Method and system for encapsulating cells in a tubular extrudate in separate cell compartments

• US 5,158,881 A
• Filed: 01/08/1990
• Issued: 10/27/1992
• Est. Priority Date: 11/17/1987
• Status: Expired due to Term

• Current Assignee: Brown University, Neurotech S.A. (LivaNova Plc)
• Original Assignee: Brown University
• Inventors: Wahlberg, Lars, Aebischer, Patrick
• Primary Examiner(s): Naff, David M.
• Application Number:
  US07/461,999
• Time in Patent Office: 1,023 Days
• Field of Search: 435/179, 435/180, 435/182, 435/288, 435/240.22, 264/4, 264/4.7, 425/382 R, 425/382.2
• US Class Current: 435/182
• 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 35/13 Tumour cells, irrespective of tissue of origin tumour vaccines A61K39/00
• 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: A61K 9/0085 Brain, e.g. brain implants; Spinal cord
• CPC Class Codes: A61K 9/0092 Hollow drug-filled fibres, tubes of the core-shell type, coated fibres, coated rods, microtubules or nanotubes
• CPC Class Codes: A61K 9/4816 Wall or shell material
• CPC Class Codes: A61K 9/4833 Encapsulating processes; Filling of capsules mechanical aspects A61J3/07
• CPC Class Codes: A61M 2210/0687 Skull, cranium
• CPC Class Codes: A61M 2210/0693 Brain, cerebrum
• CPC Class Codes: A61M 2230/005 Parameter used as control input for the apparatus
• CPC Class Codes: A61M 31/002 Devices for releasing a drug at a continuous and controlled rate for a prolonged period of time artificial gland structures or devices A61F2/022; intra-uterine contraceptive devices A61F6/14; tampons for introducing into the vagina A61F13/20, A61L15/00; suppositories or bougies for intra-vaginal or intra-uterine application A61K9/02; physical forms of medicinal preparations for sustained or differential drug release A61K9/20, A61K9/50
• CPC Class Codes: B01J 13/02 Making microcapsules or microballoons for medical preparations A61K9/50
• CPC Class Codes: B01J 13/04 by physical processes, e.g. drying, spraying
• CPC Class Codes: C12N 11/04 entrapped within the carrier, e.g. gel or hollow fibres
• CPC Class Codes: C12N 11/087 Acrylic polymers
• CPC Class Codes: C12N 11/098 formed in the presence of the enzymes or microbial cells
• CPC Class Codes: C12N 2533/30 Synthetic polymers
• CPC Class Codes: C12N 5/0012 Cell encapsulation
• CPC Class Codes: C12N 5/0614 Adrenal gland
• CPC Class Codes: C12N 5/0619 Neurons

Abstract

Methods and systems are disclosed for encapsulating viable cells which produce biologically-active factors. The cells are encapsulated within a semipermeable, polymeric membrane by co-extruding an aqueous cell suspension and a polymeric solution through a common port to form a tubular extrudate having a polymeric outer coating which encapsulates the cell suspension. For example, the cell suspension and the polymeric solution can be extruded through a common extrusion port having at least two concentric bores, such that the cell suspension is extruded through the inner bore and the polymeric solution is extruded through the outer bore. The polymeric solution coagulates to form an outer coating. As the outer coating is formed, the ends of the tubular extrudate can be sealed to form a cell capsule. In one embodiment, the tubular extrudate is sealed at intervals to define separate cell compartments connected by polymeric links.

Claims

1. A method of encapsulating viable cells, the method comprising co-extruding an aqueous cell suspension and a polymeric solution through a common extrusion port to form a tubular extrudate having a polymeric outer coating which encapsulates said cell suspension, and sealing said tubular extrudate at intervals to define seperate cell compartments connected by polymeric links.

2. The method of claim 1 wherein the method further comprises extruding the aqueous cell suspension and the polymeric solution through a common extrusion port having at least two concentric bores, such that said cell suspension is extruded through an inner bore and said polymeric solution is extruded through an outer bore.

3. The method of claim 1 wherein the step of sealing the extrudate further comprises compressing the extrudate at intervals to define separate cell compartments.

4. The method of claim 1 wherein the step of sealing the extrudate further comprises modifying the pressure under which the cell suspension or the polymeric solution is extruded, thereby collapsing the tubular extrudate at intervals to define separate cell compartments.

5. The method of claim 1 wherein the step of sealing the extrudate further comprises impeding the flow of the cell suspension at intervals to collapse the tubular extrudate and define separate cell compartments.

6. The method of claim 1 wherein the polymeric coating is coagulated in air.

7. The method of claim 1 wherein the polymeric coating is coagulated in a quenchent bath.

8. The method of claim 1 wherein the method further comprises extruding an aqueous suspension containing cells that secrete a biologically-active factor.

9. The method of claim 1 wherein the method further comprises extruding an aqueous suspension containing cells that secrete a neurotransmitter.

10. The method of claim 1 wherein the method further comprises extruding an aqueous cell suspension which contains a nutrient medium.

11. The method of claim 1 wherein the method further comprises extruding an aqueous cell suspension which also contains an anchorage substrate material.

12. The method of claim 1 wherein the method further includes extruding a polymeric solution which further comprises a water-miscible solvent component.

13. The method of claim 1 wherein the method further includes extruding a polymeric solution which further comprises a surfactant.

14. The method of claim 1 wherein the method further includes extruding a polymeric solution which further comprises an anti-inflamatory agent.

15. The method of claim 1 wherein the method further includes extruding a polymeric solution which further comprises an antioxidant.

16. The method of claim 1 wherein the method further comprises coagulating the polymeric coating and controlling the viscosity of said polymeric solution, such that upon coagulation said outer polymeric coating will form a semipermeable membrane about said cell suspension.

17. The method of claim 1 wherein the method further comprises maintaining a pressure differential between the aqueous cell suspension and the polymeric solution during co-extrusion to impede solvent diffusion from said polymeric solution into said cell suspension.

18. A system for encapsulating viable cells, the system comprising:

an extrusion head assembly having at least a first inner bore and a second, concentric, outer bore;

cell suspension supply means for supplying an aqueous cell suspension to the inner bore of said extrusion head assembly;

polymeric solution supply means for supplying a polymeric solution to the outer bore of the extrusion head assemble, such that said cell suspension and said polymeric solution can be co-extruded to form a tubular extrudate having a polymeric outer coating which encapsulates said cell suspension;

flow control means for maintaining a pressure differential between the aqueous cell suspension and the polymeric solution during co-extrusion; and

sealing means for sealing the tubular extrudate at intervals to define separate cell compartments connected by polymeric links.

19. The system of claim 18 wherein the flow control means comprises a computer adapted to control a first infusion pump in said cell suspension supply means and a second infusion pump in said polymeric solution supply means.

20. The system of claim 18 wherein the system further comprises a quenchent bath for coagulating said polymeric solution following extrusion.

21. The system of claim 18 wherein the sealing means further comprises means for compressing the extrudate at intervals during extrusion to define separate cell compartments.

22. The system of claim 18 wherein the sealing means further comprises means for modifying the pressure under which the cell suspension or the polymeric solution is extruded, thereby collapsing the tubular extrudate at intervals to define separate compartments.

23. The system of claim 18 wherein the sealing means further comprises means for impeding the flow of the cell suspension at intervals to collapse the tubular extrudate and define separate cell compartments.

24. The system of claim 18 wherein the sealing means further comprises a retraction means for moving the inner bore of said extrusion head assembly relative to the outer bore to interrupt the flow of the tubular extrudate at intervals to define separate cell compartments.

25. The system of claim 18 wherein the extrusion head assembly includes a third, concentric, outer most bore for delivery of a quenchent fluid to coagulate said polymeric solution.