System for gas treatment of a cell implant

• US 10,231,817 B2
• Filed: 09/24/2014
• Issued: 03/19/2019
• Est. Priority Date: 09/24/2013
• Status: Active Grant

• Current Assignee: Giner, Inc.
• Original Assignee: Giner Life Sciences, Inc.
• Inventors: Tempelman, Linda, Stone, Simon, Papas, Klearchos
• Primary Examiner(s): Prakash, Gautam
• Application Number:
  US14/495,644
• Publication Number:
  US 20150112247A1
• Time in Patent Office: 1,637 Days
• 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: A61K 48/0075 characterised by an aspect of the delivery route, e.g. oral, subcutaneous
• CPC Class Codes: A61M 2005/006 for gases, e.g. CO2
• CPC Class Codes: A61M 2005/14204 with gas-producing electrochemical cell
• CPC Class Codes: A61M 2202/0208 Oxygen
• CPC Class Codes: A61M 2205/7536 allowing gas passage, but preventing liquid passage, e.g. liquophobic, hydrophobic, water-repellent membranes
• CPC Class Codes: Y02E 60/36 Hydrogen production from non-carbon containing sources, e.g. by water electrolysis

Abstract

System for gas treatment of cellular implants. The system enhances the viability and function of cellular implants, particularly those with high cellular density, for use in human or veterinary medicine. The system utilizes a miniaturized electrochemical gas generator subsystem that continuously supplies oxygen and/or hydrogen to cells within an implantable and immunoisolated cell containment subsystem to facilitate cell viability and function at high cellular density while minimizing overall implant size. The cell containment subsystem is equipped with features to allow gas delivery through porous tubing or gas-only permeable internal gas compartments within the implantable cell containment subsystem. Furthermore, the gas generator subsystem includes components that allow access to water for electrolysis while implanted, thereby promoting long-term implantability of the gas generator subsystem. An application of the system is a pancreatic islet (or pancreatic islet analog) implant for treatment of Type 1 diabetes (T1D) that would be considered a bio-artificial pancreas.

Claims

1. A system for gas treatment of a cell implant, the system comprising:

(a) an electrochemical device, the electrochemical device being configured to output a first gas from a first outlet and a second gas from a second outlet, wherein the first gas and the second gas are different from one another,

(b) an implantable cell container, the implantable cell container comprising a first chamber configured to receive cells,

(c) a first gas conduit for delivering the first gas from the electrochemical device to the implantable cell container, the first gas conduit comprising a first end and a second end, the first end of the first gas conduit being fluidly coupled to the first outlet of the electrochemical device, the second end of the first gas conduit being configured to deliver the first gas to the first chamber of the implantable cell container, wherein the second end of the first gas conduit is disposed within the implantable cell container, and

(d) a second gas conduit for delivering the second gas from the electrochemical device to the implantable cell container, the second gas conduit comprising a first end and a second end, the first end of the second gas conduit being fluidly coupled to the second outlet of the electrochemical device, the second end of the second gas conduit being configured to deliver the second gas to the first chamber of the implantable cell container, wherein the second end of the second gas conduit is disposed outside of the implantable cell container.

2. The system as claimed in claim 1 wherein the second gas conduit comprises at least one gas-permeable delivery tube.

3. The system as claimed in claim 1 wherein the second gas conduit comprises at least one gas-permeable tube located above the cell containment system and at least one gas-permeable tube located below the cell containment system.

4. The system as claimed in claim 1 wherein the second gas conduit comprises a supply manifold and a plurality of gas-permeable delivery tubes.

5. The system as claimed in claim 1 wherein at least a portion of the first chamber is bounded by a selectively permeable external wall, the selectively permeable external wall being permeable to gas, and wherein the second end of the second gas conduit is disposed outside of the implantable cell container in proximity to the selectively permeable external wall.

6. The system as claimed in claim 1 wherein the implantable cell container further comprises a cell supply port and wherein the cell supply port comprises a tube.

7. The system as claimed in claim 1 wherein at least a portion of the first chamber is surrounded by an immunoisolation membrane.

8. The system as claimed in claim 5 wherein the second end of the second gas conduit is no more than 5 mm away from the selectively permeable external wall of the implantable cell container.

9. The system as claimed in claim 5 wherein at least a second portion of the first chamber is bounded by a selectively permeable internal wall, wherein the selectively permeable internal wall is permeable to gas but not to cells.

10. The system as claimed in claim 1 wherein the implantable cell container further comprises a second chamber, wherein the first chamber and the second chamber are separated by a first selectively permeable wall, the first selectively permeable wall being permeable to gas but not to cells, and wherein each of the second end of the first gas conduit and the second end of the second gas conduit is disposed within the second chamber.

11. The system as claimed in claim 10 wherein the implantable cell container further comprises a third chamber, the third chamber being configured to receive cells, and wherein the second chamber and the third chamber are separated by a second selectively permeable wall, the second selectively permeable wall being permeable to gas but not to cells.

12. The system as claimed in claim 1 wherein the implantable cell container further comprises a second chamber and a third chamber, wherein the first chamber and the second chamber are separated by a first selectively permeable wall, the first selectively permeable wall being permeable to gas but not to cells, wherein the second chamber and the third chamber are separated by a second selectively permeable wall, the second selectively permeable wall being permeable to gas but not to cells, wherein the third chamber is configured to receive cells, and wherein the second end of the first gas conduit is positioned within the second chamber.

13. The system as claimed in claim 12 wherein each of the first and second selectively permeable walls is permeable only to gas.

14. The system as claimed in claim 1 wherein the electrochemical device is a water electrolyzer and wherein the first gas is gaseous oxygen and the second gas is gaseous hydrogen.

15. The system as claimed in claim 1 wherein the electrochemical device comprises a bio-compatible membrane.

16. The system as claimed in claim 15 wherein the bio-compatible membrane is a bio-compatible vascularizing membrane.

17. The system as claimed in claim 16 wherein the electrochemical device further comprises a vapor transport membrane.

18. The system as claimed in claim 1 wherein the electrochemical device comprises a vapor transport membrane.

19. The system as claimed in claim 1 wherein the electrochemical device, the implantable cell container, the first gas conduit, and the second gas conduit are configured for implantation in a patient.

20. The system as claimed in claim 1 wherein, when the implant has a cell packing density of 6,600-8,000 islet equivalents per exposed surface area in cm² of the cell container and an overall dose of up to 100 IEQ/g rodent body weight in the cell container, the rodent recipient has a measured daily blood glucose level of 50-200 mg/dL in the absence of insulin treatment over at least a 14 day period.

21. The combination of the system as claimed in claim 1 and a quantity of cells disposed in the first chamber of the implantable cell container.