IMPLANT SURFACE COMPOSITION

Abstract

An implant structure or parts thereof having a surface composition obtainable through an anodic oxidation process is disclosed. The surface composition comprising titanium oxide in the anatase crystalline phase and at least 90% of the pores have an orifice with a mean inside diagonal distance of less than 0.1 m. It is also disclosed an implant system comprising said surface composition and a method of obtaining said surface.

Claims

1. An implant structure or parts thereof comprising: a surface composition comprising titanium oxide in the anatase crystalline phase, wherein said surface composition has a porous structure where at least 90% of pores have an orifice with a mean inside diagonal distance of less than 0.1 m.

2. The implant structure or parts thereof according to claim 1, wherein the surface composition is obtainable through an anodic oxidation process.

3. The implant structure or parts thereof according to claim 1, in which said surface composition has a mean roughness value (Sa value) of below 0.3 m.

4. The implant structure or parts thereof according to claim 1, in which at least 95% of the pores, have an orifice with a mean inside diagonal distance of less than 0.2 m.

5. The implant structure or parts thereof according to claim 1, in which said surface composition forms part of a tissue facing surface of a component of an implant system.

6. The implant structure or parts thereof according to claim 1, in which said surface composition forms part of a bore or other inner surface of a component of an implant system.

7. The implant structure or parts thereof according to claim 1, in which at least 35% by volume of said surface composition is formed by titanium oxide in the anatase phase.

8. The implant structure or parts thereof according to claim 1, in which a major content of said surface composition volume is formed by titanium oxide in the anatase phase.

9. The implant structure or parts thereof according to claim 1, in which said surface composition comprises phosphorus.

10. The implant structure or parts thereof according to claim 1, in which a coating is provided on said surface composition.

11. An implant system provided with at least one component comprising an implant structure or parts thereof according to claim 1.

12. The implant system according to claim 11, in which said implant system is a dental implant system comprising a body having a proximal end, a distal end, an outer surface extending between the proximal end and the distal end, the body having a longitudinal axis; and a. an open socket formed in a top portion of the body, the open socket comprising an inner surface extending from the distal end towards the proximal end of the body along the longitudinal axis of the body; and b. a spacer belonging to said dental implant system, which is/are intended to extend from said distal end in a hole formed in jaw bone and in soft tissue.

13. The implant system according to claim 12, in which said spacer is at least one of the components of the group comprising an abutment, an overdenture bar and a fixture supported bridge.

14. The implant system according to claim 12, in which said socket has a depth exceeding 1 mm and said inner surface is provided with said surface composition.

15. The implant system according to claim 12, in which said inner surface is provided with a thin uniform surface composition and comprises at least one thread.

16. The implant system according to claim 12, in which a portion of the implant structure or parts thereof that can be placed against the soft tissue comprises a threadless outer surface.

17. The implant system according to claim 12, in which a portion of the implant surface composition is provided with a gradient, wherein the roughness value (Sa value) of said portion is increasing from a lower value up to 0.3 m, in the apical direction.

18. The implant system according to claim 12, in which a portion of the implant structure or parts thereof that can be placed against bone tissue comprises a second surface composition having a roughness value in the range of 0.4-5 m and pore diameters in the range of 0.1-10 m.

19. The implant system according to claim 18, in which a portion of the second surface composition is provided with a gradient, wherein the roughness value is increasing, within the range of 0.4-5 m, in the apical direction.

20. The implant system according to claim 12, in which a portion of a second surface composition is provided with a gradient, wherein the roughness value is increasing, within the range of 0.4-5 m, in the apical direction.

21. A method for producing an implant or a spacer belonging to said implant, the method comprising an anodic oxidation method in which a portion of an inner or outer surface is applied in a vessel comprising an electrolyte, and the voltage is below 100 Volts and more than 30 Volts and the dwell time of the portion in the electrolyte are chosen such that a surface composition, largely or completely assuming the crystalline anatase phase, is formed, the process time being of less than 10 seconds.

22. The method according to claim 21, in which said surface composition forms part of a soft tissue facing surface of a component of an implant system.

23. The method according to 22 claim 21, in which at least 90% of pores have an orifice with a mean inside diagonal distance of less than 0.1 m.

24. The method according to claim 21, in which at least 95% of pores have an orifice with a mean inside diagonal distance of less than 0.2 m in diameter.

25. The method according to claim 21, in which said surface composition has a mean roughness value (Sa value) of below 0.3 m.

26. The method according to claim 21, in which said surface composition forms part of a bore or other inner surface of a component of a dental implant system.

27. The method according to claim 21, in which at least 35% by volume of said surface composition is formed by titanium oxide in the anatase phase.

28. The method according to claim 21, in which a major content of said surface composition is formed by titanium oxide in the anatase phase.

29. The method according to claim 21, in which a coating is provided on said surface composition in a subsequent step.

30. The method according to claim 21, in which said implant or spacer comprises titanium or an alloy thereof.

31. The method according to claim 21, in which said implant is formed by at least one of the options selected from a group comprising milling, turning, etching or an additive manufacturing technique prior to anodic oxidation.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0034] These and other aspects, features and advantages of which embodiments of the invention are capable of will be apparent and elucidated from the following description of embodiments of the present invention, reference being made to the accompanying drawings, in which

[0035] FIGS. 1A and 1B are side views of various embodiments of dental implant systems and a spacer provided with a surface according to the invention.

[0036] FIG. 2 shows a diagrammatic side view of titanium dioxide in the anatase phase being applied to an implant by means of anodic oxidation,

[0037] FIG. 3 shows a diagrammatic side view of titanium dioxide in the anatase phase being applied to a unit or soft tissue through-piece belonging to the implant,

[0038] FIG. 4A shows, in graph form, the applied current as a function of time, and

[0039] FIG. 4B shows how the voltage is related to during the anodization process, as shown in FIG. 4B.

DESCRIPTION OF EMBODIMENTS

[0040] Specific embodiments of the invention will now be described with reference to the accompanying drawings. This invention may, however, be embodied in many different forms and should not be construed as limited to the embodiments set forth herein; rather, these embodiments are provided so that this disclosure will be thorough and complete, and will fully convey the scope of the invention to those skilled in the art. The terminology used in the detailed description of the embodiments illustrated in the accompanying drawings is not intended to be limiting of the invention. In the drawings, like numbers refer to like elements.

[0041] The feature which can be regarded as characterizing an arrangement according to the invention is that the implant structure will consist of crystalline titanium dioxide which largely or completely assumes the anatase phase and that the surface structure in the micrometer range obtained by machining is preserved. In one embodiment, a large part or all of the outer surface or outer surfaces of the implant or of the spacer sleeve is provided with the crystalline titanium oxide assuming the anatase phase. However, in the preferred embodiment, the implant structure according to the invention is applied to an abutment. and the most coronal parts of the implant. The anatase layer combined with the smooth preserved structures from machining will prevent or significantly reduce microbial colonization of the surface while allowing for good integration with the surrounding tissue. The sleeve surfaces and the surfaces of the most coronal part of the dental implant according to the invention are described as follows: The sleeve and the coronal part of the implant are machined, e.g. turned, from cp titanium or Ti6Al4V alloy. The surfaces according to the invention are anodized using a method described below. They will be compared with unanodized control surfaces in the following. The surface structure was analysed by SEM and interferrometry (WYKO). The surface morphology was examined and documented using a Zeiss Ultra 55 scanning electron microscopy (SEM). Images of the surface were taken using 10 kV accelerating voltage at 500, 2000 and 8000 magnifications. The surface structure on all anodized and control components had characteristic grooves from the turning tool in the micrometer range. The anodized surfaces had a nanometer structure in the 50 nm range superimposed on the turned structure. The nanometer structure was covering the entire surface on the anodized cp titanium components, whereas only limited areas of nanometer structure were observed on the anodized alloy components.

[0042] Disks from cp titanium and titanium alloy were made by turning, and the surface roughness was measured. The mean roughness (Sa) of the surface was measured in three 630470 m areas on all samples. The measurements were performed using a WYKO NT9100 profilometry system and data were evaluated in software Vision 4.10. Before calculating Sa data were processed by extrapolation of dead pixels, tilt correction and smoothed by a 55 median filter. There was no significant difference in surface roughness for the control and anodized surfaces. The surface mean roughness Sa was 0.18, 0.18, 0.17 and 0.20 m, respectively, for the machined cp titanium and alloy controls and for anodized cp titanium and alloy, respectively. Thus, the underlying machined surface structure was preserved in the micrometer range.

[0043] Near Edge X-ray Absorption Fine Structure (NEXAFS) experiments were performed using the synchrotron source at Max-IV Laboratory in Lund, Sweden, for assessment of surface crystallinity. The spectra indicated that the anodized surface oxides were partially crystalline with anatase as dominating phase, whereas structures typical for anatase were significantly less pronounced in spectra taken from the control surfaces. The Ti cp peak maximum for the anodised surfaces along with the shoulder on the high energy side is indicative of an anatase crystal phase on these surfaces. The observed differences in the O1s spectra were also compatible with a higher anatase content on the anodically oxidised surfaces.

[0044] Further embodiments of the novel implant and spacer surfaces are set out in the attached dependent claims concerning the implant. Following is a report on an experiment showing the effect that the new surface according to the invention has on microbial colonization.

[0045] Fresh clinical isolates of Streptococcus gordonii (HC7), Streptococcus mitis (BA7) and Streptococcus sanguinis (FC2) were used in this study. Streptococcus gordonii, S. mitis and S. sanguinis were obtained from approximal dental plaque. Streptococcus gordonii was identified by positive phenotypic tests for N-acetylglucosaminidase, N-acetylgalactosaminidase, -fucosidase and -galactosidase. Identification of Streptococcus mitis was based on positive phenotypic tests for N-acetylgalactosaminidase, N-acetylglucosaminidase, -galactosidase and sialidase. while S. sanguinis was identified based on genotypic tests negative for sialidase, arbinosidase, L-fucosidase, -glucosidase and firm adherence to MSA agar.

Culture Conditions

[0046] Bacteria were grown on blood agar in an atmosphere of 5% CO.sub.2 in air at 37 C. Colonies were transferred to Bacto Todd-Hewitt broth (TH) (Becton Dickinson & Co) and grown overnight in 5% CO.sub.2 in air at 37 C. The suspension was transferred to fresh TH broth and incubated at 37 C. until the mid-exponential growth phase was reached (OD.sub.600 nm0.5). Cultures were then centrifuged (4000 g) for 10 min and the pellets were re-suspended in the same volume of TH broth diluted 1:10 in sterile PBS before use. Suspensions of the bacteria were either used alone or mixed in equal volumes to give a four-species consortium.

Preparation of Saliva

[0047] Since the dental components become exposed to saliva in the oral cavity, in the experiment we have compared the adherence of three early colonizing oral bacterial species to the unanodized control and the two surfaces generated by anodic oxidation in the presence of a saliva coating.

[0048] Bacteria-free saliva with proteins kept in their native configuration was prepared as described by Wickstrm & Svenster (2008). After ethical approval had been obtained from the Faculty of Odontology, whole saliva was collected on ice over 1 h from ten healthy volunteers. The saliva was then pooled and mixed with an equal volume of PBS, stirred gently overnight at 4 C. and centrifuged in a Beckman Coulter Avanti J-E centrifuge (20 min, 30 000 g, 4 C.). The supernatant was subjected to isopycnic density-gradient centrifugation in CsCl/0.1 M NaCl in a Beckman Coulter Optima LE-80K Ultracentrifuge at 36,000 rpm for 90 h at 15 C. Bacteria-free fractions were collected from the top of the tube and pooled before being dialysed against PBS and stored at 20 C.

Saliva Pellicle

[0049] Prior to the experiments, anodized cp titanium and alloy titanium discs and unanodized control disks cp titanium were coated overnight in 12-well culture dishes with 25% saliva in PBS at room temperature. Prior to use, unbound salivary proteins were removed from the discs by transferring to new wells filled with 3 ml PBS and incubation on a rocking platform (VWR international LLC) operating at 10 cycles min.sup.1 for 210 min.

Adhesion Assay

[0050] For the adhesion assay, saliva coated discs were placed in wells containing 3 ml of bacterial suspension containing 10.sup.7 cells per ml and maintained on the rocking platform for 2 h at 37 C. The discs were then washed with Todd-Hewitt broth diluted 1:10 in PBS (210 min) to remove loosely attached cells and stained with Live/Dead BacLight (Molecular Probes). Adhered cells were visualised using a fluorescence microscope.

Image Analysis and Statistics

[0051] Experiments were carried out three times using independent bacterial cultures. For all experiments, ten randomly selected areas were photographed were taken avoiding the centre and extreme edges of the discs, and surface coverage was determined using the BioImage-L image analysis software (Chavez de Paz, 2009). Differences in bacterial coverage were analysed ANOVA and P-values below 0.05 were considered significant.

Results

Effect of Nano-Structured Titanium Surfaces on Bacterial Adherence

[0052] For S. gordonii, S. mitis and S. sanguinis, the fluorescence microscopy images of the anodized cp Ti and alloy surfaces (N1 and N2) revealed a more sparse distribution of bacterial cells compared to the control surfaces. No obvious differences were seen between the two anodized surfaces.

[0053] Image analysis revealed that binding of S. gordonii to both the anodised cp Ti and alloy surfaces was lower than to the control (415% and 259% of control levels respectively). These reductions in adherence were significant at the 5% and 1% levels, respectively. Although adherence to the alloy surface was slightly lower than that to cp Ti, the difference in level of adherence was not significant at the 5% level. Binding of S. mitis to the anodized surfaces was also lower than to the control surface (anodized cp Ti: 334% of control and anodized alloy: 232% of control) and these reductions were significant at the 1% level. As seen for S. gordonii, there was no significant difference in binding between the anodized surfaces. For S. sanguinis, image analysis revealed the adherence to both the anodized cp Ti and alloy surfaces to be significantly lower (p<0.001) than to the control surface (152% of control and 282% of control, respectively). Unlike the other streptococcal species, S. sanguinis showed a significantly lower level of binding (p<0.05) to the anodized cp Ti as compared to the alloy surface.

[0054] These data showed that S. gordonii and S. mitis adherence to the anodized surfaces was significantly reduced compared to control and S. sanguinis showed markedly lower adherence to the two anodized surfaces. In this study, early biofilm formation on two anodized titanium surfaces was compared with a commercially pure titanium control surface. Since salivary proteins are well known to affect the binding of bacteria to oral surfaces, (Nikawa et al. 2006; Lima et al. 2008; Mei et al. 2011) the experiments were performed in the presence of a salivary pellicle in order to model the in vivo situation. The purified salivary preparation used, was previously shown to contain large salivary mucins (MUC5B and MUC7) as well as a range of proteins including gp340, lysozyme, lactoferrin, -amylase, sIgA, statherin, cystatins and prolactin-inducible protein (Dorkhan et al. 2013).

[0055] For the three of the tested species, the level of binding to the anodized surfaces was less than 50% of that to the commercially pure titanium. For S. gordonii and S. mitis, this reduction was significant at the 5% and 1% level, respectively, and for S. sanguinis the reduction was significant for the 1% level. Despite the fact that the anodized surfaces were made from of commercially pure titanium and titanium alloy respectively, both surfaces showed similar patterns of reduction in bacterial adherence compared to control.

[0056] Overall, the results of this study lead to the conclusion that the salivary pellicle formed on the anodized surfaces is different to that on the control and that this results in significantly reduced adherence of early colonizing streptococcal colonizers, especially S. sanguinis to these surfaces. This finding thus emphasises the importance of using saliva-coated surfaces in experiments to investigate bacterial colonization of dental implant materials.

[0057] Extrapolation of these data to the in vivo situation indicates that development of a new generation of titanium dental implants and spacer sleeves incorporating such anodized surfaces with preserved structure in the micrometer range obtained by machining could make a significant contribution to reducing the early stages of microbial biofilm formation at these sites. This could in turn reduce binding of later colonizers and the formation of complex, mature biofilms. It may be expected that a reduction in the overall bacterial load on the spacer sleeve surfaces and most coronal parts of the implants could tip the balance in favour of soft-tissue adhesion, allowing an improvement in the soft-tissue barrier at the sites. Thereby, the risk of peri-implant infection and implant treatment complication and failure is reduced.

[0058] The following is a description of the novel method used for manufacturing the new surfaces according to the invention: The feature which can principally be regarded as characterizing the novel method is that it comprises an anodic oxidation procedure providing a titanium oxide surface enriched with anatase and allowing for preserved underlying surface structure in the micrometer range resulting from machining. In this method, the part or parts bearing said outer layer or outer layers are applied to a liquid or electrolyte under voltage, e. g. sulphuric acid and phosphoric acid. The electrolyte composition and the voltage, current and the dwell time of the actual part or parts of the implant in the liquid are chosen so that titanium dioxide, partially assuming the anatase phase, is formed while preserving the underlying structure in the micrometer range. Different electrolyte compositions are associated with different voltages. In one embodiment, the voltage is chosen with values between 30 and 99 volts. At lower voltages, the titanium dioxide layer has too low anatase content, and at higher voltages the micrometer structure of the titanium dioxide layer is transformed to include a large number of pores in the micrometer range and the characteristic structures created during machining of the substrate body are lost.

[0059] By means of what has been proposed above, an excellent and effective reduction of microbial colonization is achieved. The layer or layers also provide the possibility of effective soft tissue integration at the part or portion that can be placed against or extend through the soft tissue. The implant production is highly advantageous because methods and procedures already known per se can be used. No modifications are needed to the actual implant or unit structure, and they can be distributed and handled in the manner already practised in the dental field. Likewise, the actual implantation work can follow already established routines, with the difference that microbial growth on the components surfaces is reduced significantly. Layers with different properties of titanium dioxide in the anatase phase may be applied to an implant by means of anodic oxidation. FIGS. 2 and 3 show a diagrammatic side view of titanium dioxide in the anatase phase being applied to an implant and a unit or soft tissue through-piece belonging to the implant.

[0060] According to FIG. 1A, an implant system 1 is provided in bone 2, e.g. a jaw bone of a patient. On top of the jaw bone there is a bed of soft tissue 3. The bone 2 is initially provided with a hole, shown symbolically by reference number 4. A fixture 5 which can be of a type known per se is arranged in the hole. The fixture 5 can thus comprise, for example, an outer thread 5a by means of which said fixture 5 can be screwed into the hole 4. The hole 4 can be threaded or unthreaded. The fixture 5 is also provided with a flange-like portion 7 which has a peripheral surface that can be placed against the soft tissue. The implant system 1 can also comprise or be connected to a unit or soft tissue through-piece 9, which can consist of or function as a spacer sleeve 9. On the soft tissue through-piece 9, the fixture 5 is intended to support a prosthesis, which is not shown here in any detail. The implant system shown in FIG. 1A is manufactured and sold by Nobel Biocare under the name NobelReplace. As the skilled person is well aware of the prosthesis (10) can also be made to be connectable to a plurality of fixtures. It is then often referred to as a bridge or a bar. The bridge can be fixture supported or spacer supported or even partly supported by any of the two together with a tooth or teeth. Moreover, the prosthesis can also be made like a single restoration and be either fixture supported or connected to a spacer or abutment. All the above alternatives are well known and described in the art and not explained in further detail here. The important finding is that at least areas of any implant system that is facing soft tissue or the oral cavity or is in contact with soft tissue is preferably equipped with a surface composition according to the present invention.

[0061] The implant according to FIG. 1A can now be provided with a machined surface with structures in the micrometer range and along all or most of its outer surface with a thin layer of titanium dioxide which completely or partially, assumes the crystalline form anatase. In the case according to FIG. 1A, the placement of the implant has resulted in exposure of its upper parts to soft tissue. Said anatase has been shown to have a powerful effect on reducing microbial growth and colonization and a stimulating effect on tissue integration, which in FIG. 1 has been illustrated by soft tissue growth 3 surrounding the coronal part of the fixture 5 and the spacer sleeve 9 surface. The anatase structure has thus made the surface of the coronal part of the implant and spacer sleeve able to resist microbial colonization and guide soft tissue formation. The topography of the structure is following the underlying structure in the micrometer range given to the implant surface when it was produced using milling or turning as production method.

[0062] The application of titanium dioxide in the anatase phase has significantly reduced bacteria growth in the area concerned. The titanium dioxide in the anatase phase combined with the machined surface topography can thus be used to effectively avoid bacteria absorption and growth in the area with the soft tissue exposure and in this way to avoid peri-implant infection. This allows for a good implant survival prognosis in the long term. Of course, the implant system 101 according to FIG. 1B can be provided with titanium dioxide along the full outer extent of the implant. The bone hole formation is indicated by 104.

[0063] It is not disclosed in detail in the drawings a dental implant system (1), in which said socket has a depth exceeding 1 mm and said inner surface is provided with said surface composition. However, the skilled person is familiar with the design of implants and a drawing of said inner surface is not necessary here. It is realized that the inner surface is provided with a uniform surface composition layer and comprises at least one thread. The method according to the invention allows for the formation of anatase in a thin surface composition that allows for even microstructure patterns to shine through the thin surface composition.

[0064] The implant surface composition may be provided with a gradient, in which the roughness of the surface composition is increasing, within the range of a lower value up to 0.3 m, in the apical direction. This feature can be applied to various embodiments by using various gradients. Especially it should be noted that the implant (5) that can be placed against the bone tissue (2) comprises a second surface composition having a roughness in the range of 0.4-5 m and pore diameters in the range of 0.1-10 m, preferably 1-7 m. Moreover, the second surface composition is provided with a gradient, in which the roughness value is increasing, within said range, in the apical direction.

[0065] FIGS. 2 and 3 show the principle of anodic oxidation, in which use is made of a vessel 15 with a liquid containing an electrolyte 19, e. g. sulphuric acid and phosphoric acid. The mode of operation shall be with potentiostatic control. The process time shall be less than 10 seconds. In an anode and cathode arrangement, the implant represents an anode 16, and a contact unit a cathode 17. The implant is completely or partially immersed in the electrolyte 19. The anode and the cathode are connected respectively to the plus pole and minus pole of a voltage source which is symbolized by 20. The voltage source 20 can comprise control members of a known type to ensure that the voltage between the anode/implant and the cathode/contact unit located in the electrolyte can be varied if necessary. Thus, the voltage U can, for a certain composition of the electrolyte, be varied or set to a first value in the range of below 100 Volts and above 30 Volts. If the electrolyte has another composition, the value is set to another value which can be in the stated range, i. e. between 30 and 100 volts, so as to obtain on the outer surface or outer surfaces in question a titanium dioxide layer according to the above, which assumes the crystalline anatase phase while preserving the underlying surface structure in the micrometer range. It will be appreciated that the titanium dioxide layer can be varied in terms of thickness and phase by controlling the voltage value by means of said control members or setting members and by moving the implant in the directions of the arrows 21. The immersion time of the surface or surface parts is also crucial in determining the structure of the titanium dioxide layer.

[0066] FIG. 3 shows the case where a soft tissue through-piece 9, spacer or unit 9 is coated completely or partially with titanium dioxide in the anatase phase, using equipment according to FIG. 2. In the present example, the entire through-piece is immersed in the liquid bath or electrolyte 19.

[0067] FIG. 4A shows how the anatase content can vary as a function of the applied current I for a certain immersion time and for a given electrolyte. The dependence of the anatase content on, inter alia, the current has been represented by the curve 21. FIG. 4B indicates a first threshold value U1 where the anatase phase occurs. As seen from FIG. 4B the voltage is held constant and/or near a value U1 throughout the process.

[0068] The implant 1 and/or the soft tissue through-piece 9 thus have a portion or portions that can be placed against the jaw bone and/or soft tissue. Each such portion can be unthreaded or can be provided with a thread, groove or pattern. Different layers can be provided on locally distinct sites or on top of one another. It can also be exposed to higher voltage in order to roughen the bone tissue facing portions somewhat more. The implant can be held in different positions or continuously moved up from the electrolyte to enable formation of a gradient. The formation of a gradient can be controlled in many different ways.

[0069] The invention is not limited to the embodiment shown above by way of example, and instead it can be modified within the scope of the attached patent claims. The present invention has been described above with reference to specific embodiments. However, other embodiments than the above described are equally possible within the scope of the invention. Different method steps than those described above, different order of the method steps, etc. may be provided within the scope of the invention. In addition, the different features and steps of the invention may be combined in other combinations than those described above. The scope of the invention is only limited by the appended patent claims.