WO2018107092A1 - Structures tubulaires à surface fonctionnalisée, et procédés de fabrication et d'utilisation de telles structures tubulaires à surface fonctionnalisée - Google Patents

Structures tubulaires à surface fonctionnalisée, et procédés de fabrication et d'utilisation de telles structures tubulaires à surface fonctionnalisée Download PDF

Info

Publication number
WO2018107092A1
WO2018107092A1 PCT/US2017/065417 US2017065417W WO2018107092A1 WO 2018107092 A1 WO2018107092 A1 WO 2018107092A1 US 2017065417 W US2017065417 W US 2017065417W WO 2018107092 A1 WO2018107092 A1 WO 2018107092A1
Authority
WO
WIPO (PCT)
Prior art keywords
tubular structure
metal substrate
metal
conductive
lumen
Prior art date
Application number
PCT/US2017/065417
Other languages
English (en)
Inventor
Harald NUHN
Tejal A. Desai
Original Assignee
The Regents Of The University Of California
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by The Regents Of The University Of California filed Critical The Regents Of The University Of California
Publication of WO2018107092A1 publication Critical patent/WO2018107092A1/fr

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C25—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES; APPARATUS THEREFOR
    • C25D—PROCESSES FOR THE ELECTROLYTIC OR ELECTROPHORETIC PRODUCTION OF COATINGS; ELECTROFORMING; APPARATUS THEREFOR
    • C25D17/00—Constructional parts, or assemblies thereof, of cells for electrolytic coating
    • C25D17/008—Current shielding devices
    • C—CHEMISTRY; METALLURGY
    • C25—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES; APPARATUS THEREFOR
    • C25D—PROCESSES FOR THE ELECTROLYTIC OR ELECTROPHORETIC PRODUCTION OF COATINGS; ELECTROFORMING; APPARATUS THEREFOR
    • C25D11/00—Electrolytic coating by surface reaction, i.e. forming conversion layers
    • C25D11/02—Anodisation
    • C25D11/022—Anodisation on selected surface areas
    • C—CHEMISTRY; METALLURGY
    • C25—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES; APPARATUS THEREFOR
    • C25D—PROCESSES FOR THE ELECTROLYTIC OR ELECTROPHORETIC PRODUCTION OF COATINGS; ELECTROFORMING; APPARATUS THEREFOR
    • C25D11/00—Electrolytic coating by surface reaction, i.e. forming conversion layers
    • C25D11/005—Apparatus specially adapted for electrolytic conversion coating
    • C—CHEMISTRY; METALLURGY
    • C25—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES; APPARATUS THEREFOR
    • C25D—PROCESSES FOR THE ELECTROLYTIC OR ELECTROPHORETIC PRODUCTION OF COATINGS; ELECTROFORMING; APPARATUS THEREFOR
    • C25D11/00—Electrolytic coating by surface reaction, i.e. forming conversion layers
    • C25D11/02—Anodisation
    • C25D11/04—Anodisation of aluminium or alloys based thereon
    • C—CHEMISTRY; METALLURGY
    • C25—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES; APPARATUS THEREFOR
    • C25D—PROCESSES FOR THE ELECTROLYTIC OR ELECTROPHORETIC PRODUCTION OF COATINGS; ELECTROFORMING; APPARATUS THEREFOR
    • C25D11/00—Electrolytic coating by surface reaction, i.e. forming conversion layers
    • C25D11/02—Anodisation
    • C25D11/26—Anodisation of refractory metals or alloys based thereon
    • C—CHEMISTRY; METALLURGY
    • C25—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES; APPARATUS THEREFOR
    • C25D—PROCESSES FOR THE ELECTROLYTIC OR ELECTROPHORETIC PRODUCTION OF COATINGS; ELECTROFORMING; APPARATUS THEREFOR
    • C25D11/00—Electrolytic coating by surface reaction, i.e. forming conversion layers
    • C25D11/02—Anodisation
    • C25D11/34—Anodisation of metals or alloys not provided for in groups C25D11/04 - C25D11/32
    • C—CHEMISTRY; METALLURGY
    • C25—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES; APPARATUS THEREFOR
    • C25D—PROCESSES FOR THE ELECTROLYTIC OR ELECTROPHORETIC PRODUCTION OF COATINGS; ELECTROFORMING; APPARATUS THEREFOR
    • C25D17/00—Constructional parts, or assemblies thereof, of cells for electrolytic coating
    • C25D17/10—Electrodes, e.g. composition, counter electrode
    • C25D17/12—Shape or form
    • C—CHEMISTRY; METALLURGY
    • C25—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES; APPARATUS THEREFOR
    • C25D—PROCESSES FOR THE ELECTROLYTIC OR ELECTROPHORETIC PRODUCTION OF COATINGS; ELECTROFORMING; APPARATUS THEREFOR
    • C25D11/00—Electrolytic coating by surface reaction, i.e. forming conversion layers
    • C25D11/02—Anodisation
    • C25D11/04—Anodisation of aluminium or alloys based thereon
    • C25D11/06—Anodisation of aluminium or alloys based thereon characterised by the electrolytes used
    • C—CHEMISTRY; METALLURGY
    • C25—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES; APPARATUS THEREFOR
    • C25D—PROCESSES FOR THE ELECTROLYTIC OR ELECTROPHORETIC PRODUCTION OF COATINGS; ELECTROFORMING; APPARATUS THEREFOR
    • C25D11/00—Electrolytic coating by surface reaction, i.e. forming conversion layers
    • C25D11/02—Anodisation
    • C25D11/04—Anodisation of aluminium or alloys based thereon
    • C25D11/12—Anodising more than once, e.g. in different baths
    • C—CHEMISTRY; METALLURGY
    • C25—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES; APPARATUS THEREFOR
    • C25D—PROCESSES FOR THE ELECTROLYTIC OR ELECTROPHORETIC PRODUCTION OF COATINGS; ELECTROFORMING; APPARATUS THEREFOR
    • C25D11/00—Electrolytic coating by surface reaction, i.e. forming conversion layers
    • C25D11/02—Anodisation
    • C25D11/04—Anodisation of aluminium or alloys based thereon
    • C25D11/16—Pretreatment, e.g. desmutting

Definitions

  • Coatings and other surface modifications are utilized to provide beneficial characteristics such as reduced wear and improved biocompatibility to a variety of devices including, for example, implantable medical devices.
  • Polymers and metal oxides are versatile materials which are used in a variety of applications including, for example, in optical coatings and as biocompatible coatings for bone implants. Accordingly, new coating techniques and devices, particularly those with applicability to polymer and metal oxide coating can be expected to positively affect a variety of important technologies including, for example, medical device fabrication.
  • a method for functionalizing a tubular structure with an array of metal oxide nanotubes may include positioning an electrode in a lumen of a tubular structure, wherein the tubular structure contains: i) a tubular polymeric scaffold surrounding the lumen and comprising an inner surface; and ii) a metal substrate overlying the inner surface, wherein the metal substrate is in electrical contact with an anode, and wherein the electrode includes: a) a conductive structure in electrical contact with a cathode; and b) one or more spacers configured to prevent electrical contact between the conductive structure and the scaffold; introducing an electrolyte solution into the lumen, thereby submerging the metal substrate and the electrode with the electrolyte solution; and generating an electrical potential difference across the electrolyte solution between the anode and the cathode, in a manner sufficient to form an array of metal oxide nanotubes on a surface of the metal substrate interfacing the lumen.
  • Figure 1 is a collection of schematic diagrams of a vascular graft made of a titanium coil covered by polyurethane tubing, according to embodiments of the present disclosure.
  • Figure 2 is an image showing titanium wire embedded in a polymeric tube, according to embodiments of the present disclosure.
  • Figure 3 is a collection of scanning electron micrography (SEM) images showing titanium oxide (Ti0 2 ) nanotubes coating a titanium wire in a titanium coil vascular graft, according to embodiments of the present disclosure.
  • Figure 4 is a schematic diagram showing variations in a vascular graft made of a titanium wire covered by polymeric tubing, according to embodiments of the present disclosure.
  • Figures 5A-5C are a collection of SEM images showing a titanium film deposited onto vascular graft material, according to embodiments of the present disclosure.
  • Figure 6 is an SEM image of a Ti0 2 nanotube coating formed over a titanium film deposited over a vascular graft material, according to embodiments of the present disclosure.
  • Figures 7A and 7B are a collection of images showing a vascular graft with an inner lumen modified with an unpatterned titanium foil functionalized with Ti0 2 nanotubes, according to embodiments of the present disclosure.
  • Figure 8 is a functionalized vascular graft implanted into the abdominal aorta of a rabbit, according to embodiments of the present disclosure.
  • Figures 9A and 9B are a collection of SEM images showing inner lumen of a vascular graft functionalized with Ti0 2 nanotubes, according to embodiments of the present disclosure.
  • Figures 10A and 10B are a collection of a schematic diagram and an image showing a device and system for coating a titanium foil-lined vascular graft with Ti0 2 nanotubes, according to embodiments of the present disclosure.
  • Figure 11 shows Table 1, listing the parameters used for coating a titanium foil-lined vascular graft with Ti0 2 nanotubes, according to embodiments of the present disclosure.
  • Figure 12 is a schematic diagram showing a tubular structure with protruding metal substrate in the form of a latch.
  • Figure 13 is an image showing an electrode of the present invention comprising a rectangular-shaped spacer.
  • Figure 14 is a schematic diagram showing a system according to one embodiment of the present disclosure.
  • Figure 15 is an image showing a test probe according to one embodiment of the present disclosure.
  • Figure 16 shows Table 2, listing the parameters used for coating a titanium foil-lined vascular graft with Ti0 2 nanotubes, according to embodiments of the present disclosure.
  • Figure 17 shows an example of a parameter that worked for coating a titanium foil-lined vascular graft with Ti0 2 nanotubes, in which nanotubes were created and exposed, and an image showing the nanotubes.
  • Figure 18 shows an example of a parameter that did not work, and an image showing the resulting material.
  • Figure 19A is a schematic diagram of a vascular graft shown in light gray with titanium foil (depicted in dark grey) carrying Ti0 2 nanotubular arrays, disposed along the inner circumference on the proximal and distal ends of the graft.
  • Figure 19B shows a graft with titanium foil inserted into an end (dark region) and a graft with no insert.
  • An “individual” refers to any animal, e.g., a mouse, rat, rabbit, goat, dog, pig, monkey, non-human primate, or a human.
  • substantially may be applied to modify any quantitative representation that could permissibly vary without resulting in a change in the basic function to which it is related. For example, a spacer may position a conductive structure somewhat away from the center of the lumen of a tubular structure, if the array of metal oxide nanotubes formed on the surface of the metal substrate is not materially altered.
  • the terms “treat,” “treatment,” “treating,” and the like refer to obtaining a desired surgical and/or physiologic effect.
  • the effect may be prophylactic in terms of completely or partially preventing a disease or symptom thereof and/or may be therapeutic in terms of a partial or complete cure for a disease and/or adverse effect attributable to the disease.
  • Treatment covers any treatment of a disease in a mammal, particularly in a human, and includes: (a) preventing the disease from occurring in a subject which may be predisposed to the disease but has not yet been diagnosed as having it; (b) inhibiting the disease, i.e., arresting its development; and (c) relieving the disease, e.g., causing regression of the disease, e.g., to completely or partially remove symptoms of the disease.
  • Polymeric as used herein, may be used to describe an organic compound composed of repeating units of one or more monomers containing carbon and hydrogen atoms.
  • the monomers can also include other atoms such as Si, O, N, P, F, and S.
  • a polymer may have a solid bulk polymer matrix.
  • Biocompatible refers to a property of a material that allows for prolonged contact with a tissue in a subject without causing toxicity or significant damage.
  • “Functionalize” as used herein, refers to modifying or associating at least the surface of a structure with a new material that confers properties that are not present in the structure alone.
  • the new material may be covalently attached, or may be non-covalently associated (e.g., coated) with the structure.
  • anode refers to a positively charged electrode of an electrolytic cell or an electrode which is capable of serving as a positively charged electrode of an electrolytic cell.
  • cathode refers to a negatively charged electrode of an electrolytic cell or an electrode which is capable of serving as a negatively charged electrode of an electrolytic cell.
  • conductive polymer means an electrically conductive polymeric material.
  • nanostructure As used herein, the terms “nanostructure”, “nanostructured” and the like refer to structures or objects modified with structures having at least one dimension greater than 0.1 nm and less than 1000 nm.
  • microstructure As used herein, the terms “microstructure”, “microstructured” and the like refer to structures or objects modified with structures having at least one dimension greater than or equal to 1 ⁇ and less than 1000 ⁇ .
  • Tubular as used herein, may describe a structure that includes a scaffold that substantially surrounds a hollow central portion, which may be called a lumen.
  • the hollow central portion may include an opening at a first end of the scaffold and/or at a second end of the scaffold opposite the first end.
  • the structure in some cases is elongated along a path defined by the first end and the second end along the center of the lumen, where a length of the path is longer than the average diameter of the lumen as measured along a plane substantially perpendicular to the path.
  • the structure is cylindrical.
  • the cross section of the structure is circular, square, rectangular, hexagonal, or irregular shaped.
  • a "nanotube” as used herein, may refer to a tubular structure, where the diameter of the lumen is on a nanometer scale.
  • Array as used herein, may describe a spatial distribution of elements on a surface, where the elements may be distributed randomly, in a substantially regular pattern, or in an irregular pattern.
  • an element of the array may touch a neighboring element, or may be defined at least in part by a structural element that is continuous with that defining at least in part a neighboring element.
  • a tubular structure e.g., a vascular graft, functionalized on the inner surface with an array of metal oxide nanotubes, and methods and devices for making the same are provided.
  • the method may include positioning a conductive structure having spacers, e.g., an electrode, inside the lumen of a tubular structure, such as a vascular graft, such that the spacer prevents an electrical short between the conductive structure and a metal surface overlying the inner surface of the tubular structure.
  • Spacers e.g., an electrode
  • the present method, and devices and systems for performing the same provide for synthesis of an array of metal oxide nanotubes, e.g., titanium oxide (Ti0 2 ) nanotubes, where the nanotubes have controlled dimensions (e.g., controlled diameter and controlled length of nanotubes in the array).
  • the dimensions of the nanotubes of the array may be varied by, e.g., adjusting the duration of applying the electrical field (e.g., duration of applying voltage), the amplitude of the applied electrical field (e.g., amplitude of the applied voltage), and/or the temperature and/or the composition of the electrolyte.
  • aspects of the present disclosure include methods of functionalizing, e.g., coating, a tubular structure or patch structure with an array of metal oxide nanotubes, using an anodization process.
  • the present method may include positioning an electrode in a lumen of a tubular structure; introducing an electrolyte solution into the lumen; and maintaining an electrical potential difference across the electrolyte solution between the electrode and the inner surface of the lumen, to coat the inner surface of the tubular structure with an array of metal oxide nanotubes, where the inner surface and the electrode are at least partially submerged in the electrolyte solution.
  • a metal substrate may overlie the inner surface, and the array of metal oxide nanotubes may be formed on the metal substrate by the anodization process, where the metal substrate and the electrode are at least partially submerged in the electrolyte solution.
  • the present method may be performed using any suitable device or system for functionalizing, e.g., coating and/or surface modifying, the inner lumen of a tubular structure with an array of metal oxide nanotubes, such as the devices and systems of the present disclosure, as described herein.
  • the functionalized tubular structure may be modified into a
  • the tubular structure may in general contain a polymeric scaffold surrounding the lumen, where the inner surface of the scaffold faces the lumen. "Face” as used herein, indicates that the surface of a structure is proximal to the object compared to another surface on the opposite side of the structure.
  • the tubular structure may further include a metal substrate that covers at least part of the inner surface, where the metal substrate exposes a surface to the lumen.
  • the patch structure comprises two surfaces and may in general contain a polymeric scaffold on the outside surface of the structure, where the inner surface of the scaffold faces the electrode.
  • the patch structure may further include a metal substrate that covers at least part of the inner surface, where the metal substrate exposes a surface to the electrode.
  • the patch structure to be functionalized, e.g., coated and/or surface modified, by the present method may include any suitable polymeric scaffold on the outer surface, and may have any suitable dimensions.
  • the patch structure to be functionalized is, e.g., a vascular patch, it may be configured to have any suitable dimensions required to, e.g., repair a blood vessel, perform a successful endarterectomy.
  • the tubular structure to be functionalized, e.g., coated and/or surface modified, by the present method may include any suitable tubular polymeric scaffold to form a lumen, and may have any suitable dimensions.
  • the tubular structure has an inner diameter (e.g., diameter of the luminal cross section, from one side of the lumen to the diametrically opposite side) of 0.1 millimeters (mm) or more, e.g., 0.5 mm or more, 1.0 mm or more, 2.0 mm or more, 5.0 mm or more, including 10 mm or more, and in some cases 100 mm or less, e.g., 50 mm or less, 10 mm or less, including 5.0 mm or less.
  • the tubular structure has an inner diameter in the range of 0.1 mm to 100 mm, e.g., 0.5 mm to 50 mm, including 1.0 mm to 10 mm.
  • the tubular structure or patch structure to be functionalized, e.g., coated and/or surface modified, by the present method has a longitudinal length, defined by the length of the structure between a first end and a second end opposite the first end, of 1.0 mm or more, e.g., 5.0 mm or more, 10 mm or more, 20 mm or more, 30 mm or more, 50 mm or more, including 100 mm or more, and in some cases has a longitudinal length of 1.0 meter (m) or less, e.g., 50 centimeters (cm) or less, 10 cm or less, 5.0 cm or less, 1.0 cm or less, 50 mm or less, including 10 mm or less.
  • the tubular structure or patch structure has a longitudinal length in the range of 1.0 mm to 1.0 m, e.g., 5.0 mm to 50 cm, 5.0 mm to 10 cm, including 1.0 cm to 10 cm.
  • the polymeric scaffold may be made of any suitable material, such as a biocompatible polymeric material.
  • the polymeric scaffold is non-degradable in a physiological environment, e.g., an implantation site in an individual's body.
  • the polymeric scaffold includes polytetrafluoroethylene (PTFE; such as Teflon®), polyethylene terephthalate (PET), and/or polyurethane (PU).
  • PTFE polytetrafluoroethylene
  • PET polyethylene terephthalate
  • PU polyurethane
  • the polymeric scaffold includes an expanded PTFE (ePTFE) material (such as GoreTex®).
  • the polymeric scaffold is a polymeric tubing, e.g., a vascular graft material.
  • the polymeric scaffold is a polymeric patch, e.g., a vascular patch material.
  • the polymeric scaffold may be a watertight material and may prevent a liquid material contained in the lumen or one side of the patch from leaking out through the wall of the scaffold.
  • the polymeric scaffold may be a woven or a non- woven material.
  • the metal substrate that covers the inner surface of the polymeric scaffold of the tubular structure or patch structure, and on which the metal oxide nanotubes are formed, as described herein, may be any suitable metal substrate. As the metal substrate overlies the inner surface of the scaffold, the metal substrate may have substantially the same form factor as the polymeric scaffold.
  • the metal substrate is a metal wire, metal mesh, or a metal foil (see, for example, Figures 1 and 4).
  • the metal wire is a metal coil (e.g., Figure 1). The metal coil may be in the form of a substantially regular spiral having a defined pitch.
  • the pitch is about 1.0 times or more, e.g., 1.2 times or more, 1.5 times or more, 2.0 times or more, 2.5 times or more, including 3.0 times or more of the width of the metal wire, and in some cases, is 5.0 times or less, e.g., 4.0 times or less, 3.0 times or less, including 2.5 times or less of the width of the metal wire.
  • the pitch of the metal coil spiral is in the range of 1.0 to 5.0 times the width of the metal wire, e.g., 1.2 to 4.0 times the width of the metal wire, 1.5 to 3.0 times the width of the metal wire, including 2.0 to 3.0 times the width of the metal wire.
  • the metal foil may have any suitable thickness.
  • the metal foil has a thickness of 0.01 ⁇ or more, e.g., 0.02 ⁇ or more, 0.05 ⁇ or more, 0.1 ⁇ or more, 0.2 ⁇ or more, 0.5 ⁇ or more, 1.0 ⁇ or more, 2.0 ⁇ or more, 5.0 ⁇ or more, including 10 ⁇ or more, and in some cases may have a thickness of 100 ⁇ or less, e.g., 50 ⁇ or less, 20 ⁇ or less, 10 ⁇ or less, 8.0 ⁇ or less, 5.0 ⁇ or less, 2.0 ⁇ or less, including 1.0 ⁇ or less.
  • the metal foil has a thickness in the range of 0.01 to 100 ⁇ , e.g., 0.02 to 50 ⁇ 0.05 to 20 ⁇ , 0.1 to 10 ⁇ , 0.1 to 8.0 ⁇ , including 0.1 to 5.0 ⁇ .
  • the metal substrate may include any suitable metal, and may be a biocompatible metal.
  • the metal substrate includes iron, cobalt, aluminum, niobium, tantalum, titanium, tungsten, zirconium, vanadium, or a mixture thereof.
  • the metal substrate includes a metal alloy, e.g., a titanium alloy, such as TiA16V4.
  • the metal substrate may be deposited on the inner surface of the tubular scaffold or patch scaffold using any suitable method. Suitable methods include, without limitation, cathodic arc deposition, electron beam physical vapor deposition, evaporative deposition, pulsed laser deposition, and sputter deposition. In some cases, the metal substrate is deposited over an intermediate layer that overlies the inner surface of the scaffold, to increase adhesion of the metal substrate to the scaffold. In some cases, the metal substrate is deposited over an intermediate layer of adhesive that overlies the inner surface of the scaffold.
  • a first plasma activation step for both the metal substrate and scaffold may increase each's interaction with the adhesive.
  • the scaffold may be plasma activated to increase adhesion to the adhesive.
  • a metal surface may be plasma activated before attaching to an adhesive to increase interaction with the adhesive.
  • the inner surface of the scaffold may be plasma activated and the surface of the metal substrate to be adhered to the inner surface of the scaffold may both be plasma activated to increase interaction with the adhesive used to attach the scaffold to the metal tube.
  • the metal substrate is adhered to the scaffold without the use of any adhesive.
  • a reactive species is deposited via plasma to the metal substrate and scaffold, resulting in a covalent linkage between the metal substrate and scaffold.
  • Exemplary biocompatible adhesives include, for example, epoxy based adhesives, such as EP21TDCS MED or MasterSil 151Med (Masterbond).
  • Other exemplary adhesives include silanes or urethanes.
  • an adhesive free, covalent bond between the polymer and the metal substrate via reactive groups e.g. Ti-OH on the foil and Si-OH on the polymers (e.g. PDMS) may also be used. These can be introduced via physical or chemical surface treatments, e.g. plasma, electro chemical or chemical (etch).
  • the metal substrate may cover any suitable portion of the inner surface of the scaffold.
  • the metal substrate overlies 10% or more, e.g., 20% or more, 30% or more, 40% or more, 50% or more, 60% or more, 70% or more, 80% or more, 90% or more, 95% or more, and up to about 100% of the inner surface of the scaffold.
  • the metal substrate may be located on the inner circumference of the tubular structure at only the proximal and distal ends. In some cases, the metal substrate may be located on the inner circumference of the tubular structure covering substantially all of the inner surface of the scaffold.
  • the metal substrate includes openings that expose the underlying inner surface of the scaffold.
  • the openings may be any suitable shape, including, without limitation, circular, round, elliptical, rectangular, squared, hexagonal, or diamond.
  • the surface of the metal substrate on which the metal oxide nanotubes are formed may be substantially smooth (e.g., without any regular or irregular microstructures), or may include microstructures. In some embodiments, a smooth surface may be obtained by electropolishing. In some cases, the surface of the metal substrate is patterned into microstructures including a groove, pillar, pit, or a combination thereof.
  • the microstructures, e.g., grooves, pillars, or pit may be any suitable shape, including, without limitation, circular, triangular, rectangular, or square.
  • the microstructures may have any suitable dimensions, ranging from sub-micrometer to micrometer range in width, spacing and/or height.
  • the surface of the metal substrate conforms to the inner surface of the scaffold which the metal substrate overlies. For example, if the scaffold is a woven structure, the surface of the metal substrate may have a micro structure that conforms to the weaves of polymeric material exposed on the inner surface of the scaffold (see, for example, Figures 3A-3C).
  • the tubular structure or patch structure includes a conductive
  • the conductive, biocompatible wire disposed between the inner surface and the metal substrate, where the conductive, biocompatible wire is in electrical contact with the metal substrate.
  • the conductive, biocompatible wire may be used to increase the conductivity along the metal substrate during synthesis of the array of nanotubes on the surface of the metal substrate, as described herein.
  • the conductive, biocompatible wire is a helical wire disposed between the inner surface and the metal substrate of the tubular or patch structure.
  • a helical, conductive, biocompatible wire increases kink-resistance and assists in keeping the lumen of the tubular structure in an open (e.g., non-collapsed) configuration.
  • a tubular structure having increased kink-resistance allows for easier manipulation of the tubular structure.
  • tubular structure is a medical device (e.g., a vascular graft)
  • a tubular structure having increased kink-resistance allows the surgeon to perform the suturing procedure easier and more efficiently.
  • a person of ordinary skill in the art would recognize any shape in which the conductive, biocompatible wire can have increased kink-resi stance and improved suturing properties.
  • a tubular structure or patch structure of the present disclosure may, in some cases, be a medical device, e.g., a surgical implant, for use to treat an individual in need.
  • the medical device is a vascular graft, stent (e.g., cardiovascular stents, peripheral stents such as saphenous vein stents, cerebrovascular stents and coils), shunt, or a vascular patch.
  • the medical device is a vein graft, a fistula, arteriovenous shunt, cerebrospinal fluid shunt, etc.
  • the tubular structure may be a graft including a proximal end and a distal end, where the proximal and distal ends connect to vascular tissue, e.g., a vein, artery, or a blood capillary and where the proximal and distal ends include a cuff or a ring of metal disposed on the inner circumference of the tubular structure such that the metal is exposed to the vascular tissue.
  • a nanotubular array is present on the cuff or ring of metal disposed at the distal ends to prevent or minimize growth of tissue, such as, scar tissue at the interface between the graft and the vascular tissue.
  • the cuff may extend up to 0.5-3 cm into the ends of the graft.
  • the tubular structure may be a graft including a proximal end and a distal end, where the proximal and distal ends connect to vascular tissue, e.g., a vein, artery, or a blood capillary and where the proximal and distal ends include a cuff or a ring of a polymer disposed on the inner circumference of the tubular structure such that the polymer is exposed to the vascular tissue.
  • a nanotubular array is present on the cuff or ring of polymer disposed at the distal ends to prevent or minimize growth of tissue, such as, scar tissue at the interface between the graft and the vascular tissue.
  • the cuff of polymer may extend up to 0.5-3 cm into the ends of the graft.
  • the array of metal oxide-free polymer microtubes or nanotubes overlies the inner surface of the scaffold at distal and proximal ends of the tubular scaffold, such that while the inner surface in the central region of the tubular scaffold is free of such an array (due to lack of presence of a polymer substrate disposed on the inner surface in the central region of the tubular scaffold), the ends of the tubular scaffold which would be in contact with vascular tissue upon grafting into a subject's vascular system, include the array of polymer nanotubes to minimize growth of scar tissue at the interface between the tubular scaffold and the vascular tissue.
  • proximal and distal ends refer to the opposite ends of a tubular structure and are same as a first and a second end.
  • the array of metal oxide-free polymer microtubes or nanotubes overlies the inner surface of the scaffold at distal and proximal ends of the tubular scaffold, such that about 1% to 10% of the length of the tubular scaffold is covered at each end.
  • the tubular structure includes in the luminal side one or more valves configured to regulate the flow of a fluid, e.g., blood, through the tubular structure when implanted in an individual.
  • the tubular structure or patch structure e.g., a tubular or patch medical device, includes surgical attachment sites or surgical attachment structures, such as suture sites or suture tabs.
  • surgical attachment sites on the tubular structure or patch structure may not have an overlying metal substrate.
  • a polymer solution (e.g., a metal- or metal oxide-free polymer solution) may be coated on the inner circumference of the tubular structure at only the proximal and distal ends of the tubular structure.
  • a polymer solution may be coated on the inner circumference of the tubular structure covering substantially all of the inner surface of the scaffold.
  • the polymer solution may be coated on the inner circumference of the tubular structure at only the proximal and distal ends of the tubular structure to provide a ring or a cuff of polymer at the ends. In some cases, such a ring or cuff may be treated to form a nanotubular array.
  • a metal- or metal oxide-free polymer sheet comprising a microtubular or nanotubular array may be attached to the inner circumference at the ends of the tubular structure.
  • Any polymer suitable for generation of nanoarrays, such as, nanotubes may be used, such as, poly(8-caprolactone) (PCL), poly(DL-lactide-co-glycolide) (PLGA), poly(DL- lactide-co-8-caprolactone) (DLPLCL), or poly(methyl methacrylate).
  • the electrode may be an electrode that is suitably adapted to be inserted into the lumen of a tubular structure, as described above, and to carry out an anodization process in the presence of an electrolyte in the lumen.
  • aspects of the present disclosure include a device for use as an electrode in the present method, and may be described with reference to Figure 10A.
  • the device includes a conductive structure 1020 that may be in electrical contact with a cathode (i.e., an electron sink, or equivalently, a current source) from the bottom of the tubular structure, and spacers 1040 associated with the conductive structure (e.g., circumscribing sections of the conductive structure, as shown in Figure 10A), which conductive structure and spacers together form an electrode.
  • a counter electrode may be provided on the inner surface of the tubular structure, where the inner surface may be overlaid by a metal substrate 1030 electrically connected to the anode (i.e., an electron source, or equivalently, a current sink).
  • the spacers are configured such that when the electrode is inserted into the luminal space of a tubular structure to be functionalized, e.g., coated and/or surface modified, the spacer prevents short circuiting of the device when the cathode is used against a counter electrode anode to maintain an electric potential difference.
  • the spacers may be configured to prevent electrical contact between the conductive structure and the metal substrate.
  • an electrode may include one or more spacers, e.g., two spacers, three spacers, four spacers, five spacers, six spacers, seven spacers, eight spacers, nine spacers, ten or more spacers.
  • spacers e.g., two spacers, three spacers, four spacers, five spacers, six spacers, seven spacers, eight spacers, nine spacers, ten or more spacers.
  • An electrode including one or more spacers may have at least 20% of the conductive structure exposed to the electrolyte (i.e., free of the spacers), e.g., at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%), at least 94%, at least 95%, at least 96%, at least 97%, at least 98%.
  • a tubular structure having a length of 20 mm may include an electrode that includes two spacers, one positioned at the bottom of the tubular structure, and the other positioned at the top of the tubular structure, wherein about 94-98%> of the conductive structure is exposed to the electrolyte (i.e., free of the spacers).
  • a tubular structure having a longer length may include an electrode that includes additional spacers, e.g. four spacers, resulting in about 60% of the conductive structure free of the spacers.
  • an electrical potential difference maintained in a suitable manner between the anode and the cathode, across the electrolyte solution, may anodize the surface of the metal substrate 1030 interfacing the lumen, thereby functionalizing, e.g., coating and/or surface modifying, the surface with one or more layers of an array of metal oxide nanotubes.
  • the spacers 1040 may also be configured to allow sufficient flow of the electrolyte and gas evacuation during the anodization process.
  • Sufficient flow of the electrolyte and gas evacuation during the anodization process may be achieved when the system or device 1000 is completely submerged into the electrolyte solution.
  • Complete submersion of the system or device in the electrolyte solution may prevent any issues that can occur at the electrolyte/air interface (e.g., corrosion of the tubular structure).
  • any suitable modifications may be made to allow a more convenient complete submersion of the device.
  • the metal surface can protrude from the top of the tubular structure 1210 (i.e., end of the tubular structure that is proximal to the electrolyte/air interface) and may be modified to include a latch 1260.
  • such a modification is made by cutting off half of the circumference for a length of the metal surface (see, e.g. Figure 12).
  • the latch is about 10 mm long, e.g., 5 mm, 6 mm, 7 mm, 8 mm, 9 mm, 11 mm, 12 mm, 13 mm, 14 mm, 15 mm, 16 mm or longer.
  • a gap between the spacer and the surface of the tubular structure can provide sufficient flow of the electrolyte and gas evacuation during the anodization process.
  • the gap is sized appropriately to allow sufficient flow of the electrolyte and gas evacuation during the anodization process.
  • a hole in the spacer or multiple holes in the spacer, e.g., spacer is porous
  • the hole is sized appropriately to allow sufficient flow of the electrolyte and gas evacuation during the anodization process.
  • a device of the present disclosure may be a counter electrode against a metal substrate electrically connected to an anode and positioned over an inner luminal surface of a tubular structure, as described herein, where the counter electrode is adapted for use in a method of functionalizing, e.g., coating, the inner luminal surface of the tubular structure with one or more layers of an array of metal oxide nanotubes, as described herein.
  • the conductive structure 1020 may be made from, or coated with, a variety of suitable materials known in the art, e.g., platinum, titanium, vanadium, gold, aluminum, copper, lead, nickel, palladium, iron, cobalt, tantalum, tungsten, graphite, tin, and alloys including one or more of the above. See, e.g., Allam and Grimes, Solar Energy Materials & Solar Cells 92 (2008) 1468-1475, the disclosure of which is incorporated by reference herein.
  • one or more of parts of the conductive structure may serve as a sacrificial part which is at least partially consumed during the anodization reaction.
  • the length and diameter of the conductive structure may vary depending on particular application of the system.
  • the conductive structure may have a diameter of from about 0.2 mm to about 5 mm or greater, e.g., from about 0.3 mm to about 5 mm, about 0.4 mm to about 5 mm, about 0.5 mm to about 5 mm, about 0.6 mm to about 5 mm, about 0.7 to about 5 mm, about 0.8 mm to about 5 mm, about 0.9 mm to about 5 mm, about 1 mm to about 5 mm, about 2 mm to about 5 mm, about 3 mm to about 5 mm, or about 4mm to about 5 mm.
  • the conductive structure may have a diameter of from about 5 mm to about 0.2 mm, e.g., from about 4 mm to about 0.2 mm, from about 3 mm to about 0.2 mm, from about 2 mm to about 0.2 mm, from about 1 mm to about 0.2 mm, from about 0.9 mm to about 0.2 mm, from about 0.8 mm to about 0.2 mm, from about 0.7 mm to about 0.2 mm, from about 0.6 mm to about 0.2 mm, from about 0.5 mm to about 0.2 mm, from about 0.4 mm to about 0.2 mm, or from about 0.3 mm to about 0.2 mm.
  • the conductive structure may be provided in a variety of forms, e.g., as a wire, cylinder, or any other suitable form.
  • the spacer 1040 may be any suitable material and shape, and may be associated with the conductive structure 1020 in any suitable manner to prevent contact between the conductive structure and the surface of the metal substrate 1030. As such, the spacer provides for at least a minimum distance between the conductive structure and the surface of the metal substrate along the length of the conductive structure, where the minimum distance is sufficient to prevent the electrical short.
  • the spacers 1040 may also be configured to allow sufficient flow of the electrolyte and gas evacuation during the anodization process.
  • the shape of the spacers may be configured to allow sufficient flow of the electrolyte and gas evacuation during the anodization process. Any shape of the spacers may be suitable.
  • the spacers can be porous to allow sufficient flow of the electrolyte and gas evacuation during the anodization process.
  • the spacer should be selected such that it is compatible and non- reactive under the selected anodization conditions, e.g., with the selected electrolyte solution.
  • the spacer is a non-conductive material (i.e., an insulator), including, for example, any suitable non-conductive polymer, co-polymer, or polymer combination.
  • Suitable non- conductive polymers may include thermoplastic polymers, e.g., acrylonitrile butadiene styrene (ABS), polyethylene (PE), polypropylene (PP), polystyrene (PS), polyvinyl chloride (PVC), and polyetheretherketone (PEEK), fluorinated polymers, e.g., polytetrafluoroethylene (PTFE) (TeflonTM), among others.
  • the non- conductive material is a ceramic material, such as, without limitation, steatite, cordierite, 100% metal oxide alumina, 100% metal oxide zirconia.
  • suitable non-conductive ceramic material includes, without limitation, zirconium barium titanate, strontium titanate (ST), calcium titanate (CT), magnesium titanate (MT), calcium magnesium titanate (CMT), zinc titanate (ZT), lanthanum titanate (TLT), and neodymium titanate (TNT), barium zirconate (BZ), calcium zirconate (CZ), lead magnesium niobate (PMN), lead zinc niobate (PZN), lithium niobate (LN), barium stannate (BS), calcium stannate (CS), magnesium aluminium silicate, magnesium silicate, barium tantalate, titanium dioxide, niobium oxide, zirconia, silica, sapphire, beryllium oxide, and zirconium tin titanate.
  • the spacer is a semi-conductive material, such as, without limitation, silicon, germanium, gallium arsenide, silicon carbide, organic semi-conductive materials, etc.
  • the spacer 1040 may have any cross-sectional shape (e.g., along a plane perpendicular to the long dimension of the conductive structure 1020 in Figure 10A) that can provide at least a minimum distance between the conductive structure and the metal substrate along the length of the conductive structure, where the minimum distance is sufficient to prevent the electrical short.
  • the spacers have a cross-sectional shape of a triangle, square, circle, ellipse, diamond, rectangle, flat sheet, cross (see, Figure 13).
  • the spacers have a cross- sectional X-shape.
  • the spacers 1040 may be associated with the conductive structure 1020 in any suitable manner. In some cases, the spacer wraps around, or circumscribes, the conductive structure along a region of the conductive structure.
  • the spacer 1040 is configured to prevent an electrical short between the conductive structure 1020 and the metal substrate 1030
  • the spacer may be configured to provide at least a minimum distance between the conductive structure and the metal substrate along the length of the conductive structure, where the minimum distance is sufficient to prevent the electrical short.
  • the spacers are configured to position the conductive structure at substantially the center of the lumen of the metal substrate along the length of the conductive structure.
  • the distance between the conductive structure and the metal substrate is in the range of a few microns to several centimeters, e.g., about 1 micron, about 5 microns, about 10 microns, about 50 microns, about 100 microns, about 500 microns, about 1000 microns, about 5000 microns, about 1 cm, about 5 cm, about 10 cm, about 15 cm or more.
  • the distance between the conductive structure and the metal substrate is in general, the difference between half the diameter of the metal substrate and half the diameter of the conductive structure.
  • the present device includes at least two, e.g., at least three, at least 4, at least 5, including at least 6, spacers 1040 associated with the conductive structure 1020.
  • the number of spacers present associate with the conductive structure may depend on the length of the inner surface of the tubular structure to be functionalized, e.g., coated and/or surface modified, the width of each spacer, and the spacing between consecutive spacers.
  • the spacers are evenly distributed along the conductive structure, where the distances between successive spacers along the conductive structures are substantially constant.
  • the present method generally includes introducing an electrolyte into the lumen of the tubular structure and at least partially submerging the metal substrate to be functionalized, e.g., coated and/or surface-modified, and the electrode structure connected to the cathode in an electrolyte solution.
  • the positioning of the electrode in the lumen and introducing the electrolyte into the lumen may be performed in any suitable order (or concurrently with each other). Any suitable amount of the electrolyte solution may be introduced into the lumen. In some cases, the amount of electrolyte solution introduced into the lumen is sufficient to substantially fill the entire volume of the lumen of the tubular structure. In some cases, the amount of electrolyte solution introduced into the lumen is sufficient to submerge all or at least a portion of the surface of the metal substrate and at least a portion of the conductive structure of the electrode.
  • electrolyte solutions may be utilized depending on the particular application of the method, e.g., the desired nanotube dimensions or morphologies, and the materials used, e.g., the composition and/or the structure of the metal substrate overlying the inner surface of the lumen and to be functionalized, e.g., coated and/or surface-modified, and the electrode.
  • Suitable electrolytes may include, for example, one or more of ammonium fluoride, a chloride salt (e.g., ammonium chloride, sodium chloride, and potassium chloride), organic nitrates,
  • the electrolyte solution may include, e.g., ethylene glycol and/or water.
  • an electrolyte solution for use in connection with the disclosed methods of funtionalizing a tubular structure includes ethylene glycol, water at a ratio of 90: 10 or more, e.g., 92:8 or more, 94:6 or more, including 95:5 or more, and ammonium fluoride of about 0.5 g/L to about 4.5 g/L, e.g., 1 g/L to about 4 g/L, 2 g/L to about 4 g/L, such as, 0.5 g/L, 1 g/L, 1.5 g/L, 2 g/L, 2.5 g/L, 3 g/L, 3.5 g/L, 4 g/L, 4.5 g/L.
  • the electrolyte solution acts as an etchant for the metal substrate to be functionalized, e.g., coated and/or surface modified.
  • the source material from which the array of nanotubes as described is derived from the electrolyte solution via a sol-gel process.
  • the electrolyte solution may include Ti(OC 3 H7) which is converted to Ti0 2 nanostrucutres, e.g., nanotubes, on a metal substrate during anodization.
  • the metal substrate on which the nanostructures, e.g., nanotubes are to be formed can include, e.g., stainless steel or CoCr. See, e.g., Kang et al. Nano Letters (2009), vol. 9, no. 2, pp. 601-606, the disclosure of which is incorporated by reference herein in its entirety.
  • a method according to the present disclosure may include maintaining the electrolyte solution at a substantially constant temperature for a period of time.
  • the substantially constant temperature is above the freezing point of the electrolyte solution and below the boiling point of the electrolyte solution.
  • the substantially constant temperature may be about 25 °C.
  • the substantially constant temperature may exceed the boiling point of the electrolyte solution where, e.g., the electrolyte solution is maintained in a relatively high-pressure environment.
  • the temperature may be adjusted or allowed to change during the time period, e.g., within a range above the freezing point of the electrolyte solution and below the boiling point of the electrolyte solution.
  • the temperature of the electrolyte solution may be controlled, e.g., maintained or adjusted, with the use of a temperature controlled vessel, e.g., a jacketed beaker, and a temperature sensor as described herein.
  • a temperature controlled vessel e.g., a jacketed beaker
  • the electrolyte solution may be mixed during the electrolysis, e.g., anodization process. In some embodiments, the electrolyte solution may be stirred during the electrolysis, e.g., anodization process.
  • the disclosed methods may include maintaining an electrical potential difference across the electrolyte solution between the anode and the cathode (i.e., between the metal substrate overlying the inner surface of the tubular polymeric scaffold and the electrode).
  • the method includes applying a constant voltage or a constant current for a period of time between the anode and the cathode.
  • the potential difference may be from about 1 mV to about 100 kV, e.g., from about 10 mV to about 10 kV, from about 100 mV to about 1 kV, from about 1 V to about 1,000 V, or about 10 V to about 100 V.
  • the potential difference may be from about 10 mV to about 100 kV, from about 100 mV to about 100 kV, from about 1 V to about 100 kV, from about 10 V to about 100 kV, from about 100 V to about 100 kV, from about 1 kV to about 100 kV, or from about 10 kV to about 100 kV.
  • the period of time may be from about 5 seconds (s) to about 5 days, e.g., about 10 s to about 5 days, about 30 s to about 5 days, about 1 minute (min) to about 5 days, about 5 min to about 5 days, about 10 min to about 5 days, about 30 min to about 5 days, about 1 hour to about 5 days, from about 5 hours to about 5 days, from about 10 hours to about 5 days, or from about 1 day to about 5 days.
  • the period of time may be from about 5 min to about 90 min, e.g, from about 10 min to about 60 min, from about 20 min to about 50 min, or from about 30 min to about 40 min.
  • the period of time is about 10 s to about 1 day, e.g., about 30 s to about 12 hours (h), about 1 min to 6 h, including 1 min to 3 h. In some cases, the period of time is about 15 min, about 30 min, about 60 min, about 90 min or about 120 min.
  • the disclosed methods include applying a substantially constant voltage in a range of from about 1 V to about 110 V (e.g., 10 V-100 V, such as 30 V-50 V) for a period of time within a range of about 4 min to 90 min (e.g., 30 min-90 min).
  • a substantially constant voltage in a range of from about 1 V to about 110 V (e.g., 10 V-100 V, such as 30 V-50 V) for a period of time within a range of about 4 min to 90 min (e.g., 30 min-90 min).
  • the constant current may be from about 1 fA to about 100 kA, e.g., from about 1 pA to about 100 kA, from about 1 nA to about 100 kA, from about 1 ⁇ to about 100 kA, from about 1 mA to about 100 kA, from about 1 A to about 100 kA, or from about 1 kA to about 100 kA.
  • the voltage and/or current may vary during the anodization process.
  • the voltage may vary between about 1 mV and about 100 kV (or within one of the ranges discussed above) during the anodization process and/or the current may vary between about 1 fA and about 100 kA (or within one of the ranges discussed above).
  • the anodization process is a two-step anodization process.
  • a two- step anodization process as used in the present methods may include a first step comprising the use of high voltage or current to prime the surface to be functionalized, and a second step comprising a lower or higher voltage or current to create the desired nanostructures.
  • the first step is performed at a voltage between 5 - 250 V.
  • the electrolyte may be replaced, then the current is set to a voltage below or above the previously applied voltage.
  • the electrolyte may be of the same composition and concentration e.g. 3 g/L NH4F, 10% water, 90% ethylene glycol or vary in composition (e.g. 0.05 - lOg/L H4F, 0.1 - 20% water, 80 99.9% ethylene glycol or the composition is changed, adding, for example HCl) to perform the second step.
  • Currents in each step can vary from 0.0001 mA to 200 mA. Temperature ranges from -5°C to 50°C.
  • the metal substrate to be functionalized may be treated prior to the electrolysis, e.g., anodization process.
  • the metal substrate to be functionalized, e.g., coated, and/or surface-modified may be electro-polished using methods known in the art prior to the electrolysis, e.g., anodization process.
  • the metal substrate to be functionalized, e.g., coated, and/or surface-modified may be subjected to one or more cleaning treatments (using, e.g., soap, acetone and/or ethanol) and/or ultrasound treatments, e.g., as described in the experimental section herein.
  • cleaning treatments using, e.g., soap, acetone and/or ethanol
  • ultrasound treatments e.g., as described in the experimental section herein.
  • the metal substrate to be functionalized may be subjected to an etching step, e.g., via plasma etching, prior to the electrolysis, e.g., anodization process.
  • metal substrate having one or more microstructures or nanostructures, e.g., metal oxide nanotubes, formed thereon using the disclosed methods may be subjected to one or more post-anodization treatments, e.g., one or more ultrasound or electro-polishing treatments.
  • post-anodization treatments may be desirable, for example, to remove surface debris (e.g., titania needles) remaining on the surface of the metal substrate following anodization.
  • a post-anodization treatment used in methods of the present disclosure is performed to increase the stability and/or density of the resulting array of metal oxide nanostructures present on a functionalized surface. In some embodiments, a post- anodization treatment is performed to increase the efficiency of obtaining metal oxide nanostructures having desired dimensions and morphologies.
  • a post-anodization treatment includes an anodization step that is performed in the absence of fluoride (e.g., performed in fluoride-free electrolyte), as described in Yu et al., ACS Applied Materials and Interfaces (2014), 6:8001-8005 and Xiong et al., The Journal of Physical Chemistry C (2011), 115:4768-4772, both disclosures of which are incorporated by reference herein.
  • the fluoride-free electrolyte used in the post-anodization treatment step contains H 3 PO 4 in ethylene glycol (EG) (e.g., 5 wt % H 3 PO 4 in EG).
  • EG ethylene glycol
  • a post-anodization treatment step does not result in any formation of a compact oxide layer.
  • Voltage range from 5-110 V, current from 0.01 mA - 500 mA.
  • H 3 PO 4 concentration from over a range from 0.1 - 10 wt%.
  • Temperature from -5°C to 50°C. Reaction time from 5 min to 120 min.
  • a post-anodization treatment involves exposing the metal oxide nanostructures to anodization procedure in a fluoride-free electrolyte for a period of about 30 min-120 min (e.g., 60 min), at a voltage of 60V-100V (e.g., 80V) at a temperature of 20 °C -50 °C (e.g., 30 °C).
  • the electrolyte may include 1-10% (e.g., 5%) phosphoric acid.
  • a post-anodization treatment used in methods of the present disclosure does not involve use of annealing to increase adhesion between the metal substrate and the metal oxide nanostructures, such as, annealing described in Xiong et al., The Journal of Physical Chemistry C (2011), 115:4768-4772.
  • the nanostructures produced by the methods described herein show improved adherence to the metal substrate without requiring an annealing step, such as, heating the functionalized metal substrate at a high temperature of around 500°C for about 5 h or 10 h.
  • an electrical circuit including a power supply connected to the anode and the cathode or cathodes of the devices or systems disclosed herein may be under computer control.
  • such an electrical circuit may include a computer controlled relay to open and close the electrical circuit for the period of time.
  • sensors may also be computer controlled.
  • the present method finds use in functionalizing, e.g., coating, a tubular structure, as described herein, with an array of metal oxide nanotubes or an array of polymer nanotubes.
  • a tubular structure with a lumen as described above, where the lumen is lined with one or more layers of an array of metal oxide nanotubes or an array of polymer nanotubes, where optionally the array is only located at the ends of the tubular structure.
  • the lumen may be substantially completely lined with one or more layers of an array of metal oxide nanotubes.
  • the lumen may be partially lined such that one or more layers of an array of metal oxide nanotubes are located at only the two ends of the tubular structure.
  • the one or more layers of an array of metal oxide nanotubes may be disposed at only the ends of the tubular structure, they may not extend to the very end or may include a gap towards the ends to provide space for insertion of suture needle to facilitate grafting of the tubular to vascular tissue without damage to the suture needle.
  • the one or more layers of an array of metal oxide-free polymer microtubes or nanotubes may be disposed at only the ends of the tubular structure, they may not extend to the very end or may include a gap towards the ends to provide space for insertion of suture needle to facilitate grafting of the tubular to vascular tissue without damage to the suture needle.
  • the one or more layers of an array of metal oxide-free polymer microtubes or nanotubes may be disposed at only the ends of the tubular structure, they may extend to the very end and may not include a gap towards the ends to provide space for insertion of suture needle.
  • Metal oxide microtubes or nanotubes disposed on the present tubular structure, or provided according to the disclosed methods and/or using the disclosed devices and/or systems generally include a lumen or bore defined by one or more side walls.
  • the microtubes or nanotubes may have a generally tubular structure, a generally conical structure, or a generally frustoconical structure.
  • a drug e.g., a bioactive compound
  • biologically active agent may be positioned in the lumen or bore of the microtubes or nanotubes described herein.
  • a material e.g., a polymeric material (e.g., an erodible polymer) may be positioned over the drug or active agent in the lumen or bore, e.g., to provide for controlled or delayed release of the drug or active agent in vivo.
  • the drug or active agent containing lumen or bore of the microtubes or nanotubes may be capped with a material, e.g., a polymeric material (e.g., an erodible polymer), e.g., provide for controlled or delayed release of the drug or active agent in vivo.
  • a material e.g., a polymeric material (e.g., an erodible polymer)
  • materials other than drugs or biologically active agents may be incorporated into the lumen or bore of the microtubes or nanotubes, e.g., where the application of the functionalized, e.g., coated, and/or surface-modified structure is for use in a context other than the medical device context.
  • Such materials may include, e.g., compounds, macromolecules, polymers, and the like.
  • the metal oxide is an oxide of one of aluminum, niobium, tantalum, titanium, tungsten, and zirconium.
  • the metal oxide nanotubes may be arranged in a densely packed array, where each nanotube contacts a neighboring nanotube on all directions (see, e.g., Figures 3 and 9B).
  • the metal oxide nanotubes may have any cross-sectional shape, and in some cases, may range from hexagonal to circular.
  • the metal oxide nanotubes and the metal oxide-free polymer microtubes or nanotubes may have any suitable dimensions.
  • metal oxide or the metal oxide-free polymer microtubes or nanotubes lining the lumen of the tubular structure have an average diameter of from about 1 nm to about 1,000 nm, e.g., from about 10 nm to about 1,000 nm, from about 50 nm to about 800 nm, from about 100 nm to about 700 nm, from about 200 nm to about 600 nm, from about 300 nm to about 500 nm, or from about 450 nm to about 500 nm.
  • metal oxide nanotubes produced according to the disclosed methods have an average diameter of from about 10 nm to about 200 nm, from about 30 nm to about 180 nm, from about 50 nm to about 160 nm, from about 80 nm to about 140 nm, or from about 100 nm to about 120 nm.
  • metal oxide nanotubes produced according to the disclosed methods have an average diameter of from about 70 nm to about 150 nm, from about 90 nm to about 120 nm, from about 80 nm to about 120 nm, from about 80 nm to about 130 nm, from about 80 nm to about 140 nm, from about 80 nm to about 150 nm, from about 70 nm to about 120 nm, from about 70 nm to about 130 nm, from about 70 nm to about 140 nm, from about 60 nm to about 120 nm, from about 60 nm to about 130 nm, from about 60 nm to about 140 nm, from about 60 nm to about 150 nm, or about 100 nm.
  • the diameter of the nanotubes may vary. In some cases, the diameter of the nanotubes varies across the array by 50% or less, e.g., 40% or less, 30% or less, 20% or less, 10%) or less, including 5.0% or less, and in some cases, may vary by 1.0% or more, e.g., 2.0 % or more, 5.0% or more, 10% or more, including 20% or more. In some embodiments, the diameter of the nanotubes varies across the array by a range or 1.0 to 50%, e.g., 2.0 to 40%, 5.0 to 30%, including 5.0 to 20%.
  • the metal oxide nanotubes may extend from the metal substrate surface such that an end of the nanotube (e.g., an end distal to the metal substrate surface) is at a distance from the metal substrate surface. The distance may also define a length of the metal oxide nanotube.
  • such metal oxide nanotubes have an average length of from about 10 nm to about 600 ⁇ , e.g., from about 10 nm to about 100 ⁇ , from about 10 nm to about 10 ⁇ , from about 10 nm to about 400 nm, from about 400 nm to about 600 nm, from about 600 nm to about 800 nm, from about 800 nm to about 1000 nm, from about 1 ⁇ to about 10 ⁇ , from about 1 ⁇ to about 50 ⁇ , from about 50 ⁇ to about 100 ⁇ , from about 100 ⁇ to about 200 ⁇ , from about 200 ⁇ to about 300 ⁇ , from about 300 ⁇ to about 400 ⁇ , from about 400 ⁇ to about 500 ⁇ , or from about 500 ⁇ ,
  • such metal oxide nanotubes have an average length of from about 400 nm to about 600 ⁇ , from about 600 nm to about 600 ⁇ , from about 800 nm to about 600 ⁇ , from about 1 ⁇ to about 600 ⁇ , from about 50 ⁇ to about 600 ⁇ , from about 100 ⁇ to about 600 ⁇ , from about 200 ⁇ to about 600 ⁇ , or from about 400 ⁇ to about 600 ⁇ m.
  • such metal oxide and the metal oxide-free polymer microtubes or nanotubes have an average length of from about 0.5 ⁇ to about 10 ⁇ , e.g., from about 1 ⁇ to about 9.5 ⁇ , from about 1.5 ⁇ to about 9 ⁇ , from about 2 ⁇ to about 8.5 ⁇ , from about 2.5 ⁇ to about 8 ⁇ , from about 3 ⁇ to about 7.5 ⁇ , from about 3.5 ⁇ to about 7 ⁇ , from about 4 ⁇ to about 6.5 ⁇ , from about 4.5 ⁇ to about 6 ⁇ , or from about 5 ⁇ to about 5.5 ⁇ .
  • the metal oxide nanotubes may generally overlie an area of the inner surface of the tubular scaffold where the metal substrate is present. In some cases, the area covered by the metal oxide nanotubes is coextensive with the area of the inner surface of the scaffold covered by the metal substrate. In some embodiments, the array of metal oxide nanotubes overlies 5% or more, e.g., 10% or more, 20% or more, 30% or more, 40% or more, 50% or more, 60 % or more, 70% or more, 80% or more, 90% or more, 95% or more, 97% or more, and up to about 100 % of the inner surface of the scaffold.
  • the array of metal oxide nanotubes overlies the inner surface of the scaffold at distal and proximal ends of the tubular scaffold, such that while the inner surface in the central region of the tubular scaffold is free of such an array (due to lack of presence of a metal substrate disposed on the inner surface in the central region of the tubular scaffold), the ends of the tubular scaffold which would be in contact with vascular tissue upon grafting into a subject's vascular system, include the array of metal oxide nanotubes to minimize growth of scar tissue at the interface between the tubular scaffold and the vascular tissue.
  • proximal and distal ends refer to the opposite ends of a tubular structure and are same as a first and a second end.
  • the array of metal oxide nanotubes overlies the inner surface of the scaffold at distal and proximal ends of the tubular scaffold, such that about 1% to 10% of the length of the tubular scaffold is covered at each end.
  • a tubular structure comprising i) a tubular polymeric scaffold surrounding a lumen and comprising an inner surface; and ii) a polymer substrate overlying the inner surface, wherein a surface of the polymer substrate interfaces the lumen and comprises an array of polymer nanotubes extending a distance from the polymer substrate surface, wherein the metal oxide-free polymer nanotubes of the array have an average diameter in the range of about 10 nm to about 1,000 nm.
  • the polymer substrate comprising the array of metal oxide- free polymer microtubes or nanotubes may be located only at the ends of the tubular polymeric scaffold to prevent formation of scar tissue at the site where the tubular polymeric scaffold is grafted onto a blood vessel.
  • the system 1000 may include a device that includes a conductive structure 1020 that is in electrical contact with a cathode from the bottom of the conductive structure, and spacers 1040 associated with the conductive structure, where the conductive structure is positioned within the lumen of a tubular structure, as described above, having a tubular polymeric scaffold 1010 and a metal substrate 1030 overlying the inner surface of the scaffold, where the metal substrate is configured to be in electric contact with an anode that serves as the counter-electrode to the cathode.
  • the conductive structure 1020 and the spacers 1040 may constitute a counter electrode to the metal substrate 1030 serving as the anode in the present system 1000.
  • the system includes a power supply connected to the anode and the cathode.
  • the conductive structure 1020 is no longer than the tubular structure, e.g. the end of the conductive structure 1020 ends flush with the end of the tubular structure.
  • the system 1400 may include a device that includes a conductive structure 1420 that is in electrical contact with a cathode from the bottom of the conductive structure, and spacers associated with the conductive structure, where the conductive structure is positioned within the lumen of a tubular structure, as described above, having a tubular polymeric scaffold 1410 and a metal substrate 1430 overlying the inner surface of the scaffold, where the metal substrate is configured to be in electric contact with an anode that serves as the counter-electrode to the cathode.
  • the metal substrate 1430 may be modified to protrude from the top of the tubular structure, and may be further modified to include a latch 1460.
  • the conductive structure 1420 and the spacers may constitute a counter electrode to the metal substrate 1430 serving as the anode in the present system 1400.
  • the system includes an electrode support 1470 and a spacer 1480 located at the bottom of the conductive structure.
  • the system includes a power supply connected to the anode and the cathode.
  • the conductive structure 1420 is no longer than the tubular structure, e.g. the end of the conductive structure 1420 ends flush with the end of the tubular structure.
  • the system may include a test probe (see, Figure 15) that grabs the latch 1460 and holds the graft in place.
  • UTILITY see, Figure 15
  • the tubular structures functionalized, e.g., coated, with one or more layers of an array of metal oxide nanotubes, as described herein, find use where the inner lumen of the tubular structure provides a conduit for a fluid material, where the metal oxide nanotube coating on the inner surface of the scaffold of the tubular structure confers desirable properties for interacting with the fluid material.
  • the tubular structure is a medical device, e.g., a surgical implant, and may be used to treat a tissue defect in an individual in need, e.g., a patient.
  • the fluid material may be any suitable fluid, such as, without limitation, blood and cerebral-spinal fluid.
  • the tubular structure e.g., vascular graft, of the present disclosure may be an antithrombotic and/or anti-inflammatory nano-tubular structure, e.g., when the tubular structure is implanted at a surgical site as a conduit for biological fluids.
  • the present tubular structure having an inner lumen surface functionalized with an array of metal oxide nanotubes, when the inner lumen is used as a conduit for a bodily fluid, e.g., blood, and comes into contact with the bodily fluid, provides for a reduced rate of fibrin deposition on the surface of the inner lumen compared to a tubular structure that does not include the functionalized surface.
  • the present tubular structure having an inner lumen surface functionalized with an array of metal oxide nanotubes can provide an anti -thrombotic effect in the absence of other anti -thrombotic agents and treatments, such as biological anti -thrombotic agents and treatments (e.g., heparin coatings, anti -thrombotic protein coatings, etc.).
  • biological anti -thrombotic agents and treatments e.g., heparin coatings, anti -thrombotic protein coatings, etc.
  • the tubular structure e.g., vascular graft
  • the tubular structure is an anti-inflammatory tubular structure for use as an implant, where the tubular structure does not include a biological or pharmaceutical anti-inflammatory/immunosuppressive agent.
  • an immunosuppressive agent include an immunosuppressive drug, such as, but not limited to tacrolimus and cyclosporine.
  • the functionalized structure created according to the present methods is a functionalized patch structure.
  • functionalized patch structures of the present disclosure find use in repairing a damage conduit (e.g., blood vessel), where the inner surface of where the metal oxide nanotube coating on the inner surface of the scaffold of the patch structure confers desirable properties for interacting with the fluid material.
  • the tubular structure or patch structure of the present disclosure finds use in treating a vascular defect in an individual in need.
  • aspects of the present disclosure includes a method of treating a vascular tissue defect in an individual including the step of implanting a tubular structure or patch structure, e.g., a vascular graft or vascular patch, as described herein, at a surgical site to replace or amend defective vascular tissue with the tubular structure or patch structure.
  • the defective vascular tissue may be any suitable vascular tissue, and may include, without limitation, an artery or a vein, an aorta, pulmonary artery or vein, coronary artery, carotid artery, femoral artery, etc.
  • the implanting may be done by, e.g., suturing the ends of the tubular structure to the disjointed ends of the vascular tissue, or suturing the ends of the patch structure to the damaged portion of the vascular tissue.
  • the present method of treating a vascular tissue defect may provide for a vascular graft that is anti -thrombotic and/or anti-inflammatory and/or prevents or minimizes formation of scar tissue, as described above.
  • the tubular structure provides for a vascular graft that is anti -thrombotic and/or anti-inflammatory in the absence of a biological antithrombotic agent, or an anti-inflammatory drug.
  • a tubular structure modified to include nanotubular arrays, as described herein, at only the ends connected to blood vessels (to bypass a defective or diseased blood vessel) is effective in minimizing fibrin deposition (in a porcine model, no fibrin deposition was detected 28 days after grafting) and formation of scar tissue.
  • the present tubular structure may also find use as other medical devices, such as stents and shunts.
  • the tubular structure is implanted within the lumen of a blood vessel to function as a stent.
  • the tubular structure is implanted in the brain to drain cerebrospinal fluid (CSF) and reduce intracranial pressure caused by CSF buildup.
  • CSF cerebrospinal fluid
  • kits that includes a functionalized tubular structure of the present disclosure, and a packaging with a compartment to hold the tubular structure.
  • the compartment of the packaging is a sterile compartment.
  • the present kit includes instructions for making and/or using a tubular structure functionalized, e.g., coated, with an array of metal oxide nanotubes of the present disclosure.
  • the instructions are generally recorded on a suitable recording medium.
  • the instructions may be printed on a substrate, such as paper or plastic, etc.
  • the instructions may be present in the kits as a package insert, in the labeling of the container of the kit or components thereof (i.e., associated with the packaging or subpackaging) etc.
  • the instructions are present as an electronic storage data file present on a suitable computer readable storage medium, e.g. CD-ROM, digital versatile disc (DVD), flash drive, Blue-ray DiscTM etc.
  • the actual instructions are not present in the kit, but methods for obtaining the instructions from a remote source, e.g. via the internet, are provided.
  • An example of this embodiment is a kit that includes a web address where the instructions can be viewed and/or from which the instructions can be downloaded.
  • the methods for obtaining the instructions are recorded on a suitable substrate.
  • Components of a subject kit can be in separate containers; or can be combined in a single container.
  • Standard abbreviations may be used, e.g., bp, base pair(s); kb, kilobase(s); pi, picoliter(s); s or sec, second(s); min, minute(s); h or hr, hour(s); aa, amino acid(s); kb, kilobase(s); bp, base pair(s); nt, nucleotide(s); i.m., intramuscular(ly); i.p., intraperitoneal(ly); s.c, subcutaneous(ly); and the like.
  • Example 1 Wire design vascular graft
  • a vascular graft made of a Titanium coil, covered by polyurethane (PU) tubing was fabricated ( Figure 1).
  • the tubing prevented leaking.
  • the spacing between the windings was 1- 1.5x the width of the wire, yielding 40-50 % titanium coverage.
  • Figure 1 Schematic of a vascular graft device.
  • the straight lines reflect the outer tubing, surrounding the functionalized coil.
  • the coil can be either made of a ribbon, or wire of any shape.
  • the 1 mm gap on the left and right of the center coil allows the surgeon to suture the device to the blood vessel, not damaging the needle by hitting the wire.
  • the straight lines in the image represent the PU coating.
  • the Titanium frame in the tubing is exposed to the blood stream.
  • Figure 2 shows the titanium wire with a round cross-section and embedded in the polymeric tube.
  • the titanium wire was coated with titanium oxide (Ti0 2 ) nanowires, as described in Example 4, and as shown by scanning electron microscopy (SEM) in Figure 3.
  • FIG. 3 Scanning electron microscopy (SEM) image of Ti0 2 nanotubes introduced to coil device. Top left: nanotubes, detached Ti0 2 nanotubes on the edge of cut Ti wire. Bottom right: Nonporous surface.
  • Figure 4 shows additional design variations of the vascular graft.
  • Example 2 Depositing titanium onto the graft material
  • Figures 5A-5C SEM image of deposited titanium film onto vascular graft material of velour ( Figure 5A), or polyethylene terephthalate (PET) ( Figures 5B, 5C). Deposition method by e-Beam ( Figures 5A, 5B), or sputtering ( Figure 5C).
  • the Ti0 2 nanotube film was introduced onto the titanium substrate deposited on the vascular graft material ( Figure 6).
  • FIG. 6 Ti0 2 Nanotube film (-100 nm) on vascular graft material (see Figures a). Titanium film was deposited by e-beam (2.0 ⁇ ).
  • Example 3 Vascular graft with thin titanium alloy foil in the inner lumen
  • vascular graft made of expanded polytetrafluoroethylene (ePTFE) was modified with an unpatterned titanium foil, functionalized with Ti0 2 nanotubes ( Figure 7A).
  • the graft was sutured into an aorta in an ex -vivo model ( Figure 7B).
  • a functionalized vascular graft measuring 3 cm long and having an inner diameter of 3mm, was implanted into the abdominal aorta of a rabbit ( Figure 8).
  • the inner lumen of the graft was coated with Ti0 2 nanotubes and the graft material was ePTFE.
  • Figures 9A and 9B show SEM images of the Ti0 2 nanotube functionalized inner lumen of the vascular graft.
  • the electrolyte contained ammonium fluoride (3g/L), in a mixture of distilled water and ethylene glycol (1 :9 ratio).
  • the dimensions (e.g., diameter and length) of the nanotubes were altered by varying the synthesis time, voltage, and temperature, as shown in Table 1 in Figure 11.
  • ePTFE was plasma activated, e.g. ammonia plasma.
  • the Titanium surface was plasma activated, Oxygen plasma, 90 seconds.
  • Plasma treatment increased the interaction with the adhesive that was used. No delamination was observed between the Titanium surface and adhesive, or between ePTFE and adhesive.
  • Exemplary biocompatible adhesives include, for example, epoxy based adhesives, such as EP21TDCS MED or MasterSil 151Med (Masterbond).
  • Other exemplary adhesives include silanes or urethanes.
  • an adhesive free, covalent bond between the polymer and the metal substrate via reactive groups, e.g. Ti-OH on the foil and Si-OH on the polymers (e.g. PDMS) may also be used. These can be introduced via physical or chemical surface treatments, e.g. plasma, electro chemical or chemical (etch).
  • a post-anodization treatment step was performed to increase the stability of the Ti02 nanotube array. This was performed by having an additional anodization step in a fluoride-free electrolyte (5 wt % H3P04 in EG).
  • Figures 10A and 10B Schematic representation of the Ti0 2 nanotube synthesis setup.
  • the counter electrode is attached to the Ti foil at either one or both ends graft.
  • Figure 10B An example of an electrode used to introduce nanotube arrays to a titanium foil lined graft.
  • Figure 11 Table 1 - Synthesis parameter for Ti-foil modified graft and resulting nanotube (NT) features.
  • Example 5 Conditions tested for the synthesis of TiO? nanotubes
  • Figure 16 Table 2 - Experimental conditions that were tested for the synthesis of Ti0 2 nanotubes.
  • Figure 17 An example of a condition that worked, in which nanotubes were created and exposed.
  • Figure 18 An example of a condition that did not work, in which nanotubes were too short, brittle, delaminated, or nanotubes were covered by an oxide film (solid, porous), attacked, dissolved, substrate-altered.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Electrochemistry (AREA)
  • Materials Engineering (AREA)
  • Metallurgy (AREA)
  • Organic Chemistry (AREA)
  • Materials For Medical Uses (AREA)
  • Prostheses (AREA)

Abstract

L'invention concerne un procédé de fonctionnalisation d'une structure tubulaire présentant un réseau de nanotubes d'oxyde métallique ou un réseau de nanotubes de polymère exempt d'oxyde métallique. Le procédé peut comprendre le positionnement d'une électrode dans une lumière d'une structure tubulaire appropriée ayant un échafaudage polymère tubulaire, la lumière étant revêtue d'un substrat métallique, et l'électrode est conçue pour éviter un contact électrique entre la partie conductrice de l'électrode et le substrat métallique ; l'introduction d'une solution d'électrolyte dans la lumière ; et la génération d'une différence de potentiel électrique dans la solution d'électrolyte entre l'électrode et le substrat métallique. L'invention concerne également une structure tubulaire fonctionnalisée présentant un réseau de nanotubes d'oxyde métallique, des dispositifs et des systèmes de fabrication d'une telle structure tubulaire, et des procédés d'utilisation d'une telle structure tubulaire.
PCT/US2017/065417 2016-12-09 2017-12-08 Structures tubulaires à surface fonctionnalisée, et procédés de fabrication et d'utilisation de telles structures tubulaires à surface fonctionnalisée WO2018107092A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201662432098P 2016-12-09 2016-12-09
US62/432,098 2016-12-09

Publications (1)

Publication Number Publication Date
WO2018107092A1 true WO2018107092A1 (fr) 2018-06-14

Family

ID=62491393

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2017/065417 WO2018107092A1 (fr) 2016-12-09 2017-12-08 Structures tubulaires à surface fonctionnalisée, et procédés de fabrication et d'utilisation de telles structures tubulaires à surface fonctionnalisée

Country Status (1)

Country Link
WO (1) WO2018107092A1 (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111593381A (zh) * 2020-05-09 2020-08-28 西北工业大学 制备中空件内壁Ni-SiC复合镀层的阳极装置
CN112680729A (zh) * 2020-11-23 2021-04-20 重庆大学 一种毛细管或异型管内表面导电电极防短路方法

Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6375826B1 (en) * 2000-02-14 2002-04-23 Advanced Cardiovascular Systems, Inc. Electro-polishing fixture and electrolyte solution for polishing stents and method
US20050038498A1 (en) * 2003-04-17 2005-02-17 Nanosys, Inc. Medical device applications of nanostructured surfaces
US20050070995A1 (en) * 2003-04-28 2005-03-31 Zilla Peter Paul Compliant venous graft
US20050261760A1 (en) * 2004-05-20 2005-11-24 Jan Weber Medical devices and methods of making the same
US20090035859A1 (en) * 2007-07-30 2009-02-05 Alfred David Johnson Method and devices for preventing restenosis in cardiovascular stents
US20100031819A1 (en) * 2006-12-18 2010-02-11 Christian Monereau Purification Of An H2/CO Mixture With Heater Skin Temperature Control
US20140090983A1 (en) * 2010-11-30 2014-04-03 Sharp Kabushiki Kaisha Electrode structure, substrate holder, and method for forming anodic oxidation layer
US20150068910A1 (en) * 2012-04-05 2015-03-12 Postech Academy-Industry Foundation Apparatus and method for anodizing inner surface of tube
US20150322583A1 (en) * 2012-12-03 2015-11-12 The Regents Of The University Of California Devices, Systems and Methods for Coating Surfaces

Patent Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6375826B1 (en) * 2000-02-14 2002-04-23 Advanced Cardiovascular Systems, Inc. Electro-polishing fixture and electrolyte solution for polishing stents and method
US20050038498A1 (en) * 2003-04-17 2005-02-17 Nanosys, Inc. Medical device applications of nanostructured surfaces
US20050070995A1 (en) * 2003-04-28 2005-03-31 Zilla Peter Paul Compliant venous graft
US20050261760A1 (en) * 2004-05-20 2005-11-24 Jan Weber Medical devices and methods of making the same
US20100031819A1 (en) * 2006-12-18 2010-02-11 Christian Monereau Purification Of An H2/CO Mixture With Heater Skin Temperature Control
US20090035859A1 (en) * 2007-07-30 2009-02-05 Alfred David Johnson Method and devices for preventing restenosis in cardiovascular stents
US20140090983A1 (en) * 2010-11-30 2014-04-03 Sharp Kabushiki Kaisha Electrode structure, substrate holder, and method for forming anodic oxidation layer
US20150068910A1 (en) * 2012-04-05 2015-03-12 Postech Academy-Industry Foundation Apparatus and method for anodizing inner surface of tube
US20150322583A1 (en) * 2012-12-03 2015-11-12 The Regents Of The University Of California Devices, Systems and Methods for Coating Surfaces

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111593381A (zh) * 2020-05-09 2020-08-28 西北工业大学 制备中空件内壁Ni-SiC复合镀层的阳极装置
CN111593381B (zh) * 2020-05-09 2022-04-19 西北工业大学 制备中空件内壁Ni-SiC复合镀层的阳极装置
CN112680729A (zh) * 2020-11-23 2021-04-20 重庆大学 一种毛细管或异型管内表面导电电极防短路方法

Similar Documents

Publication Publication Date Title
EP2925912B1 (fr) Dispositifs, systèmes et procédés pour le revêtement de surfaces
Cipriano et al. Anodic growth and biomedical applications of TiO2 nanotubes
US8337936B2 (en) Implant and method for manufacturing same
US10251975B2 (en) Surface treatment process for implantable medical device
US9440003B2 (en) Medical devices having particle-containing regions with diamond-like coatings
WO2007108450A1 (fr) Matériau à base de magnésium biodégradable pour utilisation médicale
JP2010536534A (ja) メディカルインプラントの表面にナノ構造を生成する方法
ES2675307T3 (es) Activación selectiva con plasma para implantes médicos y dispositivos de cicatrización de heridas
US20210370053A1 (en) Neuro-stimulation and Sensor Devices Comprising Low-Impedance Electrodes, and Methods, Systems And Uses Thereof
KR101701264B1 (ko) 생체이식용 금속, 금속 제조방법, 이를 이용한 임플란트 및 스텐트
WO2012158614A2 (fr) Matériaux implantables à surfaces techniques et leur procédé de fabrication
Peng et al. Surface properties and bioactivity of TiO2 nanotube array prepared by two-step anodic oxidation for biomedical applications
US20160271301A1 (en) Hybrid Corrosion Inhibiting and Bio-Functional Coatings for Magnesium-Based Materials for Development of Biodegradable Metallic Implants
WO2018107092A1 (fr) Structures tubulaires à surface fonctionnalisée, et procédés de fabrication et d'utilisation de telles structures tubulaires à surface fonctionnalisée
Jiang et al. Electrochemical corrosion behaviors of titanium covered by various TiO2 nanotube films in artificial saliva
Krasicka-Cydzik Anodic layer formation on titanium and its alloys for biomedical applications
KR101281722B1 (ko) 다공성 티타늄 산화막을 이용하여 생체활성 물질의 담지율을 높이는 임플란트 재료의 제조방법 및 이에 의한 임플란트 재료
KR101892448B1 (ko) 임플란트용 멤브레인 및 그 제조방법
WO2017130029A1 (fr) Résistance à la rayure et comportement à la corrosion de films anodiques nanotubulaires et nano-perforés sur des substrats en titane en vrac de qualité médicale
KR101649305B1 (ko) 표면에 요철이 형성된 의료용 스텐트 및 그 제조방법
TW201119692A (en) Surface treating method for titanium artificial implant
CN101607097B (zh) 一种生物多肽医疗装置及其制备方法
EP4129351A1 (fr) Procédé de production de surfaces nanostructurées sur des endoprothèses pour une biocompatibilité améliorée
khethier Abbass et al. Improving Bio Corrosion Resistance of the Single Layer of Nano Hydroxyapatite and Nano YSZ Coating on the Ti6Al4V Alloy Using Electrophoretic Deposition
Junkar et al. Synthesis of TiO2 nanostructures and their medical applications

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 17878385

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 17878385

Country of ref document: EP

Kind code of ref document: A1