# Patent

## Title
Surface treatment for an implant surface

## Abstract

A method of forming an implant to be implanted into living bone is disclosed. The method comprises the act of roughening at least a portion of the implant surface to produce a microscale roughened surface. The method further comprises the act of immersing the microscale roughened surface into a solution including potassium hydroxide to produce a nanoscale roughened surface consisting of a web-like structure superimposed on the microscale roughened surface. The nanoscale roughened surface has a property that promotes osseointegration.

## Background
CROSS-REFERENCE TO RELATED APPLICATION
This application claims the benefit of U.S. Provisional Application No. 61/613,023, filed Mar. 20, 2012, which is hereby incorporated by reference herein in its entirety.


FIELD OF THE INVENTION
This invention relates generally to implants and, in particular, to a dental implant having a nanometer-scale surface topography and methods of making the same.
BACKGROUND OF THE INVENTION
It is becoming more common to replace a missing tooth with a prosthetic tooth that is placed upon and attached to a dental implant. Dental implants are often comprised of metal and metal alloys, including titanium (Ti) and titanium alloys. The dental implant serves as an artificial root that integrates with the gingiva and the bone tissue of the mouth.
For the dental implant to function successfully, sufficient osseointegration is required. In other words, a bond between the implant and the bone must be formed and retained. The surface of the implant may be roughened to help enhance the osseointegration process. Non-limiting examples of processes for roughening an implant surface include acid etching, grit blasting, or a combination thereof, which impart roughness on the surface.
Other existing techniques involve forming a generally thin (e.g., generally less than 10 microns) coating of osseointegration material(s), such as hydroxyapatite (HA), other calcium phosphates, or other osseointegration compounds, for forming a direct chemical compound between the implant and the bone. Plasma spraying and sputtering are two major techniques that have been used to deposit, for example, HA, onto an implant.
U.S. Pat. App. Pub. Nos. 2008/02200394, 2007/0110890, and 2007/0112353 disclose methods of discrete deposition of hydroxyapatite crystals to impart a nano-scale topography. Although effective, the disclosed processes require that a residual substance (i.e. HA crystals) be left on the surface post-processing in order to impart a nano-scale topography into the surface.
U.S. Pat. App. Pub. No. 2011/0233169 discloses methods of creating nanopitting on a microscale roughened surface by immersion of the microscale roughened surface into a solution containing both hydrogen peroxide and a basic solution.
The present invention is directed to an improved implant having a nanometer-scale web-like surface topography directly imparted into the surface for improving the rate and extent of osseointegration, and methods of making the same. The methods described herein create the nanometer-scale web-like surface on a microscale roughened surface by immersion of the microscale roughened surface into a solution including potassium hydroxide.
SUMMARY OF THE INVENTION
The present invention relates to a method of forming an implant to be implanted into living bone. The method comprises the act of roughening at least a portion of the implant surface to produce a microscale roughened surface. The method further comprises the act of immersing the microscale roughened surface into a solution including potassium hydroxide to product a nanoscale roughened surface consisting of a web-like structure superimposed on the microscale roughened surface.
In another aspect, another method of forming an implant to be implanted into living bone is disclosed. The method comprises the act of removing a native oxide layer from at least a portion of the implant surface. The method further comprises the act of roughening at least the portion of the implant surface to produce a microscale roughened surface. The method further comprises the act of rinsing the microscale roughened surface in deionized water. The method further comprises the act of immersing the microscale roughened surface into a solution including potassium hydroxide to product a nanoscale roughened surface consisting of a web-like structure superimposed on the microscale roughened surface. The method further comprises the acts of passivating the nanoscale roughened surface with nitric acid, and rinsing the nanoscale roughened surface in deionized water.
The above summary of the present invention is not intended to represent each embodiment, or every aspect, of the present invention. This is the purpose of the figures and the detailed description that follow.



BRIEF DESCRIPTION OF THE DRAWINGS
The foregoing and other advantages of the invention will become apparent upon reading the following detailed description and upon reference to the drawings.
FIG. 1 is a side view of an implant according to one embodiment.
FIGS. 2a, 2b, and 2c, are a side view, an insertion end view, and a gingival end view, respectively, of an implant according to a second embodiment.
FIGS. 3a, 3b, and 3c, are a side view, an insertion end view, and a gingival end view, respectively, of an implant according to a third embodiment.
FIGS. 4a and 4b are a side view, an end view, and a cross-sectional view, respectively, of an implant according to a fourth embodiment.
FIG. 5 is a flow diagram detailing a method of forming an implant according to an embodiment of the present invention.
FIG. 6 is a side view of the implant in FIG. 1 with a roughened outer surface.
FIG. 7a is a flow diagram detailing a method of forming an implant according to another embodiment of the present invention.
FIG. 7b is a flow diagram detailing a method of forming an implant according to yet another embodiment of the present invention.
FIG. 8a is a field emission scanning electron microscope (FESEM) image showing a commercially pure titanium implant post-acid etching at 2 k×.
FIG. 8b is a field emission scanning electron microscope (FESEM) image showing a commercially pure titanium implant post-acid etching at 30 k×.
FIG. 9 is an FESEM image showing a commercially pure titanium implant post-KOH treatment at 30 k× using a method of the present invention.



DETAILED DESCRIPTION OF THE INVENTION
The present invention is directed to implants having a nanometer-scale surface topography consisting of a web-like structure and methods of making the same. An implant in the context of the present invention means a device intended to be placed within a human body such as to connect skeletal structures (e.g., a hip implant) or to serve as a fixture for a body part (e.g., a fixture for an artificial tooth). Although the remainder of this application is directed to a dental implant, it is contemplated that the present invention may also be applied to other (e.g., medical) implants.
FIG. 1 shows a standard dental implant 10 that includes a head portion 12, a lowermost end 14, and a threaded bottom portion 16. The implant 10 may, for example, be made of titanium or alloys thereof. FIGS. 2a-c, 3a-c, and 4a-b, which are discussed below, describe alternative implant designs that may also be used with embodiments of the present invention.
In the implant 10 of FIG. 1, the head portion 12 includes a non-rotational feature. In the embodiment shown, the non-rotational feature includes a polygonal boss 20 that may be engageable with a tool that screws the implant 10 into bone tissue. In the illustrated embodiment, the polygonal boss 20 is hexagonal. The polygonal boss 20 may also be used for non-rotationally engaging a correspondingly-shaped socket on a restorative or prosthetic component that is attached to the implant 10.
The exterior of the threaded bottom portion 16 facilitates bonding with bone or gingiva. The threaded bottom section 16 includes a thread 18 that makes a plurality of turns around the implant 10. The threaded bottom portion 16 may further include a self-tapping region with incremental cutting edges 17 that allows the implant 10 to be installed without the need for a bone tap. These incremental cutting edges 17 are described in detail in U.S. Pat. No. 5,727,943, titled “Self-Tapping, Screw-Type Dental Implant,” which is incorporated by reference in its entirety.
FIGS. 2a-c disclose an implant 36 that differs from the implant 10 of FIG. 1 in the details of the cutting edges 17′ and the contours of the threads defining the exterior of the threaded bottom portion 16′. When viewed in the cross-section (see FIG. 1b), the threaded outer surface 16′ is non-circular in the region of the threads and/or the troughs between the threads. This type of thread structure is described in detail in U.S. Pat. No. 5,902,109, titled “Reduced Friction, Screw-Type Dental Implant,” which is incorporated by reference in its entirety.
In FIGS. 3a-c, an implant 41 having a wide diameter in the region of the threaded bottom portion 42 is illustrated. The diameter is in the range of from about 4.5 mm to about 6.0 mm with the diameter of 5.0 mm being a fairly common dimension for a wide diameter implant. Such an implant 41 is useful to engage one or both cortical bones to provide enhanced stability, especially during the period of time after installation.
FIGS. 4a-b illustrate an implant 110 according to another embodiment that may be used with the present invention. The implant 110 includes a middle section 114 designed to extend through the gingiva. Preferably, it is a smooth surface that includes a titanium nitride coating so the underlying titanium or titanium alloy is not readily seen through the gingiva. The implant 110 also includes a threaded portion 120 that may include various thread structures and is preferably roughened to increase the osseointegration process. It is contemplated that implants other than those illustrated in FIGS. 1-4 may be used with embodiments of the present invention.
According to embodiments of the present invention, a nanoscale roughened surface is superimposed onto a microscale roughened surface on at least a portion (e.g., the threaded bottom portion) of the surface of an implant. In one embodiment, the nanoscale roughened surface is created by immersing the microscale roughened surface into a solution including potassium hydroxide.
Turning now to FIG. 5, a general method of producing a nanoscale roughened surface on an implant is set forth according to one embodiment of the present invention. At step 500, an implant is provided. At least a portion of the implant surface is roughened to a microscale roughness at step 501, for example, by acid etching and/or grit blasting the implant surface. As an example, FIG. 6 shows the implant 10 of FIG. 1 having a roughened surface 40. A nanometer scale web-like structure is then created on the microscale roughened surface by immersing the roughened surface into a solution including potassium hydroxide to produce a nanoscale roughened surface on the implant at step 502.
Referring now to FIG. 7a, another general method of forming an implant according to another embodiment of the present invention is illustrated. An implant comprised of titanium, a titanium alloy, or the like is provided at step 750. At step 754, a nanometer scale web-like structure is created on a microscale roughened surface to produce a nanoscale roughened surface on the implant. At step 756, the implant is passivated with nitric acid. The implant may then be rinsed in reverse osmosis/deionized (RO/DI) water to remove residual solvents and hydroxyapatite at step 758. The implant is then dried at step 764 and sterilized at step 766 using, for example, gamma sterilization techniques.
Referring to FIG. 7b, a more detailed method of producing a nanoscale roughened surface on an implant is illustrated according to another embodiment of the present invention. A threaded dental implant comprised of titanium or a titanium alloy is provided at step 700. The surface of the implant is generally clean and dry. A threaded bottom portion of the implant is etched or grit blasted to remove a native oxide layer from the implant surface at step 701. The native oxide layer may be removed by grit blasting with, e.g., a resorbable grit blast media (such as calcium phosphate) or by using a first acid solution, which may include aqueous hydrofluoric acid. The threaded bottom portion is then grit blasted and/or acid etched form a microscale roughened surface at step 702. “Microscale,” as used herein, should be understood to describe an article or feature generally measured in microns such as, for example, 1 micron to 100 microns. Grit blasting may be used to create peak-to-valley irregularity distances in the microscale roughened surface greater than about 10 microns. Acid etching may result from immersing the implant (or a portion thereof) in a mixture of sulfuric and hydrochloric acids, creating peak-to-peak and peak-to-valley irregularity distances in the microscale roughened surface of about 1 micron to about 3 microns. This type of roughening method utilized on commercially pure (CP) titanium is described in detail in U.S. Pat. No. 5,876,453, entitled “Implant Surface Preparation,” which is incorporated by reference in its entirety. An additional roughening method utilized on Titanium 6AL-4V ELI alloy is described in detail in U.S. Pat. App. Pub. No. 2004/0265780, entitled “Surface Treatment Process for Implants Made of Titanium Alloy,” which is also incorporated by reference in its entirety. It is contemplated that other surface roughening techniques including, but not limited to, grit blasting, titanium plasma spraying, and combinations thereof, may be used. Grit blasting the threaded bottom portion to form a microscale roughened surface generally results in peak-to-peak and peak-to-valley irregularity distances of about 10 microns to 30 microns. Grit blasting and acid etching the threaded bottom portion to form the microscale roughened surface generally results in both levels of topographies, i.e., with about 1 micron to about 3 microns peak-to-peak and peak-to-valley irregularity distances superimposed on about 10 microns to about 30 microns peak-to-peak and peak-to-valley irregularity distances on the microscale roughened surface. In one embodiment, the surface is first grit blasted to provide a first set of irregularities having peak-to-valley distances (i.e., irregularity heights) greater than about 10 microns and then acid etched to superimpose a second set of irregularities having peak-to valley distances (i.e., irregularity heights) less than 10 microns, with peak-to-peak distances of about 1 to about 3 microns.
At step 703, the microscale roughened surface is immersed into a solution including potassium hydroxide to produce a nanoscale roughened surface consisting of a nanometer scale web-like structure superimposed on the microscale roughened surface. “Nanoscale,” as used herein, should be understood to describe an article or feature generally measured in nanometers such as, for example, 1 nanometer less than 1,000 nanometers. Generally, immersion into the potassium hydroxide solution results in a surface topography having irregularities of less than 1 micron. In some embodiments, the surface topography includes irregularities within the range of about 1 nanometer to about 100 nanometers.
Immersion time and potassium hydroxide concentration are among several factors that affect the rate and amount of nanopitting superimposed onto the microscale roughness of the implant surface. For example, immersing a commercially pure titanium implant in a solution of 12-32% potassium hydroxide for 30-90 minutes at 30-100 degrees Celsius typically results in an acceptable nanoscale roughness of the implant surface. Longer immersion times may impact the micron level topographies, while potassium hydroxide concentrations of less than about 12% may result in the nano-topography not being adequately formed.
Another factor affecting the impartation of the nanometer scale web-like structure onto the microscale roughness of the implant surface is the processing temperature. At temperatures of higher than about 100 degrees Celsius, for example, the etching is accelerated and can begin to impact the micron level topographies. Thus, it may be desirable for the processing temperature to be maintained at or below about 100 degrees Celsius.
Processing temperature, immersion time, and/or potassium hydroxide concentration may be adjusted to compensate for one or more of these variables being within an otherwise unacceptable range, in order to nevertheless produce an acceptable nano-topography. For example, potassium hydroxide concentrations of less than 12% may be adjusted by increasing immersion time and/or processing temperature in order to produce an acceptable nanometer scale web-like structure on the microscale roughness of the implant surface.
Post-processing, the implant is passivated with nitric acid at step 704. At step 705, the implant is rinsed in hot deionized water (e.g. about 70 degrees Celsius to about 100 degrees Celsius) to remove any acid residuals and to potentially enhance titanium hydroxide groups on the surface.
Hydroxyapatite (HA) nanocrystals may then optionally be deposited on the nanoscale roughened surface of the implant at step 706. The HA nanocrystals may be in the form of a coating or of discrete HA nanocrystals deposited on the implant surface. The HA nanocrystals may be introduced onto the nanoscale roughened surface of the implant in the form of a colloid. A representative amount of HA in the colloid is typically in the range of about 0.01 weight percent to about 1 weight percent (e.g., 0.10 weight percent). To form the colloid, HA nanocrystals may be combined in solution with a 2-methoxyethanol solvent and ultrasonically dispersed and deagglomerated. The pH of the colloidal solution may be adjusted with sodium hydroxide, ammonium hydroxide, or the like on the other of about 7 to about 13. As such, the colloidal solution may include HA nanocrystals, 2-methoxyethanol, and a pH adjuster (e.g. ammonium hydroxide, and/or sodium hydroxide). This type of HA deposition is described in detail in U.S. Pat. App. Pub. Nos. 2007/0110890 and 2007/0112353, both titled “Deposition of Discrete Nanoparticles on an Implant Surface,” which are incorporated by reference in their entireties. The implant may then be rinsed in reverse osmosis/deionized (RO/DI) water to remove residual solvent and HA at step 708.
Optionally, a sodium lactate coating or discrete residuals of sodium lactate or another suitable non-toxic salt can be applied at step 709. This type of salt deposition is described in detail in U.S. Pat. App. Pub. No. 2009/0191507 A1, entitled “Implant Surface with Increased Hydrophilicity,” which is incorporated by reference in its entirety. The implant may then be dried (e.g., oven dried), at step 714, and sterilized at step 716 using, for example, gamma sterilization.
It is contemplated that an implant surface in accordance with the embodiments described herein may be treated by all of the following acts or any combination thereof: (1) grit blasting the implant surface to create a first set of irregularities having peak-to-valley distances greater than about 10 microns; (2) acid etching the surface to create a second set of irregularities having peak-to-valley distances of less than ten microns with peak-to-peak distances of about 1 micron to about 3 microns (e.g., superimposed on the first set of irregularities); (3) producing a nanoscale roughened surface consisting of a web-like structure superimposed on the microscale roughened surface (e.g., by immersing the microscale roughened surface into a solution including potassium hydroxide); (4) depositing HA nanocrystals on the roughened surface; and/or (5) adding a coating or discrete particles of a non-toxic salt (e.g., sodium lactate) to increase the hydrophilicity of the implant surface.
The implant surface may be characterized utilizing Field Emission Scanning Electron microscopy (FESEM). Depending upon the resolution of the instrument, the nanometer scale web-like structure may typically be witnessed at magnifications of 30 k× or higher. As discussed above, the nanometer web-like structure generally has a distribution in the range of about 1 nanometer to about 500 nanometers, and typically between about 1 nanometer and about 100 nanometers.
Example 1
FIGS. 8a and 8b are scanning electron microscope images showing a micron-level roughness imparted by an acid etching process on a commercially pure titanium implant. The image of FIG. 8a was taken at 2 k× utilizing an FESEM. The image of FIG. 8b was taken at 30 k× utilizing an FESEM.
The implant shown in FIGS. 8a and 8b was machined, cleaned, and acid etched to impart a microscale roughness on the surface of the implant using a process similar to that described in U.S. Pat. No. 5,603,338, herein incorporated by reference in its entirety. FIG. 8a demonstrates the micron-level topography imparted by this acid etching at a magnification of 2 k×. Characteristic 1-3 micron peak-to-peak micropitting is clearly defined. FIG. 8b is an FESEM image of the surface at a magnification of 30 k×.
The implant was then immersed in about 12-32% w/w potassium hydroxide at a starting temperature of about 30-100 degrees Celsius for about 30-90 minutes, according to one embodiment of the invention. Post-processing, the implant was thoroughly rinsed in de-ionized water, passivated through immersion in about 25% w/w nitric acid for about 30-90 seconds at about 50-70 degrees Celsius, followed by additional rinsing in de-ionized water and oven drying at about 200 degrees Celsius.
The additional processing imparted a nanometer level topography, as demonstrated in the FESEM image of FIG. 9. FIG. 9, which is a FESEM image at a magnification of 30 k×, demonstrates the nanoscale roughness features of the implant surface. A web-like structure in the about 1-100 nanometer range can be witnessed at this magnification.
While the present invention has been generally described relative to the part of the implant contacting bone tissue, it is contemplated that the acts of etching, acid etching, roughening, nanopitting, and depositing herein described may be performed on the entire implant.
While the present invention has been described with reference to one or more particular embodiment, those skilled in the art will recognize that many changes may be made thereto without departing from the spirit and scope of the present invention. Each of these embodiments and obvious variations thereof is contemplated as falling within the spirit and scope of the claimed invention, which is set forth in the following claims.

## Claims

1. A method of forming an implant to be implanted into living bone, the method comprising the acts of:
roughening at least a portion of the implant surface to produce a microscale roughened surface; and
immersing the microscale roughened surface into a solution including potassium hydroxide for about 30 minutes to about 90 minutes to produce a nanoscale roughened surface including a web-like structure superimposed on the microscale roughened surface, the solution having a concentration of about 12-32% w/w potassium hydroxide and a temperature of about 30° C. to about 100° C., the web-like structure being for contacting living bone.

2. The method of claim 1, wherein the implant is made of a metal selected from the group consisting of titanium or alloys thereof.

3. The method of claim 1, wherein the implant is a dental implant.

4. The method of claim 1, wherein the implant is made of titanium and the act of roughening the implant surface comprises:
removing a native oxide layer from the implant surface; and
grit blasting the implant surface.

5. The method of claim 1, wherein the implant is made of titanium and the act of roughening the implant surface comprises:
removing a native oxide layer from the implant surface; and
acid etching the implant surface.

6. The method of claim 5, wherein the act of roughening the implant surface comprises acid etching the implant surface with a solution including sulfuric acid and hydrochloric acid.

7. The method of claim 1, wherein the act of roughening the implant surface comprises:
grit blasting the surface to produce a first set of irregularities having peak-to-valley heights greater than about 10 microns; and
acid etching the surface to superimpose a second set of irregularities on the first set of irregularities, the second set of irregularities having peak-to-valley heights less than about 10 microns.

8. The method of claim 1, further comprising the acts of:
rinsing the nanoscale roughened surface in deionized water;
drying the nanoscale roughened surface.

9. The method of claim 1, further comprising the act of depositing discrete nanoparticles on the nanoscale roughened surface.

10. The method of claim 1, wherein the potassium hydroxide has a molar concentration of about 5.9M.

11. The method of claim 1, further comprising depositing at least one salt on the implant surface.

12. A method of forming an implant to be implanted into living bone, the method comprising the acts of:
removing a native oxide layer from at least a portion of the implant surface;
roughening at least the portion of the implant surface to produce a microscale roughened surface;
rinsing the microscale roughened surface in deionized water;
immersing the microscale roughened surface into a solution including potassium hydroxide for about 30 minutes to about 90 minutes to produce a nanoscale roughened surface including a web-like structure superimposed on the microscale roughened surface, the potassium hydroxide having a concentration of about 12-32% w/w and a temperature of about 30° C. to about 100° C., the web-like structure being for contacting living bone;
and
rinsing the nanoscale roughened surface in deionized water.

13. The method of claim 12, wherein the act of roughening the implant surface comprises grit blasting the implant surface.

14. The method of claim 12, wherein the act of roughening the implant surface comprises acid etching the implant surface with a solution including sulfuric acid and hydrochloric acid.

15. The method of claim 12, wherein the implant is made of a metal selected from the group consisting of titanium or alloys thereof.

16. The method of claim 12, wherein the implant is a dental implant.

17. The method of claim 12, further comprising the act of depositing discrete nanoparticles on the nanoscale roughened surface.

18. The method of claim 17, wherein the discrete nanoparticles are deposited using a solution including a 2-methoxyethanol solvent.

19. The method of claim 12, wherein the act of roughening the implant surface comprises acid etching the implant surface with a solution including sulfuric acid and hydrochloric acid.

20. The method of claim 12, wherein the potassium hydroxide has a molar concentration of about 5.9M.

21. A method of forming an implant to be implanted into living bone, the method comprising the acts of:
grit blasting the implant surface to create a first set of irregularities having peak-to-valley distances greater than about 10 microns;
acid etching the implant surface to create a second set of irregularities having peak-to-valley distances of less than ten microns with peak-to-peak distances of about 1 micron to about 3 microns;
immersing the implant surface into a solution including potassium hydroxide for about 30 minutes to about 90 minutes to produce a nanoscale roughened surface including a web-like structure superimposed on the first and second sets of irregularities, the potassium hydroxide solution having a concentration of about 12-32% w/w and a temperature of about 30° C. to about 100° C., the web-like structure being for contacting living bone;
depositing hydroxyapatite nanocrystals on the implant surface; and
applying a salt to the implant surface.

22. The method of claim 21, wherein the potassium hydroxide has a molar concentration of about 5.9M.