KR102286394B1 - Method for hydroxyapatite coating of biomaterials and biomaterials coated by hydroxyapatite using the same - Google Patents

Abstract

The present invention relates to a hydroxyapatite coating method for a biomaterial and a hydroxyapatite-coated biomaterial prepared using the same, wherein the hydroxyapatite can be effectively deposited on a functional group formed by treating the surface of the biomaterial with a phosphorylated material. there is.

Description

Hydroxyapatite coating method for biomaterials and hydroxyapatite-coated biomaterials manufactured using the same

The present invention relates to a method for coating hydroxyapatite for a biomaterial and a hydroxyapatite-coated biomaterial prepared using the same, and more particularly, to the surface of the biomaterial by modifying the surface of the biomaterial with a phosphorylated material. The present invention relates to a method for coating hydroxyapatite on a biomaterial for depositing hydroxyapatite, and a hydroxyapatite-coated biomaterial prepared using the same.

In biomedical applications, high-strength materials such as metals and oxide ceramics are used, and these bioinert and bio-adjustable materials are mainly used for orthopedic and dental implants that require high mechanical loads. As one example of such biomaterials, high-purity alumina (Al ₂ O ₃ ) bioceramics have been developed as an alternative to implanted metal alloys for hip joint prostheses and dental implants. The high hardness, low coefficient of friction and good chemical stability of alumina provide very low wear rates on the articular surfaces of orthopedic implants. However, unless the surface of alumina is modified or used directly in the joint area, alumina is a fundamental limitation as an implant material in that, like other inert biomaterials, the fibrous membrane can occur at the interface by the reaction of the living body to recognize it as a foreign material and isolate it. there is In certain circumstances, interfacial failure may occur, resulting in loosening, as observed with some early dental and orthopedic implants. Accordingly, alumina has limited application in spite of its excellent mechanical properties.

After the bioinert biomaterial/material is implanted, fibrous tissue of various thicknesses is formed around the implant, and this fibrous tissue does not form chemical bonds or biologically interact with the implant.

This kind of bonding at the tissue-implant interface basically occurs by mechanical fixation/fixation, and movement at the tissue-implant interface can rupture the interface and cause the implant to fail. One alternative to enhancing biological interactions at the tissue-implant interface is to coat the implant surface with a biologically active material such as _{hydroxyapatite (Ca 10} (PO ₄ ) ₆ (OH) _{2 ), which can provide bonding to damaged living bone.} and promotes effective regeneration and growth of bone tissue.

For coating the implant surface with hydroxyapatite, various processes such as ion sputtering, plasma spraying, electrolytic deposition, sol-gel and biomimetic methods can be used. This has the disadvantage of being complicated. In addition, compatibility at the interface with the modified material can also be an issue. Despite efforts to modify the surface of materials with excellent mechanical properties, such as alumina, it has been difficult to expect bone formation in vivo.

In addition, the conventional method for modifying the surface of the implant (material for living body) mainly consists of coating the surface of the substrate with a calcium phosphate material such as apatite or modifying it with organic molecules. will remain in

Accordingly, the present inventors confirmed that the nucleation of hydroxyapatite can be induced by treating the surface of the biomaterial with a phosphorylated material and introducing only the functional group, and deposited and thus effectively coated, and completed the present invention.

Korean Patent Publication No. 10-0751505 (2007.08.23. Announcement) Korean Patent Publication No. 10-1835684 (2018.03.07. Announcement)

An object of the present invention is to provide an effective method for coating hydroxyapatite on a biomaterial.

Another object of the present invention is to provide a hydroxyapatite-coated biomaterial prepared by using the hydroxyapatite coating method of the biomaterial.

The problem to be solved by the present invention is not limited to the problem(s) mentioned above, and another problem(s) not mentioned will be clearly understood by those skilled in the art from the following description.

In order to solve the above problems, according to one aspect of the present invention, the present invention provides hydroxyapatite (Ca ₁₀ (PO ₄ ) _{6 on the surface of the modified biomaterial after modifying the surface of the biomaterial with a phosphorylated material.} (OH) ₂ ) It provides a method for coating a hydroxyapatite coating of a biomaterial, comprising depositing.

The biomaterial may be any one of a metal, a polymer, a ceramic, and a carbon-based material.

The ceramic may be alumina (Al ₂ O ₃ ) or zirconia (ZrO ₂ ).

The polymer may be any one of Teflon, polyetheretherketone (PEEK), and polyaryletherketone (PAEK).

The metal may be any one of titanium, an alloy of titanium, and an alloy of stainless steel.

The carbon-based material may be any one of graphite, CNT, and fullerene.

The concentration of the phosphorylated material may be 0.001 to 0.05 M.

The phosphorylated material may be any one of nitrilotri(methylphosphonic acid), alkylphosphonic acid, phenylphosphonic acid, and diethylenetriaminepenta(methylene-phosphonic acid).

The precipitation may be formed by immersing the modified biomaterial in a simulated body fluid.

The immersion may be made for 1 to 7 days.

The modification may be modified by reacting the surface of the biomaterial with a phosphorylated material under hydrothermal conditions.

The hydrothermal conditions may be 120 ~ 200 ℃, 1 ~ 28 hours.

The functional group (PO ₃ H ₂ ) of the phosphorylated material may remain on the surface of the modified biomaterial.

It may be deposited using a functional group (PO ₃ H _{2 ) of the phosphorylated material as a nucleation site.}

According to another aspect of the present invention, there is provided a hydroxyapatite-coated biomaterial formed by modifying the surface of the biomaterial with a phosphorylated material and then depositing hydroxyapatite on the surface of the modified biomaterial. do.

The phosphorylated material may be any one of nitrilotri(methylphosphonic acid), alkylphosphonic acid, phenylphosphonic acid, and diethylenetriaminepenta(methylene-phosphonic acid).

The surface of the biomaterial may be modified by reacting it with a phosphorylated material under hydrothermal conditions.

The hydroxyapatite-coated biomaterial may be used for dental implants or bone implants.

According to the hydroxyapatite coating method of a biomaterial of the present invention and a hydroxyapatite-coated biomaterial prepared using the same, the biomaterial is coated with hydroxyapatite to protect the damaged bone or tooth root biologically/chemically. It has the effect of bringing about effective regeneration and growth promotion by forming bonds.

In addition, according to the hydroxyapatite coating method of a biomaterial of the present invention and a hydroxyapatite-coated biomaterial prepared using the same, the hydroxyapatite nucleus is introduced by treating the surface of the biomaterial with a phosphorylated material and introducing only the functional group. It induces formation and has the effect of effectively depositing it.

It should be understood that the effects of the present invention are not limited to the above-described effects, and include all effects that can be inferred from the configuration of the invention described in the detailed description or claims of the present invention.

1 shows a reaction in which an alumina surface is modified with NTP according to an embodiment of the present invention.
Figure 2 is a photograph measuring the contact angle of the alumina surface before (Figure 2a) and after (Figure 2b) NTP modification according to an embodiment of the present invention.
Figure 3 is a photograph measuring the contact angle of the Teflon surface before (Figure 3a) and after (Figure 3b) NTP modification according to an embodiment of the present invention.
4 is a scanning electron micrograph of the surface of alumina 1 (FIG. 4A), 3 (FIG. 4B), and 7 (FIG. 4C) after modification with NTP and immersion in SBF according to an embodiment of the present invention.
5 is alumina modified to NTP concentrations of 0.001M (Fig. 5a), 0.01M (Fig. 5b), 0.1M (Fig. 5c), 0.5M (Fig. 5d) according to an embodiment of the present invention in SBF for 7 days. It is a scanning electron micrograph of the surface after immersion.
6 is a scanning electron micrograph of the surface after surface modification of Teflon with NTP and immersion in SBF for 7 days according to an embodiment of the present invention.
7 is a scanning electron micrograph of the surface of a sample before (FIG. 7a) and after (FIG. 7b) treatment with NTP of titanium according to an embodiment of the present invention after immersion in SBF for 7 days.
8 is a scanning electron micrograph (FIG. 8a) and an enlarged scanning electron micrograph (FIG. 8b) after immersing a sample treated with graphite with NTP in SBF for 7 days according to an embodiment of the present invention.
9 is a graph showing the measurement results by photoelectron spectroscopy (XPS) after NTP treatment of alumina according to an embodiment of the present invention, FIG. 9a is for phosphorus (P), FIG. 9b is for nitrogen (N) One result was shown.
10 is a graph showing the results of measurement by X-ray diffraction (XRD) after immersing Teflon in SBF for 7 days after NTP treatment according to an embodiment of the present invention.

Hereinafter, preferred embodiments according to the present invention will be described in detail with reference to the accompanying drawings.

Advantages and features of the present invention, and a method of achieving the same, will become apparent with reference to the embodiments described below in detail in conjunction with the accompanying drawings.

However, the present invention is not limited by the embodiments disclosed below, but will be implemented in a variety of different forms, and only these embodiments allow the disclosure of the present invention to be complete, and common knowledge in the art to which the present invention pertains It is provided to fully inform those who have the scope of the invention, and the present invention is only defined by the scope of the claims.

In addition, in the description of the present invention, if it is determined that related known technologies may obscure the gist of the present invention, detailed description thereof will be omitted.

Hereinafter, the present invention will be described in detail.

Hydroxyapatite coating method for biomaterials

The present invention provides a method for coating hydroxyapatite for a biomaterial, comprising modifying the surface of the biomaterial with a phosphorylated material and depositing hydroxyapatite on the surface of the modified biomaterial.

As the biomaterial, a biomaterial known in the art may be used, and one of metal, polymer, ceramic, and carbon-based materials may be used. In particular, as the ceramic, alumina (Al ₂ O ₃ ) or zirconia (ZrO ₂ ), which has excellent mechanical properties, is used as the metal material, titanium, an alloy of titanium or stainless steel is used as the metal material, and chemically stable as the polymer is high. Teflon, PEEK (polyetheretherketone) or PAEK (polyaryletherketone), it is preferable to use graphite, CNT or fullerene as the carbon-based material.

Alumina is generally well known to exhibit inert (bioinert) properties in the body, but when the surface is treated and modified as in the present invention, alumina has the property of being able to bond with bone in vivo while maintaining excellent mechanical properties of alumina. Biomaterials can be produced.

In addition, the method of modifying the surface of the biomaterial of the present invention is a chemically stable fluorine-based polymer such as Teflon, titanium showing excellent biocompatibility and osteoconductivity, or a carbon-based material having a hydrophobic surface, such as graphite, CNT, fullerene, etc. It can also be applied to bone and induce bone formation by depositing hydroxyapatite. That is, it can be applied to the development of new biomaterials because osteoconductivity can be expressed by treating only the surface while maintaining the original properties of the material.

The concentration of the phosphorylated material is preferably 0.001 to 0.05 M. As can be seen in FIG. 5 , when nitrilotri(methylphosphonic acid), which is a phosphorylated material in a range other than the above concentration, is used, the deposition of hydroxyapatite does not occur well on the surface of the modified biomaterial. When the concentration of the phosphorylated material is increased, a large amount of functional groups (PO ₃ H ₂ ) can be treated on the surface of the biomaterial at the same temperature and time. However, in this case, it can be seen that the amount of hydroxyapatite deposited after immersion in simulated body fluid (hereinafter referred to as 'SBF') decreased.

As the phosphorylated material, monomers and polymers having 1 to 9 functional groups, phosphoric acid (-PO ₃ H ₂ ) groups, can be used at the ends of the molecule, for example, nitrilotri (methylphosphonic acid) (nitrilotri (methylphosphonic acid) acid; NTP), alkylphosphonic acid, phenylphosphonic acid, diethylenetriaminepenta (methylene-phosphonic acid), it is preferable to use any one of (diethylenetriaminepenta (methylene-phosphonic acid), It is most preferred to use nitrilotri(methylphosphonic acid).

The hydroxyapatite (Ca ₁₀ (PO ₄ ) ₆ (OH) ₂ ) is also called hydroxyapatite or hydroxyapatite. It is used as a coating agent for artificial implants to increase osseointegration.

The precipitation may be formed by immersing the modified biomaterial in a simulated body fluid. As the pseudo body fluid, those commonly known in the art may be used. When the biomaterial modified by supersaturating the phosphorylated material as described above is immersed in a pseudo body fluid, _{hydroxyapatite is deposited using a functional group (PO 3} H ₂ ) present on the surface as a nucleation site.

The immersion may be performed by immersing the modified biomaterial in a pseudo body fluid for 1 to 7 days. Referring to FIG. 4 , it can be seen that the deposition amount of hydroxyapatite increases as the time for immersing the modified biomaterial in the pseudo body fluid increases.

Referring to FIG. 1 , nitrilotri(methylphosphonic acid) is added to alumina and reacted under hydrothermal conditions to form a functional group on the alumina surface, which is immersed in a pseudo body fluid to deposit hydroxyapatite. .

The surface of the biomaterial may be modified by reacting it with a phosphorylated material under hydrothermal conditions. The hydrothermal conditions are preferably 120 to 200° C. and 1 to 28 hours, and the reaction can be carried out in an autoclave. _{The reaction temperature and reaction time of the hydrothermal conditions are optimal conditions for the functional group (PO 3} H ₂ ) to be separated from the nitrilotri (methylphosphonic acid) molecule treated on the surface of the biomaterial, and as shown in FIG. 1, the functional group (PO ₃ H ₂ ) remains on the surface of the biomaterial, and the remaining portion is removed. Outside the range of the reaction temperature and reaction time of the hydrothermal condition, the reaction in which the functional group (PO ₃ H ₂ ) is separated from the nitrilotri (methylphosphonic acid) molecule treated on the surface of the biomaterial does not occur well.

Hydroxyapatite coated biomaterial

The present invention provides a hydroxyapatite-coated biomaterial formed by modifying the surface of the biomaterial with a phosphorylated material and then depositing hydroxyapatite on the surface of the modified biomaterial.

The phosphorylated material may be any one of nitrilotri(methylphosphonic acid), alkylphosphonic acid, phenylphosphonic acid, and diethylenetriaminepenta(methylene-phosphonic acid).

The surface of the biomaterial may be modified by reacting it with a phosphorylated material under hydrothermal conditions.

A detailed description of the hydroxyapatite-coated biomaterial overlaps with that described in the hydroxyapatite coating method of the biomaterial, and thus will be omitted.

The hydroxyapatite-coated biomaterial may be used for dental implants or bone implants.

Hereinafter, preferred examples are presented to help the understanding of the present invention, but the following examples are only illustrative of the present invention and the scope of the present invention is not limited to the following examples.

Example

Hereinafter, preferred examples are presented to help the understanding of the present invention, but the following examples are only illustrative of the present invention and the scope of the present invention is not limited to the following examples.

Example 1

An alumina plate (Al ₂ O ₃ 99.5%, 100Х100Х1 mm) was used as a substrate, and it was cut into a size of 20x10x1mm and used as a specimen. The alumina plate was washed twice with ultrapure water and ethanol. For the surface modification of the alumina substrate, a nitrilotri(methylphosphonic acid) solution (NTP, N[CH ₂ P(O)(OH) ₂ ] ₃ 50 mass% in H ₂ O, Sigma-Aldrich, USA) was used.

NTP solutions were diluted to 0.001, 0.01, 0.1 and 0.5 M. Alumina substrates were subjected to hydrothermal conditions using diluted NTP solutions. The alumina substrate was placed in a Teflon® lined autoclave with ^{30 cm 3 of the NTP solution.} After the autoclave was sealed and heated at 160 °C for 24 h, the autoclave was removed from the heating oven and cooled with a fan. The sample was removed from the solution, washed with ultrapure water, and dried at 40°C.

The ability to form apatite of alumina surface-modified with NTP was evaluated by immersion in simulated body fluid (SBF) at 36.5° C. for 7 days. This SBF solution was prepared according to ISO-23317.

Example 2

It was carried out in the same manner as in Example 1, except that Teflon (PTFE plate, 10Х20Х1mm) was used as a substrate.

Example 3

It was carried out in the same manner as in Example 1 except that titanium (CP-Ti grade, 10Х20Х1mm) was used as a substrate.

Example 4

The same procedure as in Example 1 was performed except that graphite (Mitsubishi Uni B 0.7 mm sharp core) was used as a substrate.

Experimental Example 1: Wettability

After the surface of the substrate was treated with water, the contact angle of water droplets was measured to confirm wettability.

Figure 2 is a photograph measuring the wettability of the alumina surface before and after NTP modification. In FIG. 2a, alumina before NTP treatment showed a contact angle of 70.9°, and in FIG. 2b, alumina after 0.01M NTP treatment showed a contact angle of 3.3°. Therefore, it can be seen that the contact angle of the alumina surface was significantly reduced due to the NTP modification.

3 is a photograph measuring the wettability of the surface of Teflon before and after NTP modification. In FIG. 3a, Teflon before NTP treatment showed a contact angle of 122.8°, and in FIG. 3b, Teflon after 0.01M NTP treatment showed a contact angle of 53.4°. Therefore, it can be seen that the contact angle of the Teflon surface was also significantly reduced due to the NTP modification.

These results indicate that the surface of the substrate was changed to hydrophilic due to NTP modification.

Experimental Example 2: Change according to immersion time of pseudo body fluid (SBF)

The surface of the alumina specimen was modified with NTP of 0.01 M, and the surface of the alumina specimen on the 1st, 3rd, and 7th days after immersion in SBF was scanned using a scanning electron microscope (SEM, JSM5600, JEOL Co., Ltd., Japan). Changes in morphology were observed. Specimens were coated with gold sputtering prior to observation.

As shown in Figure 4, after immersion in SBF, the alumina specimen formed plate-shaped depositions on the surface. The deposition was similar to that formed on other apatite-forming substrates. As can be seen in FIGS. 4A to 4C , the deposition amount increased as the period in which the specimen was immersed in SBF increased.

Experimental Example 3: Change according to NTP concentration

The surface of the alumina specimen was modified with various NTP concentrations of 0.001M, 0.01M, 0.1M, and 0.5M prepared in Example 1, and after immersing it in SBF for 7 days, the change in surface morphology was observed with a scanning electron microscope. .

As can be seen in FIG. 5, the alumina specimens modified with NTPs of 0.001M and 0.01M formed hydroxyapatite on the surface. However, it was confirmed that hydroxyapatite was not properly formed on the surface of the alumina specimens modified with NTP of 0.1M and 0.5M.

Therefore, it can be seen that the concentration of NTP for the deposition of hydroxyapatite is preferably 0.001 to 0.05M.

6 is a photograph confirming the surface of the Teflon specimen treated with NTP 0.01M of Example 2 with a scanning electron microscope after immersion in SBF.

7 is a photograph confirming the surface with a scanning electron microscope after immersing the titanium specimen before and after treatment with NTP 0.01M of Example 3 in SBF, FIG. 7a is a photograph before NTP treatment, and FIG. 7b is a photograph after NTP treatment .

8a is a photograph confirming the surface with a scanning electron microscope after immersing the graphite treated with NTP 0.01M of Example 4 in SBF, and FIG. 8b is an enlarged photograph of FIG. 8a.

6 to 8, it can be seen that not only alumina as a biomaterial, but also Teflon, titanium, and graphite are treated with NTP to modify the surface, thereby depositing hydroxyapatite. From these results, it can be predicted that bone ingrowth will be expressed by depositing oxapatite on the surface of biomaterials even in vivo. Deposition of hydroxyapatite on the surface of fluororesin such as Teflon has not yet been reported, and even in the case of titanium, which has been relatively researched, several steps of acid treatment and hydrothermal treatment are required. The above material may be coated by depositing apatite by simply introducing a functional group of the phosphorylated material.

9 shows the presence of each element was confirmed through photoelectron spectroscopy (XPS) after the alumina surface was treated with NTP in Example 1. The NTP molecule is composed of nitrogen (N) and phosphorus (P) as shown in FIG. 1, and there is no nitrogen (N) on the surface of the substrate as shown in FIGS. 9a and 9b, and only phosphorus (P) exists, so NTP treatment It can be seen that only the phosphate group, which is a functional group of NTP, remains on the surface of the substrate.

Figure 10 is the NTP treatment of the surface of Teflon in Example 2 and after immersion in SBF for 7 days, the XRD of the surface was measured. As can be seen in FIG. 10 , it can be seen that the material deposited on the surface of Teflon is hydroxyapatite.

Specific examples of the hydroxyapatite coating method for a biomaterial according to the present invention and a hydroxyapatite-coated biomaterial prepared using the same have been described. However, within the limits not departing from the scope of the present invention, various It is obvious that implementation modifications are possible.

Therefore, the scope of the present invention should not be limited to the described embodiments, but should be defined by the following claims as well as the claims and equivalents.

That is, it should be understood that the above-described embodiments are illustrative in all respects and not restrictive, and the scope of the present invention is indicated by the claims to be described later rather than the detailed description, and the meaning and scope of the claims and All changes or modifications derived from the concept of equivalents thereof should be construed as being included in the scope of the present invention.

Claims (18)

the surface of the biomaterial,
After reforming by reacting under hydrothermal conditions with phosphorylated substances at a concentration of 0.001 to 0.05 M,
_{Depositing hydroxyapatite (Ca 10} (PO ₄ ) ₆ (OH) ₂ ) on the surface of the modified biomaterial,
The functional group of the phosphorylated material (-PO ₃ H ₂ ) remains on the surface of the modified biomaterial,
The deposition is characterized in that it is formed by using _{the functional group (-PO 3} H ₂ ) of the phosphorylated material remaining on the surface of the modified biomaterial as a nucleation site,
Hydroxyapatite coating method for biomaterials.
According to claim 1,
The biomaterial is characterized in that any one of a metal, a polymer, a ceramic, a carbon-based material,
Hydroxyapatite coating method for biomaterials.
3. The method of claim 2,
The ceramic is characterized in that alumina (Al ₂ O ₃ ) or zirconia (ZrO ₂ ),
Hydroxyapatite coating method for biomaterials.
3. The method of claim 2,
The polymer is characterized in that any one of Teflon, PEEK (polyetheretherketone), PAEK (polyaryletherketone),
Hydroxyapatite coating method for biomaterials.
3. The method of claim 2,
The metal is characterized in that any one of titanium, an alloy of titanium, and an alloy of stainless steel,
Hydroxyapatite coating method for biomaterials.
3. The method of claim 2,
The carbon-based material is characterized in that any one of graphite, CNT, fullerene,
Hydroxyapatite coating method for biomaterials.
delete According to claim 1,
The phosphorylated material is
characterized in that any one of nitrilotri (methylphosphonic acid), alkylphosphonic acid, phenylphosphonic acid, and diethylenetriaminepenta (methylene-phosphonic acid),
Hydroxyapatite coating method for biomaterials.
According to claim 1,
The deposition is characterized in that it is formed by immersing a modified biomaterial in a simulated body fluid,
Hydroxyapatite coating method for biomaterials.
10. The method of claim 9,
The immersion, characterized in that made for 1 to 7 days,
Hydroxyapatite coating method for biomaterials.
delete According to claim 1,
The hydrothermal conditions are characterized in that 120 ~ 200 ℃, 1 ~ 28 hours,
Hydroxyapatite coating method for biomaterials.
delete delete the surface of the biomaterial,
After reforming by reacting under hydrothermal conditions with phosphorylated substances at a concentration of 0.001 to 0.05 M,
It is formed by depositing hydroxyapatite on the surface of a modified biomaterial,
The functional group of the phosphorylated material (-PO ₃ H ₂ ) remains on the surface of the modified biomaterial,
The deposition is characterized in that it is formed by using _{the functional group (-PO 3} H ₂ ) of the phosphorylated material remaining on the surface of the modified biomaterial as a nucleation site,
A biomaterial coated with hydroxyapatite.
16. The method of claim 15,
The phosphorylated material is
characterized in that any one of nitrilotri (methylphosphonic acid), alkylphosphonic acid, phenylphosphonic acid, and diethylenetriaminepenta (methylene-phosphonic acid),
A biomaterial coated with hydroxyapatite.
delete 16. The method of claim 15,
Characterized in that it is used for dental implants or bone implants,
A biomaterial coated with hydroxyapatite.

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