Multi-layer hydrogel capsules for encapsulation of cells and cell aggregates

Patent metadata

Field	Value
Publication number	US-10172791-B2
Application number	US-201414776639-A
Country	US
Kind code	B2
Filing date	Mar 14, 2014
Priority date	Mar 14, 2013
Publication date	Jan 8, 2019
Grant date	Jan 8, 2019

Abstract

Biomedical devices for implantation with decreased pericapsular fibrotic overgrowth are disclosed. The device includes biocompatible materials and has specific characteristics that allow the device to elicit less of a fibrotic reaction after implantation than the same device lacking one or more of these characteristic that are present on the device. Biocompatible hydrogel capsules encapsulating mammalian cells having a diameter of greater than 1 mm, and optionally a cell free core, are disclosed which have reduced fibrotic overgrowth after implantation in a subject. Methods of treating a disease in a subject are also disclosed that involve administering a therapeutically effective amount of the disclosed encapsulated cells to the subject.

First claim

We claim:

1. A device for implantation,
the device formed from materials selected from the group consisting of polymers and semiconductors and in a form for implantation into an individual in need thereof,
wherein the device has a diameter of at least 1 mm and less than 10 mm;
wherein a surface of the device does not have flat sides;
wherein the surface of the device has surface pores having dimensions of greater than 0 nm and less than 10 μm; and
wherein the device elicits less of a fibrotic reaction after implantation than the same device having a diameter of less than 1 mm.

2. The device of claim 1 , wherein the surface of the device is neutral or hydrophilic, wherein the surface of the device does not have sharp angles, grooves, or ridges; wherein the curvature of the surface of the device is at least 0.2 and not greater than 2 on all points of the surface; and wherein the device has a spheroid-like shape.

3. The device of claim 1 comprising long-term implantable sensors or actuators.

4. The device of claim 1 in the form of a prostheses or tissue regenerating material.

5. The device of claim 1 , comprising polymer selected from the group consisting of polysaccharides, collagen, agarose, polyphosphazenes, poly(acrylic acids), poly(methacrylic acids), copolymers of acrylic acid and methacrylic acid, poly(alkylene oxides), poly(vinyl acetate), polyvinylpyrrolidone, and copolymers and blends thereof.

6. The device of claim 5 , wherein the polymer is a polysaccharide selected from the group consisting of alginate, chitosan, hyaluronan, and chondroitin sulfate.

7. The device of claim 1 , wherein the surface of the device is hydrophilic.

8. The device of claim 1 encapsulating a population of cells to be transplanted, wherein the cells to be transplanted are selected from the group consisting of mammalian secretory cells, mammalian metabolic cells, mammalian structural cells, and aggregates thereof.

9. The device of claim 8 , wherein the encapsulated cells secrete for at least 30 days a substance in an amount therapeutically effective to treat a disease.

10. The device of claim 1 , comprising a hydrogel capsule having cells encapsulated therein.

11. The device of claim 8 , comprising a hydrogel capsule having a diameter of at least 1 mm and less than 8 mm.

12. The device of claim 11 , wherein the hydrogel capsule has a diameter of between 1.5 mm and 5 mm.

13. The device of claim 8 , wherein the cells are islet cells or undifferentiated or partially differentiated precursors thereof.

14. The device of claim 8 , wherein the mammalian cells are allogeneic or autologous.

15. The device of claim 8 , wherein the mammalian cells are islet cells.

16. The device of claim 10 encapsulating cells to be transplanted,
wherein the hydrogel capsule consists of two or more layers:
a first hydrogel layer containing the cells to be transplanted, wherein the cells are selected from the group consisting of mammalian secretory cells, mammalian metabolic cells, mammalian structural cells, and aggregates thereof; and
an outer acellular barrier layer wherein the permeability of the outer acellular barrier layer limits entry of immune cells, antibodies and cytokines.

17. The device of claim 16 , wherein the hydrogel capsule has a diameter of at least 1.2 mm and the device has a diameter greater than 1.2 mm.

18. The device of claim 16 , wherein the hydrogel capsule has a diameter of at least 1.5 mm and the device has a diameter greater than 1.5 mm.

19. The device of claim 16 , wherein the cells are islet cells or undifferentiated or partially differentiated precursors thereof.

20. The device of claim 16 , wherein the mammalian cells are allogeneic or autologous.

21. The device of claim 1 encapsulating a hydrogel capsule encapsulating cells selected from the group consisting of mammalian secretory cells, mammalian metabolic cells, mammalian structural cells, and aggregates thereof.

22. The device of claim 1 encapsulating a hydrogel capsule encapsulating cells to be transplanted,
wherein the hydrogel capsule consists of three layers:
an inner acellular core optionally comprising a therapeutic, prophylactic, or diagnostic agent;
a hydrogel layer containing cells to be transplanted, wherein the cells are selected from the group consisting of mammalian secretory cells, mammalian metabolic cells, mammalian structural cells, and aggregates thereof; and
an outer acellular barrier layer wherein the permeability of the barrier layer limits entry of immune cells, antibodies and cytokines relative to entry of immune cells, antibodies and cytokines in the absence of the barrier.

23. The device of claim 1 , wherein the capsule has a mean diameter of greater than 1 mm and less than 8 mm.

24. The device of claim 22 , wherein the inner acellular core comprises a therapeutic, prophylactic, or diagnostic agent.

25. The device of claim 24 , wherein the inner acellular core comprises a therapeutic agent selected from the group consisting of anti-inflammatories, phenolic antioxidants, and anti-proliferative drugs.

26. The device of claim 24 , wherein the inner acellular core comprises a therapeutic agent which is released at the site of implantation.

27. The device of claim 1 , wherein the mammalian cells are islet cells.

28. A method of providing functional cells to an individual in need thereof comprising administering to the individual an effective amount of the device of claim 8 .

Assignees

• Massachusetts Inst Technology
• Childrens Medical Ct Corp

Inventors

• Ma Minglin
• Anderson Daniel G
• Langer Robert S
• Veiseh Omid
• Doloff Joshua Charles
• Chen Delai
• Kastrup Christian J
• Vegas Arturo Jose

Classifications

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title

• A61K9/4833

  Encapsulating processes; Filling of capsules (mechanical aspects A61J3/07) · CPC title

• A61K9/4866

  Organic macromolecular compounds · CPC title

• A61K2035/126

  Immunoprotecting barriers, e.g. jackets, diffusion chambers · CPC title

• A61K9/5036

  Polysaccharides, e.g. gums, alginate; Cyclodextrin · CPC title