Organ reconstruction

• US 20040034435A1
• Filed: 03/21/2003
• Published: 02/19/2004
• Est. Priority Date: 10/31/1997
• Status: Active Grant

• Current Assignee: Children's Medical Center Corporation
• Original Assignee: Children's Medical Center Corporation
• Inventors: Atala, Anthony
• Granted Patent: US 7,569,076 B2
• Time in Patent Office: Days
• US Class Current: 623/23.65
• CPC Class Codes: A61F 2/042 Urinary bladders
• CPC Class Codes: A61L 2430/22 for reconstruction of hollow organs, e.g. bladder, esophagus, urether, uterus
• CPC Class Codes: A61L 27/18 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
• 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 27/3813 Epithelial cells, e.g. keratinocytes, urothelial cells
• CPC Class Codes: A61L 27/3826 Muscle cells, e.g. smooth muscle cells
• CPC Class Codes: A61L 27/383 Nerve cells, e.g. dendritic cells, Schwann cells
• CPC Class Codes: A61L 27/3839 characterised by the site of application in the body materials for artificial blood vessels A61L27/507; materials for use in artificial skin A61L27/60
• CPC Class Codes: A61L 27/3882 Hollow organs, e.g. bladder, esophagus, urether, uterus
• CPC Class Codes: A61L 27/3891 as distinct cell layers
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C08L 67/04 Polyesters derived from hydroxycarboxylic acids, e.g. lactones C08L67/06 takes precedence

Abstract

The invention is directed to methods and devices for the reconstruction, repair, augmentation or replacement of laminarily organized organs or tissue structures in a patient in need of such treatment. The device comprises a biocompatible synthetic or natural polymeric matrix shaped to conform to at least a part of the luminal organ or tissue structure with a first cell population on or in a first area and a second cell population such as a smooth muscle cell population in a second area of the polymeric-matrix. The method involves grafting the device to an area in a patient in need of treatment. The polymeric matrix comprise a biocompatible and biodegradable material.

Claims

1. A method for the reconstruction, repair, augmentation or replacement of laminarily organized luminal organs or tissue structures in a patient in need of such treatment comprising the steps of:

a) providing a biocompatible synthetic or natural polymeric matrix shaped to conform to at least a part of the luminal organ or tissue structure in need of said treatment;

b) depositing a first cell population on or in a first area of said polymeric matrix;

c) depositing a second cell population of a different cell type than said first cell population in a second area of said polymeric matrix, said second area being substantially separated from said first area; and

d) implanting the shaped polymeric matrix cell construct into said patient at the site of said treatment for the formation of laminarily organized luminal organ or tissue structure.

2. The method of claim 1 wherein the biocompatible material is biodegradable.

3. The method of claim 1 wherein the biocompatible polymeric matrix is formed from a material selected from the group of materials consisting of cellulose ether, cellulose, cellulosic ester, fluorinated polyethylene, phenolic, poly-4-methylpentene, polyacrylonitrile, polyamide, polyamideimide, polyacrylate, polybenzoxazole, polycarbonate, polycyanoarylether, polyester, polyestercarbonate, polyether, polyetheretherketone, polyetherimide, polyetherketone, polyethersulfone, polyethylene, polyfluoroolefin, polyimide, polyolefin, polyoxadiazole, polyphenylene oxide, polyphenylene sulfide, polypropylene, polystyrene, polysulfide, polysulfone, polytetrafluoroethylene, polythiether, polytriazole, polyurethane, polyvinyl, polyvinlidene fluoride, regenerated cellulose, silicone, urea-formaldehyde, or copolymers or physical blends thereof.

4. The method of claim 1 wherein the biocompatible material is polyglycolic acid.

5. The method of claim 1 wherein the polymeric matrix is comprised of fibers with an interfiber distance between about 0 to 1000 μ

m.

6. The method of claim 1 wherein the polymeric matrix is comprised of fibers with an interfiber distance between about 0 to 500 μ

m.

7. The method of claim 1 wherein the polymeric matrix is comprised of fibers with an interfiber distance between about 0 to 200 μ

m.

8. The method of claim 1 wherein the polymeric matrix is coated with a biocompatible and biodegradable shaped setting material.

9. The method of claim 8 wherein the shape settling material comprise a liquid copolymer.

10. The method of claim 9 wherein the co-polymer comprises poly-DL-lactide-coglycolide.

11. The method of claim 1 wherein the first cell population is substantially a urothelial cell population.

12. The method of claim 1 wherein the second cell population is substantially a smooth muscle cell population.

13. The method of claim 1 wherein the luminal organ or tissue structure is of genitourinary organ.

14. The method of claim 13 wherein the luminal organ or tissue structure is selected from the group consisting of bladder, ureters and urethra.

15. The method of claim 14 wherein the luminal organ or tissue structure is a bladder or bladder segment and having urothelial cells deposited on the inner surface of said matrix and smooth muscle cells deposited on the outer surface of said matrix.

16. The method of claim 15 wherein the laminarily organized luminal organ or tissue structure formed in vivo exhibits the compliance of natural bladder tissue.

17. The method of claim 1 wherein said first and second cell populations are deposited sequentially.

18. The method of claim 1 wherein said first and second cell populations are deposited on separate matrix layers and said matrix layers are combined after the deposition steps.

19. A device for the reconstruction, repair, augmentation or replacement of laminarily organized luminal organs or tissue structures comprising:

an implantable, biocompatible, synthetic or natural polymeric matrix having at least two separate surfaces and shaped to conform to a at least a part of the luminal organ or tissue structure in need of said treatment, and at least two different cell populations deposited in substantially separate areas on or in said polymeric matrix to form a laminarily organized matrix/cell construct.

20. The device of claim 19 wherein the biocompatible material is biodegradable.

21. The device of claim 19 wherein the biocompatible polymeric matrix is formed from a material selected from the group of materials consisting of cellulose ether, cellulose, cellulosic ester, fluorinated polyethylene, phenolic, poly-4-methylpentene, polyacrylonitrile, polyamide, polyamideimide, polyacrylate, polybenzoxazole, polycarbonate, polycyanoarylether, polyester, polyestercarbonate, polyether, polyetheretherketone, polyetherimide, polyetherketone, polyethersulfone, polyethylene, polyfluoroolefin, polyimide, polyolefin, polyoxadiazole, polyphenylene oxide, polyphenylene sulfide, polypropylene, polystyrene, polysulfide, polysulfone, polytetrafluoroethylene, polythioether, polytriazole, polyurethane, polyvinyl, polyvinylidene fluoride, regenerated cellulose, silicone, urea-formaldehyde, or copolymers or physical blends thereof.

22. The device of claim 19 wherein the biocompatible material is polyglycolic acid.

23. The device of claim 19 wherein the polymeric matrix is comprised of fibers with an interfiber distance between about 0 to 1000 μ

m.

24. The device of claim 19 wherein the polymeric matrix is comprised of fibers with an interfiber distance between about 0 to 500 μ

m.

25. The device of claim 19 wherein the polymeric matrix is comprised of fibers with an interfiber distance between about 0 to 200 μ

m.

26. The device of claim 19 wherein the polymeric matrix is coated with a biocompatible and biodegradable shaped setting material.

27. The device of claim 26 herein the shape settling material comprise a liquid . copolymer.

28. The device of claim 27 wherein the co-polymer comprises poly-DL-lactide-coglycolide.

29. The. device of claim 19 wherein the first cell population is substantially a urothelial cell population.

30. The device of claim 19 wherein the second cell population is substantially a smooth muscle cell population.

31. The device of claim 19 wherein the luminal organ or tissue structure is of genitourinary organ.

32. The device of claim 31 wherein the luminal organ or tissue structure is selected from the group consisting of bladder, ureters and urethra.

33. The device of claim 32 wherein the luminal organ or tissue structure is a bladder or bladder segment and having urothelial cells deposited on the inner surface of said matrix and smooth muscle cells deposited on the outer surface of said matrix.

34. The device of claim 33 wherein the laminarily organized luminal organ or tissue structure formed in vivo exhibits the compliance of natural bladder tissue.

35. The device of claim 19 wherein said first and second cell populations are deposited sequentially.

36. The device of claim 19 wherein said first and second cell populations are deposited on separate matrix layers and said matrix layers are combined after the deposition steps.

37. A device for the repair, reconstruction, augmentation or replacement of damaged or missing bladder tissue in a patient in need of such treatment comprising:

an implantable, biocompatible synthetic or natural polymeric matrix shaped to conform to the part of said bladder tissue in need of said treatment and having urothelial cells deposited on and near the inside surface of said matrix, and having smooth muscle cells deposited on and near the outside surface of said matrix, wherein upon implantation into said patient, said device forms a laminarily organized luminal tissue structure having the compliance of normal bladder tissue.

38. The device of claim 37 wherein said shaped matrix is a fibrous mesh of a polymer selected from the group consisting of polyglycolic acid, polylactic acid and copolymers or blends thereof;

coated with a shape retaining material.

39. The device of claim 37 wherein said shape retaining material is a solution of a hardenable polymer.

40. The device of claim 39 wherein said hardenable polymer is poly DL-lactide-coglycolide.