Bio-artificial pancreas and a procedure for preparation of same
The present invention generally relates to implantable devices for producing insulin in diabetic animals and to methods of making same. Some embodiments include amphiphilic biomembranes for use in biological applications (e.g., as an alternative and/or supplemental insulin source). Some embodiments also include live insulin-producing cells contained within one or more amphiphilic membranes so as to prevent or diminish an immuno-response and/or rejection by the host.
1. A method for producing an implantable device for providing insulin comprising:
(A) providing at least one implantable device for producing insulin, the device comprising:
a perforated mid-section bound at the edges thereof by a seal wherein the perforated midsection includes a pattern of perforations;
and at least one filling port designed to permit the perforated mid-section to be filled with insulin producing cells;
(B) depositing on the perforated mid-section a biologically compatible polymer network; and
(C) forming at least one immunoisolatory membrane on the perforated mid-section with a biologically compatible polymer network deposited thereon;
wherein the biologically compatible network is a nanomat formed from electrospun polyurethane nanofibers.
2. The method of claim 1 , wherein the insulin producing cells are porcine endocrine cells.
3. The method of claim 1 , wherein the nanofibers have an average diameter of about 1 nanometer to about 25,000 nanometers.
4. The method of claim 1 , wherein the at least one immunoisolatory membrane is formed from a crosslinked amphiphilic co-network.
5. The method of claim 4 , wherein the crosslinked amphiphilic co-network is formed from a combination of poly(ethylene glycol), polydimethylsiloxane and tris(dimethylsilyloxy)-phenylsilane.
6. The method of claim 4 , wherein the crosslinked amphiphilic co-network is formed from a combination of poly(N,N-dimethyl acrylamide), polydimethylsiloxane and polymethylhydrosiloxane.
7. The method of claim 1 , wherein the at least one immunoisolatory membrane has bi-continuous hydrophilic and hydrophobic domains and hydrophilic pore dimensions in the range of about 3.0 nm to about 4.0 nm.
8. The method of claim 1 , wherein the at least one immunoisolatory membrane is an amphiphilic water swollen membrane having bi-continuous hydrophilic pore dimensions in the range of about 3.0 nm to about 4.0 nm.
9. The method of claim 1 , further comprising the steps of: (D) filling the device with a suitable amount of insulin producing cells; and (E) sealing the device.
10. The method of claim 1 , wherein perforated mid-section is metal.
11. The method of claim 10 , wherein the metal is selected from stainless steel, nitinol, tantalum, or titanium.
12. The method of claim 10 , wherein a conductive metal wire or ribbon is inserted into the perforated mid-section.
13. The method of claim 12 , wherein the metal is selected from stainless steel, nitinol, tantalum, or titanium.
14. The method of claim 1 , wherein perforated mid-section is rotated during deposition of the biologically compatible polymer network.
15. The method of claim 1 , wherein the perforated mid-section includes perforations having a diameter of 0.5 mm.
16. A method for producing an implantable device for providing insulin comprising:
(a) providing at least one implantable device for producing insulin, the device comprising:
a perforated mid-section bound at the edges thereof by a seal, wherein the perforated midsection includes a pattern of perforations; and
at least one filling port designed to permit the perforated mid-section to be filled with insulin producing cells;
(b) depositing on the perforated mid-section a biologically compatible polymer network;
(c) forming at least one immunoisolatory membrane on the perforated mid-section with a biologically compatible polymer network deposited thereon;
(d) implanting the device into a diabetic mammal;
(e) filling the device with a suitable amount of insulin producing cells; and
(f) sealing the device to yield the insulin producing device
wherein the biologically compatible network is a nanomat formed from electrospun polyurethane nanofibers.
17. The method of claim 16 , wherein the insulin producing cells are porcine endocrine cells.
18. The method of claim 16 , wherein the nanofibers have an average diameter of about 1 nanometer to about 25,000 nanometers.
19. The method of claim 16 , wherein the at least one immunoisolatory membrane is formed from a crosslinked amphiphilic co-network.
20. The method of claim 19 , wherein the crosslinked amphiphilic co-network is formed from a combination of poly(ethylene glycol), polydimethylsiloxane and tris(dimethylsilyloxy)-phenylsilane.
21. The method of claim 19 , wherein the crosslinked amphiphilic co-network is formed from a combination of poly(N,N-dimethyl acrylamide), polydimethylsiloxane and polymethylhydrosiloxane.
22. The method of claim 16 , wherein the at least one immunoisolatory membrane has bi-continuous hydrophilic and hydrophobic domains and hydrophilic pore dimensions in the range of about 3.0 nm to about 4.0 nm.
23. The method of claim 16 , wherein the at least one immunoisolatory membrane is an amphiphilic water swollen membrane having bi-continuous hydrophilic pore dimensions in the range of about 3.0 nm to about 4.0 nm.
24. The method of claim 16 , wherein the device is implanted in subcutaneous loci.
25. The method of claim 16 , wherein the device is implanted in intraperitoneal loci.
26. The method of claim 16 , wherein the device is replenished with additional tissue cultures of insulin producing cells.
27. The method of claim 16 , wherein perforated mid-section is metal.
28. The method of claim 27 , wherein a conductive metal wire or ribbon is inserted into the perforated mid-section.
29. The method of claim 16 , wherein perforated mid-section is rotated during deposition of the biologically compatible polymer network.
30. The method of claim 16 , wherein the perforated mid-section includes perforations having a diameter of 0.5 mm.