Bioartificial pancreas

• US 5,855,616 A
• Filed: 09/03/1996
• Issued: 01/05/1999
• Est. Priority Date: 07/30/1992
• Status: Expired due to Term

• Current Assignee: University of Toledo
• Original Assignee: University of Toledo
• Inventors: Sarver, Jeffrey G., Goldblatt, Peter J., Horner, James M., Fournier, Ronald L.
• Primary Examiner(s): BRITTINGHAM, DEBRA
• Application Number:
  US08/711,364
• Time in Patent Office: 854 Days
• Field of Search: 623/11, 623/12, 604/4, 604/175, 424/424
• 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 device for implantation into an animal comprising:

a housing having an enclosed chamber containing metabolically active cells,

at least one vascularizing compartment having an opening that provides access to surrounding tissue,

inlet means for supplying cells to the chamber,

outlet means for removing cells from the chamber, and

a semi-permeable membrane separating and in communication with the chamber and vascularizing compartment, the membrane providing immunoprotection of the active cells from the vascularizing compartment and around the implanted device, the membrane allowing passage of small molecules including nutrients and waste products between the chamber and vascularizing compartment and not allowing passage of agents of an immune system to the chamber, and

a biocompatible matrix in the vascularizing compartment to provide a neovascular formation region for enhancing growth of small capillaries for providing efficient mass transfer of substances between the chamber and the capillaries in the vascularizing compartment, the matrix having a porosity of about 40 to 95 percent and interconnecting passageways of about 10 to 120 microns.

2. An organ as defined in claim 1 in which the metabolically active cells are islets of Langerhans.

3. An organ as defined in claim 1 in which the porosity is about 80 to 85 percent.

4. An organ as defined in claim 1 wherein the vascularizing compartment contains at least one growth factor for promoting ingrowth of capillaries into the vascularizing compartment.

5. An organ 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.

6. An organ as defined in claim 1 wherein the metabolically active cells produce at least one substance of therapeutic benefit to the animal.

7. An organ as defined in claim 5 wherein the cells produce at least one of parathyroid hormone, dopamine, insulin, glucagon, calcitonin.

8. An organ as defined in claim 1 in which a disc-like layer of active cells is formed in the chamber adjacent the membrane, the layer having a thickness and a diameter, wherein the diameter of the layer is at least as great as the thickness of the layer.

9. An organ as defined in claim 1 wherein metabolically active cells metabolize at least one toxic substance that diffuses from capillaries contained in the vascularizing compartment into the chamber.

10. An organ as defined in claim 1 wherein metabolically active cells secrete insulin in response to glucose which has diffused from capillaries contained in the vascularizing compartment into the chamber.

11. An organ as defined in claim 10 wherein metabolically active cells also secrete at least one of somatostatin, pancreatic polypeptide and glucagon.

12. An organ as defined in claim 1 wherein the membrane has an average number molecular weight cut-off of less than 100,000.

13. An organ as defined in claim 1 wherein the metabolically active cells are genetically engineered.

14. A bioartificial device for implantation into an animal comprising:

a housing having an enclosed chamber containing metabolically active cells that produce at least one substance of therapeutic benefit to the animal,

at least on e vascularizing compartment having an opening that provides access to surrounding tissue, the at least one vascularizing compartment containing at least one growth factor for promoting ingrowth of capillaries into the vascularizing compartment,

inlet means for supplying cells to the chamber, outlet means for removing cells from the chamber, and

a semi-permeable membrane separating and in communication with the chamber and vascularizing compartment, the membrane providing immunoprotection of the active cells from the vascularizing compartment and around the implanted device, the membrane allowing passage of small molecules including nutrients and waste products between the chamber and vascularizing compartment and not allowing passage of agents of an immune system to the chamber, and

a biocompatible matrix in the vascularizing compartment to provide a neovascular formation region for enhancing growth of small capillaries for providing efficient mass transfer of substances between the chamber and the capillaries in the vascularizing compartment, the matrix having a porosity of about 40 to 95 percent and interconnecting passageways of about 10 to 120 microns.

15. An organ as defined in claim 14 in which the metabolically active cells are islets of Langerhans.

16. An organ as defined in claim 15 in which a layer of islets is formed adjacent the membrane, the layer having a thickness and having a diameter, wherein the diameter of the layer is at least as great as the thickness of the layer.

17. An organ as defined in claim 14 wherein the cells produce at least one of parathyroid hormone, dopamine, insulin, glucagon, calcitonin.

18. An organ as defined in claim 14 wherein metabolically active cells metabolize at least one toxic substance that diffuses from capillaries contained in the vascularizing compartment into the chamber.

19. An organ as defined in claim 14 wherein metabolically active cells secrete insulin in response to glucose which has diffused from capillaries contained in the vascularizing compartment into the chamber.

20. An organ as defined in claim 14 wherein metabolically active cells also secrete at least one of somatostatin, pancreatic polypeptide and glucagon.