KR102190171B1 - Titanium implant and method for manufacturing the same - Google Patents

Abstract

The present invention relates to a titanium implant and a method of manufacturing the same, and more particularly, to a titanium implant with improved bioactivity and bone binding strength by maintaining excellent biocompatibility of hydroxyapatite while improving the binding strength of hydroxyapatite to metal and more particularly, About.

Description

Titanium implant and method for manufacturing the same TECHNICAL FIELD

The present invention relates to a titanium implant and a method of manufacturing the same, and more particularly, to a titanium implant with improved bioactivity and bone binding strength by maintaining excellent biocompatibility of hydroxyapatite while improving the binding strength of hydroxyapatite to metal and more particularly, About.

Materials such as polymers, metals, ceramics, and composite materials were used for implants in the early stages, but their scope gradually decreased as the concept of osseointegration was established. Natural polymers such as collagen or elastin fibers are applied to human bones or skin, but their mechanical properties are insufficient. In particular, proteins such as collagen may cause immunological rejection. Metallic materials have mechanical properties similar to human bones, but their biocompatibility is low, causing harmful reactions in the body. Ceramic materials such as bioglass are biologically harmless, but have a large difference in mechanical properties. Currently, stainless steel, Cr-Co alloy, Ti, Ti alloy, and bioglass are mainly used as implant materials.

When a foreign substance enters the body, the body's immune system recognizes it as a non-self, and phagocytosis occurs by macrophages. This is because metal ions eluted from the implant surface are the targets, and excessive reactions related to immunity can develop into cancer cells, so biocompatibility is the most important factor for implants. In addition, since implants receive a combination of masticatory pressure and lateral pressure, bone bonding is also an important factor. Therefore, it is necessary to consider the tissue suitability of the implant material, the surface characteristics, the bone quality of the surgical site, the surgical procedure, and the load applied to the implant. Among these, the surface characteristics of implants have a great influence on osseointegration.

Titanium or titanium alloy as an implant material has excellent mechanical strength, and has excellent biocompatibility and corrosion resistance by forming a surface oxide layer. Furthermore, research is being conducted on a surface treatment method that increases the surface area of these materials and reduces the healing period after surgery. Implants manufactured by this surface treatment method can improve bone adhesion due to an increase in the contact area with the bone. have.

On the other hand, hydroxyapatite is known as a material that can be used directly in the living body because its structure and chemical composition are similar to the main components of tooth enamel and bone. In addition, due to its excellent bioactivity and biocompatibility, it is not only used as a material for implants used for bone tissue regeneration, but also as a drug delivery system in drug and gene delivery systems. Due to the excellent biocompatibility and biocompatibility of hydroxyapatite, it is known as a material that promotes the growth of bone tissue. However, the hydroxyapatite material is difficult to use alone due to its low physical strength.

Surface treatment methods to increase the success rate of implants include Ti plasma spray and hydroxyapatite coating. In the case of Ti plasma spray, there is a problem that Ti particles coated on the surface are separated from the implant and dispersed in the surrounding tissues to weaken bone bonding or cause inflammation.The hydroxyapatite coating method is a hydroxyapatite material because the process is performed at high temperatures. There is a problem that causes a change in the properties of

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

The present invention has been devised in view of the above points, and an object of the present invention is to provide a titanium implant having improved bioactivity and bone binding strength by maintaining excellent biocompatibility of hydroxyapatite while having excellent mechanical properties and a method of manufacturing the same.

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

According to an embodiment of the present invention, the nanohydroxyapatite 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 ~ 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 linker 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 hydroxyapatite nanorod 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 bonded 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 aminosilane compounds to bind at least one selected from a carboxyl group and an amine group to the surface of the titanium support, and a carboxyl group on the surface of the titanium support A step of linking a bio-friendly linker including an amine group and a peptide bond by a peptide bond, treating a nano-hydroxyapatite 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 It provides a method for producing a titanium implant comprising the step of connecting the bio-friendly linker connected to the surface of the titanium support and the nano-hydroxyapatite to which the carboxyl group is bonded by peptide bonds.

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 so that an amine group may be bonded 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 hydroxyapatite, thereby improving bioactivity and bone binding ability, and thus, it is possible to significantly reduce the healing period after 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 the surface of the titanium support.
2B is an SEM image of the surface of the titanium support.
2C is an SEM image of the surface of a titanium support having hydroxyapatite nanorods fixed thereon.
2D is an SEM image of the surface of a titanium support on which hydroxyapatite nanorods are fixed.
3 is a TEM image of hydroxyapatite nanorods.
4A shows the results of surface EDS analysis of the titanium support.
4B shows the results of surface EDS analysis of a titanium support having an amine group bonded to the surface.
4C shows the results of surface EDS analysis of a titanium support having an amine group bonded to the surface.
4D shows the results of surface EDS analysis of a titanium support to which hydroxyapatite nanorods are fixed on the surface.
5A is a fluorescence micrograph of the surface of the titanium support.
5B is a fluorescence micrograph of a surface of a titanium support having an amine group bonded thereto.
5C is a fluorescence micrograph of the surface of a titanium scaffold to which albumin is peptide bonded to the surface.
6 is a graph showing the results of XPS analysis of a titanium support and a titanium implant in which hydroxyapatite nanorods are fixed on the surface.
7A is a surface SEM image of the first day after culturing osteoblasts on a titanium scaffold.
Figure 7b is a surface SEM image of the first day after culturing osteoblasts on a titanium scaffold to which hydroxyapatite nanorods are fixed on the surface.
7C is a surface SEM image of the 3rd day after culturing osteoblasts on a titanium scaffold.
7D is a SEM image of the surface of the third day after culturing osteoblasts on a titanium scaffold to which hydroxyapatite nanorods are fixed on the surface.
Figure 8a is a fluorescence micrograph of the surface of a titanium scaffold treated with Live/dead staining staining.
8B is a fluorescence micrograph of the surface of a titanium scaffold to which hydroxyapatite nanorods are fixed on the surface, treated by Live/dead staining staining.
9A is a graph showing the results of measuring formazan absorbance on osteoblast activity at the first day of culture for a titanium support (Ti) and a titanium support (Ti-HA) on which hydroxyapatite nanorods are fixed.
9B is a graph showing the results of measuring formazan absorbance on osteoblast activity at the third day of culture for a titanium support (Ti) and a titanium support (Ti-HA) on which a hydroxyapatite nanorod is fixed on the surface.

As described above, the titanium material has excellent mechanical strength, but low bone bonding force, so it is difficult to use as an implant itself. In order to improve the bone bonding of titanium-based implants, a method of coating hydroxyapatite with excellent bioactivity on a titanium support may be used, but the binding force of hydroxyapatite to metal is significantly lower, so that hydroxyapatite particles are separated from the titanium support. There is a problem.

After preparing such a hydroxyapatite in a nano size, the prepared nano hydroxyapatite is fixed on the surface of a titanium support using a bio-friendly connector to improve the binding strength of hydroxyapatite to metal and at the same time maintain excellent biocompatibility of hydroxyapatite. There is an advantage of simultaneously improving the bioactivity and bone binding ability of a titanium implant.

Hereinafter, embodiments of the present invention will be described in detail with reference to the accompanying drawings so that those of ordinary skill in the art can easily implement the present invention. The present invention may be implemented in various different forms, and is not limited to the embodiments described herein.

The titanium implant according to the present invention includes a titanium support having at least one selected from a carboxyl group and an amine group bonded to the surface, covering the surface of the titanium support with a predetermined area, and a plurality of nano-hydroxylated apatites having a carboxyl group bonded to the surface and a carboxyl group, and It includes an amine group, and a bio-friendly linker that connects the titanium support and nanohydroxyapatite 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, 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 to the bio-friendly connector.

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

The nano-hydroxylated apatite 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, nanoparticles having an aspect ratio of 1.2 to 20. It can contain only rods.

When the nano-hydroxylated apatite is in the shape of a nanorod, since the surface area relative to the mass of the nano-hydroxylated apatite is larger than that of the nanoparticle, the physiological activity of the bone cells is more excellent, so that bone adhesion can be significantly improved.

When the average particle diameter of the nanoparticles exceeds 50 nm, the surface area relative to the mass of the nano-hydroxylated apatite may be lowered, thereby reducing bone adhesion, and nanoparticles having an average particle diameter of less than 10 nm are practically not easy to manufacture. May not.

When the aspect ratio of the nanorods is less than 1.2, the surface area to the mass of the nano-hydroxylated apatite decreases in proximity to the shape of the nanoparticles, thereby reducing bone adhesion, and when the aspect ratio exceeds 20, the titanium It can be difficult to bond to the support surface.

In addition, the length of the hydroxyapatite nanorod may be 30 to 500 nm. If the length of the hydroxyapatite nanorod is less than 30 nm, osteosynthesis may be deteriorated, and if it exceeds 500 nm, there may be problems such as poor surface reactivity due to steric hindrance, making it difficult to fix on the titanium support.

The nano-hydroxylated apatite may be a carboxyl group bonded to the surface in order to bond with a bio-friendly connector.

In addition, the nano-hydroxylated apatite may 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 force of the implant may be lowered.If the nano-hydroxide apatite is fixed to cover more than 50%, the physical There is a fear that the nano-hydroxylated apatite is physically stacked without being connected to the titanium support.

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

Referring to FIG. 2D, it can be seen that in the titanium implant according to an embodiment of the present invention, the nano hydroxyapatite is fixed to cover 14.6% of the surface area of the titanium support.

The bio-friendly connector may serve to fix the nano-hydroxylated apatite on the surface of the titanium support. The bio-friendly linker may be at least any one selected from an oligopeptide comprising a carboxyl group and an amine group, a polypeptide comprising a carboxyl group and an amine group, and a protein comprising a carboxyl group and an amine group, and the carboxyl group and amine group included in the bio-friendly linker By forming a peptide bond with an amine group or carboxyl group bonded to the surface of the titanium support, and a carboxyl group bonded to the surface of the nano-hydroxylated apatite, the nano-hydroxylated apatite may be immobilized on the surface of the titanium support.

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

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

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

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

Preferably, the titanium support may be treated with a solution containing an aminosilane compound, and in this case, the biocompatible linker may be more easily bonded to the titanium support than when treated with a solution containing succinic acid.

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

The aminosilane-based compound and/or succinic acid may be contained in an amount of 0.01 to 10% by weight in the solution, and when contained in an amount of less than 0.01% by weight in the solution, an amine group and/or carboxyl group bonded to the surface of the titanium support is intended It may not be bonded to a level such as that, and when it exceeds 10% by weight, the binding efficiency of the carboxyl group and/or amine group to be substantially bonded relative to the amount of the aminosilane compound and/or succinic acid added may be insufficient.

The treatment method of the solution may be a method of modifying a hydroxide with an amine group or a carboxyl group in the art, and may be an immersion method, but is not limited thereto.

As a solvent included in the solution, any conventional solvent used in the surface modification method using the aminosilane-based compound and/or succinic acid may be used without limitation, and ethanol may be used as an example, but is not limited thereto.

Next, a bio-friendly linker including a carboxyl group and an amine group is connected to the surface of the titanium support by a peptide bond.

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

Next, the nanohydroxyapatite 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 nanohydroxyapatite.

When using the amino acid to bind a carboxyl group to the surface of the nano-hydroxylated apatite, the solution may further contain a coupling agent, and the coupling agent may be applied to 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 be preferably 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 higher than that of treatment with an aqueous solution containing succinic acid. It can be even better.

The amino acid may be used without limitation as long as it has a carboxyl group in the side chain, but it may be preferably 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 based on 100 parts by weight of water. (N-hydroxysuccinimide) and 0.1 to 0.7 parts by weight of L-glutamic acid may be included.

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

The bio-friendly linker and nano hydroxyapatite may be chemically bonded and linked by a peptide bond.

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

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

(Example 1)

A titanium support (Biotem Implant) (Ti) whose surface is sand blasted is treated with an ethanol solution containing 1% by weight of APTES for 4 hours at room temperature, and amine groups are bound to the surface (Ti- NH ₂ ) was prepared. The prepared titanium support was treated with a solution containing albumin at room temperature for 24 hours to prepare a titanium support (Ti-A) having albumin-peptide bonded to the surface.

Distilled water (300ml), Ca(NO ₃ ) _2· 4H ₂ O (57.5 g) and NH ₄ OH were mixed to prepare an aqueous solution having a pH of 10.4. Distilled water (400ml) and (NH ₄ )H ₂ PO ₃ (19.75g) were added to the prepared aqueous solution, stirred at room temperature, and allowed to stand 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). Most of the obtained nano-hydroxylated apatite showed the form of a nanorod.

The obtained nano-hydroxylated apatite (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. By mixing for a period of time, a hydroxyapatite nanorod (HA-g) having a carboxyl group on the surface was prepared.

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

(Comparative Example 1)

A commercially available titanium support (biotem implant) was prepared.

(Experimental Example 1) SEM analysis

The surfaces of the titanium support (Ti) of Comparative Example 1 and the titanium support (Ti-HA) having hydroxyapatite nanorods fixed on the surface prepared in Example 1 were observed with FE-SEM (S-4300 HITACHI), and the results Is shown in Figures 2a to 2d.

2A and 2B are SEM images of the surface of the titanium support. Referring to FIG. 2D, it can be seen that the hydroxyapatite 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-hydroxylated apatite represents the shape of a nanorod, and the length of the nanorod is 30 to 500 nm.

(Experimental Example 3) EDS analysis

Surface EDS analysis 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 a hydroxyapatite nanorod 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 content (at%) of Si, C, and O elements of Ti-NH ₂ is increased compared to Ti, and through this, it is indirectly confirmed that APTES is bonded to the surface of the titanium support. I can.

Comparing FIGS. 4C and 4D, it can be seen that the content of P and Ca elements (at%) of Ti-HA is increased compared to Ti-NH ₂ , through which hydroxyapatite nanorods are bonded to the surface of the titanium support. It can be confirmed indirectly.

(Experimental Example 4) Fluorescence Microscopy

Fluorescence microscopy was performed on the surfaces 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 bonded to the surface. The results are shown in FIGS. 5A to 5C.

FITC, which reacts with an amine group as a fluorescent substance and expresses green fluorescence, was used.

Referring to FIG. 5A, it can be seen that the green fluorescence of Ti was not expressed, whereas the green fluorescence of Ti-NH ₂ and Ti-A was expressed 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 amine group on the surface of Ti-NH ₂ reacts with the albumin and the albumin is peptide bonded. It can be confirmed indirectly.

(Experimental Example 5) XPS analysis

XPS analysis was performed on a titanium support (Ti) and a titanium implant (Ti-HA) having a hydroxyapatite nanorod fixed on the surface, and the results are shown in Table 1 and FIG. 6 below.

Referring to FIG. 6, as a result of XPS analysis of the Ti surface, it can be seen that peaks of Ca and P elements did not appear, whereas peaks of Ca and P elements appeared on the Ti-HA surface.

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 above, 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. I can.

(Experimental Example 6) Observation of adhesion behavior of osteoblasts

1) FE-SEM observation

Cell adhesion was investigated in vitro in order to confirm cellular suitability to a titanium support (Ti) and a titanium implant (Ti-HA) with a hydroxyapatite nanorod fixed on the surface. After placing Ti and Ti-HA disks on a 4-well dish, a culture solution (DMEM) having an osteoblast cell concentration of 3 x 10 ⁴ cells/ml was prepared and cell seeding was performed at 1 ml each. After incubation for 24 hours and 72 hours in a 37°C, 5% CO ₂ incubator, the culture medium 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 day 1 cultivation, there was no significant difference in the number or degree of activity of cells adhered to Ti (Fig. 7A) and Ti-HA (Fig. 7B). On the other hand, as a result of culture on the third day, the cells adhered to Ti (FIG. 7c) showed a round shape, but the cells adhered to Ti-HA (FIG. 7d) were well adhered in a flat shape. Through this, it can be confirmed that Ti-HA has a good effect on initial adhesion and cell spreading of cells.

2) Live/dead staining evaluation

When introducing a hydroxyapatite nanorod to the surface of a titanium support, a titanium support (Ti) and a hydroxyapatite nanorod are fixed to the surface by using a Live/dead staining method to see how the hydroxyapatite nanorod affects cells. The titanium implant (Ti-HA) was observed with a fluorescence microscope, and the results are shown in FIGS. 8A and 8B.

Calcein-AM, a reagent used in this staining method, is converted into a fluorescent substance by reacting by an esterase in the cell when a non-fluorescent substance enters the cell, resulting in green fluorescence, 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 ionically bonds with the cell nucleus with negative ions to show red fluorescence.

Both Ti and Ti-HA did not show red fluorescence by PI, but only green fluorescence by Calcein-AM. Through this, it is judged that the hydroxyapatite nanorods introduced into the titanium scaffold do not negatively affect the physiological activity of osteoblasts.

(Experimental Example 7) Cell proliferation activity evaluation

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

The absorbance of Formazan on 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, on the first day of cultivation, the P value was 0.05 or more, and there was no significant difference in numerical value, but on the third day of cultivation, the P value was 0.05 or less, indicating a significant difference. Although there is no difference in the pattern of cell proliferation on the first day of culture, it is judged that the cell proliferation is more activated in Ti-HA from the third day.

Although an embodiment of the present invention has been described above, the spirit of the present invention is not limited to the embodiment presented in the present specification, and those skilled in the art who understand the spirit of the present invention can add components within the scope of the same idea It will be possible to easily propose other embodiments by changing, deleting, adding, etc., but it will be said that this is also 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 bonded to the surface;
A plurality of nano-hydroxylated apatites covering the surface of the titanium support with a predetermined area and having a carboxyl group bonded thereto; And
A bio-friendly linker comprising a carboxyl group and an amine group, and connecting the titanium support and nanohydroxyapatite through a peptide bond;
Titanium implant comprising a.
The method of claim 1,
The nano-hydroxylated apatite is a titanium implant 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.
The method of claim 2,
Titanium implant, characterized in that the length of the nanorod is 30 ~ 500 nm. The method of claim 1,
The nano-hydroxylated apatite is a titanium implant, characterized in that the nanorods having an aspect ratio of 1.2 to 20.
The method of claim 1,
The bio-friendly linker is a titanium implant, characterized in that at least any one selected from oligopeptides, polypeptides and proteins containing carboxyl and amine groups.
The method of claim 1,
The nano-hydroxylated apatite is a titanium implant, characterized in that fixed to cover 1 to 50% of the surface area of the titanium support.
The method of claim 1,
The titanium support is a titanium implant, characterized in that the amine group is bonded to the surface.
Treating the titanium support with a solution containing at least one selected from succinic acid and aminosilane-based compounds to bind at least one selected from carboxyl groups and amine groups to the surface of the titanium support;
Linking a bio-friendly linker comprising a carboxyl group and an amine group to the surface of the titanium support by a peptide bond;
Treating the nano-hydroxyapatite 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
Linking the bio-friendly linker connected to the surface of the titanium support and the nanohydroxyapatite to which the carboxyl group is bonded by a peptide bond;
Method of manufacturing a titanium implant comprising a.
The method of claim 8,
The method of manufacturing a titanium implant, characterized in that the amino acid having a carboxyl group and an amine group is L-glutamic acid.
The method of claim 8,
The titanium support is a method of manufacturing a titanium implant, characterized in that the amine group is bonded to the surface of the titanium support by treatment with a solution containing an aminosilane compound.

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