Bladder reconstruction

• US 7,569,076 B2
• Filed: 03/21/2003
• Issued: 08/04/2009
• Est. Priority Date: 10/31/1997
• Status: Expired due to Fees

• Current Assignee: Children's Medical Center Corporation
• Original Assignee: Children's Medical Center Corporation
• Inventors: Atala, Anthony
• Primary Examiner(s): SWEET, THOMAS
• Application Number:
  US10/394,640
• Publication Number:
  US 20040034435A1
• Time in Patent Office: 2,328 Days
• Field of Search: 623/23.65, 623/23.66, 623/1.41, 623 144- 148, 128/898, 435/1.1
• 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 replacement or repair of a bladder, or portion of a bladder, in a human patient in need of such treatment comprising the steps of:

a. providing a biocompatible synthetic, or natural, polymeric matrix structure in the shape of a bladder, or portion of a bladder, wherein said polymeric matrix is coated with a biocompatible and biodegradable shape-setting material comprising a liquefied poly-lactide-co-glycolide copolymer;

b. depositing at least one first cell population on or in said polymeric matrix; and

c. implanting the shaped polymeric matrix of step (b) into the human patient at a site of a bladder for the formation of a laminarily organized functional bladder structure.

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

3. The method of claim 1, wherein the first cell population is substantially a smooth muscle cell population.

4. The method of claim 1, wherein said matrix structure in the shape of a bladder or portion of a bladder comprises urothelial cells deposited on an inner surface of said matrix and smooth muscle cells deposited on an outer surface of said matrix.

5. The method of claim 1, wherein the bladder structure formed in vivo exhibits the compliance of natural bladder tissue.

6. The method of claim 1, wherein said polymeric matrix structure comprises multiple matrix layers and wherein said cell population is deposited on separate matrix layers and said matrix layers are combined after the deposition steps.

7. The method of claim 1, further comprising depositing a second cell population on or in said polymeric matrix, wherein the second cell population is of a different cell type than the first cell population.

8. The method of claim 7, wherein the first cell population is substantially smooth muscle cells.

9. The method of claim 7, wherein the second cell population is substantially urothelial cells.

10. The method of claim 7, wherein said first and second cell populations are deposited sequentially.

11. The method of claim 1 wherein the first cell population is a population of autologous cells.

12. The method of claim 1, further comprising step (d) wherein the implanted shaped polymeric matrix of step (c) is wrapped with omentum.

13. The method of claim 1, wherein the biocompatible polymeric matrix comprises a material selected from the group of materials consisting of cellulose ether, cellulose, cellulosic ester, fluorinated polyethylene, 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, copolymers thereof, and physical blends thereof.

14. The method of claim 1, wherein the polymeric matrix comprises polyglycolic acid.

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

m.

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

m.

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

m.

18. The method of claim 1, wherein the first cell population is a population of allogenic cells.

19. The method of claim 1, wherein the polymeric matrix is biodegradable.

20. A device for the replacement or repair of a bladder, or portion of a bladder, in a human comprising:

an implantable, biocompatible, synthetic or natural, polymeric matrix structure in the shape of a bladder or portion of a bladder having at least two separate surfaces, wherein the polymeric matrix is coated with a biodegradable shape-setting material comprising a liquefied poly-lactide-co-glycolide copolymer, and at least one first cell population deposited on or in said polymeric matrix to form an organized matrix/cell construct, wherein upon implantation of said organized matrix/cell construct into a human, said device forms a laminarily organized functional bladder structure.

21. The device of claim 20, wherein the first cell population is substantially a urothelial cell population.

22. The device of claim 20, wherein the first cell population is substantially a smooth muscle cell population.

23. The device of claim 20, wherein the said matrix structure in the shape of a bladder or portion of a bladder comprises urothelial cells deposited on an inner surface of said matrix and smooth muscle cells deposited on an outer surface of said matrix.

24. The device of claim 20, wherein the bladder structure formed in vivo exhibits the compliance of natural bladder tissue.

25. The device of claim 20, further comprising a second cell population deposited on or in said polymeric matrix, wherein the second cell population is of a different cell type than the first cell population.

26. The device of claim 25, wherein the first cell population is substantially smooth muscle cells.

27. The device of claim 25, wherein the second cell population is substantially urothelial cells.

28. The device of claim 25, wherein the first and the second cell populations are deposited sequentially.

29. The device of claim 25, wherein said polymeric matrix structure comprises multiple matrix layers and wherein the first cell population and the second cell population are deposited on separate matrix layers and said matrix layers are combined.

30. The device of claim 20 wherein the first cell population is a population of autologous cells.

31. The device of claim 20, 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, 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, copolymers thereof, and physical blends thereof.

32. The device of claim 20, wherein the polymeric matrix comprises polyglycolic acid.

33. The device of claim 20, wherein the polymeric matrix is comprised of fibers with an interfiber distance between about 0 to 1000 μ

m.

34. The device of claim 20, wherein the polymeric matrix is comprised of fibers with an interfiber distance between about 0 to 500 μ

m.

35. The device of claim 20, wherein the polymeric matrix is comprised of fibers with an interfiber distance between about 0 to 200 μ

m.

36. The device of claim 20, wherein the first cell population is a population of allogenic cells.

37. The device of claim 20, wherein the polymeric matrix is biodegradable.