. The device of claim 56, wherein the muscle tissue is cardiac muscle tissue.
- 59. The device of claim 56, wherein the scaffold comprises between 1 and 20 layers.
- 60. The device of claim 56, further comprising cells cultured on the scaffold to form a muscle substitute.
- 61. The device of claim 60, wherein the cells comprise muscle cells.
- 62. The device of claim 61, wherein the cells further comprise fibroblasts.
- 63. The device of claim 35, wherein the target tissue is esophagus tissue, wherein the scaffold comprises at least two layers of at least two arrays of microfibers, wherein a first array of microfibers is arranged to mimic the configuration of the muscle fibers in the circumferential layer of the muscularis externa of the esophagus, and wherein a second array of microfibers is arranged to mimic the configuration of the muscle fibers in the longitudinal layer of the muscularis externa of the esophagus.
- 64. The device of claim 63, further comprising cells cultured on the scaffold to form an esophagus substitute.
- 65. The device of claim 64, wherein the cells comprise muscle cells.
- 66. The device of claim 35, wherein the target tissue is cartilage tissue, wherein an arrays of microfibers is arranged to mimic the configuration of collagen fibers in fibrous cartilage tissue.
- 67. The device of claim 66, further comprising cells cultured on the scaffold to form a cartilage substitute.
- 68. The device of claim 67, wherein the cells comprise chondrocytes.
- 69. The device of claim 68, wherein the cells further comprise fibroblasts.
- 70. The device of claim 35, wherein the target tissue is a mitral heart valve, wherein the scaffold comprises a plurality of arrays of microfibers, and wherein at the plurality of arrays of microfibers is arranged to mimic the configuration of collagen fibers in the mitral heart valve.
- 71. The device of claim 70 further comprising cells cultured on the scaffold to form a mitral heart valve substitute.
- 72. The device of claim 71, wherein the cells comprise at least one of interstitial valvular cells, fibroblasts, smooth muscle cells, and endothelial cells cells.
- 73. The device of claim 71, wherein the cells further comprise fibroblasts.
CROSS-REFERENCE TO RELATED APPLICATION
[0001] This application claims the benefit of Provisional Application No. 60/359,470, filed Feb. 22, 2002, under 35 U.S.C. § 119.
GOVERNMENT RIGHTS
[0002] This invention was made with government support under R24HL064387 and RO1HD38554 awarded by the National Institutes of Health, and under EEC-9529161 awarded by the National Science Foundation. The government has certain rights in the invention.
Provisional Applications (1)
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Number |
Date |
Country |
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60359470 |
Feb 2002 |
US |