Cell-friendly inverse opal hydrogels for cell encapsulation, drug and protein delivery, and functional nanoparticle encapsulation

• US 10,647,959 B2
• Filed: 04/12/2012
• Issued: 05/12/2020
• Est. Priority Date: 04/27/2011
• Status: Active Grant

• Current Assignee: President and Fellows of Harvard College (Harvard Corporation)
• Original Assignee: President and Fellows of Harvard College (Harvard Corporation)
• Inventors: Mooney, David J., Kim, Jaeyun, Bencherif, Sidi A., Li, Weiwei Aileen
• Primary Examiner(s): Yamasaki, Robert J
• Application Number:
  US14/112,098
• Publication Number:
  US 20140178964A1
• Time in Patent Office: 2,952 Days
• Field of Search: None
• CPC Class Codes: A61L 2300/624 Nanocapsules
• CPC Class Codes: A61L 2400/08 Methods for forming porous structures using a negative form which is filled and then removed by pyrolysis or dissolution
• CPC Class Codes: A61L 27/38 containing added animal cells organs or tissue containing native cells A61L27/36
• CPC Class Codes: A61L 27/3834 Cells able to produce different cell types, e.g. hematopoietic stem cells, mesenchymal stem cells, marrow stromal cells, embryonic stem cells
• CPC Class Codes: A61L 27/52 Hydrogels or hydrocolloids
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: A61L 27/56 Porous materials, e.g. foams or sponges
• CPC Class Codes: B82Y 5/00 Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
• CPC Class Codes: C12N 2533/74 Alginate
• CPC Class Codes: C12N 5/0012 Cell encapsulation

Abstract

The invention provides polymer scaffolds for cell-based tissue engineering.

Claims

1. An inverse opal hydrogel scaffold device comprising a polymer matrix, a plurality of cells encapsulated in the polymer matrix, and a sacrificial porogen,

wherein said sacrificial porogen is a porogen polymer selected from the group consisting of an ionically-crosslinked polymer, a thermosensitive polymer, a thermoresponsive polymer, a pH-sensitive polymer, and a photocleavable polymer, and

wherein said sacrificial porogen is removable from said scaffold device by contact with a chelating agent, a change in temperature or pH, or exposure to light to form open, interconnected pores;

and

wherein said polymer matrix occupies an interstitial space between said sacrificial porogen.

2. The inverse opal hydrogel scaffold device of claim 1, wherein said plurality of cells encapsulated in said polymer matrix comprises an isolated eukaryotic cell.

3. The inverse opal hydrogel scaffold device of claim 2, wherein said polymer matrix is crosslinked.

4. The inverse opal hydrogel scaffold device of claim 2, wherein said isolated eukaryotic cell is a mesenchymal stem cell.

5. The inverse opal hydrogel scaffold device of claim 1, wherein said polymer matrix comprises a synthetic polymer.

6. The inverse opal hydrogel scaffold device of claim 1, wherein said polymer matrix comprises covalent crosslinking.

7. The inverse opal hydrogel scaffold device of claim 1, wherein said polymer matrix is selected from the group consisting of a poly(lactide-coglycolide) (PLGA), poly(acrylic acid), polyethylene glycol (PEG), and poly (vinyl alcohol).

8. The inverse opal hydrogel scaffold device of claim 1, wherein said sacrificial porogen is selected from the group consisting of alginate, collagen, and agarose.

9. The inverse opal hydrogel scaffold device of claim 1, wherein said ionically crosslinked polymer is alginate.

10. The inverse opal hydrogel scaffold device of claim 1, wherein said ionically crosslinked polymer is removable by adding a metal-chelating agent selected from the group consisting of citric acid, ethylenediamine, ethylenediaminetetraacetic acid (EDTA), diethylenetriaminepentaacetic acid (DTPA), and N,N-bis(carboxymethyl)glycine (NTA).

11. The inverse opal hydrogel scaffold device of claim 1, wherein said thermoresponsive polymer is poly(N-isopropylacrylamide).

12. The inverse opal hydrogel scaffold device of claim 1, wherein said hydrogel is modified with a cell-adhering peptide, wherein said cell-adhering peptide is Arg-Gly-Asp (RGD).

13. The inverse opal hydrogel scaffold device of claim 1, wherein said polymer matrix is crosslinked and wherein the scaffold device further comprises an agent encapsulated in said crosslinked polymer matrix.

14. The inverse opal hydrogel scaffold device of claim 13, wherein said agent is selected from the group consisting of a drug, a nanoparticle, a growth factor, and a protein.

15. The inverse opal hydrogel scaffold device of claim 14, wherein said nanoparticle is a magnetic nanoparticle or a gold nanoparticle.

16. An inverse opal hydrogel scaffold device comprising a polymer matrix, a plurality of cells encapsulated in the polymer matrix, and a sacrificial porogen,

wherein said sacrificial porogen is a porogen polymer selected from the group consisting of an ionically-crosslinked polymer, a thermosensitive polymer, a thermoresponsive polymer, a pH-sensitive polymer, and a photocleavable polymer,

wherein the hydrogel has open, interconnected pores after removal of the sacrificial porogen by contact with a chelating agent, a change in temperature or pH, or exposure to light,

wherein said polymer matrix comprises covalent crosslinking, and

wherein said polymer matrix further comprises an isolated eukaryotic cell encapsulated in said crosslinked polymer matrix which occupies an interstitial space between said sacrificial porogen.

17. The inverse opal hydrogel scaffold device of claim 16, wherein said polymer matrix comprises a synthetic polymer.

18. The inverse opal hydrogel scaffold device of claim 16, wherein said polymer matrix is selected from the group consisting of a poly(lactide-coglycolide) (PLGA), poly(acrylic acid), polyethylene glycol (PEG), and poly (vinyl alcohol).

19. The inverse opal hydrogel scaffold device of claim 16, wherein said sacrificial porogen is selected from the group consisting of alginate, collagen, and agarose.

20. The inverse opal hydrogel scaffold device of claim 16, wherein said ionically crosslinked polymer is alginate.

21. The inverse opal hydrogel scaffold device of claim 16, wherein said thermosensitive polymer is selected from the group consisting of agarose, gelatin, and collagen.

22. The inverse opal hydrogel scaffold device of claim 16, wherein said thermoresponsive polymer is poly(N-isopropylacrylamide).

23. The inverse opal hydrogel scaffold device of claim 16, wherein said isolated eukaryotic cell is a mesenchymal stem cell.

24. The inverse opal hydrogel scaffold device of claim 16, wherein the scaffold device further comprises an agent encapsulated in said polymer matrix and wherein said agent is selected from the group consisting of a drug, a growth factor, and a protein.