Bioartificial lacrimal gland

• US 7,547,447 B2
• Filed: 11/15/2004
• Issued: 06/16/2009
• Est. Priority Date: 11/15/2004
• Status: Expired due to Fees

• Current Assignee: Doheny Eye Institute, Board of Supervisors of Louisiana State University Agricultural & Mechanical College (Louisiana State University System)
• Original Assignee: Doheny Eye Institute, Board of Supervisors of Louisiana State University Agricultural & Mechanical College (Louisiana State University System)
• Inventors: Smith, Ronald E., Yiu, Samuel C., Mircheff, Austin K., Jacob, Jean, Trousdale, Mel
• Primary Examiner(s): Gitomer; Ralph
• Assistant Examiner(s): GOUGH, TIFFANY MAUREEN
• Application Number:
  US10/990,359
• Publication Number:
  US 20060104957A1
• Time in Patent Office: 1,674 Days
• Field of Search: 424/423
• US Class Current: 424/423
• CPC Class Codes: A61K 38/1808 Epidermal growth factor [EGF] urogastrone
• CPC Class Codes: A61L 27/3813 Epithelial cells, e.g. keratinocytes, urothelial 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 31/005 Ingredients of undetermined constitution or reaction products thereof

Abstract

The present invention provides a bioartificial lacrimal gland which contains at least one unit that includes (a) a permeable housing having an interior and an exterior; (b) an outlet connecting the housing interior to the housing exterior; and (c) a population of lacrimal epithelial cells within the housing interior.

Claims

1. A bioartificial lacrimal gland, comprising at least one unit, said unit comprising

(a) a permeable housing having an interior and an exterior;

(b) an outlet connecting the housing interior to the housing exterior;

(c) a population of lacrimal epithelial cells within the housing interior, wherein said gland is characterized by directional fluid secretion in which fluid exits from said housing interior to said housing exterior through said outlet; and

(d) a gate joined to said outlet.

2. The bioartificial lacrimal gland of claim 1, wherein fluid exits from said interior through said outlet at a rate of at least 6.5 μ

l/cm²/hour.

3. The bioartificial lacrimal gland of claim 1, further comprising a viscous substratum within the housing interior.

4. The bioartificial lacrimal gland of claim 1, said permeable housing having a concave interior surface.

5. The bioartificial lacrimal gland of claim 4, said permeable housing having a substantially cylindrical interior surface.

6. The bioartificial lacrimal gland of claim 4, said permeable housing having a substantially spherical interior surface.

7. The bioartificial lacrimal gland of claim 5, wherein said permeable housing is substantially tubular.

8. The bioartificial lacrimal gland of claim 7, wherein said substantially tubular permeable housing is a tube.

9. The bioartificial lacrimal gland of claim 8, said tube having a first closed end and a second end which is said outlet.

10. The bioartificial lacrimal gland of claim 1 or claim 9, wherein said permeable housing is a porous housing.

11. The bioartificial lacrimal gland of claim 10, wherein said porous housing has a pore size of between 0.01 and 10 microns.

12. The bioartificial lacrimal gland of claim 11, wherein said pore size is between 0.1 and 5 microns.

13. The bioartificial lacrimal gland of claim 1 or claim 5, wherein said permeable housing comprises a polymeric biomaterial.

14. The bioartificial lacrimal gland of claim 13, wherein said polymeric biomaterial is a homopolymeric biomaterial.

15. The bioartificial lacrimal gland of claim 13, wherein said polymeric biomaterial is a copolymeric biomaterial.

16. The bioartificial lacrimal gland of claim 1 or claim 9, wherein said permeable housing comprises a non-biodegradable biomaterial.

17. The bioartificial lacrimal gland of claim 1 or claim 9, wherein said permeable housing comprises a biodegradable biomaterial.

18. The bioartificial lacrimal gland of claim 1 or claim 9, wherein said permeable housing is a porous housing.

19. The bioartificial lacrimal gland of claim 18, wherein said porous housing is a porous membrane.

20. The bioartificial lacrimal gland of claim 1 or claim 9, wherein said permeable housing comprises a biomaterial selected from the group:

polysiloxane;

polydimethylsiloxane;

polyurethane;

polyvinylpyrrolidone;

polymethacrylate;

polyvinyl alcohol;

polyethylene;

polyethylene glycol;

poly(glycolic acid);

poly(L-lactic acid);

poly(lactic-co-glycolic acid);

collagen;

cellulose; and

a copolymer or derivative thereof.

21. The bioartificial lacrimal gland of claim 20, said permeable housing comprising at least 90% of a single biomaterial selected from the group:

polysiloxane;

polydimethylsiloxane;

polyurethane;

polyvinylpyrrolidone;

polymethacrylate;

polyvinyl alcohol;

polyethylene;

polyethylene glycol;

poly(glycolic acid);

poly(L-lactic acid);

poly(lactic-co-glycolic acid);

collagen;

cellulose; and

a copolymer or derivative thereof.

22. The bioartificial lacrimal gland of claim 9, wherein said tube has a lumen of uniform diameter.

23. The bioartificial lacrimal gland of claim 22, wherein said lumen has a diameter of no more than 2 mm.

24. The bioartificial lacrimal gland of claim 23, wherein said lumen has a diameter of between 0.1 and 0.5 mm.

25. The bioartificial lacrimal gland of claim 9, 22, 23 or 24, wherein said tube has a length of at most 10 mm.

26. The bioartificial lacrimal gland of claim 25, wherein said tube has a length of at most 5 mm.

27. The bioartificial lacrimal gland of claim 3, wherein said viscous substratum is adhered to the interior surface of said permeable housing.

28. The bioartificial lacrimal gland of claim 26, wherein said viscous substratum is a gel.

29. The bioartificial lacrimal gland of claim 28, wherein said gel is a hydrogel.

30. The bioartificial lacrimal gland of claim 27 or 29, where said viscous substratum comprises a biomaterial selected from the group collagen, hydroxymethylcellulose, hyaluronan and a copolymer or derivative thereof

31. The bioartificial lacrimal gland of claim 26 or 29, where said viscous substratum comprises one or more extracellular matrix components.

32. The bioartificial lacrimal gland of claim 31, wherein said viscous substratum comprises Matrigeltm™

.

33. The bioartificial lacrimal gland of claim 32, wherein said viscous substratum comprises Matrigeltm™

at a final concentration of 0.25 to 5 mg/ml.

34. The bioartificial lacrimal gland of claim 28, wherein said viscous substratum further comprises fetal bovine serum.

35. The bioartificial lacrimal gland of claim 1 or claim 9, wherein said lacrimal epithelial cells are arrayed in a polarized monolayer.

36. The bioartificial lacrimal gland of claim 35, wherein said polarized monolayer is adhered to said viscous substratum.

37. The bioartificial lacrimal gland of claim 1 or claim 9, wherein said lacrimal epithelial cells are selected from the group primary cells, established cells, transfected cells, human cells, primate cells, rabbit cells, and goose cells.

38. The bioartificial lacrimal gland of claim 37, wherein said lacrimal epithelial cells are human cells.

39. The bioartificial lacrimal gland of claim 37, wherein said lacrimal epithelial cells are rabbit cells.

40. The bioartificial lacrimal gland of claim 1 or claim 9, wherein said lacrimal epithelial cells express an exogenous nucleic acid molecule.

41. The bioartificial lacrimal gland of claim 40, wherein said exogenous nucleic acid molecule encodes a receptor.

42. The bioartificial lacrimal gland of claim 1 or claim 9, said gland further comprising at least one growth factor.

43. The bioartificial lacrimal gland of claim 42, wherein said growth factor is selected from the group Hepato Stim®

Culture Medium and epidermal growth factor.

44. The bioartificial lacrimal gland of claim 42, wherein said growth factor is Hepato Stim®

Culture Medium.

45. The bioartificial lacrimal gland of claim 42, comprising fetal bovine serum at a concentration of 10% and epidermal growth factor at a concentration of 5 ng/ml.

46. The bioartificial lacrimal gland of claim 1 or claim 9, said gland further comprising an immunosuppressive agent.

47. The bioartificial lacrimal gland of claim 1, wherein said gate is responsive to a stimulus.

48. The bioartificial lacrimal gland of claim 1 or claim 9, further comprising an encapsulating membrane, said membrane impermeable to antibodies and immune cells.

49. The bioartificial lacrimal gland of claim 1 or claim 9, said gland comprising a plurality of units.

50. The bioartificial lacrimal gland of claim 49, said gland comprising at least three units.

51. The bioartificial lacrimal gland of claim 49, said gland comprising at least five units.

52. The bioartificial lacrimal gland of claim 49, further comprising a unit support which holds each of said plurality of units in a defined configuration.

53. The bioartificial lacrimal gland of claim 52, wherein each of said units is held substantially in parallel.

54. The bioartificial lacrimal gland of claim 49, further comprising an encapsulating membrane, said membrane impermeable to antibodies and immune cells.

55. The bioartificial lacrimal gland of claim 49, wherein said permeable housing is a tube.

56. The bioartificial lacrimal gland of claim 55, said tube having a first closed end and a second end which is said outlet.

57. The bioartificial lacrimal gland of claim 56, further comprising a common duct, each of said outlets of said tubes being joined to said common duct.

58. The bioartificial lacrimal gland of claim 50, said common duct further comprising a gate.

59. The bioartificial lacrimal gland of claim 50, said common duct further comprising a gate.

60. The bioartificial lacrimal gland of claim 50, wherein said gate is responsive to a stimulus.