KR101278740B1 - Implants comprising water glass coating layer and preparation method thereof - Google Patents

Abstract

PURPOSE: An implant including a silicate glass coated layer and a manufacturing method thereof are provided to maintain excellent cell adhesive ability by forming pure silica on the implant surface by an acid etching process after silicate glass coating. CONSTITUTION: An implant including a silicate glass coated layer comprises a main body including titanium or a Ti alloy; and a silicate glass layer coated on the surface of the main body. The silicate glass layer is formed by acid-etching. The implant is an implantable material for use in dentistry, orthopedic surgery, dental surgery, or plastic surgery. The weight ratio of silica and alkali salt of the silicate glass is 1:1-4. The acid is selected from a group consisting of sulfuric acid, hydrochloric acid, phosphoric acid, acetic acid, and nitric acid.

Description

Implants Comprising Water Glass Coating Layer and Preparation Method Thereof

The present invention relates to an implant comprising a water glass coating layer excellent in cell adhesion and a method for producing the same.

In order to use the metal material in vivo, it has to be excellent in biocompatibility without toxicity or carcinogenicity, no side effects or rejection of the human body, and good mechanical properties such as tensile strength, elastic modulus and abrasion resistance. Strong corrosion resistance must be available to withstand the corrosive environment created. Therefore, in consideration of these requirements, suitable biomaterials include stainless steel, cobalt-based alloys, titanium, and alloys thereof.

In particular, titanium is widely used as an implant material in consideration of mechanical strength and corrosion resistance, and titanium reacts with oxygen when the surface is exposed to air in the process of being processed into an implant. Titanium oxide film is formed. However, such an oxide film is thin and sometimes breaks, and thus, surface strength and abrasion resistance are reduced, and corrosion resistance is also affected, resulting in a loss of function as a biomaterial.

Therefore, recently, in order to improve such a problem, technologies for improving the biostability as well as excellent corrosion resistance and wear resistance by modifying the surface of the implant material are being developed. Research on the development of surface treatment technology for biocompatibility and support for biocompatible tissue engineering is also in progress. Among them, techniques for modifying the surface of the implant, in particular, to provide a biocompatible implant is receiving high attention. Looking at the related arts related to this, it has a stable osteoadhesion performance over a long period of time in Korea Patent No. The surface treatment method of the implant, the film produced by the surface treatment method and the contents of the implant having the membrane is disclosed, the Republic of Korea Patent No. 675573, the biocompatibility, cell compatibility and Disclosed is a method of surface modification by forming a porous calcium phosphate thin film to have a surface having excellent bone conductivity.

Water glass is a material that is known to allow easy adhesion to substrates even with adhesives and heating at relatively low temperatures. In addition, silica glass, which is a kind of water glass, releases water-soluble silica in an aqueous solution, has a large number of silanol functional groups on its surface, and in particular, silanol groups on the surface are known to act as crystal nuclei of hydroxyapatite in the liquor. The inventors of the present invention studied the coating method of the implant using the water glass, and confirmed that the cell adhesion ability is improved through the surface properties of the implant prepared according to the method of the present invention and completed the present invention.

The present invention is to provide an implant and a method of manufacturing the excellent water-coated coated biocompatibility.

The present invention for solving the above problems provides an implant comprising a body comprising a titanium or titanium alloy and a water glass layer coated on the surface of the body.

In one embodiment of the present invention, the water glass layer may be acid-etched.

In another aspect, the present invention comprises the steps of pretreating the implant body comprising a titanium or titanium alloy; Coating water glass on the pretreated implant body; And it provides a method for producing an implant comprising the step of heat treatment.

The implant according to the present invention induces fast and powerful osteointegration and osteoinductive surface properties, which is useful for human implantable medical devices to be performed on patients in the areas of dentistry, orthopedics, oral surgery and plastic surgery. Can be. In particular, the pure silica is formed on the surface of the implant by the acid etching process after the water glass coating can be maintained even more excellent cell adhesion.

1 is a flow chart of the manufacturing process of the embodiment of the present invention.
2 is a FE-SEM photograph of the surface shape of the surface-treated Ti disk.
FIG. 3 is a graph of the surface behavior for hydroxyapatite (HA) blasted titanium (B), NaOH etched titanium (BN) after HA blast treatment and titanium (BNH) performed up to heat treatment.
4 is a FE-SEM photograph of each sample prepared according to the conditions of Table 1.
FIG. 5 is a graph of the Si / Na ratios of samples coated and heat treated at three different concentrations (10, 15, 20 vol%) of water glass and the number of coatings (1 to 3 times).
6 is a graph of Si content of a sample coated with three different concentrations (10, 15, 20 vol%) of water glass and the number of coatings (1 to 3 times) and subjected to HCl etching.
FIG. 7 is a graph showing the Si / Ti ratios of water glass at three different concentrations (10, 15, and 20 vol%) and samples coated with the number of coatings (1 to 3 times) and samples subjected to HCl etching. .
8 is an XPS analysis result graph for analysis of surface OH groups.
9 is a TF-XRD pattern results graph for the BNH, W15-3 and W15-3e samples of Table 1. FIG.
10 is a fluorescence image 5 days after cell culture as a result of cell adhesion and proliferation assay for each sample.

The present invention provides an implant comprising a body comprising titanium or a titanium alloy and a water glass layer coated on the surface of the body.

In one embodiment of the present invention, the water glass layer may be acid-etched.

The inventors of the present invention, while studying the surface treatment method of the implant for human insertion with excellent bone regeneration ability, it was confirmed that the surface adhesion with water glass improves the cell adhesion ability, in particular if the acid etching process after water glass coating Pure ion is formed on the surface of the surface by the ion exchange, and as a result, the cell proliferation is smoothly increased as the surface hydroxyl group increases, thereby completing the present invention.

As used herein, the term “implant” refers to an implant or insert made to replace lost biological tissue or to function as tissue in vivo. Individuals to be transplanted include humans, but include non-human animals.

In one embodiment of the invention, the implant may be a human insert for dental, orthopedic, oral surgery or plastic surgery.

The water glass (liquid sodium silicate) coated on the implant body including the titanium or titanium alloy may be of various kinds, but the weight ratio of the alkali salt and silica is preferably 1: 1-4, or 1: 2-3. There is no limitation, and the pH is preferably about 10-11. In addition, the viscosity of the water glass is a very important factor in the uniformity, economy and workability of the coating, the preferred viscosity of the water glass in the present invention when tested by Ford Cup # 4 (about 35 to 36 seconds at 18 ℃) It is desirable to be. When the viscosity of the water glass is smaller than the above range, the coating on the titanium alloy material is not good, and when it is thicker than this, there is a problem in that a uniform coating film is difficult to form.

Examples of an acid for etching the coated water glass may be any one or more selected from the group consisting of sulfuric acid, hydrochloric acid, phosphoric acid, acetic acid, and nitric acid, and preferably hydrochloric acid (HCl) may be used. .

After the water glass coating, an ion exchange reaction between the alkali salts present on the surface and the hydrogen of the acid is performed on the water glass by the surface etching process using an acid to form pure silica to form hydroxyl groups on the surface.

Therefore, referring to the following examples, the implant comprising a water glass layer or an acid-etched water glass layer of the present invention contains a large amount of hydroxyl groups on the surface, there is an advantage that the adhesion of the cells is easy.

In another aspect, the present invention comprises the steps of pretreating the implant body comprising a titanium or titanium alloy; Coating water glass on the pretreated implant body; And it provides a method for producing an implant comprising the step of heat treatment.

In one embodiment of the present invention, the pretreatment step is, for example, the surface-resorbable Blasting Media (RBM) method using surface-absorbent spray particles, sand-blasted large grit, and acid etched after blasting in acid ) Surface treatment method, heat treatment at temperature above 300 ° C, or anodizing (anodizing), acid treatment and surface heat treatment after base treatment, etc. can be used in the market or research commonly used, such as the surface treatment method described above In the case of a titanium or titanium alloy material, the pretreatment step may be omitted.

In addition, the pretreatment step is more specifically, blasting with hydroxyapatite powder; And it may include a step of heat treatment after the acid and base treatment, but is not limited thereto.

The acid and base treatment steps of the pretreatment step may be performed in an ultrasonic bath containing an acid and a base aqueous solution, respectively, and the heat treatment may be performed at 300 to 900 ° C. or 400 to 700 ° C., but is not limited thereto. Through the pretreatment process, the surface roughness of the implant body including titanium or titanium alloy is increased, so that the adhesion of the water glass coating layer can be more closely performed without air bubbles or cracks.

Water glass (liquid sodium silicate) used in the manufacturing method of the present invention may be of various kinds, but the weight ratio of the alkali salt and silica is preferably 1: 1-4 or 1: 2-3, but is not limited thereto. Is preferably about 10 to 11. In addition, the viscosity of the water glass is a very important factor in the uniformity, economy and workability of the coating, the preferred viscosity of the water glass in the present invention when tested by Ford Cup # 4 (about 35 to 36 seconds at 18 ℃) It is desirable to be. When the viscosity of the water glass is smaller than the above range, the coating on the titanium alloy material is not good, and when it is thicker than this, there is a problem that it is difficult to form a uniform coating film.

The coating of the water glass on the surface of the pretreated implant body may use a coating method generally used in the art, and specifically, spin coating, sputtering coating, chemical vapor deposition, dipping, and the like may be used, but is not limited thereto.

More specifically, the process of coating the water glass solution of 5 to 3 vol% using a spin coater for 30 seconds to 5 minutes may be repeated 1 to 5 times.

Thereafter, a heat treatment step of the coated water glass is performed. The heat treatment may be performed at 200 to 500 ° C. or at 200 to 400 ° C. for 1 to 5 hours or 1 to 3 hours, but is not limited thereto.

In one embodiment of the invention, an acid etch step may be further performed after the heat treatment step.

Examples of the acid of the acid etching step are not limited thereto, and any one or more selected from the group consisting of sulfuric acid, hydrochloric acid, phosphoric acid, acetic acid and nitric acid may be used, and preferably hydrochloric acid (HCl) may be used.

More specifically, the acid etching may be performed for 10 minutes to 3 hours, 30 minutes to 2 hours, or 30 minutes to 90 minutes in an ultrasonic bath containing 0.01 to 5M, 0.01 to 3M, or 0.01 to 1M of the acid aqueous solution. have.

BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, the present invention will be described in detail with reference to the following examples. However, the following examples are intended to illustrate the contents of the present invention, but the scope of the present invention is not limited to the following examples. Embodiments of the present invention are provided to more fully describe the present invention to those skilled in the art.

< Manufacturing example > Water Glass Coating-Acid Etched Ti  Manufacture of discs

Purely titanium discs (grade 4) were polished with SiC grit paper. The polished samples were blasted using 250-300 μm hydroxyapatite powder and washed with an aqueous 1 vol% HCl solution to remove impurities and hydroxyapatite residues on the surface of the cp-Ti disc in an ultrasonic bath for 2 minutes. The sample was washed again to remove HCl residues on the titanium disk surface in the ultrasonic bath. The washed samples were etched with alkali treatment for 24 hours with 5M NaOH solution and washed in an ultrasonic bath. The washed samples were heated at a temperature increase rate of 5 ° C. per minute and then heat treated at 600 ° C. for 1 hour. The manufacturing process of the above titanium substrate is shown in FIG.

The heat-treated samples 10, 15 and 20 vol% of water glass _{(WG, mNa 2 O · nSiO} 2 · (100-mn) H 2 O, m = 9.0 ~ 10.0, n = 28 ~ 30.0, S-Chemtec, Korea) solution Using a spin coater was coated for 1 minute at 5000rpm each. The coating was repeated once, twice and three times on the titanium substrate using the respective waterglass solution. The dried water glass coated Ti disks were heated at a temperature increase rate of 5 ° C. per minute and then heat-treated at 300 ° C. for 2 hours. After the heat treatment, the samples were etched in an ultrasonic bath for 1 hour with 0.1 M HCl aqueous solution, and Si-OH functional groups were formed on the Ti disk through etching of Na ₂ O of water glass.

In order to compare the surface properties and cell adhesion, various samples were prepared as shown in Table 1 below. In Table 1, Sample B is a Ti disk blasted with 250 ~ 300μm hydroxyapatite powder, Sample BN is a sample subjected to the etching process with 5M NaOH to Sample B, Sample BNH is a sample BN at 600 ℃ 1 hour Is a sample in which a heat treatment process was performed. Samples W15-1, W15-2 and W15-3, which are Examples 1 of the present invention, were coated once, twice and three times at 15 vol% WG on sample BNH, and then heat-treated at 300 ° C. for two hours. Samples W15-1e, W15-2e and W15-3e, which are Example 2 of the present invention, are samples in which 0.1M HCl was treated to each of samples W15-1, W15-2 and W15-3.

Sample name Blast B BN BNH WG coating (Example 1) W15-1 W15-2 W15-3 HCl etching (Example 2) W15-1e W15-2e W15-3e

< Experimental Example  1> Surface Characterization

One. SEM  Photo analysis

The FE-SEM photograph of the surface shape of the surface-treated Ti disk is shown in FIG. Referring to FIG. 2, the hydroxyapatite (HA) blasted titanium (B) showed a macro rough surface, and the NaOH etched titanium (BN) after the HA blast treatment and the titanium (BNH) performed up to the heat treatment were A wide range of surface roughnesses were shown, ranging from macro roughness to micro roughness. Macro roughness is produced by the hydroxyapatite powder blast, and micro roughness is believed to be due to 5M NaOH etching and heat treatment (for BNH samples).

Surface profiles and mean surface roughness values (R _a ) for hydroxyapatite (HA) blasted titanium (B), Na etched titanium after HA blast treatment (BN) and titanium (BNH) performed up to heat treatment, respectively. 3 and Table 2. From the measured average surface roughness values (R _a ), it can be seen that the NaOH etching and heat treatment processes form a surface micro rough surface to increase the average roughness of the blasted Ti sample by a small amount.

Sample B (μm) BN (μm) BNH (μm) Average Roughness (R _a ) 6.555 7.495 7.848

FIG. 4 is an FE-SEM photograph of each sample manufactured according to each condition of Table 1, and referring to FIG. 4, it can be seen that the water glass coated layer is well adhered without air bubbles or cracks between the glass layer and the Ti surface. . In addition, the thickness of the water glass layer was increased as the vol% of the water glass and the number of coatings increased (W15-1, W15-2, W15-3). The samples (W15-1e, W15-2e, and W15-3e) etched with 0.1 M HCl on a water glass coated titanium disk showed slightly different surface properties, which were the sodium silicates (mNa ₂ O · nSiO ₂₎ present on the water glass surface. ) layer is determined by since, due to the etching of the HCl eluted mNa ₂ O and hayeotgi changed to pure silica.

2. EDS  analysis

The sodium silicate layer was formed on the titanium disk surface by water glass coating and heat treatment at 600 ° C. for 2 hours. In order to obtain a pure silica layer on the titanium surface, the composition of the water glass coating layer was changed from sodium silicate to pure silica by ion-exchange through a 1-hour treatment of 0.1M HCl aqueous solution. To identify mNa ₂ O eluted from the sodium silicate layer, EDS analysis was performed before and after HCl treatment on water glass coated samples.

The Si / Na ratios of the samples coated and heat-treated at three different concentrations (10, 15, 20 vol%) of water glass and the number of coatings (1 to 3 times) are shown in FIG. 5. The Si / Na ratio was expected to be constant, but was expected to increase with increasing the concentration of water glass and the number of water glass coatings. Therefore, the increase in the Si / Na ratio is believed to be due to the partial evaporation of Na ₂ O during the heat treatment.

Si content of a sample coated with water glass at three different concentrations (10, 15, 20 vol%) and the number of coatings (1 to 3 times) and subjected to HCl etching is shown in FIG. 6. Referring to FIG. 6, the Si content was also increased as the concentration of water glass and the number of water glass coatings were increased.

FIG. 7 is a graph showing the Si / Ti ratios of water glass at three different concentrations (10, 15, and 20 vol%) and samples coated with the number of coatings (1 to 3 times) and samples subjected to HCl etching. . It was shown that the Si / Ti ratio increased as the concentration of water glass and the number of water glass coatings were increased for both water glass only samples (A, B) and samples performed up to HCl etching. This is because the detection frequency of Si increased compared to the Ti detection frequency due to the increase in the water glass concentration and the number of water glass coatings.

3. XPS  analysis

The formation of Si-OH functional groups on the surface of titanium was confirmed by X-ray photoelectron spectroscopy (ULVAC-PHI, Japan). For the qualitative and quantitative analysis of Si-OH groups, trifluoroacetic anhydride The saturated steam of (TFAA) was reacted with the hydroxy group on the Ti surface for 15 minutes at 25 ° C. so that the OH group on the surface was replaced with F ions. Then, the F ion concentration of TFAA on the Ti substrate was measured by XPS.

The results for XPS spectrum and F content are shown in FIG. 8. Referring to FIG. 8, the amount of hydroxy groups represented by the fluorine content was found to increase as the concentration of water glass and the number of coatings were increased.

4. XRD  analysis

In order to identify the phase present on the surface of the Ti disk, the surface layer of the fabricated sample was measured using TF-XRD (thin-film X-ray diffraction, PANalytical, Netherlands).

9 is a TF-XRD pattern results graph for the BNH, W15-3, and W15-3e samples of Table 1. FIG. Referring to FIG. 9, in the BNH sample, it can be seen that a thin sodium titanate layer was formed on the titanium disk surface. The Ti peak intensity was found to be reduced in the W15-3 sample, which is believed to be due to the Ti disk surface being coated with water glass. Judging from the large hill-shaped peaks and low peak intensities, the water glass layer is considered to consist mainly of uncrystallized material, while crystalline phases such as sodium silicate and SiO ₂ are present in the water glass coating layer of the W15-3 sample. Appeared. HCl treated sample W15-3e showed a different chemical composition than the W15-3 sample, where the sodium silicate peak disappeared and a strong silica peak was detected. Therefore, the XRD pattern result graph suggests that ion exchange occurred between Na ⁺ ions of the water glass layer and H ⁺ ions of HCl due to the surface treatment of HCl.

< Experimental Example  2> Cell Attachment and Proliferation Assay

Mesenchymal stem cells (MSCs) obtained from human donors were used for cell adhesion and proliferation analysis. MSCs were cultured in DMEM (Gibco-BRL, MD, USA) containing 10% FBS (Gibco-BRL) and 2-3 cells were used for cell experiments. Ti disks treated with ethylene oxide (EO) gas were placed in each well of a 12 well plate and 1 ml of cell suspension (4 × 10 ³ cells / ml) was added to each well. After 2 hours, 1 day and 5 days of incubation each disk set was harvested and fixed for 20 minutes with 3.7% paraformaldehyde. Cell nuclei were stained with 100 nM / ml DAPI (Sigma, MO, USA). Nine random sites were selected and the stained nuclei were visualized by fluorescence microscopy (Leica DM 6000B, Germany) using a UV filter (360 nm). Using the i-solution software (IMT i-Solution Inc., BC, Canada), cell nuclei for each site were counted and expressed as mean ± SD values for each site.

Fluorescence images 5 days after cell culture for each experimental sample are shown in FIG. 10.

Referring to FIG. 10, it was found that the proliferation of MSC cells on the water glass-coated titanium surface was increased compared to the groups without water glass (B, BN, BNH), and proportionally increased as the concentration of the coated water glass increased. Proliferation also increased.

In addition, HCl-treated (or Na ₂ O etched) samples showed the most increased MSC cell proliferation due to the hydroxyl groups formed on the surface of the waterglass coated Ti, and proliferated proportionally as the concentration of the coated waterglass increased. It was also found to increase. Therefore, the cell proliferation ability is affected by the presence or absence of the water glass coating layer, the thickness of the coating layer (or the number of coating and the concentration of the water glass to be coated) and the number of surface hydroxy functional groups, the presence of the water glass coating layer, the number of water glass coating and the concentration of the water glass to be coated As the surface hydroxyl group increases through HCl treatment, the cell proliferation was smoothly achieved.

While the present invention has been particularly shown and described with reference to exemplary embodiments thereof, it is to be understood that such detail is solved by the person skilled in the art without departing from the scope of the invention. will be. Accordingly, the actual scope of the present invention will be defined by the appended claims and their equivalents.

Claims (12)

An implant comprising a body comprising titanium or a titanium alloy and a water glass layer coated on the surface of the body. The method of claim 1,
The water glass layer is acid-etched implant. The method according to claim 1 or 2,
The implant is a human implant for dental, orthopedics, oral surgery or plastic surgery. The method of claim 1,
The water glass implant is a weight ratio of the alkali salt and silica is 1: 1-4. The method of claim 2,
The acid is any one or more selected from the group consisting of sulfuric acid, hydrochloric acid, phosphoric acid, acetic acid and nitric acid. Pretreating the implant body comprising titanium or titanium alloy;
Coating water glass on the pretreated implant body; And
Method for producing an implant comprising the step of heat treatment. The method according to claim 6,
The method of manufacturing an implant further comprising the step of acid etching after the heat treatment step. The method according to claim 6,
The pretreatment step
Blasting with hydroxyapatite powder; And
Method for producing an implant comprising the step of heat treatment after acid treatment and base treatment. The method according to claim 6,
The water glass is a method of producing an implant in which the weight ratio of alkali salts and silica is 1: 2-3. The method according to claim 6,
The heat treatment step is a method for producing an implant that is performed for 1 to 5 hours at 200 to 500 ℃. The method of claim 7, wherein
The acid of the step of acid etching is any one or more selected from the group consisting of sulfuric acid, hydrochloric acid, phosphoric acid, acetic acid and nitric acid. The method of claim 7, wherein
The acid etching step is performed for 10 minutes to 3 hours in an ultrasonic bath containing 0.01 to 5M acid aqueous solution.

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