Method and apparatus for sealing implantable membrane encapsulation devices

• US 5,653,688 A
• Filed: 06/06/1995
• Issued: 08/05/1997
• Est. Priority Date: 06/23/1993
• Status: Expired due to Term

• Current Assignee: Neurotech S.A. (LivaNova Plc)
• Original Assignee: Brown University
• Inventors: Dionne, Keith E., Warner, Nicholas F., Doherty, Edward J., Rein, David H., Hazlett, Tyrone F., Cain, Brian M., Mills, John F.
• Primary Examiner(s): ELGART, VANITHA M
• Application Number:
  US08/490,113
• Time in Patent Office: 791 Days
• Field of Search: 604/93, 604/8-10, 604/175, 604/185, 604/890.1, 604/891.1, 604/132, 604/57, 128/749-755, 128/762, 128/898, 435/179, 435/180, 435/182, 435/288, 435/240.22, 264/2, 425/382.2, 424/424
• US Class Current: 604/57
• CPC Class Codes: A61K 9/0024 Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L

Abstract

A sealed, implantable, encapsulation device (20) for diffusing a biologically active product or function to an individual which includes a substantially non-porous fitting (32) including an inner surface (33) defining an access port (34). A permselective, porous, membrane (21), having an interior surface (22), cooperates with the fitting inner surface (33) to form a storage cavity (23) therebetween. The membrane interior surface (22) is in substantially cell-tight dry sealing engagement with fitting (32) to seal cavity (23). Living cells (24) are disposed in the cavity (23) which are capable of secreting the biologically active product to an individual. The membrane (21) is of a material capable of permitting the passage of substances between the individual and cells required to provide the biological product or function. A plug member (35) is positioned in the access port (34) and seated in cell-tight sealing engagement with the fitting inner surface (33). A method for sealing the implantable encapsulation device (20) is also provided.

Claims

1. A sealed, implantable encapsulation device for providing a biologically active product or function to an individual, said encapsulation device comprising:

a permselective, porous membrane shaped so as to form a cell-impervious encapsulating enclosure including an exterior surface, an interior surface and an opening, said interior surface substantially defining a storage cavity and said opening providing open communication between said storage cavity and the exterior of said enclosure;

a non-permeable, non-porous fitting disposed within or about said opening so as to make a substantially cell-tight dry seal between said fitting and said enclosure, said fitting providing a cell-tight closure of said opening but further including an access bore therethrough providing open communication between said storage cavity and the exterior of said enclosure, dimensioned so as to permit introduction therethrough of living cells into said storage cavity;

living cells disposed in said storage cavity and capable of secreting a biologically active product or of providing a selected biological function to an individual after implantation, said membrane permitting passage therethrough of substances secreted by said cells and required to provide said biological product or function; and

a non-permeable, non-porous plug member cooperating with the access bore of said fitting to form a cell-tight dry seal with said fitting to seal said access bore.

2. The encapsulation device as defined in claim 1, wherein said membrane comprises a hollow fiber membrane having at least one open end thereof providing access to said storage cavity, and said fitting is annular.

3. The encapsulation device as defined in claim 2, wherein an outwardly facing surface of said annular fitting contacts said membrane interior surface to form a cell-tight dry seal closing said at least one open end of said hollow fiber.

4. The encapsulation device as defined in claim 3, further comprising an intermediate adhesive layer between said outwardly facing surface and said membrane interior surface forming thereby said cell-tight dry seal.

5. A sealed, implantable, hollow membrane encapsulation device for providing a biologically active product or function to an individual, said encapsulation device comprising:

a permselective hollow, porous membrane shaped so as to form a cell-impervious encapsulating enclosure including an exterior surface, an interior surface and at least one opening, said interior surface substantially defining a storage cavity and said at least one opening providing open communication between said storage cavity and the exterior of said enclosure;

living cells disposed in said cavity capable of secreting a biologically active product or of providing a selected biological function to an individual, said membrane permitting passage therethrough of substances secreted by said cells and required to provide said biological product or function;

sealing means at said at least one opening of said enclosure including a non-permeable, fitting contacting said at least one opening so as to make a substantially cell-tight dry seal between said fitting and said enclosure, said fitting further including an open bore extending therethrough, defining an inner surface of said fitting and dimensioned so as to permit introduction therethrough of living cells into said storage cavity; and

a non-permeable, non-porous plug member cooperating with at least a portion of the inner surface of said fitting so as to form a cell-tight dry seal closing said open bore.

6. The encapsulation device as defined in claim 5, wherein said fitting is partly disposed within said opening such that a portion of the outer surface of said fitting contacts the interior surface of said enclosure and another portion of said fitting projects outwardly from said opening, and

said plug member contacts said fitting at the portion that projects outwardly from said opening, adjacent said open bore, to form said cell-tight dry seal.

7. The encapsulation device as defined in claim 6, wherein said plug member comprises a biocompatible adhesive disposed on said outwardly projecting portion and over said open bore so as to seal said open bore.

8. The encapsulation device as defined in claim 7, wherein said adhesive is a light-curable acrylate polymer adhesive.

9. The encapsulation device as defined in claim 7, wherein said adhesive is a polyurethane adhesive.

10. The encapsulation device as defined in claim 6, wherein said fitting is comprised of a deformable tubular material, and said plug member has a transverse cross-sectional area larger than the open bore transverse cross-sectional area, such that force-fit disposition of said plug member within said open bore results in a friction fit cell-tight barrier closing said open bore.

11. The encapsulation device as defined in claim 10, wherein said plug member is substantially spherical in shape.

12. The encapsulation device as defined in claim 10, wherein said tubular material is silicone.

13. The encapsulation device as defined in claim 10, wherein said plug member is composed of stainless steel.

14. The encapsulation device as defined in claim 10, wherein said plug member is composed of teflon.

15. The encapsulation device as defined in claim 5, wherein

said plug member contacts said inner surface of said fitting, thereby closing said open bore.

16. The encapsulation device as defined in claim 5, wherein said sealing means further includes an intermediate adhesive layer between said fitting and said enclosure, forming said cell-tight dry seal therebetween.

17. The encapsulation device as defined in claim 16, wherein said adhesive is a light-curable acrylate polymer adhesive.

18. The encapsulation device as defined in claim 5, wherein said plug member is formed by in situ polymerization of a monomer in the open bore of said fitting.

19. The encapsulation device as defined in claim 5, wherein said plug member has a transverse cross-sectional area larger than the open bore transverse cross-sectional area, such that force-fit disposition of said plug member within said open bore results in a friction fit cell-tight barrier closing said open bore.

20. A method for forming a sealed, implantable, hollow membrane encapsulation device for providing a biologically active product or function to an individual, said method comprising the steps of:

(a) providing a permselective, porous membrane shaped so as to form a cell-impervious encapsulating enclosure including an exterior surface, an interior Surface and an opening, said interior surface substantially defining a storage cavity and said opening providing open communication between said storage cavity and the exterior of said enclosure;

(b) contacting said opening with a non-permeable, non-porous fitting in such a manner as to form a cell-tight dry seal between said fitting and said enclosure, wherein said fitting closes said opening and wherein said fitting is provided with an access bore extending therethrough, providing open communication between said storage cavity and the exterior of said enclosure and dimensioned so as to permit introduction therethrough of living cells into said storage cavity;

(c) depositing in said cavity, through said access port bore, living cells capable of secreting a biologically active product or of providing a selected biological function to an individual, said membrane permitting passage therethrough of substances secreted by said cells and required to provide said biological product or function; and

(d) contacting said access port bore with a plug member shaped so as to cooperate with the access bore of said fitting so as to form a cell-tight seal of said access bore.

21. The method of claim 20, wherein said fitting is substantially non-porous, and said cell-tight seal of said access bore in step (d) is accomplished by sliding a substantially non-porous plug member into the open bore of said fitting and applying an adhesive material within said access bore to hold said plug member in place.

22. A method of manufacturing a dry sealed, implantable, hollow membrane encapsulation device containing living cells, said method comprising:

(a) providing a capsule formed from a permselective, porous membrane, said capsule enclosing a storage cavity and having at least one opening to said storage cavity;

(b) disposing a non-porous, non-permeable fitting within or about said opening in such a manner as to make a cell-tight dry seal between said fitting and said opening, said fitting including an access bore therethrough providing open communication with said storage cavity;

(c) passing a filler tube through said access bore;

(d) passing living cells through said filling tube into said storage cavity while avoiding contact between said cells and said fitting;

(e) withdrawing said filler tube from said access bore;

(f) contacting a plug member with at least a portion of said access bore in such a manner as to form a cell-tight dry seal between said plug member and said fitting and completely closing said open communication through said access bore.