Cell storage and delivery system

• US 20050014252A1
• Filed: 08/17/2004
• Published: 01/20/2005
• Est. Priority Date: 09/14/2001
• Status: Active Grant

• Current Assignee: The Research Foundation for The State University of New York (State University of New York)
• Original Assignee: The Research Foundation for The State University of New York (State University of New York)
• Inventors: Chu, Benjamin, Fang, Dufei, Hsiao, Benjamin S., Zong, Xinhua, Hadjiargyrou, Michael, Kim, Kwangsok
• Granted Patent: US 7,323,190 B2
• Time in Patent Office: Days
• US Class Current: 435/325
• CPC Class Codes: A61F 2/28 Bones joints A61F2/30
• CPC Class Codes: A61F 2/30756 Cartilage endoprostheses A61F2/3603 takes precedence
• CPC Class Codes: A61K 35/32 Bones; Osteocytes; Osteoblasts; Tendons; Tenocytes; Teeth; Odontoblasts; Cartilage; Chondrocytes; Synovial membrane
• CPC Class Codes: A61K 9/70 Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug hollow drug-filled fibres A61K9/0092
• CPC Class Codes: C12N 2533/40 Polyhydroxyacids, e.g. polymers of glycolic or lactic acid (PGA, PLA, PLGA); Bioresorbable polymers
• CPC Class Codes: C12N 5/0068 General culture methods using substrates for specific animal cell type C12N5/06
• CPC Class Codes: G06Q 30/02 Marketing; Price estimation or determination; Fundraising

Abstract

Cell storage and delivery systems and methods for storing and delivering viable cells to a mammal are disclosed. The cell storage and delivery systems include a biodegradable and/or bioabsorbable fibrous matrix physically associated with viable cells to contain and release the cells at a controlled rate. The biodegradable and/or bioabsorable matrix can be formed by electrospinning fibers of biodegradable and/or bioabsorbable fiberizable material. The methods include methods for storing viable cells and for delivering viable cells to a mammal using the cell storage and delivery system.

Claims

1. A cell delivery system comprising a biodegradable and/or bioabsorbable fibrous matrix containing at least about 20 weight percent of fibers having fiber diameters in the range of about 10 up to about 1000 nanometers of a biodegradable and/or bioabsorbable fiberizable material, and viable cells physically associated with said matrix as a carrier whereby said cells are contained and released at a controlled rate.

2. A cell delivery system according to claim 1, wherein said viable cells are tissue precursor cells selected from the group consisting of differentiated cells obtained from living tissue, cells pre-selected to differentiate into specific cell types and undifferentiated cells.

3. A cell delivery system according to claim 1, wherein said biodegradable and/or bioabsorbable fiberizable material comprises a biodegradable and/or bioabsorbable polymer.

4. A cell delivery system according to claim 3, wherein said biodegradable and/or bioabsorbable polymer comprises a monomer selected from the group consisting of a glycolide, lactide, dioxanone, caprolactone, trimethylene carbonate, ethylene glycol and lysine.

5. A cell delivery system according to claim 3, wherein said biodegradable and/or bioabsorbable polymer comprises a biodegradable and/or bioabsorbable linear aliphatic polyester.

6. A cell delivery system according to claim 5, wherein said biodegradable and/or bioabsorbable linear aliphatic polyester is a polyglycolide or a copolymer poly(glycolide-co-lactide).

7. A cell delivery system according to claim 1, wherein said biodegradable and/or bioabsorbable fiberizable material comprises a material derived from biological tissue.

8. A cell delivery system according to claim 1, wherein said fibers have diameters in the range from about 20 to about 500 nanometers.

9. A cell delivery system according to claim 1, further comprising a layered structure which comprises:

said biodegradable and/or bioabsorbable matrix in the form of a relatively thick base layer,

a dispersion of cells dispersed over the surface of said base layer, and

a top coating of a biological gel material covering said dispersion of cells and adhered to the surface of said base layer.

10. A cell delivery system according to claim 9, wherein said biological gel material comprises a material selected from the group consisting of collagen, gelatin, polypeptides, proteins, hyaluronic acid and derivatives or synthetic biopolymers and their mixtures.

11. A method for delivery of viable cells to a mammal, said method comprising:

(a) providing a cell delivery system according to claim 1;

and

(b) positioning said cell delivery system at a desired location for cell delivery to the mammal.

12. A method according to claim 11, said cell delivery system further comprising a layered structure which comprises:

a relatively thick base layer of the biodegradable and/or bioabsorbable fibrous matrix,

a dispersion of viable cells dispersed over the surface of said base layer, and

a relatively thin top layer of the biodegradable and/or bioabsorbable fibrous matrix covering said dispersion of cells and adhered to the surface of said base layer, said top layer having sufficient porosity to allow transfer of O₂ and nutrients from outside the top layer to the cells and transfer of CO₂ from the cells to the outside of the top layer.

13. A method according to claim 12, wherein said cell delivery system further comprises a partition layer disposed on at least one surface of said layered structure.

14. A method according to claim 11, said cell delivery system further comprising a layered structure which comprises:

said biodegradable and/or bioabsorbable matrix in the form of a relatively thick base layer,

a dispersion of cells dispersed over the surface of said base layer, and

a top coating of a biological gel material covering said dispersion of cells and adhered to the surface of said base layer.

15. A method according to claim 14, wherein said biological gel material comprises a material selected from the group consisting of collagen, gelatin, polypeptides, proteins, hyaluronic acid and derivatives or synthetic biopolymers and their mixtures.

16. A method for storage of living cells for delivery into a mammal, said method comprising:

(a) providing a cell delivery system comprising;

(i) viable cells; and

(ii) a biodegradable and/or bioabsorbable fibrous matrix physically associated with said cells to contain and release said cells at a controlled rate;

(b) cooling said cell delivery system down to a preservation temperature under conditions which maintain the integrity of said system; and

(c) maintaining said cell delivery system at or below said preservation temperature until a time when delivery is desired.

17. A method according to claim 16, wherein said viable cells are tissue precursor cells selected from the group consisting of differentiated cells obtained from living tissue, cells pre-selected to differentiate into specific cell types and undifferentiated cells.

18. A method according to claim 16, wherein said biodegradable and/or bioabsorabale fibrous matrix is formed by electrospinning fibers of biodegradable and/or bioabsorbable fiberizable materials.

19. A method according to claim 18, wherein said biodegradable and/or bioabsorbable fiberizable material comprises a biodegradable and/or bioabsorbable polymer.

20. A method according to claim 19, wherein said biodegradable and/or bioabsorbable polymer comprises a monomer selected from the group consisting of a glycolide, lactide, dioxanone, caprolactone, trimethylene carbonate, ethylene glycol and lysine.

21. A method according to claim 19, wherein said biodegradable and/or bioabsorbable polymer comprises a biodegradable and/or bioabsorbable linear aliphatic polyester.

22. A method according to claim 21, wherein said biodegradable and/or bioabsorbable linear aliphatic polyester is a polyglycolide or a copolymer poly(glycolide-co-lactide).

23. A method according to claim 18, wherein said biodegradable and/or bioabsorbable fiberizable material comprises a material derived from biological tissue.

24. A method according to claim 18, wherein said fibers have diameters in the range from about 10 up to 1,000 nanometers.

25. A method according to claim 24, wherein said fibers have diameters in the range from about 20 to about 500 nanometers.

26. A method according to claim 16, said cell delivery system further comprising a layered structure which comprises:

a relatively thick base layer of a biodegradable and/or bioabsorbable fibrous matrix,

a dispersion of viable cells dispersed over the surface of said base layer,

a relatively thin top layer of a biodegradable and/or bioabsorbable fibrous matrix covering said dispersion of cells and adhered to the surface of said base layer, said top layer having sufficient porosity to allow transfer of O₂ and nutrients from outside the top layer to the cells and transfer of CO₂ from the cells to the outside of the top layer.

27. A method according to claim 26, further comprising a partition layer disposed on at least one surface of said layered structure.

28. A method according to claim 26, wherein said cell delivery system further comprises a supply of nutrients for said cells.

29. A method according to claim 28, wherein said nutrients are selected from the group consisting of sugars, amino acids, growth factors, vitamins, hormones, cytokines and mixtures thereof.

30. A method according to claim 28, wherein said nutrients are contained within said fibers.

31. A method according to claim 26, wherein said base layer has a thickness in the range of about 20 to about 500 microns.

32. A method according to claim 31, wherein said base layer has a thickness in the range of about 50 to about 250 microns.

33. A method according to claim 26, wherein said top layer has a thickness in the range of about 1 to about 50 microns.

34. A method according to claim 33, wherein said top layer has a thickness in the range of about 5 to about 20 microns.

35. A method according to claim 16, wherein said preservation temperature is below at least about −

50°

C.

36. A method according to claim 35, wherein said cooling step is carried out by submerging said cell delivery system in liquid nitrogen.

37. A method according to claim 16, said cell delivery system further comprising a layered structure which comprises:

a relatively thick base layer of a biodegradable and/or bioabsorbable matrix,

a dispersion of cells dispersed over the surface of said base layer, and

a top coating of a biological gel material covering said dispersion of cells and adhered to the surface of said base layer.

38. A method according to claim 37, wherein said biological gel material comprises a material selected from the group consisting of collagen, gelatin, polypeptides, proteins, hyaluronic acid and derivatives or synthetic biopolymers and their mixtures.