DENTAL IMPLANT HAVING A TOPOGRAPHIC SURFACE

Abstract

A dental implant having a surface made of a ceramic material. At least a part of the surface includes recesses and cavities formed by removal of discrete grains having an average grain size from 0.1 m to 0.6 m and/or agglomerates of these grains from the ceramic material.

Claims

1. A dental implant comprising a body having a surface made of a ceramic material, at least a part of said surface comprising recesses and cavities formed by removal of discrete grains having an average grain size from 0.1 m to 0.6 m and/or agglomerates of these grains from the ceramic material, wherein the recesses and cavities are formed in the surface by etching at least a part of the surface with an etching solution comprising hydrofluoric acid at a temperature of at least 70 C.

2. The dental implant according to claim 1, wherein a shape and dimension of the cavities and recesses correspond at least approximately to the shape and dimensions of the grains and agglomerates of grains, respectively.

3. The dental implant according to claim 1, wherein the ceramic material is based on zirconia.

4. The dental implant according to claim 1, wherein the ceramic material is yttria-stabilized zirconia.

5. The dental implant according to claim 4, wherein the yttria stabilized zirconia comprises 4.5 to 5.5 weight-% of Y.sub.2O.sub.3 and less than 5 weight-% of HfO.sub.2, the total amount of ZrO.sub.2, Y.sub.2O.sub.3 and HfO.sub.2 being more than 99.0 weight-%.

6. (canceled)

7. The dental implant according to claim 1, wherein the etching solution comprises at least 50 vol.-% of concentrated hydrofluoric acid.

8. The dental implant according to claim 7, wherein the etching solution further comprises at least one compound selected from the group consisting of phosphoric acid, nitric acid, ammonium fluoride, sulphoric acid, hydrogen peroxide and bromic acid, and mixtures thereof.

9. The dental implant according to claim 7, wherein the etching solution further comprises sulphuric acid in an amount of 50 vol.-% at most.

10. The dental implant according to claim 1, wherein the surface has a macroscopic roughness in addition to the recesses and cavities formed on said surface with said macroscopic roughness.

11. The dental implant according to claim 10, wherein the macroscopic roughness is obtainable by sandblasting, milling, and/or injection molding techniques.

12. The dental implant according to claim 1, wherein the surface has a topography having a Core Roughness Depth S.sub.k of less than 1 m.

13. The dental implant according to claim 1, wherein the surface has a topography having a negative Skewness S.sub.sk.

14. The dental implant according to claim 1, wherein crater structures are formed in the surface by the removal of the discrete grains or agglomerates.

15. A dental implant comprising a body having a surface made of yttria-stabilized zirconia, at least a part of the surface including recesses and cavities formed by removal of discrete grains having an average grain size in a range of from 0.1 m to 0.6 m and/or agglomerates thereof from the yttria-stabilized zirconia, the at least part of the surface having a topography having a Core Roughness Depth S.sub.k in a range of from 0.4 m to less than 1 m, and a negative Skewness S.sub.sk.

16. The dental implant according to claim 15, wherein the recesses and cavities are formed in the surface by etching at least a part of the surface with an etching solution comprising hydrofluoric acid at a temperature of at least 70 C.

17. The dental implant according to claim 16, wherein the etching is performed at a temperature of at least 102 C.

18. The dental implant according to claim 15, wherein the surface has been roughened by a mechanical process and/or injection molding technique.

19. A dental implant comprising a body having a surface made of yttria-stabilized zirconia, at least a part of the surface including crater structures formed by removal of agglomerates of discrete grains having an average grain size in a range of from 0.1 m to 0.6 m from the yttria-stabilized zirconia.

20. The dental implant according to claim 19, wherein a size of at least some of the crater structures is about 5 m in a direction parallel to a plane of the surface.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0031] FIG. 1 is an idealized Abbott curve from which the 2D specific Core Roughness Depth R.sub.k, the reduced Peak Height R.sub.pk and the reduced Groove Depth R.sub.ck are derived;

[0032] FIG. 2 is a graphical representation of different profiles defined by different S.sub.k and S.sub.sk values;

[0033] FIG. 3 is an SEM picture of the surface resulting from the treatment according to Example 1 in two different magnification levels, the scale given in the SEM picture corresponding to 20 m (above) and 5 m (below), respectively;

[0034] FIG. 4 is an SEM picture of the surface resulting from the treatment according to Example 2 in two different magnification levels, the scale given in the SEM picture corresponding to 20 m (above) and 5 m (below), respectively;

[0035] FIG. 5 is an SEM picture of the surface resulting from the treatment according to Example 3 in two different magnification levels, the scale given in the SEM picture corresponding to 20 m (above) and 5 m (below) respectively;

[0036] FIG. 6 is an SEM picture of the surface resulting from the treatment according to Example 4 in two different magnification levels, the scale given in the SEM picture corresponding to 20 m (above) and 5 m (below), respectively;

[0037] FIG. 7 is an SEM picture of the surface resulting from the treatment according to Example 5 in two different magnification levels, the scale given in the SEM picture corresponding to 20 m (above) and 5 m (below), respectively;

[0038] FIG. 8 is an SEM picture of the surface resulting from the treatment according to Example 6 in two different magnification levels, the scale given in the SEM picture corresponding to 20 m (above) and 5 m (below), respectively;

[0039] FIG. 9 is an SEM picture of the surface resulting from the treatment according to Example 7 in two different magnification levels, the scale given in the SEM picture corresponding to 20 m (above) and 5 m (below), respectively;

[0040] FIG. 10 is an SEM picture of the surface according to Example 8 in two different magnification levels, the scale given in the SEM picture corresponding to 50 m (above) and 20 m (below), respectively;

[0041] FIG. 11 is an SEM picture of the surface according to Example 9 in two different magnification levels, the scale given in the SEM picture corresponding to 50 m (above) and 20 m (below), respectively; and

[0042] FIG. 12 is an SEM picture of the surface obtained in a further example, the scale given in the SEM picture corresponding to 5 m.

[0043] FIG. 13 is a graph showing the S.sub.sk and S.sub.k values of Examples 1 to 11.

[0044] FIG. 14 is an graph of the fold expressions of osteocalcin and TGFbeta on Examples 1, 2, 7, and 15 relative to Example 9.

[0045] FIG. 15 shows an expression of osteonectin of Example 2 over comparative Examples 9 and 15.

DETAILED DESCRIPTION

[0046] The process of the present invention allows the surface of any part of the dental implant, such as the bone contacting region, the soft tissue contacting region or both, to be treated independently. Thus, any part of the dental implant's surface can be provided selectively with the osteointegrative topography. Likewise, the whole surface of the dental implant can be treated by the process of the present invention.

[0047] The topography obtainable by the process of the present invention can be defined by 3D specific values.

[0048] Although there is no standard for the characterization of the topography with 3D specific values, these values can be derived by a simple devolvement from the respective 2D specific values.

[0049] For two dimensions, an extra procedure for filtering with suppression of the depth of roughness leads to the roughness profile according to DIN 4776. The definitions therein can directly be transformed into three dimensions.

[0050] In particular, the topography can be defined by the 3D specific Kernal Roughness Depth (or Core Roughness Depth) S.sub.k, which, as the 2D specific Core Roughness Depth R.sub.k, can be derived from the so-called Material Ratio Curve (also known as Abbott curve).

[0051] The Abbott curve represents the height distribution of the surface's material. It is a cumulative function of the material portion of the surface at a particular depth below the highest peak of the surface. In other words, the Abbott curve describes the increase of the material portion of the surface with increasing depth of the roughness profile. At the highest peak, the material portion is 0%, while at the deepest recess (or valley) the material portion is 100%. The minimal secant slope, i.e. a defined line of best fit, separates the Abbott curve into the three following ranges:

[0052] a) the Core Roughness Depth S.sub.k [m], i.e. the depth of the roughness core profile,

[0053] b) the reduced Peak Height S.sub.pk [m], i.e. the averaged height of the peaks sticking out of the core range, and

[0054] c) the reduced Groove Depth S.sub.vk [m], i.e. the averaged depth of the grooves sticking out of the core range.

[0055] The concept of how these values are derived from the Abbott curve are well known to the person skilled in the art. It is further illustrated in FIG. 1 showing an idealized Abbott curve from which the 2D specific Core Roughness Depth R.sub.k, the reduced Peak Height R.sub.pk and the reduced Groove Depth R.sub.vk are derived. These parameters can directly be transformed to the 3D specific Core Roughness Depth S.sub.k, reduced Peak Height S.sub.pk and reduced Groove Depth S.sub.vk

[0056] As shown in FIG. 1, the Core Roughness Depth R.sub.k or, in three dimensions, S.sub.k corresponds to the vertical distance between the left and right intercepts of the line through the ends of the minimal secant slope window of the Abbott curve. The location of the minimal secant slope window can be determined by shifting it along the Abbott curve until the slope between the two intersection points becomes minimal.

[0057] The topography can further be specified by the Skewness S.sub.sk. The Skewness measures the symmetry of the variation of the surface about its mean plane. A Gaussian surface, having a symmetrical shape for the height distribution, has a Skewness of 0. A surface with a predominant plateau and deep recesses will tend to have a negative Skewness, whereas a surface having a number of peaks above average will tend to have a positive Skewness.

[0058] For a profile in two dimensions, the 2D specific Skewness R.sub.sk is according to DIN EN ISO 4287 defined by the following formula:

[00001] $R_{s .Math. k} = \frac{1}{R_{q}^{3}} .Math. \frac{1}{N} .Math. {.Math.}_{n = 1}^{N} .Math. {(z_{n} - \overset{}{z})}^{3}$

where z.sub.n is the height or depth of the respective peak or valley, respectively, z is the mean height and R.sub.q is the root-mean-square deviation of the surface.

[0059] For determining the Skewness S.sub.sk of the topography in three dimensions, the formula is transformed as follows:

[00002] $S_{s .Math. k} = \frac{1}{S_{q}^{3}} .Math. \frac{1}{M .Math. N} .Math. {.Math.}_{m = 1}^{M} .Math. {.Math.}_{n = 1}^{N} .Math. {(z_{n} - \overset{}{z})}^{3}$

where S.sub.q is the root-mean-square deviation of the surface according to the following formula:

[00003] $S_{q} = \sqrt{\frac{1}{M .Math. N} .Math. {.Math.}_{m = 1}^{M} .Math. {.Math.}_{n = 1}^{N} .Math. {(z_{n} - \overset{}{z})}^{2}}$

[0060] A detailed description how the S.sub.k and S.sub.sk values are determined in practice is given below under item 2 of the Examples.

[0061] A graphical representation of different profiles defined by different S.sub.k and S.sub.sk values is given in the table shown in FIG. 2. In this table, the profiles shown in the first line have a positive Skewness S.sub.sk, the profiles shown in the second line have a Skewness S.sub.sk of about 0 and the profiles shown in the third line have a negative Skewness S.sub.sk. The profiles shown in the left column have a (low) Core Roughness Depth S.sub.k of less than 1 m and the profiles shown in the right column have a (high) Core Roughness Depth S.sub.k of more than 1 m.

[0062] According to one embodiment, the topography obtainable by the process of the present invention has generally a Core Roughness Depth S.sub.k of less than 1 m. Preferably, the Core Roughness Depth S.sub.k is between 0.3 m and 1 m, more preferably between 0.4 m and 1 m.

[0063] As can be seen from column 1 of FIG. 2, the main portion of such a topography is in the range of the extreme values; either the high peaks or the deep scratches are dominating over the core level. A dental implant having such a surface topography has been found to be highly osteointegrative.

[0064] The Skewness S.sub.sk of the topography obtained preferably falls within the following equation (I):

S.sub.skm*S.sub.k (I)

whereby m is from 0 to 1, preferably about 0.25, more preferably about 0.1.

[0065] More preferably, the Skewness S.sub.sk is less than 0, meaning that deep grooves in the topography are dominating.

[0066] It has been found that asymmetric topographies with deep grooves are highly osteointegrative, and that thereby the absolute roughness values (S.sub.a, R.sub.max, etc.) for example referred to in EP-B-1450722 are irrelevant.

[0067] The S.sub.k and S.sub.sk values of the topography obtainable by one embodiment of the present invention strongly differs from the topographies of commercially available implants, the osteointegrative properties of which have been studied in detail. It is thus highly surprising that the completely different topography obtainable according to the process of the present invention is osteointegrative.

[0068] According to a preferred embodiment of the present invention, the ceramic material has an average grain size from about 0.1 m to about 0.6 m. Treatment of this material according to the process of the present invention leads to a surface topography with particularly high osteointegrative properties.

[0069] The term ceramic material encompasses any type of ceramic such as ceramics based on zirconia, alumina, silica or mixtures thereof, optionally comprising further constituents. Preferably, the ceramic material is based on zirconia, more preferably yttria-stabilized zirconia. Apart from the desired osteointegrative properties obtained, this material has the further advantage of a high fracture toughness and bending strength.

[0070] An example of an yttria-stabilized zirconia ceramic is described by the international standards ASTM F 1873 and ISO 13356, specifying the characteristics of, and a corresponding test method for, a biocompatible and biostable ceramic bone-substitute material based on yttria-stabilized tetragonal zirconia (yttria tetragonal zirconia polycrystals, Y-TZP) for use as material for surgical implants.

[0071] Specific examples of an yttria-stabilized zirconia are ZrO.sub.2-TZP/TZP-A Bio-HIP (ZrO.sub.2) Bioceramic available from Metoxit AG, Switzerland, and ZIOLOX available from CeramTec AG, Plochingen, Germany. Both materials offer a particularly high mechanical stability and strength, in particular when prepared by hot isostatic pressing or by sintering with subsequent hot isostatic densification. A detailed description of the ZrO.sub.2-TZP/TZP-A Bio-HIP (ZrO.sub.2) Bioceramic is given in U.S. Pat. No. 6,165,925, the disclosure of which is incorporated herein by reference.

[0072] In particular, the composition of the yttria-stabilized zirconia comprises about 4.5 to about 5.5 weight-% of Y.sub.2O.sub.3 and less than about 5 weight-% of HfO.sub.2, the total amount of ZrO.sub.2, Y.sub.2O.sub.3 and HfO.sub.2 being more than about 99.0 weight-%.

[0073] Coprecipitation is the most common method to distribute the yttria homogenously in the zirconia matrix. The stabilizing amount of yttria is added to the purified zirconium salt as an yttrium salt before the precipitation and calcination process is started, as described by Haberko K., Ciesla A., and Pron A., Ceramurgia Int. 1 (1975) 111. Alternatively, the zirconia can be stabilized by yttria-coating. This initiates a radial gradient of yttria concentration in the powder, that is distributed in it kinetically during sintering, as described by Burger, W., Richter, H. G., Piconi, C., Vatteroni, R., Cittadini, A., Boccalari, M., New Y-TZP powders for medical grade zirconia. J Mater. Sci. Mater. Med. 1997, 8 (2), 113-118.

[0074] It is further preferred that prior to the etching according to the present invention a macroscopic roughness is provided to the ceramic surface of the dental implant by sandblasting, milling and/or injection molding techniques. Thus, a dental implant having especially good osteointegrative properties is obtained.

[0075] Sandblasting is generally performed using a pressure of 1 to 12 bar, preferably 4 to 10 bar. A considerably improved macroscopic roughness is achieved when using a hard material such as boron carbide. In a further preferred embodiment, Al.sub.2O.sub.3 particles having an average diameter of 250 to 500 m are used.

[0076] As an alternative to sandblasting, the macroscopic roughness can also be provided by injection molding techniques. Injection molding techniques are known to a skilled person and are for example described in US-A-2004/0029075, the content of which is incorporated herein by reference. According to these techniques, casting molds with cavities are used, said cavities corresponding to the peaks of the molded implant's macroscopic roughness. The cavities of the casting mold are slightly greater in proportion than the peaks to be provided, taking into account the shrinking of the ceramic after injection molding. The casting molds themselves may be treated by sand blasting, anodization, laser and/or by erosion techniques in order to produce the cavities or the structured surface on the inner surface of the molds.

[0077] Injection molding techniques have the advantage that during this process no phase transformation occurs in the ceramic material which has therefore improved mechanical properties. Furthermore, the manufacture of the dental implant by injection molding circumvents the additional step of providing the macroscopic roughness and is thus quick. In addition, it has an excellent reproducibility and there is no contamination with particles from sandblasting.

[0078] It is also envisioned to provide a macroscopic roughness by milling or grinding. For this purpose, milling or grinding devices having a defined grain size are used in order to guarantee a desired macroscopic roughness of the surface.

[0079] According to a further preferred embodiment of the present invention, the etching solution comprises at least 50 vol.-%, more preferably at least 80 vol.-% of concentrated hydrofluoric acid. Etching with this etching solution leads after a relatively short etching time to a uniform topography over the whole surface treated.

[0080] The etching solution can further comprise at least one compound selected from the group consisting of phosphoric acid, nitric acid, ammonium fluoride, sulfuric acid, hydrogen peroxide and bromic acid. Preferably, the etching solution comprises sulfuric acid in an amount of 50 vol.-% at most.

[0081] The etching time depends highly on the etching solution used and typically ranges from about 10 seconds to about 120 minutes. The etching time is preferably about 1 minute to about 60 minutes, more preferably about 20 minutes to about 40 minutes and most preferably about 30 minutes.

[0082] Preferably, the etching is followed by washing the dental implant, the washing comprising the subsequent step or the subsequent steps of

[0083] c) rinsing the dental implant with a NaCl solution and/or

[0084] d) rinsing the dental implant with deionized water.

[0085] The performance of the washing step can be improved by using ultrasound. Thereby, grains, grain agglomerates or reaction products which loosely adhere to the surface are effectively removed.

[0086] Apart from the process described, the present invention also relates to a dental implant obtainable by this process.

[0087] The dental implant may be a one-part or a two-part dental implant comprising an anchoring part for anchoring the implant within the jawbone and a mounting part for receiving a prosthetic build-up construction.

[0088] Two-part systems are known in the art. They can either be inserted subgingivally or transgingivally.

[0089] According to the (closed) subgingival system, the anchoring part of the dental implant is embedded until the bone ridge so that the mucoperiosteal cover can be seen above the implant. At the end of the primary healing phase, the mounting part and the desired bridge or crown is then applied in a second operation.

[0090] According to the (open) transgingival system, the anchoring part of the implant is sunk in up to about 3 mm of the bone ridge at mucosal level, thus avoiding a secondary operation. The wound edges can be directly adapted to the implant neck portion, thereby effecting a primary soft tissue closure to the implant. Then, the desired bridge or crown is screwed or cemented onto the mounting part of the implant, generally using an intermediate abutment.

[0091] Transgingivally applied dental implants are often preferred. When implanting such an implant, the soft tissue attachment during the healing process is not disturbed by a secondary operation such as occurring with systems that heal with covered mucous lining.

[0092] For example, the dental implant of the present invention can be a two-part, transgingivally applied implant analog to the titanium implant marketed by Institut Straumann AG, Basel/Switzerland, under the tradename Straumann Dental Implant System.

[0093] The two-part dental implant preferably has an anchoring and a mounting part which are made of the same ceramic material. Thus, the anchoring part and the mounting part have the same thermal coefficient of expansion, allowing them to be closely fitted and avoiding the formation of gaps between them.

[0094] Alternatively, the dental implant of the present invention may also be a one-part dental implant. The mechanical stability of a one-part dental implant is generally higher than that of a multi-part system. In combination with the high strength of the ceramic material used, the one-part dental implant of the present invention has thus a particularly high mechanical stability. The one-part dental implant has the additional advantage that there are no interstices and thus no starting points for the formation of bacteria which may cause parodontitis or gingivitis.

[0095] The dental implant of the present invention can be directly ground, allowing it to be adapted to further elements to be mounted in a simple way.

[0096] The dental implant of the present invention can either be made fully of a ceramic material or can have a core made of another material, such as a metal, for example titanium or an alloy thereof, or another ceramic material.

[0097] The present invention encompasses dental implants of which the whole surface is made of a ceramic material and dental implants of which only a part of the surface is made of a ceramic material.

[0098] Likewise, the present invention encompasses dental implants of which only a part of the surface, e.g. the bone tissue contacting region of the anchorage part's surface, has the topography obtainable by the process of the invention. Likewise, only the region of the implant's surface contacting the soft tissue may have the topography obtainable by the process of the invention. It has been found that when using a dental implant which in the soft tissue contacting region has the topography obtainable by the process described, the blood coagulum is stabilized which further accelerates the healing process. In a further embodiment of the present invention, both the bone and the soft tissue contacting region may thus have the topography obtainable by to the process described.

[0099] It is further preferred that the anchoring part comprises a threaded section. Thereby, the implant can be implanted with the necessary primary stability so that directly subsequent to the implantation a primary treatment is made possible by applying a temporary measure. The surface of the threaded section preferably has the topography obtainable by the process of the invention in order to increase osteointegration.

EXAMPLES

1. Etching of a Surface Made of Yttria-Stabilized Zirconia Ceramic

[0100] For Examples 1 to 11, densely sintered bodies made of yttria-stabilized zirconia ceramic as described by Burger, W. et al, New Y-TZP powders for medical grade zirconia. J

[0101] Mater. Sci. Mater. Med. 1997, 8 (2), 113-118, and having the shape of a disc with a diameter of 15 mm and a thickness of 2 mm are prepared by low pressure injection molding and subsequent hot isostatic pressing. The material falls within the definition of ASTM F 1873 and ISO 13356 and is further specified by an average grain size from about 0.1 m to about 0.3 m.

[0102] For preparing the bodies, casting molds are used which optionally have been treated by erosion techniques to obtain a macroscopic roughness (or macroroughness) on the inner surface of the mold. Depending on the erosion parameters used, a pronounced or a non-pronounced macroroughness is, thus, provided to the surface of the body. Alternatively, a pronounced macroroughness can also be obtained by sandblasting the bodies with Al.sub.2O.sub.3 at a pressure of 6 bar and an average working distance of 2 cm. Both the erosion and sandblasting techniques for providing a macroroughness to the surface are known to a person skilled in the art.

[0103] The bodies according to Examples 1 to 7 and 10 to 11 are then added to an etching solution in a Teflon container at a defined etching temperature and for a defined etching time. They are then instantly rinsed with deionized water and/or ethanol for five minutes in an ultrasonic device and subsequently dried under nitrogen or hot air.

[0104] Comparative Examples 8 and 9 are not added to the etching solution.

[0105] The particulars for Examples 1 to 11 are given in Table 1.

TABLE-US-00001 TABLE 1 etching etching etching Example solution temperature time macroroughness 1 Mixture of 80 104 C. 10 minutes pronounced vol.-% HF and 20 (erosion) vol.-% H.sub.2SO.sub.4 2 Concentrated HF 104 C. 10 minutes pronounced (erosion) 3 Mixture of 85 102-104 C. 5 minutes non-pronounced vol.-% HF and 15 vol.-% H.sub.2SO.sub.4 4 Mixture of 50 102-104 C. 5 minutes non-pronounced vol.-% HF and 50 vol.-% H.sub.2O 5 Concentrated HF 102-104 C. 10 minutes non-pronounced 6 Mixture of 50 102-104 C. 5 minutes pronounced vol.-% HF and 50 (erosion) vol.-% H.sub.2O 7 Mixture of 50 102-104 C. 10 minutes non-pronounced vol.-% HF and 50 vol.-% H.sub.2O 8 No etching pronounced (comparative) (erosion only) (erosion) 9 No etching pronounced (comparative) (sandblasted only) (sandblasted) 10 Concentrated HF 102-104 C. 5 minutes non-pronounced 11 Concentrated HF 102-104 C. 5 minutes pronounced (sandblasted)

[0106] For Examples 1 to 9, the surface structure obtained by the above treatment is shown in FIGS. 3 to 11 of which

[0107] FIG. 3 is an SEM picture of the surface resulting from the treatment according to Example 1 in two different magnification levels, the scale given in the SEM picture corresponding to 20 m (above) and 5 m (below), respectively;

[0108] FIG. 4 is an SEM picture of the surface resulting from the treatment according to Example 2 in two different magnification levels, the scale given in the SEM picture corresponding to 20 m (above) and 5 m (below), respectively;

[0109] FIG. 5 is an SEM picture of the surface resulting from the treatment according to Example 3 in two different magnification levels, the scale given in the SEM picture corresponding to 20 m (above) and 5 m (below), respectively;

[0110] FIG. 6 is an SEM picture of the surface resulting from the treatment according to Example 4 in two different magnification levels, the scale given in the SEM picture corresponding to 20 m (above) and 5 m (below), respectively;

[0111] FIG. 7 is an SEM picture of the surface resulting from the treatment according to Example 5 in two different magnification levels, the scale given in the SEM picture corresponding to 20 m (above) and 5 m (below), respectively;

[0112] FIG. 8 is an SEM picture of the surface resulting from the treatment according to Example 6 in two different magnification levels, the scale given in the SEM picture corresponding to 20 m (above) and 5 m (below), respectively;

[0113] FIG. 9 is an SEM picture of the surface resulting from the treatment according to Example 7 in two different magnification levels, the scale given in the SEM picture corresponding to 20 m (above) and 5 m (below), respectively;

[0114] FIG. 10 is an SEM picture of the surface according to Example 8 in two different magnification levels, the scale given in the SEM picture corresponding to 50 m (above) and 20 m (below), respectively; and

[0115] FIG. 11 is an SEM picture of the surface according to Example 9 in two different magnification levels, the scale given in the SEM picture corresponding to 50 m (above) and 20 m (below), respectively.

[0116] As can be seen from FIGS. 3 to 9, etching according to the present invention of a surface made of an yttria-stabilized zirconia ceramic leads to a surface having crater-like structures. This surface is highly osteointegrative.

[0117] Similar structures are obtained by etching other yttria-stabilized zirconia ceramics. In a further example, a disc made of ZrO.sub.2-TZP/TZP-A Bio-HIP (ZrO.sub.2) Bioceramic available from Metoxit AG, Switzerland, is etched with a mixture of 50 vol.-% concentrated hydrofluoric acid (HF) and 50 vol.-% of concentrated phosphoric acid as etching solution, the etching time being from about 20 to about 60 seconds and the etching temperature being about 106 C. An SEM picture of the surface obtained is given in FIG. 12, the scale given in the SEM picture corresponding to 5 m.

2. Parameters Characterizing the Surface Topography

[0118] For Examples 1 to 11, the topography of the surface is quantitatively examined using a confocal 3D white light microscope (Surf, NanoFocus AG, Oberhausen, Germany) over an area of 770 m770 m to calculate the three-dimensional topography parameters S.sub.k and S.sub.sk. The lateral resolution of the microscope is 1.5 m (512512 pixels).

[0119] The specific measurement parameters are as follows:

[0120] Measuring range: 770 m770 m

[0121] Aperture: 50%

[0122] Illumination: Maximal intensity Xe-Lamp

[0123] Objective: 20

[0124] Drive: Piezo

[0125] Stepsize: 0.6 m

[0126] Algorithm: mean/fast

[0127] The ceramic samples are coated with a Au/Pd layer having a thickness of about 20 nm. To this end, a sputter coater (SCD 050; BAL-TEC AG, Liechtenstein) was used. The settings are as follows:

[0128] Coating distance: 50 mm

[0129] Evacuation: to 410.sup.1 mbar

[0130] Rinsing: with Argon

[0131] Current: 65 mA

[0132] Time: 55 s

[0133] By these settings, an Au/Pd layer having a thickness of about 20 nm is obtained.

[0134] The 3D specific Skewness S.sub.sk and Core Roughness Depth S.sub.k are calculated using a Gaussian filter with a cut-off wavelength of 10 m. The Gaussian filter used to analyze the Core Roughness Depth and its associated parameters is a specific filter described in ISO 13 565 Part 1 (DIN 4776). The cut-off wavelength .sub.c is defined, according to DIN 4768, as the wavelength of the sinusoidal wave which is separated by the filter into 50% roughness and 50% waviness.

[0135] The calculation of the roughness parameter S.sub.k and S.sub.sk is carried out by the WinSAM software (University of Erlangen, Germany).

[0136] Details to the WinSAM software:

[0137] Windows Surface Analysis Module; Version 2.6, University of Erlangen, Germany; Polynom 3. Grades, MA-Gauss-Filter 7 Punkte=cut-off (1010 m.sup.2); KFL-Analyse Amplitudendichte 10 nm.

[0138] The filter creates a separation into waviness and roughness. This derivation and therefore also the determined value for the roughness parameter is dependent on the selected cut-off wavelength .sub.c. For determining the S.sub.k and S.sub.sk values, the cut-off wavelength .sub.c is set to 10 m as given above.

[0139] The results are given in the diagram of FIG. 13 in which the S.sub.sk values and the S.sub.k values of Examples 1 to 11 are represented pointwise.

[0140] Comparatively, the S.sub.k and S.sub.sk values of the commercially available implants z-zit (Example 12) of Ziterion GmbH, Germany, Z-Lock (Example 13) of Z-Systems AG, Germany, White Sky (Example 14) of Bredent medical GmbH, Germany, and Ti-SLActive (Example 15) of Straumann, Switzerland, have also been determined according to the method described above.

[0141] As can be seen from FIG. 13, the surface topography of Examples 1 to 7 and 10 to 11 obtained according to one process in accordance with the present invention has a Core Roughness Depth S.sub.k between about 0.4 m and about 1 m. In these Examples, the Skewness S.sub.sk is less than 0. FIG. 13 also clearly illustrates that the surface topography obtained according to the present invention is completely different from the surface topography of commercially available implants, in particular SLActive (available from Straumann Holding AG, Basel CH), which have a Core Roughness Depth S.sub.k significantly higher than 1 m.

3. In Vitro Cell Tests

[0142] In vitro cell tests are carried out using the human osteosarcoma cell line MG-63 because of its ability to differentiate into mature osteoblasts.

[0143] The cell line is cultured in a mixture of Dulbecco's modified Eagles's Medium (DMEM; available from Sigma, Switzerland), Penicillin-Streptomycin Solution (100; available from Sigma, Switzerland) and FBS.

[0144] On each of the discs according to Examples 1, 2, 7, 9 and 15, approximately 9000 cells are plated.

[0145] After culturing each of the respective discs in a medium containing vitamin D3, they are removed and washed with 1 ml PBS (RT). 350 l of RLT-buffer (plus -mercaptoethanol) is added to each disc and incubated for 2 to 3 minutes.

[0146] The RLT buffer is removed by simultaneously scratching with a pipette tip over the surface of the discs (to remove all cells) and frozen at 25 C. until RNA extraction.

[0147] RNA is isolated using the QIAGENKit RNeasy Micro Kit. Then, cDNA is produced and the expression of osteocalcin, osteonectin and TGFbeta, which are known to be involved in the bone formation process, is analysed by Real time PCR. As reference gene, 18S rRNA is used. Osteocalcin, osteonectin and TGFbeta are known to be suitable biochemical markers for the bone formation process.

[0148] For the calculation of the relative fold expression of the respective marker, the Livak method or 2.sup.Ct method is used. This method is based on the assumption that target and reference genes are amplified with efficiencies close to 100% (corresponding to an amplification rate of 2). The Livak method puts the E.sub.(target)=E.sub.(reference)=2, wherein E is the efficiency of the reaction.

[0149] The threshold cycle (Ct) of the target gene is normalized to the reference gene for the test sample and the calibrator sample. As a reference gene, 18S tRNA is used, and as a calibrator sample, cells cultured on the disc of Example 9 is used.

[0150] The ACt of the test sample is defined as follows:

ct.sub.(test sample)=Ct.sub.(test sample)Ct.sub.(reference gene)

wherein the Ct of the calibrator is defined as follows:

Ct.sub.(calibrator)=Ct.sub.(test calibrator)Ct.sub.(reference calibrator)

[0151] The Ct of the test sample is normalized to the Ct of the calibrator, resulting in the Ct:

Ct=Ct.sub.(test sample)Ct.sub.(calibrator)

and the normalized expression ratio was calculated by the following formula:

Normalized expression ratio=2.sup.Ct

[0152] The fold expressions of osteocalcin and TGFbeta on Examples 1, 2, 7 and 15 relative to Example 9 are shown in FIG. 14. As can be seen from FIG. 14, all examples treated according to the present invention exhibit a higher expression of osteocalcin and TGFbeta than comparative Example 9. This substantiates the finding that the examples treated according to the present invention have improved osteointegrative properties. A higher expression of osteocalcin and TGFbeta is also found for Example 15 relating to Ti-SLActive which is well known for its high osteointegrative properties.

[0153] Example 2 has further been analysed for its expression of osteonectin. As shown in FIG. 15, Example 2 shows an expression of osteonectin superior over both comparative Example 9 and Example 15 (Ti-SLActive).

DENTAL IMPLANT HAVING A TOPOGRAPHIC SURFACE

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