Device and method to maintain vascularization near implant

• US 20030050622A1
• Filed: 09/11/2001
• Published: 03/13/2003
• Est. Priority Date: 09/11/2001
• Status: Active Grant

• Current Assignee: Cytopherx, Inc., Board of Regents of the University of Michigan (University of Michigan)
• Original Assignee: University of Michigan
• Inventors: Humes, H. David, Tziampazis, Evangelos, Fissell, William H., Buffington, Deborah A.
• Granted Patent: US 7,332,330 B2
• Time in Patent Office: Days
• US Class Current: 604/891.1
• CPC Class Codes: A61F 2/022 Artificial gland structures using bioreactors hemodialysis A61M1/16; hemofiltration A61M1/34; other extracorporeal blood treatment A61M1/36
• CPC Class Codes: A61L 2300/258 Genetic materials, DNA, RNA, genes, vectors, e.g. plasmids
• CPC Class Codes: A61L 2300/412 Tissue-regenerating or healing or proliferative agents
• CPC Class Codes: A61L 2300/414 Growth factors
• CPC Class Codes: A61L 2300/64 Animal cells
• CPC Class Codes: A61L 31/005 Ingredients of undetermined constitution or reaction products thereof
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• CPC Class Codes: A61M 1/1678 intracorporal peritoneal dialysis A61M1/28
• CPC Class Codes: A61M 1/28 Peritoneal dialysis ; Other peritoneal treatment, e.g. oxygenation
• CPC Class Codes: B33Y 80/00 Products made by additive manufacturing

Abstract

A device and a method of maintaining vascularization near an implant, especially a bioartificial hemofilter. By associating cells that excrete angiogenic factors with such an implant, vascularization to the tissue surrounding the implant can be maintained. In a bioartificial hemofilter, this facilitates filtrate transport to a collection fiber for drainage from the body. The cells can be genetically engineered, for example using an adenovirus vector encoding for vascular endothelial growth factor. Myoblasts and myotubes may be used in one embodiment of the present invention.

Claims

1. An implantable hemofilter device, comprising:

an implant body, and

first cells, wherein the first cells produce at least one angiogenic product.

2. The implantable hemofilter device of claim 1, wherein the implant body has a first surface and the first cells are supported on the first surface.

3. The implantable hemofilter device of claim 2, wherein the first surface is on the exterior of the implant body.

4. The implantable hemofilter device of claim 2, wherein the first surface is on the interior of the implant.

5. The implantable hemofilter device of claim 1, wherein the implant body has an interior space, and the first cells are in the interior space.

6. The implantable hemofilter device of claim 4, wherein the implant body comprises a porous encapsulation or entrapment body.

7. The implantable hemofilter device of claim 6, wherein the porous encapsulation body is in the form of a tube.

8. The implantable hemofilter device of claim 6, wherein the porous encapsulation body is comprised of a porous polymer.

9. The implantable hemofilter device of claim 8, wherein the porous polymer comprises at least one member selected from the group consisting of polypropylenes, polysulfones, cellulosic polymers, cellulose actetates, rayons, polyacrylonitriles, polymethylmethacrylates, polycarbonates, polyfluoroethylenes, alginates, and chitosans.

10. The implantable hemofilter device of claim 5, wherein the implant body comprises a porous encapsulation body.

11. The implantable hemofilter device of claim 10, wherein the porous encapsulation body is in the form of a tube.

12. The implantable hemofilter device of claim 10, wherein the porous encapsulation body is comprised of a porous polymer.

13. The implantable hemofilter device of claim 12, wherein the porous polymer comprises at least one member selected from the group consisting of a polypropylenes, polysulfones, cellulosic polymers, cellulose actetates, rayons, polyacrylonitriles, polymethylmethacrylates, polycarbonates, polyfluoroethylenes, alginates, and chitosans.

14. The implantable hemofilter device of claim 1, wherein the implant body is composed of at least one material selected from the group consisitng of glasses, metals, ceramics, and polymers.

15. The implantable hemofilter device of claim 1, wherein the implant body is composed of at least one polymer selected from the group consisting of a polypropylenes, polysulfones, cellulosic polymers, cellulose actetates, rayons, polyacrylonitriles, polymethylmethacrylates, polycarbonates, polyfluoroethylenes, alginates, and chitosans.

16. The implantable hemofilter device of claim 1, wherein the angiogenic product is vascular endothelial growth factor.

17. The implantable hemofilter device of claim 1, wherein the first cells are transfected with a nucleic acid sequence which encodes the angiogenic product.

18. The implantable hemofilter device of claim 1, wherein the first cells are myoblasts.

19. The implantable hemofilter device of claim 18, wherein the myoblasts form a myotube.

20. The implantable hemofilter device of claim 1, wherein the first cells are supported on the implant body with an organic component.

21. The implantable hemofilter device of claim 20, wherein the organic component comprises fibrin glue.

22. The implantable hemofilter device of claim 1, further comprising second cells.

23. The implantable hemofilter device of claim 22, wherein the second cells have a function other than producing an angiogenic product.

24. The implantable hemofilter device of claim 22, wherein the second cells have a therapeutic function.

25. The implantable hemofilter device of claim 22, wherein the second cells produce a therapeutically useful substance.

26. The implantable hemofilter device of claim 25, wherein the therapeutically useful substance is a hormone.

27. The implantable hemofilter device of claim 22, wherein the second cells produce insulin.

28. The implantable hemofilter device of claim 22, wherein the second cells are genetically modified.

29. The implantable hemofilter device of claim 22, wherein the second cells have metabolic activity.

30. The implantable hemofilter device of claim 1, which comprises at least one conduit in fluid communication with the implant body.

31. The implantable hemofilter device of claim 30, which comprises a plurality of the conduits.

32. The implantable hemofilter device of claim 31, wherein the plurality of the conduits are connected to a common outlet.

33. The implantable hemofilter device of claim 1, which is implanted in a subject.

34. The implantable hemofilter device of claim 22, which is implanted in a subject.

35. The implantable hemofilter device of claim 33, wherein the first cells are autologous to the subject.

36. The implantable hemofilter device of claim 34, wherein the first cells are autologous to the subject.

37. The implantable hemofilter device of claim 33, which further comprises a plurality of conduits in fluid commuication with the implant body, wherein the conduits are connected to a common outlet, a transdermal port, and a tube connecting the common outlet and the transdermal port.

38. The implantable hemofilter device of claim 34, which further comprises a plurality of conduits in fluid commuication with the implant body, wherein the conduits are connected to a common outlet, a transdermal port, and a tube connecting the common outlet and the transdermal port.

39. The implantable hemofilter device of claim 37, wherein the transdermal port is configured to be attached to a pump.

40. The implantable hemofilter device of claim 38, wherein the transdermal port is configured to be attached to a pump.

41. The implantable hemofilter device of claim 33, further comprising at least one conduit in fluid communication with the implant and which is connected to a body cavity of the subject.

42. The implantable hemofilter device of claim 34, further comprising at least one conduit in fluid communication with the implant and which is connected to a body cavity of the subject.

43. The implantable hemofilter device of claim 41, wherein the body cavity is an intraperitoneal cavity or a ureter.

44. The implantable hemofilter device of claim 42, wherein the body cavity is an intraperitoneal cavity or a ureter.

45. The implantable hemofilter device of claim 33, which is connected to a second implant in the patient.

46. The implantable hemofilter device of claim 34, which is connected to a second implant in the patient.

47. A method of producing the implantable hemofilter device of claim 1, comprising combining the first cells and the implant body.

48. A method of producing the implantable hemofilter device of claim 1, comprising supporting the first cells on a surface of the implant body.

49. A method of producing the implantable hemofilter device of claim 22, comprising combining the first cells, the second cells, and the implant body.

78. A method of producing a hemofilter implant, comprising:

implanting the implantantable hemofilter device of claim 1 in a subject, wherein the angiogenic product produced by the first cells induces the formation of vascular tissue near the implant.

79. A method of producing a hemofilter implant, comprising:

implanting the implantantable hemofilter device of claim 22 in a subject, wherein the angiogenic product produced by the first cells induces the formation of vascular tissue near the implant.

80. The method of claim 78, wherein the hemofilter implant is in fluid contact with a second implant in the subject.

81. The method of claim 79, wherein the hemofilter implant is in fluid contact with a second implant in the subject.

50. A method of producing an implantable hemofilter device capable of maintaining vascularization when implanted, comprising:

obtaining first cells capable of releasing an angiogenic product; and

associating the first cells with an implant body, wherein the first cells are capable of releasing the angiogenic product into a surroundings of implantable hemofilter device after implantation.

51. The method of claim 50, wherein the step of associating comprises:

seeding the first cells onto a surface of the implant body.

52. The method of claim 50, wherein the step of associating comprises:

immobilizing the first cells onto a surface of or into the implant body.

53. The method of claim 50, wherein the step of associating comprises:

coating a surface of the implant body with an organic component configured to facilitate attachment of the first cells thereto; and

attaching the first cells to the surface of the implant.

54. The method of claim 50, wherein the step of associating comprises:

converting the first cells into a differentiated first cells.

55. The method of claim 54, wherein the differentiated first cells form a myotube.

56. The method of claim 50, wherein the step of obtaining further comprises:

isolating the first cells.

57. The method of claim 50, wherein the step of obtaining comprises:

transfecting the first cells with a nucleic acid sequence that encodes the angiogenic product.

58. The method of claim 57, wherein the step of transfecting comprises:

encoding the angiogenic product in an vector; and

exposing the first cells to the vector.

59. The method of claim 58, wherein the vector is a viral vector.

60. The method of claim 58, wherein the vector is a non-viral vector.

61. The method of claim 58, wherein the vector is an adenoviral vector.

62. The method of claim 50, wherein the angiogenic product is vascular endothelial growth factor.

63. The method of claim 50, further comprising:

expanding the first cells.

64. The method of claim 50, further comprising:

implanting the hemofilter device into a recipient.

65. The method of claim 64, wherein the hemofilter device is implanted subcutaneously and/or peritoneally.

66. The method of claim 64, wherein the hemofilter device is implanted retroperitoneally.

67. The method of claim 50, further comprising:

obtaining second cells having a function other than producing an angiogenic product; and

associating the second cells with the implant body.

68. The method of claim 67, wherein the step of associating the second cells comprises:

seeding the second cells onto a second surface of the implant body.

69. The method of claim 67, wherein the step of associating comprises:

immobilizing the second cells on a second surface of or into the implant body.

70. The method of claim 67, wherein the step of associating comprises:

coating a second surface of the implant body with an organic component configured to facilitate attachment of the second cells thereto; and

attaching the second cells to the second surface of the implant.

71. The method of claim 67, wherein the step of associating comprises:

converting the second cells into differentiated second cells.

72. The method of claim 67, wherein the second cells have a therapeutic function.

73. The method of claim 67, wherein the second cells produce a therapeutically useful substance.

74. The method of claim 67, wherein the second cells produce a hormone.

75. The method of claim 67, wherein the second cells produce insulin.

76. The method of claim 67, wherein the second cells have metabolic activity.

77. The method of claim 67, wherein the second cells are genetically modified.

82. An implantable hemofilter device, comprising:

means for maintaining vascularization in a surroundings of the implant.

83. The implantable hemofilter device of claim 82, further comprising:

means for supplying a factor to an ultrafiltrate which is collected in the implant.

84. The implantable hemofilter device of claim 82, further comprising:

means for removing a liquid from the implant.

85. The implantable hemofilter device of claim 82, further comprising:

means for supplying a second cellular product to the surroundings of the implant.

86. A method of producing a hemofilter implant, comprising:

implanting the implantable hemofiliter device of claim 82 in a subject, wherein the means induces the formation of vascular tissue near the implant.

87. A method of utilizing an ultrafiltrate produced by a filtration device, comprising:

transferring an ultrafiltrate produced by a fitration device implanted in a subject to a tissue-engineered construct which is also implanted in the subject.

88. The method of claim 87, wherein the filtration device comprises an implant body and cells which produce at least one angiogenic product.

89. The method of claim 87, wherein the tissue engineered construct contains cells, and the ultrafiltrate provides the cells with oxygen and nutrients.

90. The method of claim 87, wherein the filtration device is inanimate.

91. The method of claim 87, wherein cells in the tissue-engineered construct provide a therapeutic function.

92. The method of claim 87, wherein the cells in the tissue-engineered construct produce a cellular product.

93. The method of claim 92, wherein the cellular product is a hormone.

94. The method of claim 93, wherein the hormone is insulin.

95. The method of claim 91, wherein the cells in the tissue-engineered construct have metabolic activity.