Inner-supported, biocompatible cell capsules

• US 5,786,216 A
• Filed: 11/10/1994
• Issued: 07/28/1998
• Est. Priority Date: 11/17/1987
• Status: Expired due to Term

• Current Assignee: Neurotech USA, Inc. (Woodbrook Group Holdings, Inc.)
• Original Assignee: Cytotherapeutics, Inc.
• Inventors: Dionne, Keith E., Doherty, Edward J., Hegre, Orion D., Hazlett, Tyrone F., Flanagan, Thomas R.
• Primary Examiner(s): Naff, David M.
• Application Number:
  US08/337,555
• Time in Patent Office: 1,356 Days
• Field of Search: 435/174, 435/177, 435/180, 435/182, 435/288, 435/240.22, 435/240.23, 435/240.242, 435/395, 435/400, 435/401, 435/402, 424/93.7, 424/422, 604/890.1, 604/891.1
• US Class Current: 435/402
• 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 2035/128 capsules, e.g. microcapsules
• 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
• CPC Class Codes: B01J 13/02 Making microcapsules or microballoons for medical preparations A61K9/50
• CPC Class Codes: C12N 2533/30 Synthetic polymers thermoreactive polymers, e.g. PNIPAm, C12N2539/10
• CPC Class Codes: C12N 5/0012 Cell encapsulation
• CPC Class Codes: C12N 5/0614 Adrenal gland

Abstract

A biocompatible capsule for containing cells for implantation is prepared containing an inner support that provides tensile strength to the capsule. The capsule may be a tubular semipermeable membrane such as a hollow fiber membrane having both ends sealed. A rod shaped inner support extends through the lumen and ends of the rod are attached to sealed ends of the fiber. Prior to sealing one fiber end, cells are introduced into the lumen. Cells within the capsule may be suspended in a liquid medium or immobilized in a hydrogel or extracellular matrix material, and biologically active molecules can be delivered from the capsule to surroundings or from the surroundings into the capsule. The inner support may have external features such as flutes or a roughened or irregularly-shaped surface, and may be coated with cell-adhesive substance or a cell-viability-enhancing substance. The inner support may be a hollow tube having two channels, one communicating with a filling port that permits injecting cells through the support into the capsule and the other communicating with another port that allows gas to escape through the support as cells are introduced. Anti-inflammatory agents can be incorporated into the capsule membrane to reduce immune response, and angiogenic factors and cell growth factors may be used to stimulate cell culture. Post-coating of capsule can be used to provide a protective barrier against immunogens. A tether for capsule retrieval can be formed integral with the inner support.

Claims

1. A biocompatible cell capsule for implantation, comprising:

(a) a capsule jacket connected to a chamber top at one end and a chamber bottom at the other end enclosing a cell chamber

(b) the capsule jacket comprising at least one semipermeable surface across which biologically active molecules can be delivered, and

(c) an inner support having two ends extending through the cell chamber such that one end is connected to the chamber top and the other end is connected to the chamber bottom, said inner support having a tensile strength to provide an increase in tensile strength to the capsule of at least about 350% greater than when the capsule does not contain an inner support.

2. The capsule of claim 1 wherein the cell chamber top comprises a top sealing fitting and the cell chamber bottom comprises a bottom sealing fitting.

3. The capsule of claim 2 wherein the chamber has a longitudinal axis running from the center of the top sealing fitting and the center of the bottom sealing fitting and wherein the inner support is cylindrical and arranged concentrically with the longitudinal axis.

4. The capsule of claim 1 wherein the inner support is coated with a cell-adhesive substance or a cell-viability-enhancing substance.

5. The capsule of claim 1 wherein the outer surface of the inner support is roughened.

6. The capsule of claim 5 wherein the external features are fins.

7. The capsule of claim 1 wherein the capsule top comprises an annular fitting having a slot adapted to receive the inner support.

8. The capsule of claim 7, wherein the inner support comprises a rod having a ball at one end adapted to fit within said slot in said annular fitting.

9. The capsule of claim 1 wherein at least one end of the inner support has a shape providing greater surface area available for securing the inner support to the chamber top or chamber bottom.

10. The capsule of claim 1 further comprising a tether for retrieval.

11. The capsule of claim 10 wherein said tether is integrally formed with the inner support.

12. The capsule of claim 1 wherein the capsule is immunoisolatory.

13. The capsule of claim 1 wherein the outer surface of the inner support is irregularly shaped.