Porous tissue scaffoldings for the repair of regeneration of tissue

• US 6,333,029 B1
• Filed: 06/30/1999
• Issued: 12/25/2001
• Est. Priority Date: 06/30/1999
• Status: Expired due to Term

• Current Assignee: Endo-Surgery, Inc.
• Original Assignee: Ethicon Incorporated (Johnson & Johnson)
• Inventors: Vyakarnam, Murty N., Roller, Mark B., Scopelianos, Angelo George, Zimmerman, Mark C., Gorky, David V.
• Primary Examiner(s): Acquah, Samuel A.
• Application Number:
  US09/345,096
• Time in Patent Office: 909 Days
• Field of Search: 424/424, 424/425, 424/426, 424/443, 424/444, 424/446, 424/447, 424/93.1, 514/2, 514/772.3, 514/945, 521/50, 521/134, 521/182
• US Class Current: 424/93.1
• CPC Class Codes: A61F 2/06 Blood vessels
• 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 2002/30004 the prosthesis being made from materials having different values of a given property at different locations within the same prosthesis
• CPC Class Codes: A61F 2002/30011 differing in porosity
• CPC Class Codes: A61F 2002/30014 differing in elasticity, stiffness or compressibility
• CPC Class Codes: A61F 2002/30032 differing in absorbability or resorbability, i.e. in absorption or resorption time
• CPC Class Codes: A61F 2002/30062 (bio)absorbable, biodegradable, bioerodable, (bio)resorbable, resorptive
• CPC Class Codes: A61F 2002/30677 Means for introducing or releasing pharmaceutical products, e.g. antibiotics, into the body
• CPC Class Codes: A61F 2002/30766 Scaffolds for cartilage ingrowth and regeneration
• CPC Class Codes: A61F 2002/30784 Plurality of holes
• CPC Class Codes: A61F 2002/3092 having an open-celled or open-pored structure
• CPC Class Codes: A61F 2210/0004 bioabsorbable
• CPC Class Codes: A61F 2250/0014 having different values of a given property or geometrical feature, e.g. mechanical property or material property, at different locations within the same prosthesis
• CPC Class Codes: A61F 2250/0018 differing in elasticity, stiffness or compressibility
• CPC Class Codes: A61F 2250/0023 differing in porosity
• CPC Class Codes: A61F 2250/0029 differing in bending or flexure capacity
• CPC Class Codes: A61F 2250/003 differing in adsorbability or resorbability, i.e. in adsorption or resorption time
• CPC Class Codes: A61F 2250/0067 Means for introducing or releasing pharmaceutical products into the body
• CPC Class Codes: A61L 27/18 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 27/3817 : Cartilage-forming cells, e.g. pre-chondrocytes
• CPC Class Codes: A61L 27/56 : Porous materials, e.g. foams or sponges
• CPC Class Codes: A61L 31/06 : obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds A61L31/041 takes precedence
• CPC Class Codes: A61L 31/146 : Porous materials, e.g. foams or sponges
• CPC Class Codes: C08L 67/04 : Polyesters derived from hydroxycarboxylic acids, e.g. lactones C08L67/06 takes precedence
• CPC Class Codes: Y10S 623/915 : Method or apparatus for preparing biological material

Abstract

The present patent describes a three-dimensional inter-connected open cell porous foams that have a gradient in composition and/or microstructure through one or more directions. These foams can be made from a blend of absorbable and biocompatible polymers that are formed into foams having a compositional gradient transitioning from predominately one polymeric material to predominately a second polymeric material. These gradient foams are particularly well suited to tissue engineering applications and can be designed to mimic tissue transition or interface zones.

Claims

1. A biocompatible gradient foam comprising a biocompatible gradient foam having a first location and a second location wherein the biocompatible gradient foam has a substantially continuous transition in at least one characteristic selected from the group consisting of composition, stiffness, flexibility, bioabsorption rate and pore architecture from the first location to the second location of said biocompatible gradient foam.

2. The biocompatible gradient foam of claim 1 wherein the biocompatible gradient foam is bioabsorbable.

3. The biocompatible gradient foam of claim 1 wherein the biocompatible gradient foam is made from a bioabsorbable polymer selected from the group consisting of aliphatic polyesters, poly(amino acids), copoly(ether-esters), polyalkylenes oxalates, polyamides, poly(iminocarbonates), polyorthoesters, polyoxaesters, polyamidoesters, polyoxaesters containing amine groups poly(anhydrides), polyphosphazenes, biopolymers and blends thereof.

4. The biocompatible gradient foam of claim 3 wherein the bioabsorable polymer is an aliphatic polyester.

5. The biocompatible gradient foam of claim 4 wherein the aliphatic polyester is selected from the group consisiting of homopolymers and copolymers of lactide, lactic acid, glycolide, glycolic acid), ε

-caprolactone, p-dioxanone (1,4-dioxan-2-one), trimethylene carbonate (1,3-dioxan-2-one), alkyl derivatives of trimethylene carbonate, δ

-valerolactone, β

-butyrolactone, γ

-butyrolactone, ε

-decalactone, hydroxybutyrate, hydroxyvalerate, 1,4-dioxepan-2-one, 1,5,8,12-tetraoxacyclotetradecane-7,14-dione), 1,5-dioxepan-2-one, 6,6-dimethyl-1,4-dioxan-2-one and polymer blends thereof.

6. The biocompatible gradient foam of claim 3 wherein the aliphatic polyester is an elastomer.

7. The biocompatible gradient foam of claim 6 wherein the elastomer is selected from the group consisting of copolymers of ε

-caprolactone and glycolide;

copolymers of ε

-caprolactone and (L)lactide, copolymers of p-dioxanone (1,4-dioxan-2-one) and (L)lactide, copolymers of ε

-caprolactone and p-dioxanone, copolymers of p-dioxanone and trimethylene carbonate, copolymers of trimethylene carbonate and glycolide, copolymer of trimethylene carbonate and (L)lactide and blends thereof.

8. The biocompatible gradient foam of claim 4 wherein additionally present as a constituent of the biocompatible gradient foam is a second aliphatic polyester.

9. The biocompatible gradient foam of claim 3 wherein the biocompatible gradient foam has a substantially continuous transition in composition from the first location to the second location.

10. The biocompatible gradient foam of claim 9 wherein the biocompatible gradient foam has a substantially continuous transition in composition from a first ratio of at least two different aliphatic polyesters to a second ratio of said at least two different aliphatic polyesters from the first surface to the second surface.

11. The biocompatible gradient foam of claim 3 wherein the biocompatible gradient foam has a substantially continuous transition in stiffness from the first location to the second location.

12. The biocompatible gradient foam of claim 3 wherein the biocompatible gradient foam has a substantially continuous transition in bioabsorption rate from the first location to the second location.

13. The biocompatible gradient foam of claim 3 wherein the biocompatible gradient foam has a substantially continuous transition in flexibility from the first location to the second location.

14. The biocompatible gradient foam of claim 3 wherein the biocompatible gradient foam has a substantially continuous transition in architecture from the first location to the second location.

15. The biocompatible gradient foam of claim 14 wherein the biocompatible gradient foam has a substantially continuous transition in architecture from a substantially spherical pore shape to a columnar pore shape from the first location to the second location.

16. The biocompatible gradient foam of claim 14 wherein the substantially spherical pore'"'"'s size is from about 30 μ

m to about 150 μ

m.

17. The biocompatible gradient foam of claim 14 wherein the columnar pore'"'"'s diameter is from about 100 μ

m to about 400 μ

m with a length to diameter ratio of at least 2.

18. The biocompatible gradient foam of claim 1 wherein also present in the biocompatible gradient foam is a therapeutic agent.

19. The biocompatible gradient foam of claim 1 wherein additionally present is an agent is selected from the group consisting of antiinfectives, hormones, analgesics, anti-inflammatory agents, growth factors, chemotherapeutic agents, anti-rejection agents prostaglandins, RDG peptides and combinations thereof.

20. The biocompatible gradient foam of claim 19 wherein the growth factor is selected from the group consisting of bone morphogenic proteins, bone morphogenic-like proteins, epidermal growth factor, fibroblast growth factors, platelet derived growth factor, insulin like growth factor, transforming growth factors, vascular endothelial growth factor and combinations thereof.

21. The biocompatible gradient foam of claim 1 wherein the biocompatible gradient foam is filled with a biocomptible material selected from the group consisting of bioabsorbable synthetic polymers, biocompatible, bioabsorbable biopolymers, biocompatible ceramic materials and combinations thereof.

64. The biocompatible gradient foam of claim 1 wherein the biocompatible gradient foam is formed with an insert within the biocompatible gradient foam.

65. The biocompatible gradient foam of claim 64 wherein the insert is selected from the group consisting of films, scrims, woven textiles, knitted textiles, braided textiles, orthopedic implants, tubes and combinations thereof.

70. The biocompatible gradient foam of claim 1 wherein the biocompatible gradient foam is formed into a three-dimensional shaped structure.

71. The biocompatible gradient foam of claim 70 wherein the three-dimensional shaped structure is selected from the group consisting of tubular shapes, branched tubular shapes, spherical shapes, hemispherical shapes, three-dimensional polygonal shapes, ellipsoidal shapes, toroidal shapes, conical shapes, frusta conical shapes, pyramidal shapes, both as solid and hollow constructs and combination thereof.

22. A biocompatible foam comprising a biocompatible foam having a first surface and a second surface with interconnecting pores and channels.

23. The biocompatible foam of claim 22 wherein the channels have an average length of at least 200 μ

m.

24. The biocompatible foam of claim 22 wherein the channels extend substantially from said first surface to said second surface.

25. The biocompatible foam of claim 22 wherein the biocompatible foam is bioabsorbable.

26. The biocompatible foam of claim 22 wherein the biocompatible foam is made from a bioabsorbable polymer selected from the group consisting of aliphatic polyesters, poly(amino acids), copoly(ether-esters), polyalkylenes oxalates, polyamides, poly(iminocarbonates), polyorthoesters, polyoxaesters, polyamidoesters, polyoxaesters containing amine groups poly(anhydrides), polyphosphazenes, biopolymers and blends thereof.

27. The biocompatible foam of claim 26 wherein the bioabsorable polymer is an aliphatic polyester.

28. The biocompatible foam of claim 27 wherein the aliphatic polyester is selected from the group consisitng of homopolymers and copolymers of lactide, lactic acid, glycolide, glycolic acid), ε

-caprolactone, p-dioxanone (1,4-dioxan-2-one), trimethylene carbonate (1,3-dioxan-2-one), alkyl derivatives of trimethylene carbonate, δ

-valerolactone, β

-butyrolactone, γ

-butyrolactone, ε

-decalactone, hydroxybutyrate, hydroxyvalerate, 1,4-dioxepan-2-one, 1,5,8,12-tetraoxacyclotetradecane-7,14-dione), 1,5-dioxepan-2-one, 6,6-dimethyl-1,4-dioxan-2-one and polymer blends thereof.

29. The biocompatible foam of claim 26 wherein the aliphatic polyester is an elastomer.

30. The biocompatible foam of claim 29 wherein the elastomer is selected from the group consisting of copolymers of ε

-caprolactone and glycolide;

copolymers of ε

-caprolactone and (L)lactide, copolymers of p-dioxanone (1,4-dioxan-2-one) and (L)lactide, copolymers of ε

-caprolactone and p-dioxanone, copolymers of p-dioxanone and trimethylene carbonate, copolymers of trimethylene carbonate and glycolide, copolymer of trimethylene carbonate and (L)lactide and blends thereof.

31. The biocompatible foam of claim 27 wherein additionally present as a constituent of the foam is a second aliphatic polyester.

32. The biocompatible foam of claim 26 wherein the biocompatible foam has a substantially continuous transition in composition from the first surface to the second surface.

33. The biocompatible foam of claim 32 wherein the biocompatible foam has a substantially continuous transition in composition from a first ratio of at least two different aliphatic polyesters to a second ratio of said at least two different aliphatic polyesters from the first surface to the second surface.

34. The biocompatible foam of claim 26 wherein the biocompatible foam has a substantially continuous transition in stiffness from the first surface to the second surface.

35. The biocompatible foam of claim 26 wherein the biocompatible foam has a substantially continuous transition in bioabsorption rate from the first surface to the second surface.

36. The biocompatible foam of claim 26 wherein the biocompatible foam has a substantially continuous transition in flexibility from the first surface to the second surface.

37. The biocompatible foam of claim 26 wherein the biocompatible foam has a substantially continuous transition in architecture from the first surface to the second surface.

38. The biocompatible foam of claim 37 wherein the subsantially spherical pore'"'"'s size is from about 30 μ

m to about 150 μ

m.

39. The biocompatible foam of claim 22 wherein also present in the biocompatible foam is a therapeutic agent.

40. The biocompatible foam of claim 22 wherein additonally present is an agent selected from the group consisting of antiinfectives, hormones, analgesics, anti-inflammatory agents, growth factors, chemotherapeutic agents, anti-rejection agents, prostaglandins, RDG peptides and combinations thereof.

41. The biocompatible foam of claim 40 wherein the growth factor is selected from the group consisting of bone morphogenic proteins, bone morphogenic-like proteins, epidermal growth factor, fibroblast growth factors, platelet derived growth factor, insulin like growth factor, transforming growth factors, vascular endothelial growth factor and combinations thereof.

42. The biocompatible foam of claim 22 wherein the biocompatible foam is filled with a biocomptible material selected from the group consisting of bioabsorbable synthetic polymers, biocompatible, bioabsorbable biopolymers, biocompatible ceramic materials and combinations thereof.

66. The biocompatible gradient foam of claim 22 wherein the biocompatible foam is formed with an insert within the biocompatible foam.

67. The biocompatible foam of claim 66 wherein the insert is selected from the group consisting of films, scrims, woven textiles, knitted textiles, braided textiles, orthopedic implants, tubes and combinations thereof.

72. The biocompatible foam of claim 22 wherein the biocompatible foam is formed into a three-dimensional shaped structure.

73. The biocompatible foam of claim 72 wherein the three-dimensional shaped structure is selected from the group consisting of tubular shapes, branched tubular shapes, spherical shapes, hemispherical shapes, three-dimensional polygonal shapes, ellipsoidal shapes, toroidal shapes, conical shapes, frusta conical shapes, pyramidal shapes, both as solid and hollow constructs and combination thereof.

43. A biocompatible foam comprising a biocompatible foam having interconnected pores formed from a composition containing in the range of from about 30 weight percent to about 99 weight percent ε

-caprolactone repeating units.

44. The biocompatible foam of claim 43 wherein the ε

-caprolactone repeating units are copolymerized with a comonomer selected from the group consisting of lactide, lactic acid, glycolide, glycolic acid), p-dioxanone (1,4-dioxan-2-one), trimethylene carbonate (1,3-dioxan-2-one), alkyl derivatives of trimethylene carbonate, δ

-valerolactone, β

-butyrolactone, γ

-butyrolactone, ε

-decalactone, hydroxybutyrate, hydroxyvalerate, 1,4-dioxepan-2-one, 1,5,8,12-tetraoxacyclotetradecane-7,14-dione), 1,5-dioxepan-2-one, 6,6-dimethyl-1,4-dioxan-2-one and polymer blends thereof.

45. The biocompatible foam of claim 43 having a first location and a second location wherein the biocompatible foam has a substantially continuous transition in at least one characteristic selected from the group consisting of composition, stiffness, flexibility, bioabsorption rate and pore architecture from the first location to the second location of said biocompatible foam.

46. The biocompatible foam of claim 43 wherein the interconnecting pores have a pore size in the range from about 10 μ

m to about 200 μ

m.

47. The biocompatible foam of claim 43 wherein the biocompatible foam has a porosity of in the range of from about 20 to about 98 percent.

48. The biocompatible foam of claim 43 wherein the biocompatible foam has channels.

49. The biocompatible foam of claim 48 wherein the channels have an average length of at least 200 μ

m.

50. The biocompatible foam of claim 43 wherein additionally present as a constituent of the biocompatible foam is a second aliphatic polyester.

51. The biocompatible foam of claim 45 wherein the biocompatible foam has a substantially continuous transition in composition from the first location to the second location.

52. The biocompatible foam of claim 51 wherein the biocompatible foam has a substantially continuous transition in composition from a first ratio of at least two different aliphatic polyesters to a second ratio of said at least two different aliphatic polyesters from the first location to the second location.

53. The biocompatible foam of claim 45 wherein the biocompatible foam has a substantially continuous transition in stiffness from the first location to the second location.

54. The biocompatible foam of claim 45 wherein the biocompatible foam has a substantially continuous transition in bioabsorption rate from the first location to the second location.

55. The biocompatible foam of claim 45 wherein the biocompatible foam has a substantially continuous transition in flexibility from the first location to the second location.

56. The biocompatible foam of claim 45 wherein the biocompatible foam has a substantially continuous transition in architecture from the first location to the second location.

57. The biocompatible foam of claim 56 wherein the biocompatible foam has a substantially continuous transition in architecture from a substantially spherical pore shape to a columnar pore shape from the first location to the second location.

58. The biocompatible foam of claim 56 wherein the substantially spherical pore'"'"'s size is from about 30 μ

m to about 150 μ

m.

59. The biocompatible foam of claim 56 wherein the columnar pore'"'"'s diameter is from about 30 μ

m to about 400 μ

m with a length to diameter ratio of at least 2.

60. The biocompatible foam of claim 43 wherein also present in the biocompatible foam is a therapeutic agent.

61. The biocompatible foam of claim 43 wherein additionally present is an agent selected from the group consisting of antiinfectives, hormones, analgesics, anti-inflammatory agents, growth factors, agents, anti-rejection agents, prostaglandins, RDG peptides and combinations thereof.

62. The biocompatible foam of claim 61 wherein the growth factor is selected from the group consisting of bone morphogenic proteins, bone morphogenic-like proteins, epidermal growth factor, fibroblast growth factors, platelet derived growth factor, insulin like growth factor, transforming growth factors, vascular endothelial growth factor and combinations thereof.

63. The biocompatible foam of claim 43 wherein the biocompatible foam is filled with a biocomptible material selected from the group consisting of bioabsorbable synthetic polymers, biocompatible, bioabsorbable biopolymers, biocompatible ceramic materials and combinations thereof.

68. The biocompatible foam of claim 43 wherein the biocompatible foam is formed with an insert within the biocompatible foam.

69. The biocompatible foam of claim 68 wherein the insert is selected from the group consisting of films, scrims, woven textiles, knitted textiles, braided textiles, orthopedic implants, tubes and combinations thereof.

74. The biocompatible foam of claim 43 wherein the biocompatible foam is formed into a three-dimensional shaped structure.

75. The biocompatible foam of claim 74 wherein the three-dimensional shaped structure is selected from the group consisting of tubular shapes, branched tubular shapes, spherical shapes, hemispherical shapes, three-dimensional polygonal shapes, ellipsoidal shapes, toroidal shapes, conical shapes, frusta conical shapes, pyramidal shapes, both as solid and hollow constructs and combination thereof.