KR101283780B1 - Titanium implant and preparation method thereof - Google Patents

Abstract

The present invention relates to a titanium implant and an implant produced by the method for producing the same. Specifically, the titanium implant in which the nanotube layer is formed by the anodization step is first placed in a first aqueous sodium hydrogen phosphate (NaH 2 PO 4) solution, a second aqueous sodium hydrogen phosphate (Na 2 HPO 4) solution, or a first aqueous ammonium phosphate solution ((NH 4) H 2 PO 4). To be deposited. The implant is then second submerged in saturated aqueous Ca (OH) 2 solution. The first deposition and the second deposition are repeated. The titanium implant having the first and second nanotube layers formed thereon promotes the production of hydroxyapatite (HA), thereby improving the bone adhesion and providing an implant with improved biocompatibility.

Description

Titanium implant and preparation method thereof

The present invention relates to a titanium implant and a method for producing the same.

An implant is a biomedical medical instrument that is embedded in a living body and exerts its desired function. Therefore, the implant must not only have mechanical strength to withstand repeated loads and instantaneous pressures, but also satisfy conditions such as biocompatibility and chemical compatibility.

Therefore, the most widely used materials of implant materials are titanium and some titanium alloys which are excellent in biocompatibility. Titanium has a low specific gravity and is relatively lighter than other metal materials. However, it can be improved in strength by using alloys of other metals or by proper treatment. It has a very large corrosion resistance. In addition, since there is an advantage that the adhesion (osteointegration) with the bone when embedded in the bone is currently being used most widely as an implant material.

However, the oxide film layer formed naturally in the air has a drawback that pitting corrosion is likely to occur because the thickness is too thin and not dense. For this reason, various surface treatment methods have been introduced in order to form a dense passivation film on the surface of the titanium implant and to promote bonding with the bone and induce stress distribution.

Thread formation, sand blasting, electrochemical oxidation, etc. are performed to increase mechanical retention, and anodization, plasma spraying, and alkali treatment are performed to improve the bonding properties with bone along with formation of a coating layer having excellent corrosion resistance. And surface treatment such as ion implantation are performed.

The research on the method of forming the film layer of the titanium dioxide nanotube structure by the double anodization has been actively conducted. This method is a method of electrochemically treating titanium in an aqueous electrolyte solution to form a dense titanium dioxide nanotube layer having a completely self-aligned form on the surface of titanium, thereby obtaining an oxide layer having a uniform thickness regardless of the surface shape. By controlling factors such as voltage, current, electrolyte composition and pH, the length and diameter of the nanotubes can be controlled in a certain range, as well as economic advantages.

In recent years, studies have been actively conducted to impart bioactivity to these nanotube layers and to further promote bone adhesion.

When the titanium implant according to the present invention and the titanium implant prepared by the method for manufacturing thereof are embedded in a living body, calcium phosphate coated on the surface is mediated to accelerate bone formation by accelerating the production of hydroxyapatite (HA, Hydroxyapatite) It will provide an implant with further improved suitability.

The titanium implant according to the present invention is characterized in that the implant body of the titanium material, the hydroxyapatite coating layer formed on the surface of the implant body and the titanium of the surface of the implant body is oxidized to include a titanium dioxide (TiO 2) nanotube layer.

In addition, it characterized in that it further comprises a calcium phosphate layer formed on the titanium dioxide nanotube layer.

A titanium implant according to another aspect of the present invention includes an implant body of titanium material and a titanium phosphate layer formed on the surface of the implant body by oxidizing the titanium dioxide (TiO 2) nanotube layer and the titanium dioxide nanotube layer. Characterized in that.

In addition, it characterized in that it further comprises a hydroxyapatite coating layer formed on the surface of the implant body.

In addition, the titanium material is characterized in that the titanium alloy.

According to another aspect of the present invention, there is provided a method for manufacturing a titanium implant, by oxidizing a surface of an implant body made of titanium (Ti) or a titanium alloy, thereby forming a titanium dioxide (TiO 2) nanotube layer on the surface of the implant body. And forming a calcium phosphate layer on the surface of the implant body in which the titanium (TiO 2) nanotubes are formed on the surface.

In addition, prior to forming the titanium dioxide (TiO 2) nanotubes, the implant body includes a RBM (Resorbable blasted media) treatment or SLA (Sandblast Large grit Acid etch) treatment.

In addition, the step of forming the calcium phosphate is the implant, which has undergone the step of forming a nanotube, the first sodium hydrogen phosphate (NaH 2 PO 4) aqueous solution, the second sodium hydrogen phosphate (Na 2 HPO 4) aqueous solution or the first ammonium phosphate aqueous solution ((NH 4) H 2 PO 4) The first immersion step of immersing in one or two or more aqueous solution selected from the group consisting of the first immersion step and the first immersion step of washing the implant with distilled water and the implant after the first washing step Ca (OH) 2 And a second washing step of dipping in a saturated aqueous solution and a second washing step of washing the implant that passed through the second deposition step with distilled water, and repeating the implants that went through the second washing step in the above steps.

In addition, the step of forming the calcium phosphate is a first washing step of immersing the implant that passed through the first washing step in a saturated aqueous solution of Ca (OH) 2 and a first washing step of washing the implant that passed through the first deposition step with distilled water One or two selected from the group consisting of an aqueous solution of sodium hydrogen phosphate (NaH 2 PO 4), aqueous sodium dihydrogen phosphate (Na 2 HPO 4), or aqueous ammonium monophosphate ((NH 4) H 2 PO 4) And repeating the second and the second washing step and the second and second implants are washed with distilled water.

In addition, the concentration of the first sodium hydrogen phosphate (NaH 2 PO 4) aqueous solution, the second sodium hydrogen phosphate (Na 2 HPO 4) aqueous solution or the first ammonium phosphate aqueous solution ((NH 4) H 2 PO 4) is characterized in that 0.01 to 0.5M.

The titanium implant according to the present invention is a titanium implant that promotes bone adhesion and improves biocompatibility.

In addition, the method for producing a titanium implant according to the present invention is a method for producing a titanium implant to promote bone adhesion and improved biocompatibility.

1 is a FE-SEM picture of a titanium implant according to the present invention.
FIG. 2A is a FE-SEM photograph of the machined surface of the titanium implant used in Example at a magnification of 2000 ×. FIG.
FIG. 2B is a FE-SEM photograph of the surface of a titanium implant treated with hydroxyapatite (HA, hydroxyapatite) coated in Example at a magnification of 2,000 ×.
3A is a FE-SEM photograph of the surface observed at a magnification of 5000 times after the anodizing step performed in the example.
4A to 4B are photographs of the tube shape observed at a magnification of 100,000 times by destroying the nanotube layer formed on the surface after the anodization treatment performed in the embodiment.
FIG. 5A is a FE-SEM photograph of the surface of Comparative Example 1 observed at 5,000 times, and FIG. 5B is a FE-SEM photograph of the A point of FIG. 5A observed at × 50,000 times.
FIG. 6A is a FE-SEM photograph of the surface of the embodiment observed at 5000 times, and FIG. 6B is a FE-SEM photograph of the B point of FIG. 6A observed at 50,000 times.
7 is a graph showing the results of measuring the rotational force when removing the implant of Example and Comparative Example 2.
Figure 8a is a photograph of the surface of such implant specimens after removal of the implant according to Comparative Example 2 by FE-SEM, Figure 8b is a view of the surface of such implant specimens after removing the implant according to the embodiment FE-SEM It is a photograph.

Accordingly, the present inventors made a intensive research effort to improve the prior art, and after forming a titanium dioxide nanotube layer on the surface of the implant by anodization, the calcium phosphate layer was formed through repeated calcification treatment. When implanted in this way is implanted in the living body is calcium phosphate layer formed by the repeated calcification step is mediated to produce hydroxyapatite (HA, Hydroxyapatite), thereby promoting bone adhesion and further improving biocompatibility After confirming that the present invention was completed, the present invention related to a titanium implant and an implant manufactured by the method for producing the same was completed.

Specifically, the present invention first performs an anodization step, and may include a resorbable blasted media (RBM) treatment or a sandblast large grit acid etch (SLA) treatment to increase the contact area with bone before the anodization step. In addition, pickling may be included to remove any oxide film that may be present before the anodization step. This anodization step is carried out using a solution of glycerol containing ammonium fluoride and water as an aqueous electrolyte solution. In this case, the anode is made of a material of an implant on which the titanium dioxide (TiO 2) nanotube layer is to be formed, that is, titanium or a titanium alloy, and the cathode is any one selected from the group consisting of platinum, tungsten, and silver.

In order to coat calcium phosphate on the titanium dioxide nanotube layer formed by the anodizing step, at least one selected from the group consisting of aqueous sodium hydrogen phosphate solution, second sodium hydrogen phosphate solution or aqueous ammonium phosphate solution and saturated calcium hydroxide An aqueous solution is used to carry out the calcification steps.

In the anodization step, the amount of ammonium fluoride is preferably 0.3 to 2 parts by weight, and the amount of water is preferably 10 to 30 parts by weight. If the concentration of ammonium fluoride is less than 0.3 parts by weight or more than 2 parts by weight, the nanotube structure becomes incomplete. When the amount of water is less than 10 parts by weight or more than 30 parts by weight, the length of the nanotubes formed on the surface of the implant may be too long, and damage may occur in preparation and placement of the implant.

In addition, the reaction conditions of the anodization step is carried out in the constant voltage constant current mode, the current density is a constant current density of 5 to 50mA / ㎠ so that the final voltage reaches 10 ~ 50V, the final voltage condition is maintained for 10 minutes to 2 hours Do it.

In addition, the titanium or titanium alloy used as an anode in the anodizing step is not only easy to machine by a CNC (Computeried Numerical Control) lathe, but also relatively lighter than other metals, made of an alloy with other metals, or The treatment can increase the strength. Also, in the air or underwater

It is desirable to form a very dense and excellent remodeling passivation oxide film layer has a very large corrosion resistance, and when the bone is embedded in the bone, the adhesion to the bone is good because it has high osteointegration. Meanwhile, the titanium alloy includes Ti-6Al-4V, Ti-6Al-7Nb, Ti-13Nb-13Zr, Ti-15Mo, Ti-35.3Nb-5.1Ta-7.1Zr or Ti-29Nb-13Ta-4.6Zr You can use any one selected from.

In addition, in the anodizing step, when a constant voltage is applied to the electrolyte solution under constant current conditions, a thin oxide film layer having a thickness corresponding to the applied voltage is formed. Subsequently, the surface is activated by decomposition of fluorine ions liberated from the soluble fluorine compound contained in the electrolyte solution, and a large number of pores are generated, and then the current is equalized due to the slight increase in the current and the interference between the pores. It grows into dense structured nanotubes with high self-aligned form at equilibrium while sharing.

The calcification repeating step is anodizing in one aqueous solution selected from the group consisting of a first aqueous sodium hydrogen phosphate (NaH 2 PO 4), a second aqueous sodium hydrogen phosphate (Na 2 HPO 4), or a first aqueous ammonium phosphate ((NH 4) H 2 PO 4). After the first deposition of the implant on which the titanium dioxide nanotube layer is formed for 10 to 60 seconds, the implant is first washed again in distilled water for 5 to 30 seconds. Thereafter, the implant is again immersed in a saturated aqueous Ca (OH) 2 solution for 10 to 60 seconds, and the implant is then second washed in distilled water for 5 to 30 seconds. Thereafter, the above steps are repeated in the order of first deposition, first washing, three second deposition, and second washing. The order of the first deposition and the second deposition may be reversed in the repeated calcification process.

The concentration of the first aqueous solution of sodium hydrogen phosphate (NaH 2 PO 4), the second solution of sodium hydrogen phosphate (Na 2 HPO 4) or the first solution of ammonium phosphate ((NH 4) H 2 PO 4) in the calcification iteration is preferably 0.01-0.5 M. When the concentration of the first aqueous sodium hydrogen phosphate (NaH 2 PO 4), the second aqueous sodium hydrogen phosphate (Na 2 HPO 4) or the first ammonium phosphate aqueous solution ((NH 4) H 2 PO 4) is 0.01 M or less or 0.5 M or more, calcium phosphate is formed on the implant surface. Over-produced titanium dioxide nanotube layers may not be too thickly coated or tightly bonded to the TiO 2 layer, resulting in damage during implant placement.

In addition, one solution selected from the group consisting of aqueous sodium hydrogen phosphate (NaH 2 PO 4) solution, second sodium hydrogen phosphate (Na 2 HPO 4) solution or first ammonium phosphate solution ((NH 4) H 2 PO 4) in the calcification iteration treatment step and Ca (OH) 2) The temperature of the saturated aqueous solution is maintained at 50-90 ° C, and the repetition of the process in the calcification iteration step is carried out in the range of 10 to 100 times.

Hereinafter, the present invention will be described in detail with reference to the preferred embodiments, which will be readily apparent to those skilled in the art to which the present invention pertains. The present invention may, however, be embodied in many different forms and should not be construed as limited to the embodiments set forth herein.

Example :

To increase the contact area with the bone, the implant is subjected to hydroxyapatite (HA) coating before anodizing. Titanium implants with a diameter of 2 mm Ⅹ 4 mm in length were prepared for HA-hydroxyapatite (HA) coating, and then mixed with hydroxyapatite so that the ratio of bioabsorbable average particle diameter of 100-150㎛ and 90㎛ was 50:50 parts by weight. (HA, hydroxyapatite) powder was sprayed at a pressure of 4 atm. Thereafter, in order to remove any possible oxide film, the pickling treatment was performed with 20% HNO 3 aqueous solution for 10 minutes, and then ultrasonically washed with acetone and alcohol solution for 5 minutes and dried. Thereafter, the solution was pickled again for 10 seconds in a solution in which HNO 3, HF, and H 2 O were mixed at 12: 7: 81 parts by weight.

Then, as an anodization step, an implant specimen and a platinum plate were respectively connected to the anode and the cathode of the DC electrostatic source device. The two electrodes were placed in the electrolyte solution so as to face each other at a position about 20 mm apart. After that, the voltage was raised to 20V under a current density condition of 20 mA / cm 2 and maintained for 1 hour under constant voltage conditions. The electrolyte solution was prepared by mixing 79 g of glycerol, 20 parts by weight of tertiary distilled water, and 1 part by weight of NH 4 F.

Thereafter, 100 mL of 0.05M NaH 2 PO 4 aqueous solution was prepared for repeated calcification treatment and maintained at 80 ° C., and a saturated 100 mL solution of Ca (OH) 2 was prepared to maintain the temperature at 100 ° C. The calcification repeated treatment step was then first immersed in 0.05 M NaH 2 PO 4 aqueous solution at 80 ° C. for 1 minute. After that, the first washing was performed for 5 seconds in deionized water at 25 ° C. Thereafter, the solution was second deposited in a saturated aqueous solution of Ca (OH) 2 at 100 ° C. for 1 minute. Thereafter, the mixture was second washed in deionized water at 25 ° C. for 5 seconds. This calcification treatment step was carried out by repeating the process 20 times.

The implant was then placed in an electric furnace (Ajeon Industrial Co, Ltd, Korea) to remove impurities from the surface of the implant, which had undergone structural stabilization and calcification repeated steps of the anodized titanium dioxide (TiO2) nanotube layer. The rate was raised to 500 ° C. at 10 ° C./min and held for 2 hours.

Comparative example :

Comparative example  One

An aqueous 0.05 M NaH 2 PO 4 solution and a saturated aqueous solution of Ca (OH) 2 were prepared, and the implant was then deposited for the same time as in Example, but the calcification treatment step was not repeated, and the remaining steps were performed in the same manner as in Example.

Comparative example  2

The surface of the implant was treated in the same manner as in the Examples, except that the implant was not subjected to the anodization step and the calcification repetition step performed in the above examples, and to hydroxyapatite (HA, Hydroxyapatite) coating and pickling treatment.

Experimental Example :

< Experimental Example  1> Examples and Comparative example  1 of Hydroxyapatite ( HA , Hydroxyapatite ) Precipitation  Comparison of bioactivity according to whether or not

In order to compare the precipitation pattern and biocompatibility of hydroxyapatite (HA) with and without repeated calcification step, the following experiment was performed with the implant according to Example 1 and Comparative Example 1.

Specifically, to investigate biocompatibility, the pH and inorganic ions were immersed in a simulated body fluid (SBF) for 3 days, and then precipitated from hydroxyapatite (HA). Investigate. All specimens were autoclaved at 120 ° C. for 20 minutes and then deposited in SBF and maintained for 5 days in a 37 ° C., 5% CO 2 atmosphere incubator. SBF is 0.185 g / L calcium chloride dehydrate, 0.09767 g / L magnesium sulfate, sodium hydrogen carbonate in Hanks solution (H2387, Sigma Chemical Co, USA) Prepared by adding 0.350 g / L, the pH was adjusted to 7.4 using 1N HCl aqueous solution.

Table 1 below shows the results of energy dispersive spectroscopy (EDS) analysis on the surfaces of Comparative Example 1 and Example 1 according to the present experiment.

As shown in Table 1, the concentrations of Ca and P, which are the basic components of bone, were shown to be greatly increased in Example 1 compared to Comparative Example 1.

In addition, the implants according to the Example and Comparative Example 1 after performing these experiments were observed through a field emission scanning electron microscope (FE-SEM, S800, Hitachi, Japan).

5A is a FE-SEM photograph of the surface of Comparative Example 1 observed at 5000 times, and FIG. 5B is a FE-SEM photograph of the A point of FIG. 5A observed at 50,000 times. In Comparative Example 1, known titanium dioxide Only the nanotube layer was observed, and no apparent precipitation pattern of hydroxyapatite (HA) was observed.

On the other hand, Figure 6a is a FE-SEM picture of the surface of the embodiment observed at × 5000 times, Figure 6b is a FE-SEM picture of the B point of Figure 6a by × 50,000 times, in the embodiment hydroxyapatite (HA, In the early stage of precipitation of hydroxyapatite, the appearance of protrusion structure over the entire surface was observed.

Therefore, it can be seen from the results of the example that the calcification repeated treatment step was performed to produce hydroxyapatite (Hydroxyapatite, HA) on the implant surface in comparison with Comparative Example 1. Therefore, it can be seen that the biocompatibility of the Example is higher than that of Comparative Example 1.

< Experimental Example  2> Examples and Comparative example  Rotational force at removal after implant implantation of 2 ( Torque Through measurement Osteoadhesiveness  Comparative experiment

Eight implants prepared according to the examples were placed on the distal side of both tibia diaphysis of four rats to test their ability to bind with bone. General anesthesia was performed by injecting ketamine and xylazine with 80-100 mg / kg and 10-20 mg / kg, respectively, and 2% lidocaine with epinephrine (1: 100,000). Additional local anesthesia was performed at the surgical site. The hair at the surgical site was shaved off, sterilized using a betadine scrub, and elevated with a full-plate valve. The implant was placed by penetrating the implant embedding site to a depth of 4 mm with a 1.5 mm diameter surgical drill. After implant placement, soft tissue was sutured with absorbent sutures and amoxicillin antibiotics were orally administered 1 ml / kg. After 4 weeks, the torque was measured when the implant was removed using a digital torque gauge (9810P, Aikoh Engineering Co, Japan) having a precision of 0.1 Ncm after the sacrifice of the test animal.

7 is a result of measuring the rotational force when removing the implant of Example and Comparative Example 2 according to the present experiment. According to this, in the comparative example 2, 10.8 +/- 3.7 N * cm was shown and 28.1 +/- 2.4 N * cm in the Example. Through this, it was confirmed that the statistically significant difference between the Example and Comparative Example 2 (P <0.01). Therefore, in the case of the embodiment it is necessary to have a higher rotational force when removing the implant placed, it can be seen that the case of the embodiment is increased bone adhesion than the case of Comparative Example 2.

< Experimental Example  3> Examples and Comparative example  2 of Surface cohesion  Comparative experiment

In addition, the implant according to the Example and Comparative Example 2 after the experiment according to Experimental Example 2 was observed through a field emission scanning electron microscope (FE-SEM, S800, Hitachi, Japan). That is, FIG. 8A is a photograph of the surface of such an implant specimen observed by FE-SEM after measuring the rotational force when removing the implant according to Comparative Example 2, and FIG. 8B illustrates the removal of the implant according to the embodiment. The surface of the implant specimen removed after the rotational force was measured by FE-SEM. In Comparative Example 2, the new bone was broken from the implant specimen in the removed implant surface, but the new bone was attached and aggregated in the implant surface in spite of the fracture of the removed implant surface. That is, when the implant is manufactured according to the embodiment including the calcification iteration process step, it was found that the surface cohesion between the surface-treated material and the implant is improved compared to the case of manufacturing the implant according to Comparative Example 2.

< Experimental Example  4> Examples and Comparative example  2 of EDS  Comparison of biocompatibility according to experimental results

After performing the experiment according to Experimental Example 2, the EDS experiment for Example and Comparative Example 2 was carried out. Table 2 below shows the results.

As can be seen in Table 2, the concentration of Ca and P was confirmed that Example 1 was higher than in Comparative Example 2. Therefore, it could be confirmed that the case of Example is higher biocompatibility than the case of Comparative Example 2.

While the present invention has been particularly shown and described with reference to exemplary embodiments thereof, it is to be understood that the invention is not limited to the disclosed exemplary embodiments, but, on the contrary, is intended to cover various modifications and equivalent arrangements included within the spirit and scope of the appended claims. It is natural.

Claims (10)

Implant body made of titanium;
Hydroxyapatite coating layer;
A titanium dioxide (TiO ₂ ) nanotube layer formed by oxidizing titanium on the surface of the implant body; And
It includes; calcium phosphate layer,
Titanium implant, characterized in that the hydroxyapatite coating layer, titanium dioxide nanotube layer and calcium phosphate layer is sequentially stacked on the surface of the implant body.
delete Implant body made of titanium;
A titanium dioxide (TiO 2) nanotube layer formed by oxidizing titanium on the surface of the implant body; And
Contains a calcium phosphate layer;
The titanium implant, characterized in that the titanium dioxide nanotube layer and the calcium phosphate layer is sequentially stacked on the surface of the implant body.
delete The method according to claim 1 or 3,
Titanium implant, characterized in that the titanium material is a titanium alloy.
(a) oxidizing the surface of the implant body of titanium (Ti) or titanium alloy material to form a layer of titanium dioxide (TiO 2) nanotubes on the surface of the implant body; And
(b) forming a calcium phosphate layer on the surface of the implant body on which the titanium dioxide (TiO 2) nanotubes are formed;
Titanium implant manufacturing method comprising a.
The method according to claim 6,
A method for manufacturing a titanium implant, characterized in that the implant body is subjected to RBM (Resorbable blasted media) treatment or SLA (Sandblast Large grit Acid etch) treatment before forming the titanium dioxide (TiO 2) nanotubes.
The method according to claim 6,
Forming the calcium phosphate layer is
(a) The implant, which has undergone the step of forming the nanotubes, may be treated with an aqueous solution of sodium hydrogen phosphate (NaH ₂ PO ₄ ), aqueous solution of sodium hydrogen phosphate (Na ₂ HPO ₄ ), or aqueous solution of ammonium phosphate ((NH ₄ ) H). A first deposition step of immersing in one or two or more aqueous solutions selected from the group consisting of ₂ PO ₄ );
(b) a first washing step of washing the implant that has undergone the first deposition step with distilled water;
(c) a second deposition step of immersing the implant passed through the first washing step in a saturated aqueous solution of Ca (OH) ₂ ;
(d) a second washing step of washing the implant that has undergone the second deposition step with distilled water; And
(e) repeating the implants subjected to the second cleaning step in steps (b) to (e);
Titanium implant manufacturing method characterized in that.
The method according to claim 6,
Forming the calcium phosphate layer is
(a) a first deposition step of immersing the implant passed through the first washing step in a saturated aqueous solution of Ca (OH) ₂ ;
(b) a first washing step of washing the implant that has undergone the first deposition step with distilled water;
(c) The implants having undergone the step of forming the nanotubes may be treated with a _first aqueous sodium hydrogen phosphate (NaH ₂ PO ₄ ) solution, a second aqueous sodium hydrogen phosphate (Na ₂ HPO ₄ ) solution, or an aqueous first ammonium phosphate solution ((NH ₄ ) H A second deposition step of depositing in at least one aqueous solution selected from the group consisting of ₂ PO ₄ );
(d) a second washing step of washing the implant that has undergone the second deposition step with distilled water; And
(e) repeating the implants subjected to the second cleaning step in steps (b) to (e);
Titanium implant manufacturing method characterized in that.
10. The method according to claim 8 or 9,
The concentration of the first sodium hydrogen phosphate (NaH 2 PO 4) aqueous solution, the second sodium hydrogen phosphate (Na 2 HPO 4) aqueous solution or the first ammonium phosphate aqueous solution ((NH 4) H 2 PO 4) is 0.01 to 0.5M method of producing a titanium implant.

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