Self-assembled thin film coating to enhance the biocompatibility of materials

• US 20020037383A1
• Filed: 04/13/2001
• Published: 03/28/2002
• Est. Priority Date: 04/14/2000
• Status: Abandoned Application

• Current Assignee: Virginia Tech Intellectual Properties, Inc.
• Original Assignee: Virginia Polytechnic Institute and State University
• Inventors: Spillman, William B. Jr., Claus, Richard O., Wang, You-Xiong
• Application Number:
  US09/833,788
• Publication Number:
  US 20020037383A1
• Time in Patent Office: Days
• US Class Current: 428/36.91
• CPC Class Codes: A61L 27/34 Macromolecular materials
• CPC Class Codes: A61L 31/10 Macromolecular materials
• CPC Class Codes: B05D 1/185 applying monomolecular layers B05D1/204 takes precedence
• CPC Class Codes: B82Y 30/00 Nanotechnology for materials or surface science, e.g. nanocomposites
• CPC Class Codes: B82Y 40/00 Manufacture or treatment of nanostructures
• CPC Class Codes: B82Y 5/00 Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
• CPC Class Codes: Y10T 428/139 Open-ended, self-supporting conduit, cylinder, or tube-type article
• CPC Class Codes: Y10T 428/1393 Multilayer [continuous layer]

Abstract

We make a substrate biocompatible by contacting it with a starting material and initiating alternating charge layer electrostatic self-assembly to form a thin film. Starting materials may be poly(vinylpyrrolidone), poly{bis-(carboxylatophenoxy)phosphazene}, poly(methacrylic acid), poly(l-lysine), poly(ethylene glycol), poly(D-glucosamine), poly(l-glutamic acid), poly(diallyldimethylamine), poly(ethylenimine), hydroxy fullerene, long-sidechain fullerene, or other polymers that participate in electrostatic self-assembly. The thin film fabrication advantageously may be at room temperature. A biocompatible thin film that is uniform and homogeneous can be provided. Optionally, ZrO₂, Al₂O₃ or TiO₂ nanoclusters also may be used in the film assembly. The film may be used in a drug delivery device or a medical device. The film may be used for tissue engineering. We also provide a biocompatible composition in which are present a plurality of layers electrostatically self-assembled from at least a polymer or fullerene as mentioned. The substrate is not particularly limited, and may be quartz, glass, plastic, metal or ceramic, a material for a bone implant, bioactive glass, polyester or other polymers, plastic or rubber tubing, bandaging material, composite material, insulator material, semi-conductor material, an artificial hip, a pacemaker, a catheter, a stent or other substrates.

Claims

1. A process of making a substrate biocompatible comprising the steps of:

contacting at least a portion of a charged substrate with an oppositely charged starting material and by electrostatic self-assembly constructing a multi-layered film of alternating charged molecular layers on the substrate, wherein the starting material is selected from the group consisting of;

poly(vinylpyrrolidone), poly{bis(carboxylatophenoxy)phosphazene},

poly(methacrylic acid)

poly(l-lysine),

poly(ethylene glycol),

poly(D-glucosamine),

poly(l-glutamic acid),

poly(diallyldimethylamine),

poly(ethylenimine),

hydroxy fullerene and

long-sidechain fullerene.

2. A process according to claim 1, wherein also participating in the electrostatic self-assembly is a metal oxide selected from the group consisting of ZrO₂, Al₂O₃ and TiO₂.

3. A process according to claim 1, wherein individual monolayer thickness is about 0.1 nm to 100 nm.

4. A process according to claim 1, wherein the contacting is by dipping the substrate into a solution.

5. A process according to claim 1, wherein the substrate is quartz.

6. A process according to claim 1, wherein the substrate is selected from the group consisting of glasses, plastic, metals and ceramic.

7. A process according to claim 1, wherein said constructing step is performed at room temperature.

8. A process according to claim 1, wherein the substrate is suitable for tissue engineering.

9. A process according to claim 1, wherein the substrate is a titanium alloy.

10. A process according to claim 9, wherein the titanium alloy is Ti₆A₁₄V.

11. A process according to claim 1, wherein the substrate is suitable for bone implant.

12. A process according to claim 11, wherein the substrate is bioactive glass.

13. A process according to claim 1, wherein the substrate consists essentially of a polymer.

14. A process according to claim 13, wherein the polymer is polyester.

15. A drug delivery device, comprising a substrate made biocompatible by a process according to claim 1 and at least one drug.

16. A medical device having at least one surface that is made biocompatible by the process of claim 1.

17. A medical device according to claim 16, further comprising cells seeded onto said multi-layered film.

20. A biocompatible composition of claim 19 wherein said plurality of layers electrostatically self-assembled is at least 100 layers.

21. A biocompatible composition according to claim 20, wherein the thin film is uniform and homogeneous.

22. A biocompatible composition according to claim 21, wherein the thin film is of thickness greater than about 1 nm.

24. The biocompatible material of claim 19, wherein at least one appropriately charged metal oxide nanocluster is included.

25. The biocompatible material of claim 24, wherein ZrO₂ is included.

26. The biocompatible material of claim 24, wherein Al₂O₃ is included.

27. The biocompatible material of claim 24, wherein TiO₂ is included.

28. The biocompatible material of claim 19, wherein the thin film is prepared from a water soluble polymer.

29. The biocompatible material of claim 28, wherein the thin film is prepared from poly(vinylpyrrolidone).

30. The biocompatible material of claim 28, wherein the thin film is prepared from poly{bis(carboxylatophenoxy)phosphazene}.

31. The biocompatible material of claim 28, wherein the thin film is prepared from poly(methacrylic acid).

32. The biocompatible material of claim 28, wherein the thin film is prepared from poly(l-lysine).

33. The biocompatible material of claim 28, wherein the thin film is prepared from poly(ethylene glycol).

34. The biocompatible material of claim 28, wherein the thin film is prepared from poly(D-glucosamine).

35. The biocompatible material of claim 28, wherein the thin film is prepared from poly(l-glutamic acid).

36. The biocompatible material of claim 28, wherein the thin film is prepared from poly(diallyldimethylamine).

37. The biocompatible material of claim 28, wherein the thin film is prepared from poly(ethylenimine).

38. The biocompatible material of claim 28, wherein the thin film is prepared from hydroxy fullerene.

39. The biocompatible material of claim 28, wherein the thin film is prepared from long-side chain fullerene.

40. A medical device according to claim 23, wherein the thin film has a surface not contacting the substrate that has a charge to increase cell adhesion for cell growth.

41. A medical device according to claim 23, wherein the substrate is tubing used in dialysis.

42. A medical device according to claim 23, wherein the substrate is tubing used in heart lung machines.

43. A medical device according to claim 23, wherein the substrate is plastic tubing.

44. A medical device according to claim 23, wherein the substrate is rubber tubing.

45. A medical device according to claim 23, wherein the substrate is bandaging material.

46. A medical device according to claim 23, wherein the substrate is composite material.

47. A medical device according to claim 23, wherein the substrate is metal material.

48. A medical device according to claim 23, wherein the substrate is insulator material.

49. A medical device according to claim 23, wherein the substrate is semi-conductor material.

50. A medical device according to claim 23, wherein the substrate is an artificial hip.

51. A medical device according to claim 50, wherein the artificial hip is of titanium.

52. A medical device according to claim 23, wherein the substrate is a pacemaker.

53. A medical device according to claim 52, wherein said pacemaker includes plastic.

54. A medical device according to claim 23, wherein the substrate is a catheter.

55. A medical device according to claim 23, wherein the substrate is a stent.

57. A process according to claim 56, wherein also participating in the electrostatic self-assembly is a metal oxide selected from the group consisting of ZrO₂, Al₂O₃ and TiO₂.

58. A process according to claim 56,wherein individual monolayer thickness is about 0.1 nm to 100 nm.

59. A process according to claim 56, wherein the contacting is by dipping the substrate into a solution.

60. A process according to claim 56, wherein the substrate is quartz.

61. A process according to claim 56, wherein the substrate is selected from the group consisting of glasses, plastic, metals and ceramic.

62. A process according to claim 56, wherein said constructing step is performed at room temperature.

63. A process according to claim 56, wherein the substrate is suitable for tissue engineering.

64. A process according to claim 56, wherein the substrate is a titanium alloy.

65. A process according to claim 64, wherein the titanium alloy is Ti₆A₁₄V.

66. A process according to claim 56, wherein the substrate is suitable for bone implant.

67. A process according to claim 66, wherein the substrate is bioactive glass.

68. A process according to claim 56, wherein the substrate consists essentially of a polymer.

69. A process according to claim 68, wherein the polymer is polyester.

70. A drug delivery device, comprising a substrate made biocompatible by a process according to claim 56 and at least one drug.

71. A medical device having at least one surface that is made biocompatible by the process of claim 56.

72. A medical device according to claim 71, further comprising cells seeded onto said multi-layered film.

18. A biocompatible composition consisting essentially of a plurality of layers electrostatically self-assembled from a starting material selected from the group consisting of:

poly(vinylpyrrolidone), poly{bis(carboxylatophenoxy)phosphazene},

poly(methacrylic acid)

poly(l-lysine),

poly(ethylene glycol),

poly(D-glucosamine),

poly(I-glutamic acid),

poly(diallyldimethylamine),

poly(ethylenimine),

hydroxy fullerene and

long-sidechain fullerene.

19. A biocompatible composition comprising a plurality of layers electrostatically self-assembled from a starting material selected from the group consisting of:

poly(vinylpyrrolidone), poly{bis(carboxylatophenoxy)phosphazene},

poly(methacrylic acid)

poly(l-lysine),

poly(ethylene glycol),

poly(D-glucosamine),

poly(l-glutamic acid),

poly(diallyldimethylamine),

poly(ethylenimine),

hydroxy fullerene and

long-side chain fullerene.

23. A biocompatible medical device or drug delivery device comprising:

a substrate; and

, provided on the substrate,

a thin film electrostatically self-assembled starting with a solution of at least one starting material selected from the group consisting of;

poly(vinylpyrrolidone),

poly{bis(carboxylatophenoxy)phosphazene},

poly(methacrylic acid),

poly(l-lysine),

poly(ethylene glycol),

poly(D-glucosamine),

poly(l-glutamic acid),

poly(diallyldimethylamine),

poly(ethylenimine),

hydroxy fullerene and

long-side chain fullerene.

56. A process of making a substrate biocompatible comprising the steps of:

contacting at least a portion of a charged substrate with an oppositely charged starting material and by electrostatic self-assembly constructing a multi-layered film of alternating charged molecular layers on the substrate, wherein the starting material is a polymer.

73. A biocompatible material consisting essentially of a plurality of layers electrostatically self-assembled from a starting material that is a polymer.

74. A biocompatible material comprising a plurality of layers electrostatically self-assembled from a starting material that is a polymer.

75. A biocompatible material according to claim 74, wherein said plurality of layers electrostatically self-assembled is at least 100 layers.

76. A biocompatible material according to claim 75, wherein the thin film is uniform and homogeneous.

77. A biocompatible material according to claim 76,wherein the thin film is of thickness greater than about 1 nm.

79. The biocompatible material of claim 74, wherein at least one appropriately charged metal oxide nanocluster is included.

80. The biocompatible material of claim 79, wherein ZrO₂ is included.

81. The biocompatible material of claim 79, wherein Al₂O₃ is included.

82. The biocompatible material of claim 79, wherein TiO₂ is included.

78. A biocompatible medical device or drug delivery device comprising:

a substrate; and

, provided on the substrate,

a thin film electrostatically self-assembled starting with a solution of at least one starting material that is a polymer.

83. A device for contacting a biological material, comprising

a substrate;

and

a multilayered coating positioned on at least a portion of a surface of said substrate wherein adjacent layers of said multilayered coating are held together by ionic attraction, and wherein at least one layer of said multilayered coating is made from a material that is relatively more biocompatible than a substrate material in said substrate, whereby said multilayer coating renders the device biocompatible with said biological material.

84. The device of claim 83 wherein said at least one layer is selected from the group consisting of

poly(vinylpyrrolidone), poly{bis(carboxylatophenoxy)phosphazene},

poly(methacrylic acid)

poly(l-lysine),

poly(ethylene glycol),

poly(D-glucosamine),

poly(l-glutamic acid),

poly(diallyldimethylamine),

poly(ethylenimine),

hydroxy fullerene and

long-sidechain fullerene.

85. The device of claim 83 wherein said multilayered coating includes greater than 10 individual layers.

86. The device of claim 83 wherein said multilayered coating includes at least two layers made from different materials.

87. A method of rendering a device biocompatible with a biological material, comprising the step of applying a multilayered coating on at least a portion of a surface of a substrate wherein adjacent layers of said multilayered coating are held together by ionic attraction, and wherein at least one layer of said multilayered coating is made from a material that is relatively more biocompatible than a substrate material in said substrate.