WO2018124375A1

WO2018124375A1 - Method for manufacturing implant having hydrophilic surface

Info

Publication number: WO2018124375A1
Application number: PCT/KR2017/001371
Authority: WO
Inventors: 김주석; 권미경; 이현아
Original assignee: 주식회사 네오바이오텍
Priority date: 2016-12-30
Filing date: 2017-02-08
Publication date: 2018-07-05
Also published as: KR20180078620A

Abstract

Disclosed in this disclosure is a method for manufacturing an implant having a hydrophilic surface which provides superior osseointegration or cell attachment properties by performing an SLA treatment and a hydrothermal treatment on an implant made of titanium or a titanium alloy to form CaTiO₃ on the surface of the implant.

Description

Method for preparing an implant having a hydrophilic surface

The present invention relates to a method of making an implant having a hydrophilic surface. More specifically, the present invention relates to a method for manufacturing an implant that can provide improved bone adhesion or cell adhesion properties by treating the implant surface of titanium through the combination of a plurality of treatment processes.

In dentistry, implants are implanted in the upper and lower jaw in place of natural teeth that are lost in the areas where the teeth are missing. Implant materials, design, surface characteristics, bone mass and bone quality, surgical procedures, loading conditions and the oral environment of patients can be exemplified as factors influencing the function of the implant and stable bone adhesion. Therefore, when the implant is implanted into the alveolar bone in the oral cavity, it is necessary to select a material having good biocompatibility with respect to the living tissue, so as to select a material having no side effects with the living tissue. In this connection, metal materials such as titanium (or titanium alloy), cobalt alloy, stainless steel, platinum, iridium, niobium, tantalum and the like can be used.

Among the metals exemplified above, titanium (Ti) or titanium alloy is a material having good biocompatibility and corrosion resistance, and when used as an implant material, the dissolution rate is slow and the dissolved product is chemically inert, thereby allowing the growth of bone and Bone adhesion occurs at the interface. However, titanium or titanium alloys generally do not have direct bonding with bone tissue due to bioinertness. For this reason, various attempts have been made to increase the success rate of the implant and to shorten the healing time by applying the bioactive material to the surface of the metallic implant by applying a surface treatment to the implant. As such, the surface treatment imparting activity to the surface of titanium or titanium alloy can reduce the period of fixation to the alveolar bone because it can induce rapid bone adhesion without causing inflammation in the alveolar bone.

Recently, due to the rapid development of nanotechnology, a method of forming a nanostructured oxide layer on a metal surface such as titanium in the implant material field has been studied. In this regard, the homogeneous nanotube TiO ₂ layer has been reported to be beneficial to the bone adhesion because it expands the specific surface area in contact with the bone, the bone adhesion reaction by the hydroxyapatite (HAp) coating method is a titanium surface There is a problem that peeling easily occurs in the thick film layer because the strong bonding between the coating layer and the coating layer is difficult.

Alternatively, the calcification circulation treatment method, which has a similar effect to the HAp coating method and can form a thin film layer, is used, and surface treatments such as chemical acid treatment, injection treatment using fine particles, anodization treatment, and plasma injection treatment are performed. Techniques to stabilize the formation of blood clot at the interface between the implant and bone, promote differentiation of osteoblast cells, and improve bone healing around the implant early after the procedure are known.

As such, there is a continuing need for implant surface treatment techniques with high wettability (or hydrophilicity) or superior adhesion and stability to induce faster initial fusion.

The present disclosure is to provide a surface treatment method for producing a titanium-based implant having excellent bone adhesion properties with improved properties, specifically hydrophilicity and stability compared to the conventional surface treatment technology of titanium or titanium alloy implants .

According to one embodiment of the invention,

a) providing an implant of titanium or titanium alloy material;

b) sandblasting and acid etching (SLA) the implant surface;

c) separately, preparing an electrolyte containing a calcium ion source; And

d) forming CaTiO ₃ on the surface of the SLA-treated implant by hydrothermally reacting the SLA-treated implant in the presence of the electrolyte solution;

Provided is a method of making an implant having a hydrophilic surface.

In an exemplary embodiment, the calcium ion source may be CaO, CaCl ₂ or a combination thereof.

In an exemplary embodiment, the electrolyte may include a mixture of 0.005 to 0.05 M CaO aqueous solution and 3 to 8 M CaCl ₂ aqueous solution.

In an exemplary embodiment, the hydrothermal reaction may be carried out for 1 to 6 hours at a temperature of 150 to 250 ℃ and pressure conditions of 15 to 25 bar.

According to an exemplary embodiment, the water contact angle of the surface of the implant passed through step d) may be 20 ° or less.

According to an exemplary embodiment, the contact angle of the implant surface of the titanium or titanium alloy material provided in step b) may be at least 100 °.

The method for producing an implant having a hydrophilic surface according to an embodiment of the present disclosure is such that the implant of titanium or titanium alloy material has excellent bone adhesion or cell adhesion properties by combining a plurality of surface treatment steps with improved hydrophilicity and stability. Provide advantages.

Therefore, broad commercialization is expected in the future.

1 is a view showing a schematic process sequence of the surface treatment method of a titanium-based implant according to an embodiment of the present invention;

2A and 2B each show scanning electron microscopy (SEM) photographs showing the microsurface of titanium disks surface-treated (or coated) according to Example 1 and SLA-treated titanium discs according to Comparative Example 1 in Example 2; ego;

3A and 3B are diagrams showing contact angle measurement results of titanium disks surface-treated (or coated) according to Example 1 and SLA-treated titanium disks according to Comparative Example 1 in Example 3;

FIG. 4A shows test results by crystal violet staining after cell adhesion for titanium disks surface-treated (or coated) according to Example 1 and SLA-treated titanium disks according to Comparative Example 1 in Example 4; FIG. A graph representing; And

4B is a photograph staining osteoblasts attached to the titanium disk surface-treated (or coated) according to Example 1 and the SLA-treated titanium disk according to Comparative Example 1 in Example 4.

The present invention can all be achieved by the following description. The following description is to be understood as describing preferred embodiments of the invention, but the invention is not necessarily limited thereto. In addition, the accompanying drawings are for ease of understanding, and the present invention is not limited thereto. Details of individual components may be appropriately understood by specific gist of the related description to be described later.

In the present specification, when "includes" any component, it means that it may further include other components and / or steps, unless stated otherwise.

1 shows a schematic process sequence of the surface treatment method of a titanium-based implant according to an embodiment of the present invention. Hereinafter, the individual steps constituting the entire process will be described in detail.

SLA Treatment Steps for Titanium Implants

According to one embodiment of the present disclosure, an implant of titanium material is used. In this case, the titanium-based implant may be made of pure titanium or titanium alloy. In this regard, titanium alloys include (i) titanium (Ti) and (ii) aluminum (Al), silicon (Si), vanadium (V), niobium (Nb), zirconium (Zr), molybdenum (Mo), and chromium. (Cr), tin (Sn), tantalum (Ta), and palladium (Pd) may be made of a combination of metals selected from at least one. Specific examples of titanium alloys include Ti-6Al-4V, Ti-6Al-7Nb, Ti-13Nb-13Zr, Ti-8Al-1Mo-1V, Ti-6Al-6V-2Sn, Ti-35.3Nb-5.1Ta-7.1Zr , Ti-29Nb-13Ta-4.6Zr, Ti-29Nb-13Ta-2Sn, Ti-29Nb-13Ta-4.6Sn, Ti-29Nb-13Ta-6Sn, Ti-16Nb-13Ta-4Mo, Ti-6Al-5Zr-0.5 Mo-0.2Si, Ti-6Al-2Sn-4Zr-2Mo-0.08Si, Ti-5.5Al-3.5Sn-3Zr-1Nb-0.5Mo-0.3Si, Ti-6Al-3Sn-4Zr-0.5Mo-0.5-Si , Ti-4Al-4Mo-2Sn-0.5Si, Ti-4Al-4Mo-4Sn-0.5Si, Ti-6Al-2Sn-4Zr-6Mo, Ti-3Al-8V-6Cr-4Zr-4Mo, Ti-15Mo-3Nb -3Al-0.2Si, Ti-15V-3Cr-3Sn-3Al or Ti / Pd.

In one embodiment, the sandblasted, large grit, acid etched (SLA) treatment method typically results in micro grit sand blasting on the surface of the titanium alloy to form micron level surface roughness, followed by acid etching ( acid etching) to further form a finer micron surface roughness. As a result, the surface area of the titanium implant is increased, so that pores of various sizes formed on the surface may form a sponge-like network structure.

According to one embodiment, ceramic particles, specifically alumina particles, are sprayed onto the surface of the titanium implant for sandblasting. In this case, the average particle diameter (size) of the ceramic particles may be, for example, about 100 to 550 μm, specifically about 140 to 500 μm, and more specifically about 180 to 425 μm. In addition, the injection pressure may range from, for example, about 1 to 10 atm, specifically about 2 to 7 atm, more specifically about 3 to 5 atm. For this purpose, sandblasting equipment known in the art can be used, which can be connected to a pressurized air circuit and configured to spray ceramic grit.

As such, the biocompatibility of the titanium implant is increased to some extent by sandblasting, and the surface of the titanium implant may be subsequently cleaned or cleaned using pressurized air and / or ultrasonic waves.

Subsequently, a process of treating the sandblasted titanium surface with the acid composition is performed, where the acid composition may contain hydrochloric acid and sulfuric acid.

The aforementioned sandblasting and acid etching conditions are provided for illustrative purposes, and the present invention is not necessarily limited thereto.

After completion of the above-described SLA treatment process, a subsequent process of washing to remove residual acid components, washing by ultrasonic wave and then drying may be performed.

Preparation Steps of the Electrolyte Solution

According to one embodiment of the present disclosure, a hydrothermal reaction or treatment using a basic electrolyte may be additionally performed on the surface of the SLA-treated titanium implant. To this end, a basic electrolyte is prepared separately, which contains a calcium ion source. The calcium ion source can be specifically CaO, CaCl ₂ or a combination thereof, more specifically a combination of CaO and CaCl ₂ . In this connection, CaO is effective to facilitate the coating of components (that is, CaTiO ₃ coating layer) formed on the surface of titanium based upon a subsequent hydrothermal reaction Meanwhile, CaCl ₂ offers a good bioactivity (bioactivity).

In an exemplary embodiment, the electrolyte is about 0.005 to 0.05 M (specifically about 0.008 to 0.04 M, more specifically about 0.01 to 0.03 M) aqueous CaO solution and about 3 to 8 M (specifically about 3.5 to 7 M) And, more specifically, about 4-6 M) of a CaCl ₂ aqueous solution.

Hydrothermal reaction stage

According to one embodiment, as described above, the SLA treated titanium implant is hydrothermally reacted in the presence of an electrolyte containing a calcium ion source. This hydrothermal reaction can be carried out by the following Scheme 1.

Scheme 1

Ti + 2H ₂ O → TiO ₂ + 2H ₂

TiO ₂ + 2H ₂ O → Ti (OH) ₄

Ti (OH) ₄ + Ca ²⁺ → CaTiO ₃ + 2H ⁺ + H ₂ O

According to the above reaction formula, the calcium ion supplied from the electrolyte reacts with TiO ₂ formed on the implant surface to form CaTiO ₃ , and thus CaTiO ₃ can be advantageously applied under oral environment because it has good stability as well as hydrophilicity. .

In an exemplary embodiment, the temperature of the hydrothermal reaction can be adjusted, for example, within the range of about 150 to 280 ° C, specifically about 160 to 250 ° C, more specifically about 180 to 220 ° C.

In addition, the reaction pressure may, for example, be in the range of about 4 to 40 bar, specifically about 10 to 35 bar, more specifically about 15 to 25 bar. In this regard, the inside of the reactor is provided with an inert gas, for example helium, argon, xenon, nitrogen and the like can be used.

In addition, the hydrothermal reaction can be carried out, for example, over about 1 to 6 hours, specifically about 2 to 5 hours, more specifically about 3 to 4 hours. However, the present invention is not limited to the above reaction conditions.

After completion of the hydrothermal reaction, the titanium-based implant treated in the subsequent process may be washed with water (eg, ultrapure water) and injected into alcohol (eg, ethanol) to perform ultrasonic cleaning. This cleaning and washing process can be performed once or twice or more.

As described above, a CaTiO ₃ layer is formed on the surface of the titanium-based implant where the hydrothermal reaction is completed, thereby increasing hydrophilicity. By way of example, the water contact angle of the surface of the titanium implant before the hydrothermal reaction is low hydrophilic, for example at least about 100 °. On the other hand, the water contact angle of the titanium-based implant surface-treated according to the present embodiment may be, for example, about 20 ° or less, specifically about 15 ° or less, more specifically about 13 ° or less. As a result, adhesion characteristics with surrounding tissues can be significantly improved even after oral transplantation.

The present invention can be more clearly understood by the following examples, which are only intended to illustrate the present invention and are not intended to limit the scope of the invention.

Example 1

Preparation of Surface Treated Implants

-SLA surface treatment

Commercially available 10 mm × 1.6 mm titanium disks were used as specimens. For SLA treatment, the ceramic particles were sprayed at 3 atm with an average particle diameter of 70 μm with a gap of 3 cm between the nozzle and the surface of the titanium disc, then placed in pure water, ultrasonically cleaned for 10 minutes, and dried with compressed air. Then, macro-micropores were formed on the surface of the titanium disc by an acid treatment method using an aqueous mixed acid solution of hydrochloric acid and sulfuric acid. And ultrasonic washing with distilled water and dried.

Hydrothermal reaction

SLA surface treated titanium disks were fastened to the jig. Separately, 0.02 M aqueous CaO solution and 5.4 M aqueous CaCl ₂ solution were prepared, followed by stirring for 15 minutes. CaO aqueous solution and CaCl ₂ aqueous solution were mixed in a volume ratio of 1: 1, and stirred for another 15 minutes to prepare an electrolyte solution.

After preparing the electrolyte solution, a titanium disc having a jig fastened in a Hastelloy hydrothermal reactor was deposited on the prepared electrolyte solution. Thereafter, an argon atmosphere was formed in the reactor by purging three times with argon gas, and subjected to hydrothermal reaction for 3 hours under a reaction temperature of 200 ° C. and a reaction pressure of 20 bar.

After the hydrothermal reaction was completed, the jig was taken out to clean the treated titanium disc in ultrapure water, and ultrasonic cleaning was performed for 30 minutes in ethanol (aqueous solution). The ultrasonically cleaned jig in ethanol was transferred to ultrapure water and then further ultrasonically washed and dried for 60 minutes to obtain a surface treated titanium disc.

Comparative Example 1

A titanium disk surface-treated in the same manner as in Example 1 was obtained except that no hydrothermal reaction was performed.

Example 2

Micro Surface Analysis of Specimens

The microsurface shape of the titanium disks prepared in each of Example 1 and Comparative Example 1 was observed by Scanning Electron Microscopy (SEM), and the results are shown in FIGS. 2A and 2B. According to the drawings, it can be seen that an additional coating layer is formed while the SLA treated surface is maintained by the hydrothermal reaction.

Example 3

Hydrophilicity test

In order to evaluate the hydrophilicity of the titanium disk surface prepared in each of Example 1 and Comparative Example 1, the contact angle was measured, and the results are shown in Figures 3a and 3b. In this regard, the contact angle measurement was performed by measuring the contact angle of the analogous liquid formed on the surface of the specimen using a static drop method. For accurate contact angle measurement, pictures were taken with equipment equipped with a video camera, and the average values were obtained after measuring left and right contact angles.

According to Figure 3a, the contact angle of the titanium disk surface-treated according to Example 1 was 104.718 °, whereas the contact angle of the titanium disk surface-treated according to Comparative Example 1 was measured to 12.766 °, the surface treatment according to Example 1 It can be seen that the hydrophilicity of the titanium disk surface is significantly increased through.

Example 4

Cell adhesion test

The cell adhesion test was performed on the titanium disk surface-treated according to each of Example 1 and Comparative Example 1. The osteoblasts (MG63 cell) to each of the titanium disk was attached to one ㅧ 10 ⁴ cell / 100 ㎕. After 3 hours, the degree of attachment of osteoblasts to the specimens was measured at 595 nm by ELISA Reader using crystal violet staining. As can be seen in Figures 4a and 4b, it can be seen that the titanium disk according to Example 1 increased the initial cell adhesion capacity compared to the titanium disk according to Comparative Example 1, which may be attributed to the increased hydrophilic surface Can be.

All simple modifications and variations of the present invention fall within the scope of the present invention, and the specific scope of the present invention will be apparent from the appended claims.

Claims

a) providing an implant of titanium or titanium alloy material;

b) sandblasting and acid etching (SLA) the implant surface;

c) separately, preparing an electrolyte containing a calcium ion source; And

d) forming CaTiO 3 on the surface of the SLA-treated implant by hydrothermally reacting the SLA-treated implant in the presence of the electrolyte solution;

Including, a method of producing an implant having a hydrophilic surface.
The method of claim 1, wherein the calcium ion source is CaO, CaCl 2 or a combination thereof.
The method of claim 2, wherein the electrolyte comprises a mixture of 0.005 to 0.05 M CaO aqueous solution and 3 to 8 M CaCl 2 aqueous solution.
The method of claim 1, wherein the hydrothermal reaction is performed for 1 to 6 hours under a temperature of 150 to 250 ° C. and a pressure of 4 to 40 bar.
The method of claim 1, wherein the water contact angle of the surface of the implant that has passed through step d) is 20 ° or less.
The method of claim 1, wherein the contact angle of the implant surface of titanium or titanium alloy, which has been subjected to step b), is at least 100 °.
The method of claim 1, wherein the titanium alloy is (i) titanium (Ti) and (ii) aluminum (Al), silicon (Si), vanadium (V), niobium (Nb), zirconium (Zr), molybdenum (Mo) ), Chromium (Cr), tin (Sn), tantalum (Ta) and palladium (Pd) at least one selected from the group consisting of a metal selected from the group consisting of implants having a hydrophilic surface.
The method of claim 1, wherein the step b) comprises the steps of: sandblasting the ceramic particles having an average particle diameter of 180 to 425 ㎛ by spraying pressure of 1 to 10 atm; And

Acid etching the implant surface of the sand blasted titanium or titanium alloy using an acid composition containing sulfuric acid and hydrochloric acid;

Method for producing an implant having a hydrophilic surface comprising a.
The method of claim 8, wherein the acid etching is performed at 50 to 120 ° C. for 4 to 60 minutes.