Bioartificial pancreas

• US 5,425,764 A
• Filed: 12/01/1993
• Issued: 06/20/1995
• Est. Priority Date: 07/30/1992
• Status: Expired due to Term

• Current Assignee: Medical College of Ohio
• Original Assignee: University of Toledo
• Inventors: Sarver, Jeffrey G., Fournier, Ronald L., Goldblatt, Peter J., Horner, James M.
• Primary Examiner(s): Willse, David H.
• Assistant Examiner(s): BRITTINGHAM, DEBRA
• Application Number:
  US08/161,172
• Time in Patent Office: 566 Days
• Field of Search: 604/4, 604/175, 623/11, 623/66
• US Class Current: 623/23.64
• CPC Class Codes: A61F 2/022 Artificial gland structures using bioreactors hemodialysis A61M1/16; hemofiltration A61M1/34; other extracorporeal blood treatment A61M1/36

Abstract

An implantable bioartificial pancreas device having an islet chamber containing glucose responsive and insulin-secreting islets of Langerhans or similar hormone secreting cells, one or more vascularizing chambers open to surrounding tissue, a semi-permeable membrane between the islet and vascularizing chambers that allows passage of small molecules including insulin, oxygen and glucose and does not allow passage of agents of the immune system such as white cells and antibodies, the vascularizing chambers containing a growth factor soaked fibrous or foam matrix having a porosity of about 40 to 95%, the matrix providing small capillary growth and preventing the blood from clotting in the lower chamber.

Claims

1. A bioartificial pancreas for implantation into an animal comprising a housing having an enclosed chamber containing islets of Langerhans, inlet means for supplying islets to the islet chamber, outlet means for removing islets from the islet chamber, at least one vascularizing chamber having an opening on one end thereof that provides access to surrounding tissue, and a semi-permeable membrane separating and in communication with the islet chamber and vascularizing chamber, the membrane providing immunoprotection of the islets from a vascular area within the vascularizing chamber and around the implanted pancreas, the membrane having an average number molecular weight cut-off less than 100,000, selectively allowing passage of small molecules including oxygen and insulin between the islet and vascularizing chambers and not allowing passage of agents of an immune system to the islet chamber, and a biocompatible fibrous or porous foam matrix disposed in the vascularizing chamber to provide a neovascular formation region for enhancing growth of small capillaries for providing efficient mass transfer of substances between the islet chamber and the capillaries in the vascularizing chamber, the fibrous or foam matrix having a porosity of about 40 to 95 percent and interconnecting passageways having an average pore size of about 10 to 120 microns, the fibrous and foam matrix being of an organic or inorganic material, the organic material composed principally of carbon, oxygen, and hydrogen atoms, or sulfur atoms, oxygen atoms and hydrogen atoms, or carbon atoms, oxygen atoms hydrogen atoms and nitrogen atoms, the inorganic materials being composed of at least one of carbon, titanium, silica, sodium, calcium, strontium, magnesium, zinc and boron atoms.

2. A pancreas as defined in claim 1 in which the fibrous or foam matrix is keratin.

3. A pancreas as defined in claim 1 in which the matrix is a polyolefin.

4. A pancreas as defined in claim 1 in which the matrix is glass fibers.

5. A pancreas as defined in claim 1 in which the matrix is stainless steel.

6. A pancreas as defined in claim 1 in which the matrix is polyurethane.

7. A pancreas as defined in claim 1 in which the pancreas has a thickness is about 1 to 10 mm.

8. A pancreas as defined in claim 1 in which the matrix has a pore size of about 50 to 100 microns in a foam.

9. A pancreas as defined in claim 1 in which the matrix is a non-halogenated organic polymer.

10. A pancreas as defined in claim 1 in which the matrix is a plant or animal protein containing material.

11. A pancreas as defined in claim 1 in which the porosity is about 50 to 90 percent.

12. A pancreas as defined in claim 1 in which the porosity is about 80 to 85 percent.

13. A pancreas as defined in claim 1 wherein the vascularizing chamber contains at least one growth factor for promoting ingrowth of capillaries into the vascularizing chamber.

14. A pancreas as defined in claim 1 in which the islets of Langerhans are from animal sources.

15. A bioartificial pancreas as defined in claim 1 in which a layer of islets is formed adjacent the membrane, the layer having a thickness and having a diameter that is greater than its thickness.

16. A bioartificial organ for implantation into an animal comprising a housing having a first enclosed chamber containing metabolically active cells, at least one vascularizing chamber having an opening on one end thereof that provides access to surrounding tissue, inlet means for supplying cells to the first chamber, outlet means for removing cells from the first chamber, and a semi-permeable membrane separating and in communication with the first chamber and vascularizing chamber, the membrane providing immunoprotection of the active cells from the vascular area within the vascularizing chamber and around the implanted device, the membrane allowing passage of small molecules including nutrients and waste products between the first and vascularizing chambers and prohibiting passage of agents of an immune system to the first chamber, and a biocompatible fibrous or porous foam matrix in the vascularizing chamber to provide a neovascular formation region for enhancing growth of small capillaries for providing efficient mass transfer of substances between first chamber and the capillaries in the vascularizing chamber, the fibrous or foam matrix having a porosity of about 40 to 95 percent and interconnecting passageways of about 10 to 120 microns, the fibrous or foam matrix being of an organic or inorganic material, the organic material composed principally of carbon, oxygen, and hydrogen atoms or sulfur atoms, oxygen atoms and hydrogen atoms, or carbon atoms, oxygen atoms, hydrogen atoms and nitrogen atoms, the inorganic materials being composed of at least one carbon, titanium, silica, sodium, calcium, strontium, magnesium, zinc and boron atoms.

17. An organ as defined in claim 16 wherein the metabolically active cells produce at least one substance of therapeutic benefit to the animal.

18. An organ as defined in claim 17 wherein the cells produce at least one of parathyroid hormone, dopamine, insulin, glucagon, calcitonin.

19. An organ as defined in claim 16 wherein metabolically active cells produce at least one substance of experimental interest.

20. An organ as defined in claim 16 wherein metabolically active cells metabolize at least one toxic substance that diffuses from capillaries contained in the vascularizing chamber into the first chamber.

21. An organ as defined in claim 16 wherein metabolically active cells secrete insulin in response to glucose which has diffused from capillaries contained in the vascularizing chamber into the first chamber.

22. An organ of claim 21 wherein metabolically active cells also secrete at least one of somatostatin, pancreatic polypeptide and glucagon.

23. An organ as defined in claim 16 wherein the metabolically active cells are genetically engineered.

24. An organ as defined in claim 16 in which the fibrous or foam matrix is keratin.

25. An organ ad defined in claim 16 in which the matrix is a polyolefin.

26. An organ as defined in claim 16 in which the matrix is glass fibers.

27. An organ as defined in claim 16 in which the matrix is stainless steel.

28. An organ as defined in claim 16 in which the matrix is polyurethane.

29. An organ as defined in claim 16 in which a disc-like layer of active cells is formed in the upper chamber adjacent the membrane, the layer having a thickness and a diameter that is greater than or equal to the thickness.

30. A bioartificial organ for implantation into an animal comprising a housing having a first enclosed chamber containing metabolically active cells, at least one vascularizing chamber having an opening on one end thereof that provides access to surrounding tissue, inlet means for supplying cells to the first chamber, outlet means for removing cells from the first chamber, and a semi-permeable membrane separating and in communication with the first chamber and vascularizing chamber, the membrane providing immunoprotection of the active cells from the vascular area within the vascularizing chamber and around the implanted device, the membrane allowing passage of small molecules including nutrients and waste products between the first and vascularizing chambers and not allowing passage of agents of an immune system to the first chamber, and a biocompatible fibrous or porous foam matrix in the vascularizing chamber to provide a neovascular formation region for enhancing growth of small capillaries for providing efficient mass transfer of substances between first chamber and the capillaries in the vascularizing chamber, the fibrous or foam matrix having a porosity of about 40 to 95 percent and interconnecting passageways of about 10 to 120 microns, the fibrous or foam matrix being of an inorganic material, the inorganic material being composed of one or more of carbon, titanium, silica, sodium, calcium, strontium, magnesium, zinc and boron atoms.

31. An organ as defined in claim 30 in which the matrix is an organic polymer having carbon, hydrogen and oxygen atoms.