Medical device applications of nanostructured surfaces

• US 20050038498A1
• Filed: 07/29/2004
• Published: 02/17/2005
• Est. Priority Date: 04/17/2003
• Status: Abandoned Application

• Current Assignee: Nanosys Incorporated (Shoei Electronic Materials, Inc.)
• Original Assignee: Nanosys Incorporated (Shoei Electronic Materials, Inc.)
• Inventors: Alfaro, Arthur A., Collier, Matthew D., Rogers, Erica J., Gertner, Michael E., Dubrow, Robert S., Kronenthal, Richard L., Sloan, L. Douglas
• Application Number:
  US10/902,700
• Publication Number:
  US 20050038498A1
• Time in Patent Office: Days
• US Class Current: 623/1.150
• CPC Class Codes: A61L 2400/12 Nanosized materials, e.g. nanofibres, nanoparticles, nanowires, nanotubes; Nanostructured surfaces
• CPC Class Codes: A61L 2400/18 Modification of implant surfaces in order to improve biocompatibility, cell growth, fixation of biomolecules, e.g. plasma treatment
• CPC Class Codes: A61L 31/14 Materials characterised by their function or physical properties , e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 41/00 Drugs used in surgical methods, e.g. surgery adjuvants for preventing adhesion or for vitreum substitution
• CPC Class Codes: B82Y 30/00 Nanotechnology for materials or surface science, e.g. nanocomposites
• CPC Class Codes: Y10T 428/259 Silicic material

Abstract

This invention provides novel nanofiber enhanced surface area substrates and structures comprising such substrates for use in various medical devices, as well as methods and uses for such substrates and medical devices.

Claims

1. A medical device comprising a body structure having one or more surfaces having a plurality of nanostructured components associated therewith.

2. The device of claim 1, wherein the medical device is an intracorporeal or extracorporeal device, a temporary or permanent implant, a stent, a vascular graft, an anastomotic device, an aneurysm repair device, an embolic device, or an implantable device.

3. The device of claim 1, wherein the plurality of nanostructured components comprises a plurality of nanofibers.

4. The device of claim 3, wherein the plurality of nanofibers comprise an average length of from about 1 micron to at least about 500 microns, from about 5 micron to at least about 150 microns, from about 10 microns to at least about 125 microns, or from about 50 microns to at least about 100 microns.

6. The device of claim 3, wherein the plurality of nanofibers comprise a material independently selected from the group consisting of:

silicon, glass, quartz, plastic, metal and metal alloys, polymers, TiO, ZnO, ZnS, ZnSe, ZnTe, CdS, CdSe, CdTe, HgS, HgSe, HgTe, MgS, MgSe, MgTe, CaS, CaSe, CaTe, SrS, SrSe, SrTe, BaS, BaSe, BaTe, GaN, GaP, GaAs, GaSb, InN, InP, InAs, InSb, PbS, PbSe, PbTe, AlS, AlP, AlSb, SiO₁, SiO₂, silicon carbide, silicon nitride, polyacrylonitrile (PAN), polyetherketone, polyimide, an aromatic polymer, and an aliphatic polymer.

7. The device of claim 1, wherein the nanostructured components comprise hollow nanotubular structures.

8. The device of claim 1, wherein the nanostructured components comprise nanowires.

9. The device of claim 3, wherein the nanofibers are attached to the one or more surfaces of the body structure by growing the nanofibers directly on the one or more surfaces.

10. The device of claim 3, wherein the nanofibers are attached to or otherwise associated with the one or more surfaces of the body structure by covalently attaching the nanofibers to the one or more surfaces.

11. The device of claim 1, wherein the body structure is made from at least a first material, and the plurality of nanostructured components are incorporated into the at least first material.

12. The device of claim 1, wherein the nanostructured components are attached to the one or more surfaces of the body structure, the medical device further comprising one or more biologically compatible or bioactive coatings applied to the one or more nanostructured surfaces.

13. The medical device of claim 1, wherein the plurality of nanostructured components enhance one or more of adhesion, non-adhesion, friction, patency, or anti-biofouling of the device with one or more tissue surfaces of a body of a patient.

82. The device of claim 3, wherein the plurality of nanofibers comprise an average density of from about 0.11 nanofibers per square micron to at least about 1000 nanofibers per square micron, from about 1 nanofiber per square micron to at least about 500 nanofibers per square micron, from about 10 nanofibers per square micron to at least about 250 nanofibers per square micron, or from about 50 nanofibers per square micron to at least about 100 nanofibers per square micron.

5. The device of claim 3, wherein the plurality of nanofibers comprise an average diameter of from about 5 nm to at least about 1 micron, from about 5 nm to at least about 500 nm, from about 20 nm to at least about 250 nm, from about 20 nm to at least about 200 nm, from about 40 nm to at least about 200 nm, from about 50 nm to at least about 150 nm, or from about 75 nm to at least about 100 nm.

5-1. (cancelled)

14. A vascular stent comprising a plurality of nanostructured components associated with one or more surfaces of the stent.

15. The stent of claim 14, wherein the plurality of nanostructured components comprises a plurality of nanofibers.

16. The stent of claim 15, wherein the plurality of nanofibers comprise a material independently selected from the group consisting of:

silicon, glass, quartz, plastic, metal and metal alloys, polymers, TiO, ZnO, ZnS, ZnSe, ZnTe, CdS, CdSe, CdTe, HgS, HgSe, HgTe, MgS, MgSe, MgTe, CaS, CaSe, CaTe, SrS, SrSe, SrTe, BaS, BaSe, BaTe, GaN, GaP, GaAs, GaSb, InN, InP, InAs, InSb, PbS, PbSe, PbTe, AlS, AlP, AlSb, SiO₁, SiO₂, silicon carbide, silicon nitride, polyacrylonitrile (PAN), polyetherketone, polyimide, an aromatic polymer, and an aliphatic polymer.

17. The stent of claim 14, wherein the nanostructured components comprise hollow nanotubular structures.

18. The stent of claim 14, wherein the nanostructured components comprise nanowires.

19. The stent of claim 15, wherein the nanofibers are attached to the one or more surfaces of the stent by growing the nanofibers directly on the one or more surfaces.

20. The stent of claim 15, wherein the nanofibers are attached to the one or more surfaces of the stent by separately covalently attaching the nanofibers to the one or more surfaces.

21. The stent of claim 14, wherein the stent is made from one or more materials selected from Nitinol, nickel alloy, tin alloy, stainless steel, cobalt, chromium, gold, polymer, or ceramic.

22. The stent of claim 14, wherein the stent comprises a drug compound that is directly adsorbed to or otherwise associated with the nanostructured surface via the use of one or more silane groups.

23. The stent of claim 14, wherein the stent comprises a drug compound that is adsorbed to or otherwise associated with the nanostructured surface via the use of one or more linker molecules.

24. An aneurysm repair device comprising a graft member which is configured to be positioned within a patient'"'"'s body in a region of an aneurysm, the graft member comprising a plurality of nanostructured components associated with one or more surfaces of the graft member.

25. The device of claim 24, wherein the plurality of nanostructured components comprises a plurality of nanofibers.

26. The device of claim 25, wherein the plurality of nanofibers comprise a material independently selected from the group consisting of:

silicon, glass, quartz, plastic, metal or metal alloys, polymers, TiO, ZnO, ZnS, ZnSe, ZnTe, CdS, CdSe, CdTe, HgS, HgSe, HgTe, MgS, MgSe, MgTe, CaS, CaSe, CaTe, SrS, SrSe, SrTe, BaS, BaSe, BaTe, GaN, GaP, GaAs, GaSb, InN, InP, InAs, InSb, PbS, PbSe, PbTe, AlS, AlP, AlSb, SiO₁, SiO₂, silicon carbide, silicon nitride, polyacrylonitrile (PAN), polyetherketone, polyimide, an aromatic polymer, and an aliphatic polymer.

27. The device of claim 24, wherein the nanostructured components comprise hollow nanotubular structures.

28. The device of claim 24, wherein the nanostructured components comprise nanowires.

29. The device of claim 25, wherein the nanofibers are attached to the one or more surfaces of the graft member by growing the nanofibers directly on the one or more surfaces.

30. The device of claim 25, wherein the nanofibers are attached to the one or more surfaces of the graft member by attaching the nanofibers to the one or more surfaces.

31. The device of claim 24, wherein the graft member is made from one or more of treated natural tissue, laboratory-engineered tissue, and synthetic polymer fabrics.

32. The device of claim 24, wherein the graft member is made from a synthetic polymer selected from Dacron, Teflon, metal or alloy mesh, ceramic or glass fabrics.

33. The device of claim 24, wherein the graft member comprises one or more biocompatible coatings applied to the one or more nanostructured surfaces of the graft member.

34. The device of claim 24, wherein the graft member is configured to be positioned within an aorta of the patient in a region of an aneurysm.

35. The device of claim 24, wherein the graft member is configured to be positioned proximate to a side wall of a vessel that supplies blood to or from the brain in a region of an aneurysm.

36. A device for creating an anastomosis in a patient by coupling a first vessel to a second vessel in an end-to-end or end-to-side anastomosis, the device comprising a tubular member comprising a plurality of nanostructured components associated with one or more surfaces of the tubular member.

37. The device of claim 36, wherein the plurality of nanostructured components comprises a plurality of nanofibers.

38. The device of claim 37, wherein the plurality of nanofibers comprise a material independently selected from the group consisting of:

silicon, glass, quartz, plastic, metal, polymers, TiO, ZnO, ZnS, ZnSe, ZnTe, CdS, CdSe, CdTe, HgS, HgSe, HgTe, MgS, MgSe, MgTe, CaS, CaSe, CaTe, SrS, SrSe, SrTe, BaS, BaSe, BaTe, GaN, GaP, GaAs, GaSb, InN, InP, InAs, InSb, PbS, PbSe, PbTe, AlS, AlP, AlSb, SiO₁, SiO₂, silicon carbide, silicon nitride, polyacrylonitrile (PAN), polyetherketone, polyimide, an aromatic polymer, and an aliphatic polymer.

39. The device of claim 36, wherein the nanostructured components comprise hollow nanotubular structures.

40. The device of claim 36, wherein the nanostructured components comprise nanowires.

41. The device of claim 37, wherein the nanofibers are attached to the one or more surfaces of the tubular member by growing the nanofibers directly on the one or more surfaces.

42. The device of claim 37, wherein the nanofibers are attached to the one or more surfaces of the tubular member by attaching the nanofibers to the one or more surfaces.

43. The device of claim 36, wherein the tubular member is made from one or more of treated natural tissue, laboratory-engineered tissue, de-natured animal tissue, stainless steel, metal, alloys, ceramic or glass fabrics, polymers, plastic, silicone, and synthetic polymer fabrics.

44. The device of claim 36, wherein the tubular member comprises a T-tube for performing an end-to-side anastomosis.

45. The device of claim 36, wherein the tubular member comprises one or more biocompatible or bioactive coatings applied to the one or more nanostructured surfaces of the tubular member.

46. The device of claim 36, wherein the tubular member has a cross-sectional shape selected from circular, semi-circular, elliptical, and polygonal.

47. The device of claim 36, wherein one of the first vessel and second vessel comprises a synthetic bypass graft vessel.

48. The device of claim36, wherein the tubular member comprises a straight tube.

49. An implantable orthopedic device comprising a body structure comprising a plurality of nanostructured components associated with one or more surfaces of the body structure.

50. The device of claim 49, wherein the plurality of nanostructured components comprises a plurality of nanofibers.

51. The device of claim 50, wherein the plurality of nanofibers comprise a material independently selected from the group consisting of:

silicon, glass, quartz, plastic, metal, polymers, TiO, ZnO, ZnS, ZnSe, ZnTe, CdS, CdSe, CdTe, HgS, HgSe, HgTe, MgS, MgSe, MgTe, CaS, CaSe, CaTe, SrS, SrSe, SrTe, BaS, BaSe, BaTe, GaN, GaP, GaAs, GaSb, InN, InP, InAs, InSb, PbS, PbSe, PbTe, AlS, AlP, AlSb, SiO₁, SiO₂, silicon carbide, silicon nitride, polyacrylonitrile (PAN), polyetherketone, polyimide, an aromatic polymer, and an aliphatic polymer.

52. The device of claim 49, wherein the nanostructured components comprise hollow nanotubular structures.

53. The device of claim 49, wherein the nanostructured components comprise nanowires.

54. The device of claim 50, wherein the nanofibers are attached to the one or more surfaces of the body structure by growing the nanofibers directly on the one or more surfaces.

55. The device of claim 50, wherein the nanofibers are attached to the one or more surfaces of the body structure by attaching the nanofibers to the one or more surfaces.

56. The device of claim 49, wherein the body structure is made from one or more of treated natural tissue, laboratory-engineered tissue, de-natured animal tissue, stainless steel, metal, alloys, ceramic or glass fabrics, polymers, plastic, silicone, and synthetic polymer fabrics.

57. The device of claim 49, wherein the body structure comprises one or more biocompatible or bioactive coatings applied to the one or more nanostructured surfaces of the body structure.

58. The device of claim 49, wherein the implantable orthopedic device is selected from at least one of the following:

total knee joints, total hip joints, ankle, elbow, wrist, and shoulder implants including those replacing or augmenting cartilage, long bone implants such as for fracture repair and external fixation of tibia, fibula, femur, radius, and ulna, spinal implants including fixation and fusion devices, maxillofacial implants including cranial bone fixation devices, artificial bone replacements, dental implants, orthopedic cements and glues comprised of polymers, resins, metals, alloys, plastics and combinations thereof, nails, screws, plates, fixator devices, wires and pins.

59. A bioengineered scaffold device for providing a scaffold for nerve regeneration comprising a base membrane or matrix having a plurality of nanostructured components associated therewith.

60. The scaffold device of claim 59, wherein the membrane or matrix is made from one or more of the following materials:

natural or synthetic polymers, electrically conducting polymers, metals, alloys, ceramics, glass fabrics, or silicone.

61. The scaffold device of claim 60, wherein the base membrane or matrix is made from an electrically conducting polymer.

62. The device of claim 59, wherein the plurality of nanostructured components comprise a plurality of nanofibers or nanowires.

63. The device of claim 59, wherein the nanostructured surface of the membrane or matrix is impregnated or bound with one or more drugs, cells, fibroblasts, nerve growth factors (NGF), cell seeding compounds, neurotrophic growth factors or genetically engineered cells producing such factors, VEGF, or laminin to encourage axonal elongation and functional nerve performance.

64. The device of claim 59, wherein the plurality of nanostructured components are embedded in a biocompatible polymer.

65. A medical device for implantation in the uterus or fallopian tubes comprising a surface and a plurality of nanofibers associated with the surface.

66. A medical device in which one or more surfaces are adapted to resist crystallization of body fluids comprising a surface and a plurality of nanofibers associated with the surface.

67. A medical device in which one or more surfaces are adapted to resist thrombus formation comprising a surface and a plurality of nanofibers associated with the surface.

68. A medical device in which one or more surfaces are adapted to resist tissue in-growth comprising a surface and a plurality of nanofibers associated with the surface, said nanofibers adapted to be hydrophobic.

69. A method of therapeutically treating a patient comprising contacting a region of said patient with a medical device comprising a surface and plurality of nanofibers associated with said surface.

70. A method of administering a drug compound to a body of a patient comprising:

providing a drug-eluting device comprising at least one surface, a plurality of nanofibers associated with the surface, and a drug compound associated with the plurality of nanofibers;

introducing the drug-eluting device into a body of a patient; and

delivering the drug compound into the body of the patient.

71. The method of claim 70, wherein the drug-eluting device comprises a coronary stent.

72. The method of claim 71, wherein the drug compound comprises paclitaxel or sirolimus.

73. The method of claim 70, wherein the drug compound is adsorbed to the nanofiber surface of the drug-eluting device.

74. The method of claim 70, wherein the drug compound is attached to the nanofiber surface via the use of one or more silane groups.

75. The method of claim 70, wherein the drug compound is attached to the nanofiber surface via the use of one or more linker molecules.

76. The method of claim 70, wherein the drug compound is covalently or ionically attached to the nanofiber surface of the drug-eluting device.

77. The method of claim 70 wherein the drug-eluting device comprises a coronary stent, and the delivering the drug compound comprises eluting the drug compound at the site of a lesion in a coronary vessel.

78. The method of claim 77, wherein the drug compound elutes into the coronary vessel at the site of the lesion following expansion of the coronary stent.

79. The method of claim 78, wherein the nanofiber surface is configured such that the drug compound elutes slowly over time.

80. The method of claim 70, wherein the plurality of nanofibers are embedded in a polymer coating to provide enhanced durability to the nanofibers.

81. The method of claim 70, wherein the drug compound is selected from one or more of the following:

anti-inflammatory immunomodulators such as Dexamethasone, M-prednisolone, Interferon, Leflunomide, Tacrolimus, Mizoribine, statins, Cyclosporine, Tranilast, and Biorest;

antiproliferative compounds such as Taxol, Methotrexate, Actinomycin, Angiopeptin, Vincristine, Mitomycin, RestenASE, and PCNA ribozyme;

migration inhibitors such as Batimastat, Prolyl hydroxylase inhibitors, Halofuginone, C-proteinase inhibitors, and Probucol; and

compounds which promote healing and re-endothelialization such as VEGF, Estradiols, antibodies, NO donors, and BCP671.