Cell storage and delivery system

• US 20030054035A1
• Filed: 09/14/2001
• Published: 03/20/2003
• 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 6,790,455 B2
• Time in Patent Office: Days
• US Class Current: 424/486
• 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 bioabsorbable 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 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 bioabsorabale fibrous matrix is formed by electrospinning fibers of biodegradable and/or bioabsorbable fiberizable materials.

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

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

6. A cell delivery system according to claim 4, wherein said biodegradable and/or bioabsorbable polymer comprises a biodegradable and/or bioabsorbable linear aliphatic polyester.

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

8. A cell delivery system according to claim 3, wherein said biodegradable and/or bioabsorbable fiberizable material comprises a material derived from biological tissue.

9. A cell delivery system according to claim 3, wherein said fibers have diameters in the range from about 10 up to 1,000 nanometers.

10. A cell delivery system according to claim 9, wherein said fibers have diameters in the range from about 20 to about 500 nanometers.

11. A cell delivery system according to claim 3, 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 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, and

an optional partition layer disposed on at least one surface of said layered structure.

12. A cell delivery system according to claim 11, further comprising a supply of nutrients for said cells.

13. A cell delivery system according to claim 12, wherein said nutrients are selected from the group consisting of sugars, amino acids, growth factors, vitamins, hormones, cytokines and mixtures thereof.

14. A cell delivery system according to claim 12, wherein said nutrients are contained within said fibers.

15. A cell delivery system according to claim 11, wherein said system is capable of being frozen and returned to room temperature without adversely affecting the integrity of the fibrous layers or the viability of the cells.

16. A cell delivery system according to claim 11, wherein said base layer has a thickness in the range of about 20 to about 500 microns.

17. A cell delivery system according to claim 16, wherein said base layer has a thickness in the range of about 50 to about 250 microns.

18. A cell delivery system according to claim 11, wherein said top layer has a thickness in the range of about 1 to about 50 microns.

19. A cell delivery system according to claim 18, wherein said top layer has a thickness in the range of about 5 to about 20 microns.

20. A cell delivery system according to claim 3, 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.

21. A cell delivery system according to claim 20, 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.

22. 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.

23. A method according to claim 22, 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.

24. A method according to claim 22, wherein said biodegradable and/or bioabsorabale fibrous matrix is formed by electrospinning fibers of biodegradable and/or bioabsorbable fiberizable materials.

25. A method according to claim 24, wherein said biodegradable and/or bioabsorbable fiberizable material comprises a biodegradable and/or bio absorbable polymer.

26. A method according to claim 25, 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.

27. A method according to claim 25, wherein said biodegradable and/or bioabsorbable polymer comprises a biodegradable and/or bioabsorbable linear aliphatic polyester.

28. A method according to claim 27, wherein said biodegradable and/or bioabsorbable linear aliphatic polyester is a polyglycolide or a copolymer poly(glycolide-co-lactide).

29. A method according to claim 24, wherein said biodegradable and/or bioabsorbable fiberizable material comprises a material derived from biological tissue.

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

31. A method according to claim 30, wherein said fibers have diameters in the range from about 20 to about 500 nanometers.

32. A method according to claim 24, 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, and

an optional partition layer disposed on at least one surface of said layered structure.

33. A method according to claim 32, wherein said cell delivery system further comprises a supply of nutrients for said cells.

34. A method according to claim 33, wherein said nutrients are selected from the group consisting of sugars, amino acids, growth factors, vitamins, hormones, cytokines and mixtures thereof.

35. A method according to claim 33, wherein said nutrients are contained within said fibers.

36. A method according to claim 32, wherein said base layer has a thickness in the range of about 20 to about 500 microns.

37. A method according to claim 36, wherein said base layer has a thickness in the range of about 50 to about 250 microns.

38. A method according to claim 32, wherein said top layer has a thickness in the range of about 1 to about 50 microns.

39. A method according to claim 38, wherein said top layer has a thickness in the range of about 5 to about 20 microns.

40. A method according to claim 22, wherein said preservation temperature is below at least about −

50°

C.

41. A method according to claim 40, wherein said cooling step is carried out by submerging said cell delivery system in liquid nitrogen.

42. A method according to claim 24, 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.

43. A method according to claim 42, 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.

44. A method for delivery of viable cells to 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; and

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

45. A method according to claim 44, 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.

46. A method according to claim 44, wherein said biodegradable and/or bioabsorabale fibrous matrix is formed by electrospinning fibers of biodegradable and/or bioabsorbable fiberizable material.

47. A method according to claim 46, wherein said biodegradable and/or bioabsorbable fiberizable material comprises a biodegradable and/or bioabsorbable polymer.

48. A method according to claim 47, 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.

49. A method according to claim 47, wherein said biodegradable and/or bioabsorbable polymer comprises a biodegradable and/or bioabsorbable linear aliphatic polyester.

50. A method according to claim 49, wherein said biodegradable and/or bioabsorbable linear aliphatic polyester is a polyglycolide or a copolymer poly(glycolide-co-lactide).

51. A method according to claim 46, wherein said biodegradable and/or bioabsorbable fiberizable material comprises a material derived from biological tissue.

52. A method according to claim 46, wherein said fibers have diameters in the range from about 10 up to 1,000 nanometers.

53. A method according to claim 52, wherein said fibers have diameters in the range from about 20 to about 500 nanometers.

54. A method according to claim 46, 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, and

an optional partition layer disposed on at least one surface of said layered structure.

55. A method according to claim 54, wherein said cell delivery system further comprises a supply of nutrients for said cells.

56. A method according to claim 55, wherein said nutrients are selected from the group consisting of sugars, amino acids, growth factors, vitamins, hormones, cytokines and mixtures thereof.

57. A method according to claim 55, wherein said nutrients are contained within said fibers.

58. A method according to claim 54, wherein said cell delivery system is capable of being frozen and returned to room temperature without adversely affecting the integrity of the fibrous layers or the viability of the cells.

59. A method according to claim 54, wherein said base layer has a thickness in the range of about 20 to about 500 microns.

60. A method according to claim 59, wherein said base layer has a thickness in the range of about 50 to about 250 microns.

61. A method according to claim 54, wherein said top layer has a thickness in the range of about 1 to about 50 microns.

62. A method according to claim 61, wherein said top layer has a thickness in the range of about 1 to about 20 microns.

63. A method according to claim 46, 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.

64. A method according to claim 63, 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.