Thin film cell encapsulation devices

Patent metadata

Field	Value
Publication number	US-11236301-B2
Application number	US-201916661500-A
Country	US
Kind code	B2
Filing date	Oct 23, 2019
Priority date	Mar 23, 2015
Publication date	Feb 1, 2022
Grant date	Feb 1, 2022

Abstract

Thin film devices, e.g., multilayer thin film devices, that encapsulate cells for transplantation into a subject are provided. Also provided are methods of using and methods of preparing the subject devices. The thin film devices include a first porous polymer layer and a second porous polymer layer that define a lumen therebetween and encapsulate a population of cells within the lumen. The thin film devices can promote vascularization into the lumen of the device via the pores in the first polymer layer and/or second polymer layer; limit foreign body response to the device; limit ingress of cells, immunoglobulins, and cytokines into the lumen via the first and the second polymer layers; and release from the first polymer layer and/or the second polymer layer molecules secreted by the population of cells.

First claim

What is claimed is:

1. A device comprising an exterior surface comprising polycaprolactone (PCL) polymer, wherein said exterior surface is configured to be in contact with a bodily fluid or a bodily tissue of a subject, and wherein, when said device is implanted in a subject for at least 5 months, a level of fibrosis around said device has a fibrosis score of Grade 2 or less, as measured by histology, and wherein said PCL polymer has a number average molecular weight (Mn) of 50-200 kDa.

2. The device of claim 1 , wherein said exterior surface is coated with a molecule that promotes vascularization of said device, a molecule that inhibits an immune response to said device, a molecule that inhibits an inflammatory response to said device, or any combination thereof.

3. The device of claim 1 , wherein said exterior surface is coated with one or more molecules selected from the group consisting of: vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), fibroblast growth factor (FGF-1), angiopoietin, monocyte chemoattractant protein-1 (MCP-1), alpha v beta 3 , alpha v beta 5 , CD-31, VE-cadherin, ephrin, plasminogen activators, angiogenin, Del-1, acid fibroblast growth factor (aFGF), basic fibroblast growth factor (bFGF), follistatin, granulocyte colony-stimulating factor (G-CSF), hepatocyte growth factor (HGF), leptin, placental growth factor, platelet-derived endothelial growth factor (PD-ECGF), and any combination thereof.

4. The device of claim 1 , wherein said device further comprises a lumen.

5. The device of claim 4 , wherein said lumen is configured to encapsulate a plurality of cells, a plurality of therapeutic molecules, or both.

6. The device of claim 5 , wherein said device is configured such that said plurality of therapeutic molecules are capable of diffusing out of said lumen, out of said device, or both.

7. The device of claim 5 , wherein said plurality of cells are selected from the group consisting of: bone marrow cells, mesenchymal stem cells, stromal cells, pluripotent stem cells, induced pluripotent stem cells, embryonic stem cells, blood vessel cells, precursor cells derived from adipose tissue, bone marrow derived progenitor cells, intestinal cells, islets, Sertoli cells, beta cells, progenitors of islet cells, progenitors of beta cells, peripheral blood progenitor cells, stem cells isolated from adult tissue, retinal progenitor cells, cardiac progenitor cells, osteoprogenitor cells, neuronal progenitor cells, genetically transformed cells, and any combination thereof.

8. The device of claim 1 , wherein said device further comprises a first layer of biocompatible polymer and a second layer of biocompatible polymer.

9. The device of claim 8 , wherein said first layer of biocompatible polymer, said second layer of biocompatible polymer, or both, comprise a plurality of nanopores.

10. The device of claim 8 , wherein said first layer of biocompatible polymer, said second layer of biocompatible polymer, or both, are selected from the group consisting of: methacrylate polymer, polyethyleneimine, polyethyleneimine-dextran sulfate, poly(vinylsiloxane) ecopolymerepolyethyleneimine, phosphorylcholine, poly(ethyl methacrylate), polyurethane, poly(ethylene glycol), poly(lactic-glycolic acid), hydroxyapatite, poly(lactic acid), polyhydroxyvalerte and copolymers thereof, polyhydroxybutyrate and copolymers thereof, polycaprolactone, polydiaxanone, polyanhydride, polycyanocrylate, poly(amino acids), poly(orthoesters), polyesters, collagen, gelatin, cellulose polymer, chitosans, alginates, and any combination thereof.

11. The device of claim 1 , wherein said device is configured to be implanted into said subject.

12. The device of claim 11 , wherein said device is configured to be implanted into said subject by subcutaneous implantation, omentum implantation, intraperitoneal implantation, or intramuscular implantation.

13. The device of claim 11 , wherein said device is configured to be implanted into brain, spinal cord, pancreas, liver, uterus, skin, bladder, kidney, or muscle of said subject.

14. The device of claim 1 , wherein said subject is selected from the group consisting of: a human, a monkey, a dog, a cat, a cow, a horse, a pig, a sheep, a goat, a bear, a panda, a lion, a tiger, a leopard, an elephant, a zebra, a giraffe, a gorilla, a dolphin, and a whale.

15. A method comprising implanting into a subject in need thereof a device according to claim 1 , wherein said device further comprises a therapeutically effective amount of one or more therapeutic molecules, thereby treating said subject in need thereof.

16. The method of claim 15 , wherein said subject in need thereof has or is suspected of having diabetes mellitus.

17. The method of claim 16 , wherein said device further comprises a therapeutically effective amount of a plurality of insulin-secreting cells.

18. The method of claim 15 , wherein said device is implanted in said subject in need thereof for at least 5 months.

19. The method of claim 18 , wherein said device does not elicit a significant foreign body response.

20. The device of claim 1 , wherein said device is circular, elliptical, square, rectangular, or a combination thereof.

21. The device of claim 1 , wherein said device is fabricated from PCL polymer.

Assignees

• Univ California

Inventors

• Desai Tejal Ashwin
• Nyitray Crystal
• Chang Ryan

Classifications

• A61K9/0024 Primary

  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 title

• A61F2/022

  Artificial gland structures using bioreactors (hemodialysis A61M1/16; hemofiltration A61M1/34; other extracorporeal blood treatment A61M1/36) · CPC title

• C12N5/0012 Primary

  Cell encapsulation · CPC title

• C12N5/0676

  Pancreatic cells · CPC title

• A61K47/34

  Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers (A61K47/10 takes precedence) · CPC title