Tissue engineering composite

• US 20020022883A1
• Filed: 06/12/2001
• Published: 02/21/2002
• Est. Priority Date: 06/13/2000
• Status: Active Grant

• Current Assignee: Clemson University
• Original Assignee: Clemson University
• Inventors: Burg, Karen J.L.
• Granted Patent: US 6,991,652 B2
• Time in Patent Office: Days
• US Class Current: 623/8
• CPC Class Codes: A61F 2/0059 Cosmetic or alloplastic implants A61F2/10 - A61F2/16, A61F2/28 take precedence
• 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: A61F 2/3099 for temporo-mandibular [TM, TMJ] joints endoprostheses for mandibular reconstruction A61F2/2803
• CPC Class Codes: A61F 2/442 Intervertebral or spinal discs, e.g. resilient non-disc-shaped intervertebral inflatable pockets A61F2/441; non-disc-shaped intervertebral fusion implants A61F2/4455
• CPC Class Codes: A61F 2002/2817 Bone stimulation by chemical reactions or by osteogenic or biological products for enhancing ossification, e.g. by bone morphogenetic or morphogenic proteins [BMP] or by transforming growth factors [TGF]
• CPC Class Codes: A61F 2002/30062 (bio)absorbable, biodegradable, bioerodable, (bio)resorbable, resorptive
• CPC Class Codes: A61F 2210/0004 bioabsorbable
• CPC Class Codes: A61F 2310/00365 Proteins; Polypeptides; Degradation products thereof
• CPC Class Codes: A61F 2310/00982 Coating made of collagen
• CPC Class Codes: A61L 27/48 with macromolecular fillers
• CPC Class Codes: A61L 27/50 Materials characterised by their function or physical properties , e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
• CPC Class Codes: A61L 27/52 Hydrogels or hydrocolloids
• CPC Class Codes: A61L 27/56 Porous materials, e.g. foams or sponges

Abstract

The invention provides a biocompatible composite for use in a living subject for purposes of repairing damaged tissues and reconstructing a new tissue. The composite includes a biodegradable or absorbable three-dimensional support construct, a liquid or viscous fluid forming a gel matrix or viscous fluid when delivered to an area of interest in a living subject. The biodegradable construct provides an ideal surface for cell or cell extract attachment, while the gel matrix or viscous fluid acts as both a carrier material and a separator for maintaining the space between the constructs as well as the structural integrity of the developing issue.

Claims

1. A composite for use in a living subject comprising a biocompatible three-dimensional porous support construct, and a carrier comprising a liquid or viscous fluid forming a gel matrix or viscous fluid when delivered into the body of a living subject.

2. The composite of claim 1, wherein said three-dimensional construct is a biodegradable or absorbable material.

3. The composite of claim 2, wherein said three-dimensional construct is a material selected from the group consisting of chitosan, agarose, alginate, collagen, hyaluronic acid, and carrageenan, demineralized bone matrix, and the like, and copolymers of the same.

4. The composite of claim 2, wherein said three-dimensional construct is a material selected from the group consisting of polylactide, chondroitin sulfate, polyesters, polyethylene glycols, polycarbonates, polyvinyl alcohols, polyacrylamides, polyamides, polyacrylates, polyesters, polyetheresters, polymethacrylates, polyurethanes, polycaprolactone, polyphophazenes, polyorthoesters, polyglycolide, copolymers of lysine and lactic acid, copolymers of lysine-RGD and lactic acid, and the like, and copolymers of the same.

5. The composite of claim 1, wherein said three-dimensional construct is less than about 1.5 mm in diameter.

6. The composite of claim 1, wherein said gel matrix or viscous fluid is a biodegradable or absorbable material.

7. The composite of claim 6, wherein said gel matrix or viscous fluid is a material selected from the group consisting of agarose, alginate, carrageenan and chitosan, and derivatives thereof.

8. The composite of claim 6, wherein said gel matrix or viscous fluid is a material selected from the group consisting of derivatives of polylactide, chondroitin sulfate, polyesters, polyethylene glycols, polycarbonates, polyvinyl alcohols, polyacrylamides, polyamides, polyacrylates, polyesters, polyetheresters, polymethacrylates, polyurethanes, polycaprolactone, polyphophazenes, polyorthoesters, polyglycolide, copolymers of lysine and lactic acid, copolymers of lysine-RGD and lactic acid, dextran, dextrin, starch, cellulose, demineralized bone matrix and the like and copolymers of the same.

9. The composite of claim 1, wherein said gel matrix or viscous fluid is a non-biodegradable material.

10. The composite of claim 9, wherein said non-biodegradable gel matrix or viscous fluid is a hydrated triblock polymer poly(ethylene oxide)-poly(propylene oxide)-poly(oxide).

11. The composite of claim 1, wherein said gel matrix or viscous fluid has a viscosity of from 10 to about 1000 cps.

12. The composite of claim 1, wherein the volume ration of said three-dimensional construct to said carrier is from abut 1:

2 to about 5;

1.

15. The composite of claim 14, wherein said three-dimensional construct is a biodegradable or absorbable material.

16. The composite of claim 15, wherein said three-dimensional construct is a material selected from the group consisting of chitosan, agarose, alginate, collagen, hyaluronic acid, and carrageenan, demineralized bone matrix, and the like, and copolymers of the same.

17. The composite of claim 15, wherein said three-dimensional construct is a material selected from the group consisting of polylactide, chondroitin sulfate, polyesters, polyethylene glycols, polycarbonates, polyvinyl alcohols, polyacrylamides, polyamides, polyacrylates, polyesters, polyetheresters, polymethacrylates, polyurethanes, polycaprolactone, polyphophazenes, polyorthoesters, polyglycolide, copolymers of lysine and lactic acid, copolymers of lysine-RGD and lactic acid, and the like, and copolymers of the same.

18. The composite of claim 14, wherein said three-dimensional construct is less than about 1.5 mm in diameter.

19. The composite of claim 14, wherein said carrier is a biodegradable or absorbable material.

20. The composite of claim 19, wherein said carrier is a material selected from the group consisting of chitosan, polylactide, chondroitin sulfate, polyesters, polyethylene glycol, and derivatives thereof.

21. The composite of claim 19 wherein said carrier is a material selected from the group consisting of derivatives of polylactide, chondroitin sulfate, polyesters, polyethylene glycols, polycarbonates, polyvinyl alcohols, polyacrylamides, polyamides, polyacrylates, polyesters, polyetheresters, polymethacrylates, polyurethanes, polycaprolactone, polyphophazenes, polyorthoesters, polyglycolide, copolymers of lysine and lactic acid, copolymers of lysine-RGD and lactic acid, dextran, dextrin, starch, cellulose, demineralized bone matrix and the like and copolymers of the same.

22. The composite of claim 14, wherein said carrier is a non-biodegradable material.

23. The composite of claim 22, wherein said non-biodegradable carrier is a hydrated triblock polymer poly(ethylene oxide)-poly(propylene oxide)-poly(oxide).

24. The composite of claim 14, wherein said carrier has a viscosity of from 10 to about 1000 cps.

25. The composite of claim 14, wherein the volume ration of said three-dimensional construct to said carrier is from abut 1:

2 to about 5;

1.

26. The composite of claim 14, wherein said three-dimensional construct further comprises a coating of a material selected from the group consisting of fibronectin, vitronectin, collagens, polylysine, laminins, alginate-RGD hydrogel and polypeptides derived from extra-cellular matrices.

27. The composite of claim 14, wherein said three-dimensional construct further comprises a signal for modifying cell adhesion, growth, or migration.

28. The composite of claim 14, wherein said signal is selected from growth factors, hormones, extracellular matrix proteins, and cell adhesion peptides.

30. The composite of claim 29, wherein said three-dimensional construct further comprises a coating of a material selected from the group consisting of fibronectin, vitronectin, collagens, polylysine, laminins, alginate-RGD hydrogel and polypeptides derived from extra-cellular matrices.

31. The composite of claim 29, wherein said three-dimensional construct further comprises a signal for modifying cell adhesion, growth, or migration.

32. The composite of claim 29, wherein said signal is selected from growth factors, hormones, extracellular matrix proteins, and cell adhesion peptides.

13. A composite for use in a living subject comprising:

a biocompatible porous three-dimensional construct comprising a material selected from the group consisting of alginate, collagen, polylactide, polyethylene glycol, polycaprolactone, polycolide, polydioxanone, and derivatives and copolymers thereof and having a size no greater than about 1.5 mm in diameter, and

a carrier comprising a liquid or viscous fluid forming a gel matrix or a viscous fluid when injected into the body of a living subject said gel matrix or viscous fluid selected from the group consisting of biodegradable materials and non-biodegradable materials, each have a viscosity of from 10 to 1000 cps.

14. A composite for use in a living subject comprising:

a biocompatible three-dimensional construct, a carrier comprising a liquid or viscous fluid forming a gel matrix or viscous fluid when injected into the body of a living subject, and cells disposed in said biocompatible three-dimensional support construct.

29. A composite for use into a living subject comprising:

a biocompatible porous three-dimensional construct comprising a material selected from the group consisting of alginate, collagen, polylactide, polyethylene glycol, polycaprolactone, polycolide, polydioxanone, and derivatives and copolymers thereof and having a size no greater than about 1.5 mm in diameter,

a carrier comprising a liquid or viscous fluid capable of forming a carrier when injected into the body of a living subject said gel matrix selected form the group consisting of biodegradable materials and non-biodegradable materials, each having a viscosity of from 10 to 1000 cps; and

cells disposed in said biocompatible three-dimensional construct.

33. A composite for use in a living subject comprising:

a biocompatible three-dimensional construct, a carrier comprising a liquid or viscous fluid forming a gel matrix or viscous fluid when injected into the body of a living subject, and cells disposed in said carrier.

34. The composite of claim 33, wherein said three-dimensional construct is a biodegradable or absorbable material.

35. The composite of claim 34, wherein said three-dimensional construct is a material selected from the group consisting of chitosan, agarose, alginate, collagen, hyaluronic acid, and carrageenan, demineralized bone matrix, and the like, and copolymers of the same.

36. The composite of claim 34, wherein said three-dimensional construct is a material selected from the group consisting of polylactide, chondroitin sulfate, polyesters, polyethylene glycols, polycarbonates, polyvinyl alcohols, polyacrylamides, polyamides, polyacrylates, polyesters, polyetheresters, polymethacrylates, polyurethanes, polycaprolactone, polyphophazenes, polyorthoesters, polyglycolide, copolymers of lysine and lactic acid, copolymers of lysine-RGD and lactic acid, and the like, and copolymers of the same.

37. The composite of claim 33, wherein said three-dimensional construct is less than about 1.5 mm in diameter.

38. The composite of claim 33, wherein said carrier is a biodegradable or absorbable material.

39. The composite of claim 33, wherein said carrier is a material selected from the group consisting of chitosan, polylactide, chondroitin sulfate, polyesters, polyethylene glycol, and derivatives thereof.

40. The composite of claim 38, wherein said carrier is a material selected from the group consisting of derivatives of polylactide, chondroitin sulfate, polyesters, polyethylene glycols, polycarbonates, polyvinyl alcohols, polyacrylamides, polyamides, polyacrylates, polyesters, polyetheresters, polymethacrylates, polyurethanes, polycaprolactone, polyphophazenes, polyorthoesters, polyglycolide, copolymers of lysine and lactic acid, copolymers of lysine-RGD and lactic acid, dextran, dextrin, starch, cellulose, demineralized bone matrix and the like and copolymers of the same.

41. The composite of claim 33, wherein said carrier is a non-biodegradable material.

42. The composite of claim 41, wherein said non-biodegradable carrier is a hydrated triblock polymer poly(ethylene oxide)-poly(propylene oxide)-poly(oxide).

43. The composite of claim 33, wherein said carrier has a viscosity of from 10 to about 1000 cps.

44. The composite of claim 33, wherein the volume ration of said three-dimensional construct to said carrier is from abut 1:

2 to about 5;

1.

45. The composite of claim 33, wherein said three-dimensional construct further comprises a coating of a material selected from the group consisting of fibronectin, vitronectin, collagens, polylysine, laminins, alginate-RGD hydrogel and polypeptides derived from extra-cellular matrices.

46. The composite of claim 33, wherein said three-dimensional construct further comprises a signal for modifying cell adhesion, growth, or migration.

47. The composite of claim 33, wherein said signal is selected from growth factors, hormones, extracellular matrix proteins, and cell adhesion peptides.

48. The composite of claim 33, wherein said three-dimensional support construct further includes cells dispersed therein.

50. The composite of claim 49, wherein said three-dimensional construct further comprises a coating of a material selected from the group consisting of fibronectin, vitronectin, collagens, polylysine, laminins, alginate-RGD hydrogel and polypeptides derived from extra-cellular matrices.

51. The composite of claim 49, wherein said three-dimensional construct further comprises a signal for modifying cell adhesion, growth, or migration.

52. The composite of claim 49, wherein said signal is selected from growth factors, hormones, extracellular matrix proteins, and cell adhesion peptides.

49. A composite for use in a living subject comprising:

a biocompatible porous three-dimensional construct comprising a material selected from the group consisting of alginate, collagen, polylactide, polyethylene glycol, polycaprolactone, polycolide, polydioxanone, and derivatives and copolymers thereof and having a size no greater than about 1.5 mm in diameter,

a carrier comprising a liquid or viscous fluid capable of forming a gel matrix or viscous fluid when injected into the body of a living subject said gel matrix selected form the group consisting of biodegradable materials and non-biodegradable materials, each having a viscosity of from 10 to 1000 cps; and

cells disposed in said biocompatible three-dimensional support construct and said carrier.

53. A method of providing cells or tissue in a living subject comprising delivering into an area of interest in said living subject a composite comprising:

(a) a biocompatible three-dimensional support construct having a porous structure which supports cell adhesion, growth and migration; and

(b) a carrier comprising a liquid or viscous fluid forming a gel matrix or viscous fluid when delivered into the body of a living subject.

54. The method of providing cells or tissue in a living subject according to claim 53 wherein said composite further comprises;

(c) cells disposed in said carrier, wherein said carrier embeds the cells dispersed therein and prevents undue compression of the construct.

55. The method of providing cells or tissue in a living subject according to claim 53 wherein said composite further comprises;

(c) cells disposed in said support construct.

56. The method of providing cells or tissue in a living subject according to claim 53 wherein said composite further comprises;

(c) cells disposed in said support construct and in said carrier, wherein said carrier embeds the cells dispersed therein and prevents undue compression of the construct.

57. The method of providing cells or tissue in a living subject according to claim 53, wherein delivery of said composite is by injection.

58. The method of providing cells or tissue in a living subject according to claim 53, wherein said composite further comprises seeding said cell or tissue in said biodegradable or absorbable three-dimensional carrier;

and culturing said cell or tissue in vitro.

59. The method of providing cells or tissue in a living subject according to claim 53, wherein said construct further comprises a signal for modifying cell adhesion, growth, or migration.

60. The method of providing cells or tissue in a living subject according to claim 53, wherein said signal is selected from growth factors, hormones, extracellular matrix proteins, and cell adhesion peptides.

61. The method of claim 53, wherein said carrier has a viscosity of from 10 to about 1000 cps.

62. The method of claim 53, wherein said carrier is biodegradable.

63. The method of claim 53, wherein said carrier comprises a material selected from the group consisting of agarose, alginate, carreenan and chitosan, and derivatives thereof.

64. The method of claim 53, wherein the area of interest in said living subject is a spinal disc in the human.

65. The method of claim 53, wherein the area of interest in said living subject is a bone in the human.

66. The method of claim 53, wherein the area of interest in said living subject is a nipple in the human.

67. The method of claim 53, wherein the area of interest in said living subject is a breast in the human.

68. The method of claim 53, wherein the area of interest in said living subject is a face or head of the human.

69. The method of claim 53, wherein the area of interest in said living subject is cartilage.

70. The method of claim 53, wherein the area of interest in said living subject is trunk soft tissue.

71. The method of claim 53, wherein the area of interest in said living subject is temporomandibular region.

72. The method of claim 53, wherein the area of interest in said living subject is alveolar ridge region.

73. A method for repairing a defect in a breast of a female patient, comprising:

providing an injectable composite comprising a biocompatible, biodegradable three-dimensional support construct made of collagen and containing cells obtained from said patient and selected from the group consisting of fibroblasts, smooth muscle cells, endothelial cells, mesenchymal cells, and a carrier comprising an alginate carrier, and

injecting said composite into the area of the defect in the breast of the patient.

74. A method for repairing a defect in a breast of a female patient, comprising:

providing an injectable composite comprising a biocompatible, biodegradable three-dimensional support construct made of collagen and containing cells obtained from a cell bank and selected from the group consisting of fibroblasts, smooth muscle cells, endothelial cells, mesenchymal cells, and a carrier comprising an alginate carrier, and

injecting said composite into the area of the defect in the breast of the patient.

75. A method for repairing a defect in a breast of a female patient, comprising:

providing an injectable composite comprising a biocompatible, biodegradable three-dimensional support construct made of polylactide based material and containing cells obtained from said patient and selected from the group consisting of fibroblasts, smooth muscle cells, endothelial cells, mesenchymal cells, and a carrier comprising an alginate carrier, and

injecting said composite into the area of the defect in the breast of the patient.

76. A method for repairing a facial defect in a patient, comprising:

providing an injectable composite comprising a biocompatible, biodegradable three-dimensional support construct made of collagen and containing cells obtained from said patient and selected from the group consisting of fibroblasts, smooth muscle cells, endothelial cells, mesenchymal cells, and a carrier comprising an alginate carrier, and

injecting said composite into the area of the defect in the breast of the patient.

77. A method for repairing a facial defect in a patient, comprising:

providing an injectable composite comprising a biocompatible, biodegradable porous three-dimensional support construct made from collagen and, a carrier comprising alginate; and

injecting said composite into the area of the defect in the face of the patient.

78. A method for repairing a defect in a nipple of a female patient, comprising:

providing an injectable composite comprising a biocompatible, biodegradable porous three-dimensional construct of collagen, and a carrier comprising alginate; and

injecting said composite into the area of the defect in the nipple of the patient.

79. A method for repairing a spinal disc in a patient, comprising:

providing an injectable composite comprising a biocompatible, biodegradable porous three-dimensional construct of collagen, said construct containing intervertebral disc cells obtained from said patient, and a carrier comprising alginate; and

injecting said composite into the spinal disc in the patient.

80. A method for repairing a defect in a bone of a patient, comprising:

providing an injectable composite comprising a biocompatible, biodegradable three-dimensional construct made from polylactide osteoblast cells obtained from said patient, and a carrier comprising alginate, and

injecting said composite into the defective area of the bone in the patient.