Medical device applications of nanostructured surfaces

• US 20050221072A1
• Filed: 03/24/2005
• Published: 10/06/2005
• 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: Kronenthal, Richard L., Alfaro, Arthur A., Rogers, Erica J., Gertner, Michael E., Dubrow, Robert S., Sloan, L. Douglas, Collier, Matthew D.
• Application Number:
  US11/090,895
• Publication Number:
  US 20050221072A1
• Time in Patent Office: Days
• US Class Current: 428/292.100
• CPC Class Codes: A61F 2/30767 Special external or bone-contacting surface, e.g. coating for improving bone ingrowth
• CPC Class Codes: A61F 2/36 Femoral heads ; Femoral endoprostheses
• CPC Class Codes: A61F 2/3662 Femoral shafts
• CPC Class Codes: A61F 2/3676 Distal or diaphyseal parts of shafts
• CPC Class Codes: A61F 2002/30113 circular
• CPC Class Codes: A61F 2002/30322 differing in surface structures
• CPC Class Codes: A61F 2002/30827 Plurality of grooves
• CPC Class Codes: A61F 2002/3084 Nanostructures
• CPC Class Codes: A61F 2002/3631 with an integral complete or partial peripheral collar or bearing shoulder at its base
• CPC Class Codes: A61F 2230/0006 circular
• CPC Class Codes: A61F 2250/0026 differing in surface structures
• CPC Class Codes: A61F 2310/00616 Coating made of titanium oxide or hydroxides
• CPC Class Codes: A61F 2310/0097 Coating or prosthesis-covering structure made of pharmaceutical products, e.g. antibiotics
• CPC Class Codes: A61F 2310/00982 Coating made of collagen
• CPC Class Codes: A61K 47/6957 the form being a device or a kit, e.g. stents or microdevices
• CPC Class Codes: A61L 2400/12 Nanosized materials, e.g. nanofibres, nanoparticles, nanowires, nanotubes; Nanostructured surfaces
• CPC Class Codes: A61L 2430/02 for reconstruction of bones; weight-bearing implants
• CPC Class Codes: A61L 27/3821 Bone-forming cells, e.g. osteoblasts, osteocytes, osteoprogenitor cells
• CPC Class Codes: A61L 27/3839 characterised by the site of application in the body materials for artificial blood vessels A61L27/507; materials for use in artificial skin A61L27/60
• 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: B82Y 5/00 : Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
• CPC Class Codes: Y10T 428/249924 : Noninterengaged fiber-containing paper-free web or sheet which is not of specified porosity

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. In one particular embodiment, methods for enhancing cellular functions on a surface of a medical device implant are disclosed which generally comprise providing a medical device implant comprising a plurality of nanofibers (e.g., nanowires) thereon and exposing the medical device implant to cells such as osteoblasts.

Claims

1. A method for enhancing osteoblast functions on a surface of a medical device implant comprising providing a medical device implant comprising a plurality of nanofibers grown thereon and exposing said medical device implant to osteoblast cells.

2. The method according to claim 1, wherein the nanofibers comprise nanowires having an average length of from about 1 micron to at least about 100 microns.

3. The method according to claim 2, wherein the nanowires have an average density on the medical device implant of from about 20 nanowires per square micron to at least about 100 nanowires per square micron.

4. The method of claim 1, 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 method of claim 1, wherein the medical device implant 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.

8. The method of claim 1, wherein the medical device implant contains 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.

9. The method of claim 1, wherein the medical device implant contains one or more agents selected from the group consisting of medicated coatings, drug-eluting coatings, drugs or other compounds, hydrophilic coatings, smoothing coatings, collagen coatings, and human cell seeding coatings.

5-6. -6. (canceled)

10. A method for the repair or regeneration of tissue comprising contacting cells with a nanostructured surface comprising a plurality of nanofibers having an average length of at least about 1 micron and an average density of at least about 1 nanofiber per square micron.

11. The method of claim 10, wherein the nanostructured surface is implanted in an animal and contacted with the cells.

12. The method of claim 10, wherein the nanostructed surface is seeded with cells and the nanostructued surface and cells are placed in a cell culturing device and the cells are allowed to multiply on the nanostructured surface.

13. The method of claim 10, wherein the cells comprise osteoblasts.

14. The method of claim 10, wherein the cells are selected from the group consisting of myocytes, adipocytes, fibromyoblasts, ectodermal cell, muscle cells, osteoblasts, chondrocytes, endothelial cells, pancreatic cells, hepatocytes, bile duct cells, bone marrow cells, neural cells, genitourinary cells and combinations thereof.

15. The method of claim 10, wherein the nanostructured surface contains one or more agents 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.

16. The method of claim 10, wherein the nanostructured surface contains one or more agents selected from the group consisting of:

medicated coatings, drug-eluting coatings, drugs or other compounds, hydrophilic coatings, smoothing coatings, collagen coatings, and human cell seeding coatings.

17. The method of claim 12, wherein after the cells are allowed to multiply on the nanostructured surface, the nanostructured surface and the cells are implanted into an animal.

18. The method of claim 10, wherein the nanofibers are attached to the nanostructured surface by growing the nanofibers directly on the surface.

19. The method of claim 10, wherein the nanofibers are attached to or otherwise associated with the nanostructured surface by covalently attaching the nanofibers to the surface.

20. The method of claim 10, wherein the nanofibers have an average length of at least about 25 microns and an average density of at least about 20 nanofibers per square micron.

21. The method according to claim 10, wherein the nanofibers comprisie nanowires having an average length of from about 25 microns to at least about 100 microns.

22. The method according to claim 10, wherein the nanofibers comprise nanowires having an average density on the medical device implant of from about 20 nanowires per square micron to at least about 100 nanowires per square micron.

23. The method of claim 10, 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.

24. The method of claim 10, wherein the plurality of nanofibers comprise nanowires made from silicon.

25. The method of claim 24, wherein the silicon nanowires have a coating of a titanium oxide compound deposited thereon.

26. The method of claim 25, wherein the titanium oxide compound comprises titanium dioxide.

27. The method of claim 25, wherein the titanium oxide coating is deposited by atomic layer deposition.

28. The method of claim 10, wherein at least a portion of the nanostructured nanofiber surface is functionalized with a coating material to render it hydrophobic, lipophobic, or amphiphobic.

29. The method of claim 28, wherein the coating material comprises one or more material selected from the group consisting of:

Teflon®

, Tri-sil, tridecafluoro 1,1,2,2,tetrahydrooctyl-1-tricholorosilane, a fluoride containing compound, a silane containing compound, PTFE, hexamethyldisilazane, an aliphatic hydrocarbon containing molecule, an aromatic hydrocarbon containing molecule, a halogen containing molecule and paralyene.

30. The method of claim 29, wherein the coating material is deposited by one or more of sputtering, atomic layer deposition and a plasma process.

31. The method of claim 30, wherein at least a portion of the nanofiber surface with the coating material deposited thereon is functionalized to promote cellular adhesion and/or proliferation.

32. The method of claim 31, wherein the nanofiber surface is functionalized with one or more of fibronectin, collagen, or an RGD containing peptide.

33. A method for enhancing osteoblast functions on a surface of a medical device implant comprising providing a medical device implant comprising a plurality of silicon nanofibers and exposing said medical device implant to osteoblast cells.

34. The method of claim 33, wherein the silicon nanofibers are grown directly on the medical device implant.

35. The method of claim 33, wherein the silicon nanofibers have a length of at least about 1 micron.

36. The method of claim 33, wherein the silicon nanofibers have a length of at least about 10 microns

37. The method of claim 33, wherein the silicon nanofibers are grown on the surface of the medical device implant by a VLS growth process.

38. A method for enhancing osteoblast adhesion and/or proliferation on a medical device implant surface comprising growing a plurality of nanofibers directly on the surface.

39. The method of claim 38, wherein the nanofibers comprise silicon nanofibers.

40. The method of claim 38, wherein the nanofibers have a length of at least about 1 micron.

41. The method of claim 40, wherein the nanofibers have a length of at least about 10 microns

42. The method of claim 39, wherein the silicon nanofibers are grown on the surface of the medical device implant by a VLS growth process.

43. An orthopedic or dental implant comprising a substrate having a surface and a plurality of silicon nanofibers deposited on the surface.

44. The implant of claim 43, wherein the silicon nanofibers are grown directly on the substrate surface.