KR20200053928A - Titanium implant and method for manufacturing the same - Google Patents

Abstract

The present invention relates to a titanium implant and a manufacturing method thereof and, more specifically, to a titanium implant with improved bioactivity and bone-binding ability by maintaining excellent biocompatibility of hydroxyapatite while improving the binding ability of the hydroxyapatite to metal, and to a manufacturing method thereof. In addition, the titanium implant comprises: a titanium support; a plurality of nano-hydroxyapatite; and a bio-friendly connector.

Description

Titanium implant and method for manufacturing the same

The present invention relates to a titanium implant and a method for manufacturing the same, and more specifically, to improve the binding strength of apatite hydroxide to a metal and to maintain excellent biocompatibility of the apatite hydroxide, thereby improving the bioactivity and bone bonding strength of the titanium implant and a method of manufacturing the same. It is about.

In the early implant, materials such as polymers, metals, ceramics, and composite materials were used, but their scope gradually decreased as the concept of bone fusion was established. Natural polymers such as collagen or elastin fibers are applied to human bones and skin, but lack mechanical properties, and proteins such as collagen can cause immunological rejection. Metallic materials have similar mechanical properties to human bones, but have low biocompatibility and cause harmful reactions in the body. Ceramic materials, such as bioglass, are biohazardous, but have significant mechanical property differences. Currently, stainless steel, Cr-Co-based alloys, Ti, Ti alloys, and bioglass are mainly used as implant materials.

When foreign substances enter the body, they are recognized by the body's immune system as non-magnetic and phagocytosis by macrophages occurs. This is the target of metal ions eluted from the surface of the implant, and biocompatibility is the most important factor in implants because these reactions with immunity can develop into cancer cells. In addition, because the implant receives a combination of masticatory pressure and lateral pressure, bone bonding strength is also an important factor. Therefore, consideration should be given to the tissue compatibility of the implant material, surface properties, bone quality at the surgical site, surgical procedures, and the load applied to the implant. Among these, the surface characteristics of the implant greatly influence the bone adhesion.

Titanium or titanium alloy as an implant material has excellent mechanical strength, and has the advantage of excellent biocompatibility and corrosion resistance through the formation of a surface oxide layer. Furthermore, research is being conducted on surface treatment methods that increase the surface area of these materials to reduce postoperative healing period, and implants manufactured by these surface treatment methods can improve bone adhesion due to an increase in contact area with bone. have.

Meanwhile, hydroxyapatite is known to be a material that can be used directly in a living body because its structure and chemical composition are similar to those of dental enamel and bone. In addition, because of its excellent bioactivity and biocompatibility, it is used not only as a material for implants used for bone tissue regeneration, but also as a drug delivery system in drug and gene delivery systems. It is known as a material that promotes the growth of bone tissue due to the excellent biocompatibility and biocompatibility of apatite hydroxide. However, the apatite hydroxide material has a problem that it is difficult to use alone because of its low physical strength.

Surface treatment methods for increasing the success rate of implants include Ti plasma spray and apatite hydroxide coating. In the case of Ti plasma spray, the Ti particles coated on the surface are separated from the implant and dispersed in surrounding tissues, thereby weakening the bone binding force or causing inflammation, and the apatite hydroxide coating method is apatite hydroxide material because the process is performed at high temperature There is a problem that causes a change in properties.

Republic of Korea Patent Publication No. 10-2009-0069645

The present invention has been made in view of the above points, and has an object to provide a titanium implant having improved bioactivity and bone-binding ability by maintaining excellent biocompatibility of apatite hydroxide while simultaneously having excellent mechanical properties and a method for manufacturing the same.

In order to solve the above problems, the present invention is a titanium support having at least one selected from a carboxyl group and an amine group attached to a surface, covering the surface of the titanium support with a predetermined area, and a plurality of nano-hydroxylated apatites having a carboxyl group attached to the surface. And it provides a titanium implant comprising a carboxyl group and an amine group, a bio-friendly linker connecting the titanium support and nano-hydroxylates through peptide bonds.

According to an embodiment of the present invention, the nano-hydroxylated apatites may include at least one selected from nanoparticles having an average particle diameter of 10 to 50 nm, and nanorods having an aspect ratio of 1.2 to 20.

In addition, according to an embodiment of the present invention, the length of the nanorod may be 30 to 500 nm.

In addition, according to an embodiment of the present invention, the nano-hydroxylated apatite may be a nanorod having an aspect ratio of 1.2 to 20.

In addition, according to an embodiment of the present invention, the bio-friendly linkage may be at least one selected from oligopeptides, polypeptides and proteins including carboxyl groups and amine groups.

In addition, according to an embodiment of the present invention, the apatite hydroxide nanorods may be fixed to cover 1 to 50% of the surface area of the titanium support.

In addition, according to an embodiment of the present invention, the titanium support may have an amine group bound to the surface.

In addition, the present invention is a step of treating a titanium support with a solution containing at least one selected from succinic acid and an aminosilane-based compound to bond at least one selected from a carboxyl group and an amine group to the titanium support surface, a carboxyl group on the titanium support surface And linking the bio-friendly linker comprising an amine group by peptide bonding, treating nano-apatite with an aqueous solution containing amino acids having a succinic acid or carboxyl group and an amine group, and bonding the carboxyl group to the surface of the nano-hydroxyapatite. It provides a method for producing a titanium implant comprising the step of connecting a bio-friendly linker connected to the surface of the titanium support, and a nano-hydroxylate coupled to a carboxyl group by peptide bonding.

According to an embodiment of the present invention, the amino acid may be L-glutamic acid.

In addition, according to an embodiment of the present invention, the titanium support may be treated with a solution containing an aminosilane-based compound, and an amine group may be bound to the surface of the titanium support.

The titanium implant according to the present invention has excellent mechanical properties and at the same time maintains excellent biocompatibility of apatite hydroxide, thereby improving bioactivity and bone binding power, and accordingly, it is possible to significantly reduce the healing period after implant implantation.

1 is a schematic diagram of a method of manufacturing a titanium implant according to an embodiment of the present invention.
2A is an SEM image of a titanium support surface.
2B is an SEM image of the titanium support surface.
Figure 2c is a SEM image of the titanium support surface is apatite hydroxide nanorods are fixed to the surface.
Figure 2d is a SEM image of the surface of the titanium support is fixed apatite hydroxide nanorods on the surface.
3 is a TEM image of a hydroxide nanoparticles.
Figure 4a shows the results of the surface EDS analysis of the titanium support.
Figure 4b shows the results of the surface EDS analysis of the titanium support with an amine group bonded to the surface.
Figure 4c shows the results of the surface EDS analysis of the titanium support with an amine group bonded to the surface.
Figure 4d shows the results of the surface EDS analysis of the titanium support is fixed apatite nanorods on the surface.
5A is a fluorescence micrograph of the titanium support surface.
5B is a fluorescence micrograph of the surface of the titanium support having an amine group attached to the surface.
Figure 5c is a fluorescence micrograph of the surface of the titanium support peptide is albumin on the surface.
FIG. 6 is a graph showing XPS analysis results for a titanium support and a titanium implant with apatite hydroxide nanorods fixed on the surface.
7A is a surface SEM image of the day 1 after culturing osteoblasts on a titanium support.
Figure 7b is a surface SEM image of the day 1 after culturing osteoblasts on a titanium support with apatite hydroxide nanorods fixed on the surface.
Figure 7c is a surface SEM image of the day 3 after culturing osteoblasts on a titanium support.
Figure 7d is a surface SEM image of the day 3 after culturing osteoblasts on a titanium support with apatite hydroxide nanorods fixed on the surface.
8A is a fluorescence micrograph of the titanium support surface treated with Live / dead staining staining.
Figure 8b is a fluorescence micrograph of the surface of the titanium support with apatite hydroxide nanorods fixed on the surface, treated with Live / dead staining staining.
9A is a graph showing the results of measuring formazan absorbance for osteoblast activity in the first day of culture for a titanium support (Ti) and a titanium support (Ti-HA) with apatite hydroxide nanorods fixed on the surface.
9B is a graph showing the results of measuring formazan absorbance for osteoblast activity at day 3 of culture for a titanium support (Ti) and a titanium support (Ti-HA) with apatite hydroxide nanorods fixed on the surface.

As described above, the titanium material has excellent mechanical strength, but has low bone bonding strength, and thus is difficult to be practically used as the implant itself. In order to improve the bone bonding strength of the titanium-based implant, a method of coating a titanium hydroxide with excellent bioactivity on a titanium support can be used, but the binding strength of the apatite hydroxide to a metal is remarkably low so that the apatite particles in the human body are separated from the titanium support. There are problems.

After preparing the hydroxide apatite in a nano size, by fixing the prepared nano-hydroxyapatite on the surface of the titanium support using a bio-friendly linkage, it improves the binding strength of the apatite to a metal and maintains excellent biocompatibility of the apatite. Titanium implant has the advantage of simultaneously improving the bioactivity and bone binding capacity.

Hereinafter, exemplary embodiments of the present invention will be described in detail with reference to the accompanying drawings so that those skilled in the art to which the present invention pertains can easily practice. The present invention can be implemented in many different forms and is not limited to the embodiments described herein.

The titanium implant according to the present invention is a titanium support having at least one selected from a carboxyl group and an amine group attached to a surface, a surface of the titanium support covering a predetermined area, and a plurality of nano-hydroxylated apatites and carboxyl groups having a carboxyl group attached to the surface, and It includes an amine group, and a bio-friendly linker connecting the titanium support and nano-apatite through a peptide bond.

The titanium support may be used to secure excellent mechanical strength of the implant. The titanium support may be a conventional titanium support used as an implant material in the art, and may be, for example, a titanium disk surface-treated to improve the surface area, but is not limited thereto. In addition, the shape of the titanium support may be a shape suitable for use as an implant, for example, a screw shape, but is not limited thereto. In addition, at least one selected from a carboxyl group and an amine group may be provided on the surface of the titanium support to bind the bio-friendly linker.

The nano-hydroxylated apatite is fixed to the surface of the titanium support to improve the bioactivity and bone bonding power of the implant.

The nano-hydroxylated apatites may include at least one selected from nanoparticles having an average particle diameter of 10 to 50 nm, and nanorods having an aspect ratio of 1.2 to 20, and more preferably nano having an aspect ratio of 1.2 to 20 It can only contain rods.

When the nano-hydroxylated apatite is in the shape of a nanorod, the surface area of the nano-hydroxylated apatite is larger than that of the nanoparticles, so that the physiological activity of the bone cells is more excellent, and thus the adhesion of the bone can be significantly improved.

When the average particle diameter of the nanoparticles exceeds 50 nm, there is a fear that the surface area of the nano-hydroxyapatite decreases compared to the mass, thereby deteriorating bone adhesion, and the nanoparticles having an average particle diameter of less than 10 nm are substantially not easy to manufacture. It may not.

When the aspect ratio of the nanorods is less than 1.2, there is a possibility that the surface area of the nanohydroxyapatite decreases in mass compared to the shape of the nanoparticles, resulting in a decrease in bone adhesion, and when the aspect ratio exceeds 20, the titanium due to steric hindrance It can be difficult to bond to the support surface.

In addition, the length of the apatite hydroxide nanorods may be 30 to 500 nm. If the length of the apatite hydroxide nanorods is less than 30 nm, bone adhesion may be deteriorated, and if it exceeds 500 nm, there may be problems such as difficulty in fixing on the titanium support due to poor surface reactivity due to steric hindrance.

The nano-hydroxylate apatite may be a carboxyl group attached to the surface in order to bind with a bio-friendly linker.

In addition, the nano-hydroxylate apatite can be fixed to cover 1 to 50%, preferably 5 to 30% of the surface area of the titanium support. If the nano-hydroxylated apatite is fixed to cover less than 1% of the surface area of the titanium support, the bioactivity or bone-binding power of the implant may be lowered, and the nano-hydroxylated apatite may be physically immobilized to cover more than 50%. As a superposition, there is a fear that the nano-hydroxylated apatite is physically laminated without being connected to a titanium support.

In addition, when the nano-hydroxylated apatite covers 5 to 30% of the surface area of the titanium support, the bioactivity of the implant and bone-binding ability may be more excellent.

Referring to Figure 2d, it can be seen that the titanium implant according to an embodiment of the present invention is fixed so that the nano-hydroxylate apatite covers the surface area of the titanium support 14.6%.

The bio-friendly connecting body may serve to fix the nano-hydroxylate apatite on the surface of the titanium support. The bio-friendly linker may be at least one selected from oligopeptides comprising a carboxyl group and an amine group, a polypeptide including a carboxyl group and an amine group, and a protein including a carboxyl group and an amine group, and the carboxyl group and amine group included in the bio-friendly linker The nano-hydroxylated apatite can be fixed on the surface of the titanium support by forming a peptide bond with an amine group or a carboxyl group attached to the surface of the titanium support and a carboxyl group attached to the surface of the nano-hydroxyapatite.

More preferably, when the amine group is bonded to the surface of the titanium support, the connection efficiency of the bio-friendly linker may be further improved.

The bio-friendly linkage may be at least one selected from globulin, insulin and albumin, preferably albumin.

Next, a method for manufacturing a titanium implant according to the present invention will be described.

First, a titanium support is treated with a solution containing at least one selected from succinic acid and an aminosilane-based compound to bond at least one selected from carboxyl and amine groups to the surface of the titanium support.

Preferably, the titanium support may be treated with a solution containing an aminosilane-based compound, and in this case, a biocompatible linkage may be more readily coupled to the titanium support than when treated with a solution containing succinic acid.

The aminosilane-based compound is preferably APTES ((3-Aminopropyl) triethoxysilane).

The aminosilane-based compound and / or succinic acid may be included in the solution in an amount of 0.01 to 10% by weight, and when included in the solution in an amount of less than 0.01% by weight, an amine group and / or a carboxyl group bound to the surface of the titanium support When the amount exceeds 10% by weight, the binding efficiency of the carboxyl group and / or the amine group that is substantially bound to the amount of the aminosilane-based compound and / or succinic acid added may be insufficient.

The method for treating the solution may use a method of conventionally modifying hydroxide to an amine group or a carboxyl group, and may be, for example, an immersion method, but is not limited thereto.

The solvent included in the solution may be used without limitation as long as it is a common solvent used in the surface modification method using the aminosilane-based compound and / or succinic acid, and may be, for example, ethanol, but is not limited thereto.

Next, a bio-friendly linkage comprising a carboxyl group and an amine group is connected to the titanium support surface by peptide bonding.

The method of connecting the bio-friendly linker to the surface of the titanium support may be performed by immersing the titanium support in a solution containing the bio-friendly linker, but is not limited thereto.

Next, the nano-hydroxylate is treated with succinic acid or an aqueous solution containing an amino acid having a carboxyl group and an amine group to bind the carboxyl group to the surface of the nano-hydroxylate.

When the carboxyl group is bonded to the surface of the nano-hydroxylated apatite using the amino acid, the solution may further include a coupling agent, and the coupling agent may be used in an activation method using water-soluble carbodiimide (WSC) known in the art. The coupling agent used may be used without limitation, preferably NHS (N-hydroxysuccinimide) and EDC (1-Ethyl-3- (3-dimethylaminopropyl) -carbodiimide).

In addition, the nano-hydroxylated apatite may preferably be treated with an aqueous solution containing an amino acid having a carboxyl group and an amine group, and in this case, the binding efficiency of the carboxyl group bound to the surface of the nano-hydroxylated apatite is more than treated with an aqueous solution containing succinic acid. It can be even better.

The amino acid may be used without limitation as long as it is an amino acid having a carboxyl group in the side chain, but may preferably be L-glutamic acid. When the amino acid is L-glutamic acid, the aqueous solution containing the amino acid is 0.1 to 0.5 parts by weight of EDC (N-ethyl-N '-(3-dimethylaminopropyl) carbodiimide), 0.1 to 0.5 parts by weight of NHS (N-hydroxysuccinimide) and 0.1-0.7 parts by weight of L-glutamic acid.

Next, the titanium support to which the bio-friendly linker is connected and the nano-hydroxylate connected to the carboxyl group are connected.

The bio-friendly linker and nano-hydroxylated apatite may be chemically bound and linked by peptide bonds.

The nano-apatite hydroxide may be mixed with a solvent capable of maintaining dispersibility, for example, water, and then treated with, for example, an immersion method on a titanium support to which the bio-friendly linker is connected.

In order to cover the surface of the titanium support with an area of a desired level, the apatite hydroxide nanoparticles may be included in the solvent in an amount of 0.001 to 1% by weight in the solvent.

(Example 1)

Titanium support (Ti-) on which the surface is treated with sand blasted titanium support (Biotem Implant) (Ti) with an ethanol solution containing 1% by weight of APTES at room temperature for 4 hours at room temperature. NH ₂ ) was prepared. A solution containing albumin on the prepared titanium support was treated at room temperature for 24 hours to prepare a titanium support (Ti-A) in which albumin is peptide-bonded to the surface.

Distilled water (300ml), Ca (NO ₃ ) _{2 ·} 4H ₂ O (57.5g) and NH ₄ OH were mixed to prepare an aqueous solution of pH 10.4. Distilled water (400ml) and (NH ₄ ) H ₂ PO ₃ (19.75g) were added to the prepared aqueous solution, and the mixture was stirred at room temperature and left standing for 4 days to obtain a white powder. The obtained powder was washed with distilled water and dispersed in 1-butanol to prevent agglomeration of the powder, followed by vacuum drying. The dried powder was heat-treated at 700 ° C for 4 hours to obtain nano-hydroxyapatite (HA). The obtained nanohydroxyapatite mostly showed the shape of a nanorod.

The obtained nano-apatite hydroxide (0.6 g) was mixed with distilled water (200 ml), EDC (0.5 g) and NHS (0.5 g) at room temperature for 2 hours, and L-glutamic acid (0.55 g) was added to the mixture to add 12. The mixture was mixed for a time to prepare a hydroxide nanoparticle (HA-g) having a carboxyl group on its surface.

The aqueous solution containing HA-g was treated with Ti-A at room temperature for 24 hours to peptide-bond the amine group contained in the albumin of Ti-A and the carboxyl group of HA-g. The obtained titanium support was washed with distilled water to obtain a titanium implant (Ti-HA) with apatite hydroxide nanorods fixed on its surface.

(Comparative Example 1)

A commercial product, a titanium support (Biotem Implant) was prepared.

(Experimental Example 1) SEM analysis

The titanium support (Ti) of Comparative Example 1 and the surface of the titanium support (Ti-HA) with apatite hydroxide nanorods fixed on the surface prepared in Example 1 were observed with FE-SEM (S-4300 HITACHI), and the result was obtained. 2A to 2D.

2A and 2B are SEM images of the titanium support surface. Referring to Figure 2d, it can be seen that the apatite hydroxide nanorods cover 14.6% of the surface area of the titanium support.

(Experimental Example 2) TEM analysis

TEM analysis was performed on the nano-hydroxylated apatite (HA) prepared in Example 1, and the results are shown in FIG. 3.

Referring to FIG. 3, it can be seen that the prepared nano-hydroxylate apatite shows the shape of the nanorod, and the length of the nanorod is 30-500 nm.

(Experiment 3) EDS analysis

EDS analysis of the surface of each specimen was performed on a titanium support (Ti), a titanium support (Ti-NH ₂ ) with an amine group bonded to the surface, and a titanium implant (Ti-HA) with apatite hydroxide nanorods fixed on the surface, The results are shown in FIGS. 4A to 4D.

When comparing FIGS. 4A and 4B, it can be seen that the Si, C, and O element contents (at%) of Ti-NH ₂ increased compared to Ti, and indirectly confirm that APTES is bonded to the titanium support surface. You can.

When comparing FIGS. 4C and 4D, it can be seen that the P and Ca element contents (at%) of Ti-HA increased compared to Ti-NH ₂ , and that the apatite hydroxide nanorods were bonded to the titanium support surface. You can check indirectly.

(Experimental Example 4) Fluorescence microscopy

Fluorescence microscopy was performed on the surface of each specimen of a titanium support (Ti), a titanium support (Ti-NH ₂ ) with an amine group bonded to the surface, and a titanium support (Ti-A) with an albumin peptide bound to the surface. The results are shown in FIGS. 5A to 5C.

FITC was used to express green fluorescence by reacting with an amine group as a fluorescent material.

Referring to FIG. 5A, Ti does not express green fluorescence, while Ti-NH ₂ and Ti-A show green fluorescence as shown in FIGS. 5B and 5C. Through this, the hydroxyl group (-OH) on the surface of the titanium support (Ti) reacts with APTES to provide an amine group on the surface of the titanium support, and the point where the albumin reacts with the amine group on the surface of the Ti-NH ₂ surface and albumin is peptide-bonded. You can check indirectly.

(Experimental Example 5) XPS analysis

XPS analysis was performed on the titanium support (Ti) and titanium implant (Ti-HA) with apatite hydroxide nanorods fixed on the surface, and the results are shown in Tables 1 and 6 below.

Referring to FIG. 6, it can be seen that as a result of XPS analysis of the Ti surface, Ca and P element peaks were not observed, while the Ti-HA surface showed Ca and P element peaks.

division at% C O P Ca Ti Ti 17.82 59 0 0.53 22.66 Ti-HA 6.45 68.98 6.1 9.94 8.53

Referring to Table 1, it can be seen that the P-element is 6.1% and the Ca element is 9.94% on the Ti-HA surface, which is significantly higher than that of Ti. Can be.

(Experimental Example 6) Observation of the adhesion behavior of osteoblasts

1) FE-SEM observation

Cell adhesion was examined in vitro in order to confirm cellular suitability for titanium support (Ti) and titanium implant (Ti-HA) with apatite hydroxide nanorods fixed on the surface. After placing Ti and Ti-HA disks in a 4-Well dish, a culture medium (DMEM) having an osteoblast cell concentration of 3 x 10 ⁴ cells / ml was prepared, and cell seeding was performed by 1 ml. After incubation for 24 hours and 72 hours in a 37 ° C, 5% CO ₂ incubator, the culture solution was removed, carefully washed with PBS, and fixed with 2.5% (w / v) glutaldehyde, followed by FE-SEM image. The adhesion behavior was observed through and the results are shown in FIGS. 7A to 7D.

As a result of the first day culture, there was no significant difference in the number or activity of cells adhered to Ti (FIG. 7A) and Ti-HA (FIG. 7B). On the other hand, as a result of day 3 culture, cells adhered to Ti (FIG. 7C) exhibited a rounded shape, but cells adhered to Ti-HA (FIG. 7D) were confirmed to adhere well in a flat shape. Through this, it can be seen that Ti-HA has a good effect on cell adhesion and cell spreading.

2) Live / dead staining dye evaluation

When the apatite nanorods are introduced to the surface of the titanium support, the titanium support (Ti) and the apatite hydroxide nanorods are fixed to the surface using the Live / dead staining staining method to confirm the effect of the apatite hydroxide nanorods on the cells. Titanium implant (Ti-HA) was observed with a fluorescence microscope, and the results are shown in FIGS. 8A and 8B.

As a reagent used in this staining method, Calcein-AM, which was a non-fluorescent substance, enters the cell, reacts with an intracellular ester hydrolase (esterase), converts it to a fluorescent substance, and becomes green fluorescent, and propidium iodide (PI) is alive. Since it cannot pass through the cell membrane, it enters only dead cells whose cell membrane is damaged, and ion-bonds with the cell nucleus that exhibits negative ions, resulting in red fluorescence.

In both Ti and Ti-HA, red fluorescence by PI did not appear and only green fluorescence by Calcein-AM was expressed. Through this, it is determined that the apatite hydroxide nanorods introduced into the titanium support does not negatively affect the physiological activity of osteoblasts.

(Experimental Example 7) Evaluation of cell proliferation activity

After placing Ti and TI-HA in a 4-well dish, a culture medium (DMEM) having an osteoblast cell concentration of 3 x 10 ⁴ cells / ml was prepared, and cell seeding was performed by 1 ml. After incubation for 1 or 3 days in a 37 ° C, 5% CO ₂ incubator, WST assay was performed to evaluate cell proliferation activity.

The absorbance of Formazan for the activity of osteoblasts against Ti and TI-HA is shown in FIGS. 9A and 9B. When the results were analyzed through Student's T-Test, there was no significant difference in the P value of 0.05 or more on the first day of culture, but a significant difference in the P value of 0.05 or less on the third day of culture. This does not differ in the pattern of cell proliferation on day 1 of culture, but from day 3, it is considered that cell proliferation is more activated in Ti-HA.

Although one embodiment of the present invention has been described above, the spirit of the present invention is not limited to the embodiments presented herein, and those skilled in the art to understand the spirit of the present invention may add elements within the scope of the same spirit. However, other embodiments may be easily proposed by changing, deleting, adding, or the like, but this will also be considered to be within the scope of the present invention.

Claims (10)

A titanium support having at least one selected from a carboxyl group and an amine group attached to a surface;
A plurality of nano-hydroxylated apatites covering the surface of the titanium support with a predetermined area and having a carboxyl group bonded to the surface; And
A bio-friendly linker comprising a carboxyl group and an amine group, and connecting the titanium support and nano-hydroxylates via peptide bonds;
Titanium implant containing.
According to claim 1,
The nano-hydroxylated apatites are titanium implants comprising at least one selected from nanoparticles having an average particle diameter of 10 to 50 nm, and nanorods having an aspect ratio of 1.2 to 20.
According to claim 2,
Titanium implant, characterized in that the length of the nanorods 30 ~ 500 nm. According to claim 1,
The nano-hydroxylated apatite is a titanium implant, characterized in that the nano-rod having an aspect ratio of 1.2 to 20.
According to claim 1,
The bio-friendly linkage is a titanium implant, characterized in that at least one selected from oligopeptides, polypeptides and proteins comprising carboxyl and amine groups.
According to claim 1,
The titanium hydroxide implant is characterized in that the nanorod is fixed to cover 1 to 50% of the surface area of the titanium support.
According to claim 1,
The titanium support is titanium implant, characterized in that the amine group is bonded to the surface.
Treating a titanium support with a solution containing at least one selected from succinic acid and an aminosilane-based compound to bond at least one selected from carboxyl and amine groups to the surface of the titanium support;
Connecting a biocompatible linker comprising a carboxyl group and an amine group to the titanium support surface by peptide bonding;
A step of treating nanoapatite with an aqueous solution containing succinic acid or an amino acid having a carboxyl group and an amine group to bind a carboxyl group to the surface of the nano-hydroxyapatite; And
A step of connecting a bio-friendly linker linked to the surface of the titanium support and nano-hydroxylated apatite bound with a carboxyl group by peptide bonding;
Method of manufacturing a titanium implant comprising a.
The method of claim 8,
A method for producing a titanium implant, characterized in that the amino acid having the carboxyl group and amine group is L-glutamic acid.
The method of claim 8,
The titanium support is treated with a solution containing an aminosilane-based compound, and a method of manufacturing a titanium implant is characterized in that an amine group is bonded to the surface of the titanium support.

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