The overall goal of this proposed SBIR project is to develop a miniaturized implantable oxygen generator that will continuously supply oxygen to cells within an immunoisolation cell implant device. This will maintain cellular viability and function at high cell densities thus minimizing overall implant size. The oxygen generator will be powered by a remotely rechargeable battery. The first proposed application of this platform technology is pancreatic islet implant for the treatment of Type 1 diabetes (T1D). The combination of the oxygenator with a well-characterized immunoisolation device is termed a bioartificial pancreas with implantable oxygen supply (BAPIOS). The implantable oxygen generator is also a platform technology that could be combined with other cell implant devices and other therapeutic cell types for other cellular therapies for conditions such as liver failure, Parkinson's disease, (para)thyroid disease and hemophilia. Pancreatic islet allotransplantation is in U.S. clinical trials. There are also results from leading centers demonstrating insulin independence for more than 5 years for 50% of the recipients. However, widespread clinical application of for T1D is hindered by two critical barriers: 1) the need for systemic immunosuppression for the current intraportal liver transplant site;and 2) by the finite and low supply of human islet tissue (a few thousand suitable donors per year). The use of biocompatible, retrievable, cell isolating devices may address these critical barriers by enabling the more effective and efficient use of allogeneic islets without immunosuppression and the eventual use of stem cell-derived or xenogeneic islets with minimum or no immunosuppression. Autotransplantation (for pancreatitis patients and pre-cancer diagnosis) could also benefit from a simple implant procedure with retrievability and cellular immunoisolation. Current cell implant devices have insufficient oxygen (even with prevascularization of the device) to provide the high cellular densities required for practically-sized clinical implants. The proposed technology would include the first implantable, continuous oxygen supply with integrated rechargeable battery.
The Specific Aims of the 12 month Phase I project are:
Aim 1 : Design and fabrication of a miniature oxygen generator (oxygenator);
Aim 2 : In vitro evaluation of the Ph I miniature oxygenator and the oxygenated implant device;
Aim 3 : Preliminary in vivo testing in a diabetic nude rat model;
and Aim 4 : Design of complete bioartificial pancreas with implantable oxygen supply (BAPIOS) for implementation in Ph II.
This aim i ncludes a fully implantable oxygenator as well as customization of the cell implant device for this application. This Ph I feasibility stuy will provide the groundwork for final design and fabrication of a fully implantable oxygenated cell implant in Phase II and large animal studies ultimately leading to the treatment of T1D in humans.

Public Health Relevance

The goal of this project is to develop a bioartificial pancreas that includes a rechargeable, miniature oxygen generator that can be implanted in the body. The oxygen produced will be a critical enabler of compact cell therapy implants. The priority application for this transformative platform technology is a pancreatic islet implant with the potential to cure diabetes.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Small Business Innovation Research Grants (SBIR) - Phase I (R43)
Project #
1R43DK100999-01
Application #
8633290
Study Section
Special Emphasis Panel (ZDK1-GRB-2 (O3))
Program Officer
Arreaza-Rubin, Guillermo
Project Start
2013-09-15
Project End
2014-08-31
Budget Start
2013-09-15
Budget End
2014-08-31
Support Year
1
Fiscal Year
2013
Total Cost
$224,933
Indirect Cost
Name
Giner, Inc.
Department
Type
DUNS #
066594979
City
Newton
State
MA
Country
United States
Zip Code
02466