Multi-Layer Hydrogel Capsules for Encapsulation of Cells and Cell Aggregates
AssigneeMassachusetts Institute of Technology
InventorsMinglin Ma, Daniel G. Anderson, Robert S. Langer, Omid Veiseh, Arturo Jose Vegas, Joshua Charles Doloff
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Abstract
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.
Claims20
Hydrogel capsules encapsulating cells,
- wherein the capsules consist of three layers,
- a first an inner acellular core layer,
- a second hydrogel layer containing cells to be transplanted selected from the group consisting of mammalian secretory, metabolic and structural cells and aggregates thereof, and
- an outer acellular barrier or structural layer.
The capsules of claim 11, wherein the hydrogel is a polysaccharide selected from the group consisting of alginate, chitosan, hyaluronan, and chondroitin sulfate.
Hydrogel capsules encapsulating cells,
- wherein the capsules consist of two or more layers,
- a hydrogel layer containing cells to be transplanted selected from the group consisting of mammalian secretory, metabolic and structural cells and aggregates thereof, and
- an outer acellular barrier or structural layer,
- wherein the capsule has a diameter of at least 1 mm and less than 8 mm and elicits less of a fibrotic reaction after implantation than the same capsule having a diameter of less than 1 mm.
A method of making hydrogel capsules encapsulating cells,
- wherein the capsules consist of three layers,
- a first an inner acellular core layer,
- a second hydrogel layer containing cells to be transplanted selected from the group consisting of mammalian secretory, metabolic or structural cells or aggregates thereof, and
- an outer acellular barrier or structural layer comprising
- Providing an electrospraying device with a nozzle that consists of three separate concentric tubes at its outlet,
- Pumping a hydrogel forming material, optionally including one or more anti-inflammatory drugs or imaging reagents, into the innermost tube of the nozzle,
- Pumping a second stream that contains hydrogel forming material and cells to be encapsulated into the middle tube of the nozzle, and
- Pumping a third stream that contains a hydrogel forming material into the outermost tube,
- Wherein the three streams meet at the outlet of the nozzle, and the viscosity of the hydrogel solution prevents any significant intermixing among the three streams, so that droplets with three distinct concentric layers are formed under the electric field, and
- Allowing the droplets to fall into a gel bath which contains divalent ions to crosslink the hydrogel and form and triple-layer capsules.
A method of making hydrogel capsules encapsulating cells,
- wherein the capsules consist of two or more layers,
- a hydrogel layer containing cells to be transplanted selected from the group consisting of mammalian secretory, metabolic or structural cells or aggregates thereof, and
- an outer acellular barrier or structural layer,
- wherein the capsule has a diameter of at least 1 mm and less than 8 mm and elicits less of a fibrotic reaction after implantation than the same capsule having a diameter of less than 1 mm, comprising
- providing a first hydrogel fluid and a second hydrogel fluid, the first having cells suspended therein, to a two-fluid co-axial electro-jet, where the relatively high viscosity of the two fluids and short interaction time between them prevents the fluids from intermixing under electrostatic force,
- forming microdroplets with core-shell structures and
- crosslinking the microdroplets to form hydrogel capsules in a gelling bath containing divalent crosslinking ions.
Dependencies are inferred from the claim text.