BIOCOMPATIBILITY LAYER AND COATED OBJECTS

• US 20110189493A1
• Filed: 07/31/2009
• Published: 08/04/2011
• Est. Priority Date: 07/31/2008
• Status: Active Grant

• Current Assignee: Bio-Gate AG, Fraunhofer Gesellschaft Zur Foerderung Der Angewandten Forsching E.V.
• Original Assignee: Bio-Gate AG, Fraunhofer Gesellschaft Zur Foerderung Der Angewandten Forsching E.V.
• Inventors: Ott, Matthias, Vissing, Klaus-Dieter, Hielscher, Wolfgang, Dölle, Christopher, Wagener, Michael, Grunwald, Ingo, Salz, Dirk
• Granted Patent: US 8,992,590 B2
• Time in Patent Office: Days
• US Class Current: 428/446
• CPC Class Codes: A61L 27/34 Macromolecular materials
• CPC Class Codes: A61L 29/085 Macromolecular materials
• CPC Class Codes: A61L 31/10 Macromolecular materials
• CPC Class Codes: B05D 1/62 Plasma-deposition of organic layers plasma deposition in general C23C14/00, C23C16/00
• CPC Class Codes: C23C 16/30 Deposition of compounds, mixtures or solid solutions, e.g. borides, carbides, nitrides
• CPC Class Codes: C23C 16/56 After-treatment

Abstract

The present invention relates to the use of a crosslinked, silicon-containing layer containing, substantially consisting of or consisting of silicon, O, C, H, optionally N which can be produced by plasma polymerization and/or crosslinking of organosilicon liquids by a plasma process and/or UV radiation of a wavelength of less than 250 nm, without using metals of an atomic number of more than 14, as a biocompatible surface, for imparting to a surface or providing a surface with a non-genotoxic effect. The invention also relates to correspondingly coated articles and to processes for the production thereof.

Claims

1. A method for rendering a surface non-genotoxic, comprising applying to the surface a crosslinked silicon-containing layer containing silicon, O, C, H, and optionally N, which is produced by plasma polymerization and/or crosslinking of organosilicon liquids by a plasma process and/or UV radiation of a wavelength of less than 250 nm, without using metals of an atomic number of more than 14, said layer having an atomic ratio of oxygen to silicon of 0.75 to 2.2 and an atomic ratio of carbon to silicon of 0.1 to 2.5, measured by XPS.

2. The method as claimed in claim 1, wherein the layer either improves or reduces the adhesion of biomolecules and/or prokaryotic or eukaryotic cells to the surface.

15. The method as claimed in claim 1, further including the steps of:

reducing adhesion of pathogenic settlements, and/or

reducing thrombogenesis, and/or

reducing the occurrence of humoral and cellular immune reactions, and/or

reducing nonspecific adsorption of peptides, proteins, lipids, carbohydrates and/or nucleic acids on the surface, and/or

allowing spatially restricted growth of cell cultures on the surface and/or

increasing the wettability by aqueous fluids, in particular blood,

compared to a corresponding uncoated surface.

21. The method as claimed in claim 2, further including the steps of:

reducing adhesion of pathogenic settlements, and/or

reducing thrombogenesis, and/or

reducing the occurrence of humoral and cellular immune reactions, and/or

reducing unspecific adsorption of peptides, proteins, lipids, carbohydrates and/or nucleic acids on the surface, and/or

allowing spatially restricted growth of cell cultures on the surface, and/or

increasing the wettability by aqueous fluids, in particular blood,

compared to a corresponding uncoated surface.

3. A method for increasing or reducing the adhesion of biomolecules and/or prokaryotic or eukaryotic cells to a layer, the method comprising applying to a surface a crosslinked silicon-containing layer containing silicon, O, C, H, and optionally N, which is produced by plasma polymerization and/or crosslinking of organosilicon liquids by a plasma process and/or UV radiation of a wavelength of less than 250 nm, without using metals of an atomic number of more than 14, said layer having an atomic ratio of oxygen to silicon of 0.75 to 2.2 and an atomic ratio of carbon to silicon of 0.1 to 2.5, measured by XPS,

provided that in case the adhesion of biomolecules and/or cells is to be reduced, the crosslinked silicon-containing layer does not consist of carbon, silicon, oxygen and hydrogen and optionally usual impurities, and in the ESCA spectrum of the layer, upon calibration on the aliphatic portion of the C 1s peak at 285.00 eV, compared to a trimethylsiloxy-terminated polydimethylsiloxan (PDMS) with a kinematic viscosity of 350 mm²/s at 25°

C. and a density of 0.97 g/mL at 25°

C.,

the Si 2p peak has a bond energy value which is shifted by at most 0.45 eV to higher or lower bond energies, and

the O 1s peak has a bond energy value which is shifted by at most 0.50 eV to higher or lower bond energies.

22. The method as claimed in claim 3, further including the steps of:

reducing adhesion of pathogenic settlements, and/or

reducing thrombogenesis, and/or

reducing the occurrence of humoral and cellular immune reactions, and/or

reducing unspecific adsorption of peptides, proteins, lipids, carbohydrates and/or nucleic acids on the surface, and/or

allowing spatially restricted growth of cell cultures on the surface, and/or

increasing the wettability by aqueous fluids, in particular blood,

compared to a corresponding uncoated surface.

4. A non-genotoxic medical technical article, comprising a surface region of the article with a crosslinked silicon containing layer containing silicon, O, C, H, and optionally N, which is produced by plasma polymerization and/or crosslinking of organosilicon liquids by a plasma process and/or UV radiation of a wavelength of less than 250 nm, without using metals of an atomic number of more than 14, said layer having an atomic ratio of oxygen to silicon of 0.75 to 2.2 and an atomic ratio of carbon to silicon of 0.1 to 2.5, measured by XPS, the article being selected from the group consisting of:

a) a membrane, pipe or tube, oxygenator membrane, catheter, angioplasty balloon, stent, cannula, sensor and probe;

b) an implantable article selected from the group consisting of;

medical nails, clasps, threads and screws, bone attachment nails, stents or vessel prostheses, injection systems, catheters, cardiovascular implants, artificial organs, pacemakers and a power source thereof, prostheses, orthopedic implants, artificial joint, a socket and a counterpart cooperating therewith, a hip or knee prosthesis, a spine prosthesis, cochlea implants, artificial heart valves, heart valve rings, intraocular lenses, artificial corneas, pumps or other devices for releasing substances in the body, and epitheses;

c) a container for receiving and/or transporting bodily fluid, tissue or the constituents thereof of a living being or of biomolecules including peptides, proteins, lipids, carbohydrates, nucleic acids or active substances prepared therewith;

d) an article for the at least partial covering of skin or a mucous membrane of a living being including wounds; and

e) an article otherwise in contact with bodily fluid, tissue or the constituents thereof of a living being or with biomolecules, including peptides, proteins, lipids, carbohydrates, nucleic acids or active substances prepared therewith during intended use.

5. The article as claimed in claim 4, characterized in that the article has a region of the silicon-containing layer with

a) a water contact angle of not more than 35°

, or

b) a water contact angle of at least 90°

.

6. The article as claimed in claim 4, characterized in that the silicon-containing layer consists, apart from hydrogen, to at least 98 atom %, of the elements silicon, carbon and oxygen and preferably of from 0.1% to 2% of nitrogen, measured by XPS.

7. The article as claimed in claim 6, characterized in that the silicon-containing layer has 3-15 atom % of carbon, based on all the elements apart from hydrogen, determined according to XPS.

8. The article according to claim 4, characterized in that the carbon atoms of the silicon-containing layer have a proportion of 5 to 35% of carbon atoms with a bond to one oxygen atom (“

C—

O carbon”

), measured by XPS.

9. The article according to claim 4, characterized in that the carbon atoms of the silicon-containing layer have a proportion of 5 to 20% of carbon atoms with bonds to two oxygen atoms (“

COO carbon”

), measured by XPS.

10. The article as claimed in claim 4, characterized in that the silicon-containing layer is produced by crosslinking a methylsiloxane precursor, preferably hexamethyldisiloxane, by plasma polymerization, in particular by low pressure or atmospheric pressure plasma polymerization, or by crosslinking a silicone oil without chemically reactive groups under the effect of a plasma or UV radiation of a wavelength of less than 250 nm, in particular excimer radiation.

11. The article as claimed in claim 10, characterized in that after the precursor or silicone oil was crosslinked and the silicon-containing layer was at least partly oxidized, preferably by plasma effect, flame treatment, oxy-fluorination, laser treatment or a treatment with excimer lamps.

12. The article as claimed in claim 4, characterized in that the silicon-containing layer has a layer thickness of at most 2 μ

m, preferably at most 1 μ

m, more preferably at most 500 nm, and of at least 5 nm, preferably at least 10 nm and more preferably at least 15 nm.

13. A process for the production of an article as claimed in claim 4, comprising the steps of:

a) preparing a crosslinked, silicon-containing layer with an atomic ratio of oxygen to silicon of 0.75 to 2.2, and an atomic ratio of carbon to silicon of 0.1 to 2.5, measured by XPS, and

b) oxidizing at least portions of the layer prepared in step a).

14. The process as claimed in claim 13, characterized in that to delimit the area to be oxidized, a mask is used, preferably a detachable self-adhesive mask, more preferably an adhesive tape, or a printed mask and/or a substance which can be at least partially dissolved or dispersed, preferably in water and is preferably removed after step b).

16. A method for imparting a non-genotoxic effect to a surface comprising applying to the surface a crosslinked silicon-containing layer consisting of silicon, O, C, H, optionally N which can be produced by plasma polymerization and/or crosslinking of organosilicon liquids by a plasma process and/or UV radiation of a wavelength of less than 250 nm, without using metals of an atomic number of more than 14, having an atomic ratio of oxygen to silicon of 0.75 to 2.2 and an atomic ratio of carbon to silicon of 0.1 to 2.5, measured by XPS.

17. A method for increasing or reducing the adhesion of biomolecules and/or cells (pro- or eukaryotes) to a layer by using a crosslinked silicon-containing layer consisting of silicon, O, C, H, and optionally N, which is produced by plasma polymerization and/or crosslinking of organosilicon liquids by a plasma process and/or UV radiation of a wavelength of less than 250 nm, without using metals of an atomic number of more than 14, said layer having an atomic ratio of oxygen to silicon of 0.75 to 2.2 and an atomic ratio of carbon to silicon of 0.1 to 2.5, measured by XPS, the adhesion of biomolecules and/or cells (pro- or eukaryotes),

provided that in case the adhesion of biomolecules and/or cells is to be reduced, the crosslinked silicon-containing layer does not consist of carbon, silicon, oxygen and hydrogen and optionally usual impurities, and in the ESCA spectrum of the layer, upon calibration on the aliphatic portion of the C 1s peak at 285.00 eV, compared to a trimethylsiloxy-terminated polydimethylsiloxan (PDMS) with a kinematic viscosity of 350 mm²/s at 25°

C. and a density of 0.97 g/mL at 25°

C.,

the Si 2p peak has a bond energy value which is shifted by at most 0.45 eV to higher or lower bond energies, and

the O 1s peak has a bond energy value which is shifted by at most 0.50 eV to higher or lower bond energies.

18. A non-genotoxic medical technical article, comprising a surface region of the article with a crosslinked silicon-containing layer consisting of silicon, O, C, H, optionally N which can be produced by plasma polymerization and/or crosslinking of organosilicon liquids by a plasma process and/or UV radiation of a wavelength of less than 250 nm, without using metals of an atomic number of more than 14, having an atomic ratio of oxygen to silicon of 0.75 to 2.2 and an atomic ratio of carbon to silicon of 0.1 to 2.5, measured by XPS, the article being selected from the group consisting of:

a) a membrane, pipe or tube, in particular oxygenator membrane, catheter, angioplasty balloon, stent, cannula, sensor and probe,

b) an implantable article selected from the group consisting of;

medical nails, clasps, threads and screws, in particular bone attachment nails, stents or vessel prostheses, injection systems, catheters, cardiovascular implants, artificial organs, in particular pacemakers and a power source thereof, prostheses, orthopedic implants, in particular artificial joint mouse, in particular a socket and a counterpart cooperating therewith such as a hip or knee prosthesis, a spine prosthesis, cochlea implants, artificial heart valves, heart valve rings or intraocular lenses, artificial corneas, pumps or other devices for releasing substances in the body and epitheses,

c) a container for receiving and/or transporting bodily fluid, tissue or the constituents thereof of a living being or of biomolecules, preferably peptides, proteins, lipids, carbohydrates, nucleic acids or active substances prepared therewith,

d) an article for the at least partial covering of skin or mucous membrane of a living being and preferably of wounds,

e) an article otherwise in contact with bodily fluid, tissue or the constituents thereof of a living being or with biomolecules, preferably peptides, proteins, lipids, carbohydrates, nucleic acids or active substances prepared therewith during intended use.

19. The article of claim 18, characterized in that the carbon atoms of the silicon-containing layer have a proportion of 5 to 35% of carbon atoms with a bond to one oxygen atom (“

C—

O carbon”

), measured by XPS.

20. The article of claim 18, characterized in that the carbon atoms of the silicon-containing layer have a proportion of 5 to 20% of carbon atoms with bonds to two oxygen atoms (“

COO carbon”

) measured by XPS.