DENTAL IMPLANT

Abstract

A dental implant including an implant surface having at least partially a contact angle of less than 20, the implant surface being at least partially covered by a protective layer having a keratin hydrolyzate.

Claims

1. A dental implant comprising an implant surface having at least partially a contact angle of less than 20, the implant surface being at least partially covered with a protective layer comprising a keratin hydrolyzate wherein the protective layer has a water content of less than 10% by weight.

2. The dental implant according to claim 1, wherein the keratin hydrolyzate has a mean molecular weight of less than 20'000 Da.

3. The dental implant according to claim 1, wherein the keratin hydrolyzate layer has a thickness of 30 to 200 nm.

4. The dental implant according to claim 3, wherein the keratin hydrolyzate layer has a thickness of 30 to 90 nm.

5. The dental implant according to claim 1, wherein the protective layer is essentially free from any salt.

6. The dental implant according to claim 1, wherein the protective layer additionally comprises a salt.

7. The dental implant according to claim 1, wherein the dental implant is made of ceramic.

8. The dental implant according to claim 1, the surface is provided with surface roughness Sa in a range between 2 and 10 m.

9. The dental implant according to claim 1, wherein the implant has a machined surface.

10. The dental implant according to claim 1, wherein the protective layer has a water content of less than 1% by weight.

11. A method for preparing a dental implant according to claim 1 comprising at least the following steps: a) providing the surface of a dental implant having at least partially contact angle of less than 20, b) covering at least partially the surface of the dental implant with a solution or suspension comprising the keratin hydrolyzate, and c) drying the dental implant in order to obtain a protective layer.

12. The method according to claim 11, wherein in step b) the surface is covered by dipping the dental implant into an aqueous solution or suspension.

13. The method according to claim 11, wherein in step c) the water is removed by microwave treatment, by airstream or by drying in a convection oven or a vacuum oven.

14. The method according to claim 11, wherein aqueous solution or suspension comprises the hydrolyzed keratin in a concentration of 0.1 to 10% (w/v).

15. The method according to claim 11, wherein the dental implant covered with the protective layer is sterilized in a further step by ethylene oxide.

Description

FIGURES

[0050] The present invention is further illustrated by the following figures and examples:

[0051] FIG. 1 refers to a first embodiment of the present invention;

[0052] FIG. 2 refers to a second embodiment of the present invention;

[0053] FIG. 3 refers to a third embodiment of the present invention;

[0054] FIG. 4 refers to a forth embodiment of the present invention;

[0055] FIG. 5 refers to a fifth embodiment of the present invention;

[0056] FIGS. 6a to 6c refer to static contact angle for different protective layers with different synthetic parameters for the coating procedure. FIG. 6a shows SCA (static contact angle) changing the coating time. FIG. 6b shows SCA changing the volume of the coating. FIG. 6c shows SCA having machined surfaces instead of SLA surfaces.

[0057] FIG. 7a shows the surface microroughness measured on discs variated by keratin concentration change. FIG. 7b shows the microroughness measurement of ZLA coated dental implants.

[0058] FIG. 8a shows the static contact angle of keratin protection layer at low and high concentrations. FIG. 8b shows the static contact angle of low concentration protection layers with and without a water washing pre-treatment.

[0059] FIG. 9 shows the static contact angle affected by EO sterilization or climatic stress cycle.

[0060] FIG. 10 shows static contact angle of protection layers at low concentration and different storage times.

[0061] FIGS. 11a and 11b show a 3D surface representation from ZLA dental implants roughness measurements in the apex zone.

[0062] FIG. 1 shows an anchoring part 1 of a two-part implant system. Such an anchoring part 1 is made of a ceramic material, preferably of an yttria stabilized zirconia. Said anchoring part 1 is in a cylindrical shape, having an apical end 25 with a body portion 20 and a coronal end 35 with a neck portion 30 intended to receive an abutment, and a transition portion 40 being arranged in axial direction A between the body portion 20 and the neck portion 30. The neck portion 30 includes an unthreaded part 31 which is in coronal direction outwardly tapering and ends in a shoulder portion 32 with an inwardly-tapering surface. The body portion 20 is intended to be directed against the bone tissue in the implanted state, whereas the neck portion 30 is intended to be directed against the soft tissue in the implanted state. The transition portion 40 may be directed towards the soft tissue and the bone tissue depending on the depth to which the implant is screwed or on the tissue reaction. The surface of the body portion 20 has a contact angle of less than 20, which is preferably entirely covered with the protective layer 10.

[0063] FIG. 2 shows another embodiment of the present invention. In contrast to the embodiment of FIG. 1, not only the body portion 20 but also the transition portion 40 of the anchoring part is at least partly, preferably entirely coated with said protective layer 10. Preferably, in apical direction, at least 25%, most preferably at least 50% of the circumferential surface area of the transition portion is covered with the protective layer 10. Preferably, also at least a part preferably the entire surface of the transition portion has a contact angle of less than 20, before covering it with the protective coating 10. However, it is also possible, that only the surface of the body portion of the dental implant has a contact angle of less than 20, but the protective layer covers both, body portion and transition portion. This allows to ensure that also the hydrophilic surface of the edges is fully protected by the protective layer.

[0064] FIG. 3 shows another embodiment of the present invention. In contrast to the embodiment of FIG. 1, not only the body portion 20 but also the transition portion 40 and the neck portion 30 except for the shoulder portion 32 are completely coated with the protective layer 10. Also at least a part, preferably the entire surface of the transition portion and at least a part of the neck portion has a contact angle of less than 20, before covering it with the protective layer 10. It could be shown, that a hydrophilic surface not only ensures a good osseointegration but also positively influences the adherence to the soft tissue. However, it is also possible, that only the surface of the body portion of the dental implant and optionally part of the transition portion has a contact angle of less than 20, but the protective layer covers both, body portion and transition portion.

[0065] FIG. 4 shows an anchoring part 101 of a so-called bone level implant. Such a bone level implant is usually embedded completely in the bone, that is to say to the height of the alveolar crest. Said anchoring part 101 is made of a ceramic material, preferably of an yttria stabilized zirconia. The anchoring part 101 is in a cylindrical shape, having an apical end 125 with a body portion 120 and a coronal end 135 intended to receive an abutment. In contrast to the dental implant shown in FIG. 1, the anchoring part of a bone level implant has no neck portion. The body portion 120 is intended to be entirely directed against the bone tissue in the implanted state. The surface of the body portion 120 has a contact angle of less than 20, which is entirely covered with the protective layer 110.

[0066] FIG. 5 shows a monotype dental implant 200. Said monotype dental implant 200 is made of a ceramic material, preferably of an yttria stabilized zirconia. It comprises an anchoring part 205 having a threaded section 210. The anchoring part 205 at its upper end 215 transitions via a slightly enlarged conical neck portion 220 to the outside into a mounting part 225 being integral therewith and extending within an extension of the longitudinal axis 230 of the threaded section. Said anchoring part 205 is in a cylindrical shape, having an apical end 235 with a body portion 240 and a coronal end 245 with a neck portion 220, and a transition portion 250 being arranged in axial direction A between the body portion 240 and the neck portion 220.

[0067] The mounting part 220 has a frusto-conical or a conical shape and may be provided with at least one a flattening 230 at one side thereof.

[0068] At the side opposite the at least one flattening 260 there may be a groove 265 within the outer surface that extends from the coronal front surface of the mounting part 225 toward the apical side and ends in a conical section which forms the transition to the conical section of the anchoring part 205. The flattening 260 in combination with the groove 265 located on the opposite side functions to provide a positive a screwing tool which has a plug-in seat matched thereto. Alternatively, the mounting part may be provided with other means for receiving a screwing tool. The body portion 240 is intended to be directed against the bone tissue in the implanted state and the neck portion 220 is intended to direct against the soft tissue, whereas the transition portion 250 may direct against the bone tissue or the soft tissue depending on the patient. The surface of the body portion 240 has a contact angle of less than 20, which is at least partly, preferably entirely covered with the protective layer 270. Optionally, not only the body portion 240 but also the transition portion 250 of the anchoring part is hydrophilic. Preferably, the transition portion 250 has a contact angle of less than 45, preferably of less than 20, which is covered by the protective layer 270. Preferably, at least 25%, most preferably at least 50% of the apical circumferential surface area of the transition portion is covered with said protective layer 250. This allows more flexibility when implanting the implant and ensures that the whole surface, which is intended to be in contact with the bone tissue, is hydrophilic.

EXAMPLES

Material

[0069] The term ZLA within the context of the present invention stands for yttria stabilized zirconia, i.e. 3Y-TZP according to DIN ISO 12677, having a sand blasted (corundum 0.1-0.4 mm, 6 bar) and acid etched surface (for example HF). The used keratin hydrolyzate was Nutrilan Keratin LM, BASF (CAS-Nr. 69430-36-0) with a molecular weight of 2000 g/mol. Ker:MgCl.sub.2 stands for a Nutrilan Keratin LM:MgCl.sub.2 ratio of 9:1, whereby the keratin solution had a concentration of 1 mg/ml and the MgCl.sub.2 solution had a concentration of 0.05M.

[0070] Within the context of the present invention, low concentration stands for about 1 mg/ml (i.e. for example 1 mg Nutrilan Keratin LM in 1 ml water which was obtained by adding 870 l water per 100 ml of Nutrilan Keratin having a concentration of 115 mg/ml). The expression high concentration stands for about 30 mg/ml.

O.SUB.2 .Plasma Cleaning (Hydrophilic Treatment, HPL Treatment)

[0071] Samples used for coating experiments were cleaned and stored as follows:

[0072] Open the gas bottle and connect the O.sub.2 plasma cleaner and the valve to plasma. Press the pump button and wait until the pressure is lower than 8*10.sup.2 mbar to switch on the gas. Give more gas flow (until 4-5*10.sup.1 mbar) and wait 5 minutes. Lower the gas flow to 1*10.sup.1 mbar and press the Generation button. Make sure that the parameters are set to 4 minutes (or two cycles of 2 minutes) and 35 W. Turn flow to 0 and switch off the gas. Stop pumping and open the chamber (Ventilation button). Take the samples holders from inside. Place the samples to be cleaned. Start cleaning procedure. Measure the contact angle of 3 samples to make sure that the process was successful (contact angle must be of a value of 0 degrees).

Coating ProcedureDiscs

[0073] The sample was dipped in the dipping solution for 3 minutes on the coating beakers under sonication, placed on a Teflon mesh, placed in a shaker at 150 rpm for three minutes to get a more homogeneous coating and dried. The drying was carried out with recirculating air at 55 C. for 15 minutes in order to dry the coating on the samples.

[0074] Storage: the samples were stored in 24 well plates under laminar flow if no EO sterilization was performed.

Coating ProcedureImplants

[0075] Same procedure as for disks, with the following exceptions: No implants holder was used. They were submerged one by one in the coating solution and taken out with ceramic tweezers. Further, the implants were not placed in a Teflon mesh for trying, but directly in the implants primary package.

Static Contact Angle

[0076] The experimental procedure was carried out according to DIN 55660-2:2011-12. Usually, the static contact angles were determined using a sessile drop test with ultrapure water (EasyDrop DSA20E, Kruss GmbH). The water droplets with a size of 0.1 L for hydrophilic and 0.3 L for hydrophobic discs of 5 mm diameter were dosed using an automated unit. Values for contact angles were calculated by fitting a circular segment function to the contour of the droplet placed on the surface.

[0077] Contact angles were determined for two different cases: (a) without washing the protection layer away and (b) after rinsing the samples with UPw for 15 seconds followed by blow drying in a stream of air in order to remove the coating.

[0078] As shown in FIGS. 6a to 6c, the protective layer according to the present invention can be produced in a reproducible manner. It was shown that neither the coating duration (30 seconds vs 180 seconds; FIG. 6a) nor the volume of the coating solution (2 ml vs 12.5 ml; FIG. 6b) has a significant influence on the static contact angle (SCA). In addition, it was shown that other surfaces, such as machined instead of SLA, showed improved wettability, and therefore higher hydrophilicity than the non-coated machined surfaces. (Fig. FIG. 6c).

[0079] Further, in FIG. 8a it is shown that an increase of the keratin hydrolyzate concentration (1 mg/mL for KerL vs. 30 mg/mL for KerH) does not change the hydrophilicity (no EO sterilization, n=1 measurement, t=1 week, protective layer not washed). As shown in FIG. 8b other protection layers (such as glucose) at low concentration (1 mg/mL) cannot provide with the desired contact angles under 25.

[0080] Among the investigated protective layers at low concentrations only the discs coated with low-concentration keratin hydrolyzate could fulfil the criteria of having a contact angle below 25 without additional washing step performed by the clinical, ensuring sufficient hydrophilicity of the surface at the time of implantation (FIG. 9; static contact angle of protective layers at low concentration (1 mg/mL) and keratin layer at low and high concentrations (1 mg/mL vs. 10 mg/mL); EO sterilization; n=2 samples; t=4 weeks). If higher concentrations of sugary protection layers were used, such as fructose at 30 mg/mL, lower contact angles were also seen, even though longer storage times involved showed possible sugary layers deteriorement (FIG. 10; static contact angle of protective layers at 4 and 52 weeks storage time; EO sterilization; n=3 samples; PL not removed).

Dynamic Contact Angle

[0081] Following the Wilhelmy plate method by means of a tensiometer (Lauda TE 3, Lauda Dr. R. Wobser GmbH & Co. KG), when a solid is submerged into a liquid and afterwards extracted from the liquid, the surface tension can be calculated from the necessary force that is needed for that specific solid.

[0082] The dynamic contact angle performed on coated ZLA implants showed that a coating with keratin hydrolyzate resulted in superhydrophilic implant surfaces, significantly outperforming their counterparts.

Thickness Estimation by Microbalance

[0083] Effective microroughness values calculated using the 3D roughness values to be determined according to relevant procedure defined by Straumann Research with a low-pass Gaussian filter at 30 m cut-off. Values of non-coated samples are used for all calculations, since that is the available surface for a coating.

[00001]$\mathrm{Thickness}=\frac{\mathrm{weight}}{\mathrm{Area}*\mathrm{density}}*\left(\frac{1+\mathrm{eff}.\mathrm{microroughness}}{100}\right)$

Samples Preparation Before Weight Measurement

[0084] The samples have to be dried before weight measurement (15 minutes in the oven at 55 C.; afterwards 110 C. for 40 minutes).

[0085] The weight difference of the discs before and after coating resulted in the following thickness estimation:

TABLE-US-00001 Estimated Protective thickness Density layer (nm) (mg/mm.sup.3) FruMgH 1349.54 1.03 KerMgL 66.40 1.06 GluMgH 615.54 1.01 DexMgH 618.50 1.1

Surface Microroughness

[0086] Since the samples have a specific micro surface roughness after sandblasting and acid etching, depending on the coating, the specific roughness parameters will change. These parameters are defined by the ISO 25178:

[0087] Ssk (AU): Skewness represents the symmetry of the surface heights in relation to the mean plane. If the parameter is larger than 0, peaks are predominant in front of valleys, while if the parameter is smaller than 0, valleys are predominant.

[0088] Sa (m) and Sz (m) Arithmetic mean height and maximum height represent a measure of the surface texture, containing information about the peaks and valleys, as well as information about the spacing in among those surface characteristics.

[0089] Sdr (m): Developed interfacial area ratio represents the percentage of additional surface area that has to be added in relation to a complete flat surface without a texture.

[0090] Before analyzing the samples, they should be shortly rinsed under Argon gas in order to remove dust from the environment.

[0091] Parameters used: (objective lens: 20/0.45Mplan FL N; horizontal step distance: 0.22 m; illumination: 70% exposure time/algorithm/quality: 28.5 ms/quick/max; gain: 1.5 dB).

[0092] In FIG. 7 the surface roughness Sa is shown with respect to the the keratin layer and the concentration thereof. A higher keratin concentration results in a decrease of Sa pointing to a flatter surface. In addition, FIG. 7b shows the effect of keratin and fructose on the surface roughness for implant materials. In the absence of any coating, Sa is mainly in the range of 0.4 to 0.6 m. Introduction of keratin results in a maintenance of the surface microroughness, while introduction of fructose layer results in a typical out of range SLA microroughness.

[0093] Microroughness measurements of the coated implants, specifically Sa values, were compared between the apex (tip of the implant) and the 6th thread starting from the apex of the implant (FIG. 7b). In a qualitative examination, differences between the uncoated surface (FIG. 11a) and the surface coated with the protective layer (FIG. 11b) show that they both have a lot of hills and valleys at different heights.

Packaging Climatic Stress Cycle Applied to Y-TZP Materials

[0094]

TABLE-US-00002 TABLE 1 Climatic conditions (with tolerance limits) to be applied Relative Temp Time Humidity Step Cycle ( C.) (h) (RH, %) 1 Ambient 23 6 30-80 2 Hot-wet 50 16 95 3 Ambient 23 1 50 4 Cold 33 16 Not controlled 5 Ambient 23 1 50 6 Hot-dry 60 16 10

[0095] In order to check if the protective layers would be damaged under critical conditions during their storage, the cycle in Table 1 was applied after EO sterilization and the contact angle of the samples was measured and compared to the contact angle of the samples without going under this stress cycle.

[0096] As shown in FIG. 9, overall, no effect due to climatic stress could be detected (tendency of the contact angle to increase, i.e. more hydrophobic).

Kinetic Aging Test

[0097] Aging parameters are established according to ASTM F1980-16

[0098] Accelerated Aging of Sterile Barrier Systems for Medical Devices.

[0099] At 2=30, the higher intensity for the tetragonal phase was measured, with a depth of approximately 9.4 m. The maximum depth penetration in the sample was about 20 m, depending on the specific sample and if the mentioned was coated or not. The measure was performed from 10 to 40 incident ray degree

Sterility Test

[0100] In order to test if the coatings provide antimicrobial activity, each sample was incubated in Lysogeny broth with E. coli bacteria. E. coli was pre-cultured one day before the infection start. At the time of the infection, a dissolution of the bacteria in fresh media to reach a concentration of 1*106 bacteria/mL were incubated (to test the amount of bacteria, Optical Density (OD) at 600 nm was measured and adjusted to 0.001). A control group was added, where no sample was added. From this control, the number of bacteria after 1 day is measured and compared to the samples of interest.

[0101] The bioburdent test consists of 7 days incubation of the samples in a LB media. Afterwards, OD-values of medium are taken to quantify the bacterial growth. If bacteria is observed, plating for CFU determination is needed.

[0102] Each protective layer was analyzed with three different replicates.

Sterility Test in BBF SteriXpert

[0103] All samples were EO sterilized before analysis. The PLs were not removed, but cultivated in the media, so that sterilization was tested on the surface of the discs and in the dissolved components of the protective layers.

[0104] A caso broth was incubated at 30 C. in aerobic conditions during 14 days. Different media was used for each sample. Afterwards, visual analysis was performed to see if there were bacterial growth in the caso, according to ISO 11737-2. The analyzed microorganisms were the following: [0105] Aerobic spore forming bacteria [0106] Staphylococci [0107] Micrococci [0108] Moulds [0109] Yeasts

[0110] In this case, one replicate was used for each PL.

Blood Wettability of Implants

[0111] As a proof of concept, the implants were dipped into blood. The blood was obtained fresh, and the implants were dipped into the blood for 10 seconds at the speed of 0.166 mm/second. After keeping for 6 minutes the implants in the blood (at 1.66 mm depth), the uncoated implant did not wet with blood media. Keratin layers quickly adsorbed blood, which resulted in an increasing quick red coloration of the threads from the apex upwards (after one minute it was already at the maximum blood adsorption).

[0112] Figure . . . Blood wettability of implants after 6 minutes made at the DCA instrument (at 1.66 mm depth from the first contact to the apex). (a) NoCoating (b) KerL