WO2009058351A2 - Surfaces de spinulose - Google Patents

Surfaces de spinulose Download PDF

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Publication number
WO2009058351A2
WO2009058351A2 PCT/US2008/012348 US2008012348W WO2009058351A2 WO 2009058351 A2 WO2009058351 A2 WO 2009058351A2 US 2008012348 W US2008012348 W US 2008012348W WO 2009058351 A2 WO2009058351 A2 WO 2009058351A2
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WO
WIPO (PCT)
Prior art keywords
spinulose
polymer
titanium
metal
coated
Prior art date
Application number
PCT/US2008/012348
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English (en)
Other versions
WO2009058351A3 (fr
Inventor
Christina K. Thomas
Luke J. Ryves
Daniel M. Storey
Barbara S. Kitchell
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Chameleon Scientific Corporation
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Publication date
Priority claimed from US11/932,831 external-priority patent/US8158216B2/en
Priority claimed from US12/152,698 external-priority patent/US20090287302A1/en
Application filed by Chameleon Scientific Corporation filed Critical Chameleon Scientific Corporation
Priority to EP08844879A priority Critical patent/EP2257653A4/fr
Publication of WO2009058351A2 publication Critical patent/WO2009058351A2/fr
Publication of WO2009058351A3 publication Critical patent/WO2009058351A3/fr

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    • C—CHEMISTRY; METALLURGY
    • C23—COATING METALLIC MATERIAL; COATING MATERIAL WITH METALLIC MATERIAL; CHEMICAL SURFACE TREATMENT; DIFFUSION TREATMENT OF METALLIC MATERIAL; COATING BY VACUUM EVAPORATION, BY SPUTTERING, BY ION IMPLANTATION OR BY CHEMICAL VAPOUR DEPOSITION, IN GENERAL; INHIBITING CORROSION OF METALLIC MATERIAL OR INCRUSTATION IN GENERAL
    • C23C—COATING METALLIC MATERIAL; COATING MATERIAL WITH METALLIC MATERIAL; SURFACE TREATMENT OF METALLIC MATERIAL BY DIFFUSION INTO THE SURFACE, BY CHEMICAL CONVERSION OR SUBSTITUTION; COATING BY VACUUM EVAPORATION, BY SPUTTERING, BY ION IMPLANTATION OR BY CHEMICAL VAPOUR DEPOSITION, IN GENERAL
    • C23C14/00—Coating by vacuum evaporation, by sputtering or by ion implantation of the coating forming material
    • C23C14/06—Coating by vacuum evaporation, by sputtering or by ion implantation of the coating forming material characterised by the coating material
    • C23C14/14—Metallic material, boron or silicon
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/28—Materials for coating prostheses
    • A61L27/30—Inorganic materials
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/28—Materials for coating prostheses
    • A61L27/34—Macromolecular materials
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • C—CHEMISTRY; METALLURGY
    • C23—COATING METALLIC MATERIAL; COATING MATERIAL WITH METALLIC MATERIAL; CHEMICAL SURFACE TREATMENT; DIFFUSION TREATMENT OF METALLIC MATERIAL; COATING BY VACUUM EVAPORATION, BY SPUTTERING, BY ION IMPLANTATION OR BY CHEMICAL VAPOUR DEPOSITION, IN GENERAL; INHIBITING CORROSION OF METALLIC MATERIAL OR INCRUSTATION IN GENERAL
    • C23C—COATING METALLIC MATERIAL; COATING MATERIAL WITH METALLIC MATERIAL; SURFACE TREATMENT OF METALLIC MATERIAL BY DIFFUSION INTO THE SURFACE, BY CHEMICAL CONVERSION OR SUBSTITUTION; COATING BY VACUUM EVAPORATION, BY SPUTTERING, BY ION IMPLANTATION OR BY CHEMICAL VAPOUR DEPOSITION, IN GENERAL
    • C23C14/00—Coating by vacuum evaporation, by sputtering or by ion implantation of the coating forming material
    • C23C14/22—Coating by vacuum evaporation, by sputtering or by ion implantation of the coating forming material characterised by the process of coating
    • C23C14/225—Oblique incidence of vaporised material on substrate
    • C—CHEMISTRY; METALLURGY
    • C23—COATING METALLIC MATERIAL; COATING MATERIAL WITH METALLIC MATERIAL; CHEMICAL SURFACE TREATMENT; DIFFUSION TREATMENT OF METALLIC MATERIAL; COATING BY VACUUM EVAPORATION, BY SPUTTERING, BY ION IMPLANTATION OR BY CHEMICAL VAPOUR DEPOSITION, IN GENERAL; INHIBITING CORROSION OF METALLIC MATERIAL OR INCRUSTATION IN GENERAL
    • C23C—COATING METALLIC MATERIAL; COATING MATERIAL WITH METALLIC MATERIAL; SURFACE TREATMENT OF METALLIC MATERIAL BY DIFFUSION INTO THE SURFACE, BY CHEMICAL CONVERSION OR SUBSTITUTION; COATING BY VACUUM EVAPORATION, BY SPUTTERING, BY ION IMPLANTATION OR BY CHEMICAL VAPOUR DEPOSITION, IN GENERAL
    • C23C14/00—Coating by vacuum evaporation, by sputtering or by ion implantation of the coating forming material
    • C23C14/22—Coating by vacuum evaporation, by sputtering or by ion implantation of the coating forming material characterised by the process of coating
    • C23C14/24—Vacuum evaporation
    • C23C14/32—Vacuum evaporation by explosion; by evaporation and subsequent ionisation of the vapours, e.g. ion-plating
    • C23C14/325—Electric arc evaporation
    • C—CHEMISTRY; METALLURGY
    • C23—COATING METALLIC MATERIAL; COATING MATERIAL WITH METALLIC MATERIAL; CHEMICAL SURFACE TREATMENT; DIFFUSION TREATMENT OF METALLIC MATERIAL; COATING BY VACUUM EVAPORATION, BY SPUTTERING, BY ION IMPLANTATION OR BY CHEMICAL VAPOUR DEPOSITION, IN GENERAL; INHIBITING CORROSION OF METALLIC MATERIAL OR INCRUSTATION IN GENERAL
    • C23C—COATING METALLIC MATERIAL; COATING MATERIAL WITH METALLIC MATERIAL; SURFACE TREATMENT OF METALLIC MATERIAL BY DIFFUSION INTO THE SURFACE, BY CHEMICAL CONVERSION OR SUBSTITUTION; COATING BY VACUUM EVAPORATION, BY SPUTTERING, BY ION IMPLANTATION OR BY CHEMICAL VAPOUR DEPOSITION, IN GENERAL
    • C23C14/00—Coating by vacuum evaporation, by sputtering or by ion implantation of the coating forming material
    • C23C14/22—Coating by vacuum evaporation, by sputtering or by ion implantation of the coating forming material characterised by the process of coating
    • C23C14/54—Controlling or regulating the coating process
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2400/00—Materials characterised by their function or physical properties
    • A61L2400/18—Modification of implant surfaces in order to improve biocompatibility, cell growth, fixation of biomolecules, e.g. plasma treatment

Definitions

  • the invention relates to structured surfaces and films, and particularly to nanostructured spinulose surfaces produced by modified plasma vapor deposition of a vaporizable material onto a surface.
  • Nanostructured surfaces of GLAD films have been suggested as having possible applications in chiral optics and, due to magnetic anisotropy, possible development of information storage devices because of the ability to deposit materials such as silicon in the form of nanostructured helical columns.
  • Hawkeye and Brett (2007) reviewed GLAD films and foresee applications in solar energy conversion, fuel cells, gas sensors, catalysts and electrochemical capacitors.
  • Corrosion is a persistent problem with metals exposed to air and water; for example, the harsh environments encountered by steel rebars used in highways and bridges has led to increased use of deicing salts, which has accelerated corrosion damage.
  • deicing salts which has accelerated corrosion damage.
  • films on metal surfaces have been investigated in efforts to develop suitable protective coatings.
  • Polymer coatings on metals are found to be useful in several applications, ranging from corrosion-inhibiting surfaces to biocompatible thin films on medical devices. Polymers with low coefficients of friction are desirable in catheters and guidewires used in surgical procedures and in permanently implanted devices such as stents and valves. Metals are used in the fabrication of several types of implants; however, bare metals used in stents, for example, may provide a focus for restenosis, due to neointimal proliferation subsequent to implantation. Polymer coated stents have, in some instances, appeared to reduce the potential for the inflammation and thrombogenic reactions leading to restenosis. Many polymers are not suitable for implanted devices because of flexing or expansion upon implantation, in addition to peeling, cracking or detachment from the underlying metal substrate.
  • WO/1995/004839 describes pretreating metal guidewires with a hydrocarbon plasma deposited residue over the metal, which in turn acts as a tie layer for a subsequently applied outer hydrophilic polymer coating.
  • Polymer films have been textured to provide enhanced adhesion of plasma deposited metals.
  • the morphology of the polymer surface is characterized by mounds and dimples, but the adherence of the polymer to an underlying surface is not addressed and the polymer structured surface is dependent on regulation of polymer phase kinetics (U.S. Pat. No. 6,099,939).
  • Methods for producing metal spinulose surfaces using a modified plasma vapor deposition are disclosed.
  • the present invention solves many of the troublesome problems frequently encountered with sloughing and peeling of polymers used to coat and protect surfaces, particularly the biocompatible polymers currently used to coat surfaces of medical devices.
  • Spinulose metal surfaces and films promote strong cell adherence and when coated with a polymer will retain the spinulose nanostructural features that promote cell adherence.
  • the spinulose surfaces of the present invention are unique and distinctly different in physical appearance from the metal "whiskers” often seen in digital circuits as tiny hair-like projections.
  • the surfaces and films produced by the disclosed vapor deposition methods have a spiney or spike-like appearance with pointy projections over the surface, which are readily distinguished from columnar or rod-like structures and are distinctly different from other reported nanostructured surfaces.
  • PVD Physical vapor deposition
  • a class of processes that involve the deposition of material, often in the form of a thin film, from a condensable vapor which has been produced from a solid precursor by physical means.
  • PVD processes include evaporation, sputtering, laser ablation and arc discharge.
  • PVD can involve chemical reactions, such as from multiple sources, or by addition of a reactive gas.
  • the nano plasma deposition (NPD) method to produce spinulose surfaces is a modified form of physical vapor deposition (PVD).
  • PVD physical vapor deposition
  • Several features of the method are distinguishable from currently used methods for forming nanostructured metal surfaces by physical vapor deposition.
  • the majority of reported deposition methods, as discussed, are vapor-liquid-solid (or vapor-solid), chemical vapor deposition (CVD) processes or electron beam evaporation.
  • the present invention utilizes a process based on vapor deposition, employing a plasma arc deposition procedure where low voltage, ( ⁇ 100 V), high current, (> 5 A), discharge ablates a metal cathode in an evacuated chamber and an inert atmosphere so that the metal is deposited onto a substrate surface.
  • high current, (> 5 A) high current
  • discharge ablates a metal cathode in an evacuated chamber and an inert atmosphere so that the metal is deposited onto a substrate surface.
  • the novel spinulose surface of a nano plasma deposited (NPD) metal using the described conditions exhibits features significantly different in appearance from previously reported vapor deposited metals and metal compounds.
  • NPD nano plasma deposited
  • the spikes can be controlled in height and number by the number of cycles employed, which is a relatively small number on the order of about 3 up to at least 15 or so, at least for the particular metal examples used to illustrate the invention.
  • Spinulose surfaces are believed to be possible with a range of metals, although it is expected that some modifications may be required in the cycling conditions.
  • Ti titanium
  • Zr zirconium
  • the novel spinulose surfaces can be created as films without the supporting substrate.
  • Ti or Zr for example, may be deposited on a carbon substrate and the resulting spinulose film, can be isolated by burning off the carbon.
  • Other readily removable or degradable substrates can be envisioned, such as those which can be easily removed without altering the integrity of the film by dissolving a salt or similar dissolvable substrate.
  • Substrates suitable as temporary matrices for film deposition include various salts. Sodium or potassium chloride, for example, can be readily dissolved after NPD deposition of Ti or other metals.
  • the particulate surface remaining after dissolution can be recovered as a film or powder and used as a high surface area catalyst in bioreactors or in a number of other applications based on the unique nanostructure.
  • As drug delivery vehicles spinulose and other nanostructured particles with low surface energy can act as a reservoir or support for chemicals or biomolecules.
  • a slowly dissolving salt matrix for example can be used to release an attached drug in a time dependent manner.
  • the nanostructural features of metals deposited by the described NPD method are different from ion plasma deposited films where deposition is conducted for specified time periods at different voltages or by varying the other deposition parameters. Serendipitously, it was found that a cycling or intermittent deposition from metal targets produced the unexpected spinulose surface features on the deposited metal films. While globular nanostructures were observed with cobalt, copper, nickel, hafnium, 316L stainless steel, nitanol, titanium 6-4, and silver, titanium and zirconium formed distinct spinulose nanostructured surfaces. Aluminum exhibited distinct surface features under the deposition conditions, although the surface was devoid of spikes and globules and appeared as bead-like rounded structures interspersed between larger round particles.
  • Aluminum metal deposited under the same conditions described for Ti and Zr has a stacked appearance with a geometric cube-like structure different from the structures observed with Ti and other metals. While spinulose surfaces for aluminum and other metals were not observed under the conditions used to produce spinulose Ti nanostructured surfaces, it may be possible to generate spinules by using modifications of the disclosed deposition procedures, such as, but not necessarily limited to, longer intervals between deposition cycles, distance from target and chamber pressure.
  • Spinulose nanostructured Ti surfaces can be formed as coatings or films on virtually any metal, plastic or ceramic surface, including stainless steel, titanium, CoCrMo, nitinol, glass or silicon, as well as on silicone, poly(methylmethacrylate) (PMMA), polyurethane (PU), polyvinyl chloride (PVC), polyethylene terephthalate glycol (PETG), polyetheretherketone (PEEK), polytetrafluoroethylene (PTFE), polyethylene terephthalate (PET), ultra high molecular weight polyethylene (UHMWPE), and polypropylene (PP).
  • PMMA poly(methylmethacrylate)
  • PU polyurethane
  • PVC polyvinyl chloride
  • PETG polyethylene terephthalate glycol
  • PEEK polyetheretherketone
  • PTFE polytetrafluoroethylene
  • PET polyethylene terephthalate
  • UHMWPE ultra high molecular weight polyethylene
  • PP polypropylene
  • a particular embodiment of the invention is a polymer-coated titanium or zirconium spinulose surface. Titanium or zirconium spinulose surfaces or films can be prepared on any type of substrate whether metal, polymer, glass, or ceramic.
  • the spinulose nanostructured substrate surfaces produced by the modified NPD method demonstrates that under certain controlled deposition conditions, a unique "spikey" metal film or coating can be produced on virtually any substrate.
  • the present invention demonstrates that such spikey surfaces generated from titanium or zirconium are surprisingly well suited for top coating with a wide range of polymers. Appropriate polymers can be selected as required for specialized utilities such as protective coatings, anchors or matrices, biocompatibility and controlled elution coatings.
  • polymers are durably attached to surfaces that would otherwise exhibit only weak or unpredictable attachment polymer attachment.
  • the thickness of polymer films can be controlled by the deposition method; for example, several dipping steps after initial dipping or formation of a polymer layer on a spinulose surface can be used to provide thicknesses varying up to several microns.
  • the unique structure of the spinulose surface is produced by controlled nanoplasma deposition.
  • a polymer can be dispersed on this surface also using a vapor deposition method, but in some cases more conveniently by simple dipping.
  • Many agents including bioactive materials such as therapeutic drugs, can be effectively co-deposited or serially deposited with the polymer. Drugs and other bioactive agents can be attached to the polymer either before or after deposition.
  • the agent When co-deposited with a polymer and depending on the polymer, the agent can be released or eluted from the polymer matrix in a time-dependent manner. Controlled time release profiles can be developed for agents deposited in combination with a coating polymer.
  • the invention provides a method to efficiently attach polymers to uniquely spinulose substrate surfaces.
  • the nanostructured surfaces exhibit excellent adhesion and durability, while avoiding use of complicated, hazardous and inefficient chemistry; e.g., the silane, photo-, thermo-couplings conventionally used for polymer attachment, to an underlying substrate, as well as ultraviolet and heating steps that may cause surface damage.
  • An additional advantage of the invention is the option to use polymers with functional groups, in effect providing an additional functional feature to the surface without employing additional steps to modify the deposited polymer.
  • polymer films deposited on metal spinulose surfaces are highly resistant to shear and thermal peeling. Compared to polymer coatings on smooth or roughened surfaces such as metal surfaces, polymer coatings cannot be removed in comparable pull tests.
  • An advantage of preparing polymer surface films on spinulose metal surfaces is the application of many types of polymers to spinulose mtetal surfaces by any of a number of application methods.
  • a simple dipping procedure can be used, which is rapid and inexpensive compared to other surface coating methods, including spraying, casting, spin coating and plasma deposition.
  • thermosetting polymers polymerized from monomers requiring either low or high polymerization temperatures.
  • a spinulose surface for example, can be contacted with either low or high polymerization temperatures as required for many thermosetting polymers.
  • High polymerization temperatures can be employed without significant changes to a spinulose metal surface, such as Ti which has a melting temperature of over 1000 0 C.
  • Photopolymerizable molecules requiring use of ultraviolet light or other radiation also do not affect the underlying spinulose metal surface.
  • a wide range of polymers are suitable for coating on spinulose metal surfaces.
  • a drug can be loaded onto a spinulose metal surface or polymer coated spinulose surface and used to create a controllable drug delivery system; for example using a biodegradable polymer(s)/co-polymer(s) for controlled release.
  • a bioactive agent can be dispersed or dissolved in an inert polymer that is then cast or sprayed on a spinulose metal surface.
  • Functional polymers can also be used. Examples include monofunctional or bifunctional thiol, amino, maleimidyl, p-nitrophenyl, carboxyl, aldehyde active and/or N- hydroxysuccimidyl activated ester PEG polymers or any polymer derivative, and the like, adhered to a spinulous surface which can serve as a platform for attachment of biological molecules. Depending on the choice of polymer, one can introduce other desirable characteristics to the substrate surface.
  • Examples include conjugation of biomolecules to the active sites of a dicarboxylic acid-PEG while simultaneously utilizing the PEG chain of the same molecule for protein passivation; improving cell adhesion by introducing not only an underlying nanostructured surface, but also a nanostructured surface topically modified with a biological polymer, such as collagen fibronectin, vitronectin, laminin and the like.
  • a biological polymer such as collagen fibronectin, vitronectin, laminin and the like.
  • An additional feature of the metal spinulose surfaces is the ability to attract several types of cells, including fibroblast cells, including human skin fibroblast cells, human gingival fibroblast cells and human periodontal ligament fibroblast cells, as well as osteoblast cells and human umbilical endothelial cells.
  • fibroblast cells including human skin fibroblast cells, human gingival fibroblast cells and human periodontal ligament fibroblast cells, as well as osteoblast cells and human umbilical endothelial cells.
  • the disclosed spinulose surfaces are useful in implant devices where adhesion and proliferation of cells are important in bone or other types of restoration.
  • Spinulose as defined in the Random House Unabridged Dictionary refers to a spiney appearance and in Webster's New International Dictionary Third Edition, as “covered with small spines”. Spinules, or small or minute spine, are distinguished in appearance from larger, more hair-like appendages commonly characterized as whiskers or columnar structures and which are typically wire or rod-like in appearance. [0040] Spinulose metal surfaces are produced under special nano plasma deposition conditions. The surfaces are unique in appearance, showing distinctly pointed spikey projections over the surfaces.
  • substantially is intended to indicate a limited range of up to 10% of any value indicated.
  • PVD Physical vapor deposition
  • a class of processes that involve the deposition of material, often in the form of a thin film, from a condensable vapor which has been produced from a solid precursor by physical means.
  • PVD processes include evaporation, sputtering, laser ablation and arc discharge.
  • PVD can involve chemical reactions, such as from multiple sources, or by addition of a reactive gas.
  • Electron beam evaporation is use of an electron beam to heat a metal so that it evaporates.
  • the vapor can be deposited on a surface.
  • Chemical vapor deposition is the growth of material from a gas phase precursor, due to reaction or reactions that often occur on a surface. The reactions are frequently promoted by using an elevated substrate temperature. Alternatively the reactions can be achieved by enhancing the reactivity of the precursors using a plasma (PECVD) or hot wire.
  • PECVD plasma vapor deposition
  • Atomic layer deposition is a CVD method involving growing materials by pulsing multiple precursors that react with a surface in a self-limiting manner.
  • Biomolecules are agents or materials that have some biological interactions; e.g., drugs, proteins, cells and bioorganisms such as bacteria and viruses.
  • FIG.l is a sketch of a typical ion plasma deposition apparatus showing a pure metal cathode target 1; substrate 2; substrate holder 3; vacuum chamber 4; power supply for target 5; and arc control 6. Not shown is an inlet into the vacuum chamber 4 for introducing a gas flow, which may be an inert gas, or reactive gas such as oxygen.
  • a gas flow which may be an inert gas, or reactive gas such as oxygen.
  • FIG. 8 is a FEG-SEM image of Ag/AgO deposited by nanoplasma deposition onto a spinulose titanium surface on a titanium substrate
  • FIG. 9 is an FEG-SEM image of PLLA coated spinulose titanium scratched with a conospherical scratch probe with increasing normal load.
  • FIG. 10 is an FEG-SEM image of PLLA coated on smooth titanium scratched with a conospherical scratch probe with increasing normal load.
  • FTG. 11 is an elution profile of silver from Ag/ AgO deposited on a spinulose titanium surface without a PLLA polymer coating (o) compared with silver eluted from Ag/ AgO coated on a spinulose titanium surface with PLLA polymer coating (x). Elutions were performed in phosphate buffered saline (Ix PBS) and mL/cm [Ag] measured by ICP.
  • Ix PBS phosphate buffered saline
  • FIG. 14 is a sketch of the electrode apparatus for taking impedance measurements of spinulose coated and bare electrode using an MCP-BR2822 portable LCR meter (A).
  • FIG. 15 is the impedance modulus of spinulose and unmodified 0.005" stainless wire electrodes -250 um length, measured in 0.45% (w/v) NaCl( a q) at room temperature.
  • Nanoplasma deposition is a vapor deposition method that has been modified to produce uniquely nanotextured spinulose metal surfaces and films.
  • the surfaces are stable, provide a strong matrix for cell attachment and growth, and are highly adherent to polymer coatings.
  • Polymer surface coatings over the spinulose metal surfaces retain the spinulose surface nanofeatures and offer an additional platform for incorporating dual functionality onto substrate surfaces, either as attachments to the polymer itself or as overlying protective coatings.
  • the spinulose surface features of NPD deposited metals contribute to reaction with external environments and to binding with other materials.
  • Adherent polymer coatings and films on spinulose surfaces make it possible to protect a metal substrate from external forces and/or to endow a substrate surface with functional or linking groups suitable for attaching biomolecules such as drugs.
  • Polymers of many different types are suitable for applying to a NPD spinulose nanoparticulate surface, including hydrophilic, hydrophobic and functionalized polymers.
  • PLLA coated spinulose titanium for example, exhibits strong adhesion compared to the poor adhesion of PLLA coated over smooth titanium.
  • Polymer coatings may act as time release barriers for selected bioactive agents, particularly those used on medical devices.
  • poly-L-lactic acid PLLA
  • PLLA and poly(lactic-co- glycolic acid) (PLGA) coatings were applied as diffusion barriers over reservoirs of Ag/AgO deposited on spinulose titanium substrates. Silver released from surface-deposited Ag/AgO is recognized as having antimicrobial properties and has been used as an antimicrobial agent externally and as a coating on implanted or internally used devices.
  • Nanotextured spinulose metal surfaces can be produced by controlled NPD of a metal on a wide range of substrate surfaces.
  • Nanoplasma deposited titanium and/or zirconium, for example, deposited under the specific conditions described herein exhibit features significantly different in appearance and properties from conventionally vapor deposited metals and metal compounds.
  • a nano-rough surface initially appears as spikes on round particulates, growing into a spiky or spinulose surface when the deposition is cycled under controlled conditions.
  • the deposition method of the invention is a modified ion plasma deposition process in which a plasma is generated from a metal target and deposited onto a substrate in a controlled atmosphere environment under reduced pressure.
  • the nano plasma deposition process is basically a vacuum deposition of ionized material generated as a plasma by applying voltage and current to a cathode target such that ionized particles are deposited on a substrate.
  • the metal plasma initially deposits as nanoparticulates, atoms and ions, which after further deposition under the described controlled deposition cycling conditions will form a unique nanostructured surface.
  • Unique surface features of the deposited metals are formed under vacuum and/or in an inert atmosphere, typically an inert gas such as argon, using a cycling process.
  • the presence of oxygen or nitrogen may result in formation of metal oxides or nitrides, resulting in surface features different from the nanostructures formed from deposition of substantially pure metals.
  • the spinulose nanostructured surfaces produced under defined NPD deposition conditions have been produced with commercially pure titanium (grade 2) and with zirconium, the latter containing up to 4.5% hafnium in some samples.
  • commercially pure titanium grade 2
  • zirconium zirconium
  • spinulose-type surfaces were not observed with aluminum, cobalt, copper, nickel, (pure) hafnium, 316L stainless steel, nitinol, silver or titanium 6-4 deposited from metal targets on stainless steel substrates.
  • these metals form other types of unusual nanostructured surfaces, which are different from the spinulose appearance of deposited titanium or zirconium.
  • the nanostructured surfaces are basically globular or stacked globular in shape.
  • NPD aluminum surfaces are markedly different from Ti and Zr and the other metals cyclically deposited NPD metals. Pure aluminum metal deposited under the same conditions described for titanium and/or zirconium has a stacked appearance with a geometric cube-like structure different from the structures observed with titanium and other metals. While spinulose surfaces for aluminum and other metals are not observed under the conditions used to produce spinulose titanium or zirconium nanostructures, it may be possible to generate surface spinules by using modifications of the disclosed deposition procedures, such as, but not necessarily limited to, longer intervals between deposition cycles, distance from target and chamber pressure.
  • Spinulose nanostructured titanium and zirconium surfaces can be formed as coatings or films on virtually any metal, plastic, ceramic or glass substrate surface, including stainless steel, titanium, CoCrMo, nitinol, glass or silicon, as well as on silicone, poly(methylmethacrylate) (PMMA), polyurethane (PU), polyvinyl chloride (PVC), polyethylene terephthalate glycol (PETG), polyetheretherketone (PEEK), polytetrafluoroethylene (PTFE), polyethylene terephthalate (PET), ultra high molecular weight polyethylene (UHMWPE), and polypropylene (PP).
  • PMMA poly(methylmethacrylate)
  • PU polyurethane
  • PVC polyvinyl chloride
  • PETG polyethylene terephthalate glycol
  • PEEK polyetheretherketone
  • PTFE polytetrafluoroethylene
  • PET polyethylene terephthalate
  • UHMWPE ultra high molecular weight polyethylene
  • PP
  • the process for producing spinulose Ti and Zr surfaces and the globular type surfaces observed with other metals, except aluminum utilizes a nano plasma deposition method comprising generation of a plasma from a metal cathode.
  • Distance of the deposition target from the substrate can affect the nanostructural features of the deposited metal and surface coverage and can be adjusted to the particular apparatus configurations and deposition conditions.
  • the substrate is housed in a vacuum chamber and, while the base pressure does not appear critical for spinulose Ti formation, the selected pressure, gas flow, cycling time, distance from the cathode and other parameters can influence properties such as spinulose height and surface density.
  • Deposition is preferably conducted in an inert gas atmosphere, e.g., argon, in order to avoid any chemical reaction with the metal being deposited.
  • Titanium will react with some gases; for example, when nitrogen is present in the system, TiN may form.
  • the deposited TiN is not spinulous; rather, as reported by others using conventional vapor deposition, the nanostructured Ti surface typically has projections that are more whisker-like or column-like in appearance.
  • an argon atmosphere is employed, care being taken to use gas of high purity so that trace components do not react with the ionized titanium or other metal produced in the plasma.
  • Deposition is performed using a periodic deposition or cycling process. Gas flow and plasma discharge into the vacuum chamber are allowed to progress for a specified period of time. Gas flow is then reduced to near zero or, alternatively stopped completely, and plasma discharge is discontinued for a defined period of time before the cycle is reinitiated.
  • the cycling is an unusual step and is believed to be important in producing the observed Ti and Zr spinulose structures. Images of initially deposited Ti or Zr show that the metal ion plasma first deposits as substantially round nanoparticles. With additional cycling, the particulates develop a more spike-like structure with increasing surface coverage as the number of cycles is increased.
  • nanostructured spinulose surfaces of the present invention are distinctly different from whiskered type metal surfaces, columnar types of thin film surfaces and from the intergranular etched polymer surfaces to which an immersion plated metal is applied for the purpose of increasing peel strength.
  • the spinulose surfaces, when coated with a polymer, can be used for controlled release of bioactive or other agents.
  • Titanium spinulose surfaces on a metal, polymer, ceramic or glass substrate surface are highly nanostructured, but maintain basic structure when coated with Ag/AgO, polymers, or thin layers of drugs/biomolecules, as can be seen from the SEM images.
  • a substrate surface is first modified with nano plasma deposited (NPD) titanium or zirconium nanoparticulates, followed by application of the polymer onto the spinulose nanoparticulate surface.
  • NPD nano plasma deposited
  • the application may be by casting, spraying, dipping, electrospinning, or similar methods.
  • it may be advantageous to apply a polymer by vapor deposition, such as a plasma-enhanced chemical vapor deposition.
  • Some monomers may polymerize on the spinulose surface and can be used to form very thin films.
  • Nanostructured spinulose metal surfaces act as scaffolds for polymer surfacing or for molecules initially deposited onto such spinulose surfaces.
  • biomolecules and/or bioactive agents such as drugs and antimicrobials, e.g., silver
  • nano or molecular plasma deposition or by other conventional and well-known deposition methods, such that the nanostructure of the spinulose surface is preserved.
  • IPD Ag/AgO plasma vapor deposition
  • Adhesive properties of PLLA on a spinulose nanostructured titanium surface are enhanced as demonstrated when using a conspherical scratch probe with increasing load normal to test the interfacial adhesion of PLLA to the spinulose nanostructured titanium substrate.
  • the PLLA coating displayed good adhesion even around the severely damaged areas.
  • the same test with PLLA coated smooth titanium results in delamination of a region around the load, causing buckling and cracking of the polymer film.
  • the impedence of spinulose titanium coated stainless steel wires useful as leads or electrodes was compared with impedence of bare (uncoated) stainless steel wires.
  • Such spinulose titanium coated wires and leads can be used in the fabrication of miniaturized devices used in a variety of medical implants.
  • Human Osteoblast cells (CRL-11372) were purchased from American Type Culture Collection (Rockville, MD) as frozen cultures in complete media: 1:1 Ham's F12 medium and Dulbecco's modified Eagle's medium without phenol red with 2.5 mM L-glutamine, 10% I 7 BS and 0.3 ⁇ g/ml G418. Before use, the vials were thawed, centrifuged and the cells resuspended in complete media before transfer into a culture device and incubated at 34° C in 5% carbon dioxide. The cells were then subcultured in complete media after treating with trypsin-EDTA at either 34°C or 39°C. Doubling time was 36 hr at 33.5° C and 96 hr at 38.0° C. If not used immediately, the cells were stored frozen in complete media with DMSO added to each vial.
  • Human fibroblast cells (CRL- 1502) were purchased from American Type Culture Collection as frozen cultures in complete media containing Eagle's minimal essential medium with Earle's BSS and 2 mM L-glutamine (EMEM) modified to contain 1.0 mM sodium pyruvate, 0.1 M non-essential amino acids, 1.5 g/L sodium bicarbonate supplemented with 10% FBS and 10 U/mL penicillin/streptomycin.
  • EMEM L-glutamine
  • Human endothelial cells were purchased from VEC Technologies (Rensselaer, NY) as frozen cultures in MCDB-131 media.
  • Cathode material was titanium or zirconium 702 (UNS R60702 containing up to 4.5% hafnium).
  • Nanostructured spinulose titanium or zirconium surfaces can be produced by a modified cyclic plasma arc deposition procedure termed nanoplasma deposition (NPD).
  • NPD nanoplasma deposition
  • the vapor deposition apparatus for producing the metal ion plasmas can be used both for conventional metal plasma deposition and the cyclic modification used to produce spinulose surfaces and films.
  • the apparatus is shown in FIG. 1.
  • the metal cathode targets are disposed in a vacuum chamber.
  • An inert gas, typically argon, is not required but may be introduced into the evacuated chamber and deposition commenced.
  • the substrate 2 is generally positioned 6-28 inches from the target and deposition is conducted intermittently for periods of approximately 1-20 minutes. During the intervals between depositions, there is no plasma discharge and the inert gas flow optionally can be reduced or stopped completely if desired.
  • the intervals between depositions can be varied and are about 5-90 min with a typical run of about 3-27 cycles.
  • argon was typically used as an inert gas at 100 seem, depositions of 5 min at 90 min rest intervals, 9 cycles, 300 amps and 13 inches from the cathode.
  • Surface coverage with spinulose titanium typically ranged from 85-98%.
  • Distance from the cathode was also varied from 8-13 in a number of runs with ⁇ c ranging from 0° to 80°, gas flow 100-300 seem and variation of rest interval from 5-90 min. Over two hundred variations were run, showing that these parameters can to varied to control surface coverage and spinule height, which ranged from over 1 ⁇ m to less than 0.2 ⁇ m.
  • Spinulites could be produced by this method on any of a number of substrates, including stainless steel, nitinol, CoCrMo alloy, silicon, titanium, anodized titanium, glass, silicone, poly(methyl methacrylate) PMMA, polyurethane (PU), polytetrafluoroethylene (PTFE), polyvinyl chloride) (PVC), polyethylene terephthalate (PET), ultra high molecular weight polyethylene (UHMWPE), polyethylene terephthalate glucol (PETG), polyetheretherketone (PEEK)and polypropylene (PP).
  • substrates including stainless steel, nitinol, CoCrMo alloy, silicon, titanium, anodized titanium, glass, silicone, poly(methyl methacrylate) PMMA, polyurethane (PU), polytetrafluoroethylene (PTFE), polyvinyl chloride) (PVC), polyethylene terephthalate (PET), ultra high molecular weight polyethylene (UHMWPE), polyethylene
  • the selected substrate is ultrasonically cleaned in detergent (ChemCrest #275 at 160 0 F), rinsed in deionized water and dried in hot air prior to the deposition process.
  • the clean substrate is then placed in the chamber and exposed to nano-plasma deposition (NPD) using the special deposition conditions described.
  • the cathode is commercially pure titanium cathode (grade 2) or zirconium 7021.
  • the substrate is mounted in the vacuum chamber at distances from 6-28 in from the cathode (measured from the centre of the cathode).
  • the angle between the substrate surface normal and a line from the centre of the cathode to the substrate, ⁇ c can be varied in the range of 0-80°.
  • the angle between the depositing flux and the substrate surface, ⁇ s, is varied in the range of 0-80°.
  • the chamber is pumped to a base pressure of between 1.33 mPa-0.080 mPa.
  • the arc current is varied from a 15-400 A with an argon burn pressure of 0.1-5.5 mT.
  • each cycle consisting of plasma discharge intervals (varied over the range 1 to 20 minutes) followed by intervals where there is no discharge and or gas flow (between 5 and 810 minutes), except that gas flow can be optionally maintained.
  • Each process consisted of 3-27 cycles.
  • NPD deposited particles from titanium or zirconium plasmas are typically round and will differ in size and distribution depending on power and/or time of deposition. Under the described specified deposition conditions, the titanium or zirconium metal particles develop nanosized spike-like protrusions, which were observed as spinules or small thorny spines as shown in FIG. 2 for titanium. FlG.
  • Example 2- Polymer Coated Ionic Plasma Deposited (IPD) Silver/Silver Oxide
  • IPD Ionic Plasma Deposition
  • Ag/AgO was deposited onto a spinulose titanium surface coated on a titanium substrate. As shown by SEM in FIG. 8, the spinulose features of the titanium are maintained after Ag/ AgO deposition.
  • a 4% w/v poly-L-lactic acid polymer (PLLA) solution in chloroform was cast from a pipette over the surface of a Ag/AgO deposited by IPD on a smooth titanium substrate.
  • the polymerized coating was only weakly adherent to the underlying silver surface as evidenced by peeling of the film shortly after immersion in phosphate buffered saline (PBS) or deionized water at 37° C in less than one day.
  • PBS phosphate buffered saline
  • a spinulose titanium surface was formed on a smooth titanium substrate as described in Example 1.
  • Ag/ AgO was deposited on the spinulose surface by ion plasma deposition (IPD) from a silver cathode as described in Example 2 with use of a silver target.
  • a film of PLLA was then cast over the Ag/ AgO as described in Example 2.
  • the coated Ag/AgO was placed in deionized water, physiological saline or PBS at 37° C.
  • FIG. 11 shows an elution profile in PBS for silver after 43 days comparing silver profiles of PLLA coated Ag/AgO and uncoated Ag/AgO deposited on a spinulose titanium surface.
  • the Ag/AgO remaining on the PLLA coated spinulose titanium surface was higher than the amount deposited on the Ag/AgO spinulose titanium only surface. Even after soaking for at least 43 days in deionized water, the polymer film remained well adhered to the spinulose surface.
  • the substrates were placed in wells using sterilized tweezers and exposed to UV light for one hour. The substrates were then rinsed with 2.OmL of room temperature (Ix PBS). The desired amount of room temperature Complete Media (supplemented with FBS and antibiotic) was added to each well. The cells were seeded onto the substrates at 3500 cells/cm 2 and incubated at 34°C, 5% CO 2 for seven days. Following incubation, the media and non-adherent cells were removed. The substrates were then rinsed with room temperature Ix PBS and fixed with 4% paraformaldehyde. The nuclei of adherent cells were fluorescently stained with Hoescht stain and counted using a fluorescent microscope.
  • Example 7 Reduction of Electrode Impedance Using Spinulose Titanium Surfaces
  • the impedance of conventional electrodes increases to an undesirable level.
  • This example shows that by applying a spinulose titanium surface to miniaturized electrode devices, the constraint of reducing electrode area characterized by increasing impedance can be eliminated.
  • the spinulose titanium surface consisting of micron- sized high aspect ratio titanium structures, gives a higher conductive material area for the same geometric area.
  • the electrode impedance can be decreased.
  • Impedance measurements were taken at 100 Hz, IkHz and 10 kHz for both spinulose coated and bare wire (-250 um in length) using an MCP-BR2822 portable LCR meter, set to a series equivalent circuit, as seen in FIG. 14. 0.45% w/v NaCl was used as an electrolyte in a 150 mL beaker.
  • the electrodes were held at a distance apart using a plate drilled with holes one centimeter apart, center to center, on top of the beaker.
  • the beaker and the electrodes were placed inside an 8"x8"x8" box made of 0.020" thick titanium sheet. This box was connected to ground in an attempt to reduce electrical interference.
  • FIG. 15 shows that compared to the bare wire electrodes, the spinulose coated electrodes, with a greater surface area, had a lower impedance over all frequencies measured.

Abstract

La présente invention concerne des surfaces métalliques de spinulose produites par un processus de dépôt cyclique de nanoplasma modifié. Ces surfaces de spinulose uniques sont extrêmement adhérentes vis-à-vis des cellules et des molécules bioactives et de polymère, y compris des ostéoblastes, des fibroblastes et des cellules endothéliales. On peut recouvrir les surfaces de spinulose nanostructurées d'une large gamme de polymères, afin de former des revêtements de surface de polymère; lesdits revêtements sont particulièrement utiles sur des implants, des cathéters, des fils guides, des stents et d'autres dispositifs médicaux destinés à des applications in vivo.
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US11/932,831 US8158216B2 (en) 2007-10-31 2007-10-31 Spinulose titanium nanoparticulate surfaces
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