KR102010467B1 - Metal biomaterial and method for manufacturing the same - Google Patents

Abstract

Rigidly deforming the metal material including titanium; And forming a coating layer comprising molybdenum disulfide (MoS ₂ ) on the surface of the plastically deformed metal material.

Description

Metal biomaterial and its manufacturing method {METAL BIOMATERIAL AND METHOD FOR MANUFACTURING THE SAME}

A metal biomaterial and a method of manufacturing the same. In particular, it relates to a metal biomaterial excellent in strength, antimicrobial activity and biocompatibility, and a method of manufacturing the same.

Metal biomaterials are used to replace hard tissues of the human body, and stainless steel and titanium alloys (Ti-6Al-4V) are mainly used. However, due to the toxicity of the elements of stainless steel and titanium alloys, there is a recent trend of risk of use, and pure titanium is attracting attention as a substitute for long-term use safely in the human body. Pure titanium has been attracting attention as a biomaterial because it has no toxicity in human body and has excellent biocompatibility and corrosion resistance, but its strength is not as good as that of commercially available materials, so there is a problem in prolonged use in the human body, thereby limiting its application field.

In order to improve the mechanical properties of pure titanium, a severe plastic deformation process is used, and there is an equal-channel angular pressing process. However, the ultrafine grained pure titanium prepared by the Jiangsu process has the disadvantage of risk of infection when used as a medical device because bacteria deposition can occur well even though it has good biocompatibility.

Bacterial infection can occur not only right after surgery but also in the blood or lymph pathway. Therefore, the complete removal of bacteria on the surface of the medical device is not able to completely prevent the postoperative infection, and requires a method of approaching the surface of the medical device to prevent bacterial infection while maintaining biocompatibility. To solve this problem, a coating method using a polymer (PMMA, PEG, etc.) has been developed, but the polymer has a fatal disadvantage that it can be maintained for only about 8 to 12 days due to decomposition in the human body. On the other hand, 2D (Two-dimension) material can be used stably in the environment of the human body, and unlike polymers, in particular, long-term use is possible because decomposition does not occur in the human body.

Prior Art Document 1: JUNG, H. S. et al., RCS Adv., (2016) Vol. 6, pp. 26719-26724

MoS ₂ (molybedenum disulfide) provides a metal biomaterial and a method of manufacturing a metal that can maintain the biocompatibility while maximizing the antimicrobial effect by increasing the wettability of the surface of the pure titanium surface and increase the amount of active oxygen generated on the surface .

Metal biomaterial manufacturing method according to an embodiment of the present invention comprises the steps of rigidly deforming the metal material including titanium; And forming a coating layer including molybdenum disulfide (MoS ₂ ) on the surface of the plastically deformed metal material.

The rigid deformation of the metal material may include: providing a metal material having a titanium purity of 90% by weight or more and having a rod shape; Compressing the metal material in an isopath angle; And drawing out the compressed metal material.

In the step of compressing the metal material in a constant channel angle, the metal material may be repeatedly compressed a plurality of times so that the average grain size of the metal material is 100 nm or less.

In the step of compressing the metal material in a constant channel angle, the metal material may be processed at 100 ° C. or more.

In the forming of the coating layer, the coating layer may be formed on the surface of the metal using 3-APTES (3-aminopropyltriethoxysilane).

After the step of rigidly deforming the metal material, corroding the surface of the plastically deformed metal material; may further include.

In the step of corroding the surface of the metal material, the metal material is etched using a corrosion solution, wherein the corrosion solution may include 1 to 15 parts by weight of hydrofluoric acid solution based on 100 parts by weight of the nitric acid solution and the nitric acid solution.

In the step of corroding the surface of the metal material, the metal material may be etched in the corrosion solution for 1 to 30 minutes.

Metal biomaterial according to an embodiment of the present invention is a metal material having a titanium purity of 90% by weight or more, the average grain size of 100nm or less; And a coating layer disposed on the surface of the metal material and including molybdenum disulfide (MoS ₂ ).

The thickness of the coating layer may be 1 to 100nm.

The tensile strength of the metal material may be 1000 MPa or more.

The contact angle of the surface of the metal biomaterial may be 45 ° or less, and the surface energy may be 55 mJ / m ^{2 or} more.

The metal biomaterial according to an embodiment of the present invention is not only decomposed well in the human body, but also has excellent antibacterial properties and is not well deposited, so that the coating on the surface of the metal material formed of titanium material having a purity of 90 wt% or more Can function as an optimal metal biomaterial.

Furthermore, ultra-high mechanical properties can lead to downsizing of medical devices. In addition, the price competitiveness of MoS ₂ can increase the applicability as a medical device industry.

1 is a diagram illustrating a step of forming a coating layer according to an embodiment of the present invention.
2 is a view showing the ultra-high mechanical properties of the ultrafine grain microstructure photograph and the ultrafine grains formed after the isopath angle compression process according to an embodiment of the present invention.
FIG. 3 shows Comparative Example 1 (Sample Name, Ti) and Coated Comparative Example 2 (Coarse Grain (Sample Name, MS-Ti), Example 1 (Sample Name, MS-ECAP) which were not coated according to an embodiment of the present invention. ) And Example 2 (sample name, MS-eECAP) are the results of SEM (Scanning electron microscopy).
4 is a result of observing the surface roughness by the AFM (atomic force microscope) method according to an embodiment of the present invention.
5 is a result of observing the components of MoS2 coated on the surface according to an embodiment of the present invention through X-ray photoelectron spectroscopy (XPS).
Figure 6 is a view showing the result of the coating result, the improved wettability of the surface according to an embodiment of the present invention.
7 is a view showing the results of improved cell proliferation because the surface wettability is improved according to an embodiment of the present invention.
8 is a view showing the results of improved antimicrobial properties after bacterial culture according to an embodiment of the present invention. In addition, it is a view showing the result of measuring the reactive oxygen species (ROS) through the amount of Single oxygen sensor green (SOSG).
Figure 9 shows the implant specimen prepared according to an embodiment of the present invention is inserted into the artificial bone.
10 is a view showing that the coated surface according to an embodiment of the present invention maintains the coating layer including MoS ₂ both before and after artificial bone insertion.

The terminology used herein is for reference only to specific embodiments and is not intended to limit the invention. As used herein, the singular forms “a,” “an,” and “the” include plural forms as well, unless the phrases clearly indicate the opposite. As used in the specification, the meaning of “comprising” embodies a particular characteristic, region, integer, step, operation, element and / or component, and the presence of another characteristic, region, integer, step, operation, element and / or component or It does not exclude the addition.

When a portion is referred to as "on" or "on" another portion, it may be directly on or on the other portion or may be accompanied by another portion therebetween. In contrast, when a part is mentioned as "directly above" another part, no other part is intervened in between.

Unless defined otherwise, all terms including technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. Commonly defined terms used are additionally interpreted to have a meaning consistent with the related technical literature and the presently disclosed contents, and are not interpreted in an ideal or very formal sense unless defined.

In addition, unless otherwise indicated,% means weight% and 1 ppm is 0.0001 weight%.

In an embodiment of the present invention, the meaning of further including an additional element means to include iron (Fe), which is the balance by an additional amount of the additional element.

Hereinafter, embodiments of the present invention will be described in detail so that those skilled in the art can easily practice. As those skilled in the art would realize, the described embodiments may be modified in various different ways, all without departing from the spirit or scope of the present invention.

Metal Biomaterial Manufacturing Method

Metal biomaterial manufacturing method according to an embodiment of the present invention comprises the steps of rigidly deforming the metal material including titanium; And forming a coating layer including molybdenum disulfide (MoS ₂ ) on the surface of the plastically deformed metal material.

After the rigid plastic deformation of the metal material, the method may further include corroding the surface of the plastically deformed metal material.

The rigid deformation is a step for miniaturizing the average grain size of the metal material. Severe plastic deformation refers to deformation that reduces the grain size to nanometers by causing plastic deformations of tens to hundreds of times in crystalline materials compared to normal plastic deformation.

By rigidly deforming the metal material, the average grain size of the metal material can be reduced to the nanometer level. Thereby, the strength of a metal material can be improved. In addition, the ductility of the metal material can be improved.

Specifically, the step of rigidly deforming the metal material may have a titanium purity of 90% by weight or more, and may include preparing a metal material in the form of a rod, compressing the metal material through an isopath angle, and drawing a compressed metal material.

More specifically, in the step of compressing the metal material in an equal path angle, the metal material may be repeatedly compressed a plurality of times so that the average grain size of the metal material is 100 nm or less. Moreover, a metal material can be compressed at 100 degreeC or more.

In the case of stainless steel or titanium alloy (Ti-6Al-4V), which is used as a conventional metal biomaterial, a rod having a titanium purity of 90% by weight or more due to the possibility of danger as a biomaterial due to the toxicity of elements of the alloy ( rod) metal material can be provided.

Thereafter, the metal material may be processed by using an equal-channel angular pressing (ECAP) process. In this case, the equal channel angle compression may be repeatedly performed a plurality of times. In this process, the average grain size of the metal material may be reduced to 100 nm or less.

Meanwhile, the constant channel angle compression may be performed at 100 ° C. or higher. When the temperature is less than 100 ° C, the molding of the metal material may be limited, so the temperature is controlled to 100 ° C or more.

By drawing the compressed metal material, it is possible to reduce the diameter of the rod-shaped metal cross section by 44% or more than before the rigid deformation.

Next, the surface of the plastically deformed metal material can be corroded. This is to increase the roughness of the metal material and improve the hydrophilicity by forming a homogeneous pore structure on the surface of the metal material through corrosion. Accordingly, the coating layer may be effectively formed on the surface of the metal material.

Specifically, the metal material may be etched using the corrosion solution, and the corrosion solution may include 1 to 15 parts by weight of hydrofluoric acid solution based on 100 parts by weight of nitric acid solution and nitric acid solution.

The caustic solution may be a mixture of nitric acid solution and hydrofluoric acid solution. If the proportion of hydrofluoric acid solution in the corrosive solution is too low, not only does the corrosion process take a long time, but the surface roughness may not be well formed, and if it is too high, there may be a risk of explosion. Therefore, 1 to 15 parts by weight of hydrofluoric acid solution is added to 100 parts by weight of nitric acid solution.

On the other hand, the metal material may be etched in the corrosion solution for 1 to 30 minutes.

If etched for less than 1 minute, surface roughness may not be improved, and if etched for more than 30 minutes, further roughness improvement may be difficult to expect. Therefore, the metal material is etched into the corrosion solution for 1 to 30 minutes.

Next, a coating layer containing molybdenum disulfide (MoS ₂ ) is formed on the surface of the metal material.

In the case of a metallic material formed of a titanium material having a purity of 90% by weight or more, although biocompatibility is excellent, bacterial deposition may occur well, and there may be a risk of infection when used as a medical device.

Therefore, the formation of a coating layer that can prevent bacterial infection is required. In the case of a conventional coating layer of a polymer material such as PMMA, PEG, since the decomposition is made in the human body it is not possible to use long-term.

On the other hand, in the case of the coating layer containing molybdenum disulfide (MoS ₂ ), not only does not decompose well in the human body, but also has excellent antimicrobial properties and bacteria are not deposited well, so the metal material is formed of titanium material having a purity of 90% by weight or more. It can be coated on the surface to function as an optimal metal biomaterial.

Specifically, a coating layer may be formed on the metal material surface using 3-APTES (3-aminopropyltriethoxysilane).

Since both titanium and molybdenum disulfide (MoS ₂ ) have a negatively charged electrostatic attraction, the use of 3-APTES (3-aminopropyltriethoxysilane), which has a positively charged static attraction, is used to form molybdenum disulfide (MoS ₂ ) on the surface of the titanium-containing metal. It is possible to effectively form a coating layer comprising a). 3-aminopropyltriethoxysilane (3-APTES) can combine with the hydroxyl group (-OH) of titanium to form a terminally activated positively charged amine group (R-NH2). Molybdenum disulfide (MoS ₂ ) on the surface by the electrostatic attraction and can be effectively formed a nano-thick thin film through spin coating.

Metal biomaterial

Metal biomaterial according to an embodiment of the present invention is a titanium purity of 90% by weight or more, the average grain size is located on the surface of the metal material and the metal material of 100nm or less, and includes a coating layer containing molybdenum disulfide (MoS ₂ ).

The metal material is made of titanium by 90% by weight, and thus contains no toxic alloying elements as a biomaterial.

The average grain size of the metal material is formed to 100 nm or less, which is excellent in strength and ductility of the metal material. Accordingly, the tensile strength of the metal material may be 1000 MPa or more.

In addition, the surface area is improved by miniaturization of the grain size, so that the coating layer may be firmly formed.

On the other hand, in the case of the coating layer located on the metal material surface, it includes molybdenum disulfide (MoS ₂ ). As mentioned above, not only does not decompose well in the human body, but also has excellent antimicrobial properties and does not easily deposit bacteria, and thus is coated on a metal surface formed of titanium material having a purity of 90% by weight or more, thereby providing optimal metal biomaterial. It can function as a material.

The contact angle of the surface of the metal biomaterial on which the coating layer including molybdenum disulfide (MoS ₂ ) is formed may be 45 ° or less, and the surface energy may be 55 mJ / m ^{2 or} more.

That is, a metal biomaterial excellent in strength, antimicrobial activity and biocompatibility can be expected.

The thickness of the coating layer may be 1 to 100nm. If the thickness of the coating layer is less than 1nm, the antimicrobial activity may be weak, if the thickness of the coating layer exceeds 100nm, there may be a problem between the coating layer and the metal surface may cause a sustainability problem. Therefore, the thickness of the metal coating layer is controlled to 1 to 100 nm.

Hereinafter, specific examples of the present invention will be described. However, the following examples are only specific examples of the present invention, and the present invention is not limited to the following examples.

Example

Example 1: MS-ECAP

Pure titanium grade 4 was used as the metal material and the composition is shown in Table 1 below.

Alloy composition (at%) Ti Fe C O N H Example Bal. 0.3 0.052 0.34 0.015 0.015

Equal-channel angular pressing (ECAP) process was used to produce metals with ultrafine grains. Grade 4 rod-shaped metals with a diameter of 12 mm and coarse grains were used eight times at 200 ° C. -pass) Isoform angle compression was performed. Thereafter, a drawing process was performed to obtain a rod-shaped metal material having a diameter of 6.7 mm.

Next, as shown in FIG. 1, a coating layer including molybdenum disulfide (MoS ₂ ) was formed on the surface of the metal material using 3-APTES (3-aminopropyltriethoxysilane).

Example 2: MS-eECAP

To prepare a metal biomaterial in the same manner as in Example 1, before forming the coating layer on the metal surface, the surface of the metal material for 10 minutes using a corrosion solution containing 10 parts by weight of hydrofluoric acid solution with respect to 100 parts by weight of nitric acid solution and nitric acid solution Etched. Thereafter, a coating layer was formed in the same manner as in Example 1.

(Comparative Example 1: Ti)

A separate coating layer was not formed on the surface of the rod-shaped pure titanium grade 4 having the composition of Table 1 above.

(Comparative Example 2: MS-Ti)

The coating layer was formed on the surface of the metal material consisting of rod-shaped pure titanium Grade 4 having the composition of Table 1 in the same manner as in Example 1.

Property evaluation

(Physical property evaluation of metal materials)

Before the coating layer was formed, physical properties of the metal material of Example 1 and the metal material of Comparative Example 2 were evaluated. 2 is a microstructure image of a metal material obtained after the isopath angle compression process and drawing process. As can be seen in FIG. 2, it can be seen that the ultra-fine grain Ti metal of Example 1 having a grain size of about 100 nm than that of the Ti metal of Comparative Example 2 having coarse grains showed ultra high strength having a tensile strength of about 1166 MPa. Can be.

(Microstructure and surface observation)

3, scanning electron microscope (SEM) photographs of Example 1, Example 2, Comparative Example 1, and Comparative Example 2 may be confirmed. An atomic force microscope (AFM) photograph of Example 1, Example 2, Comparative Example 1, and Comparative Example 2 may be confirmed through FIG. 4.

As can be seen in Figure 3, it can be seen that a greater amount of molybdenum disulfide (MoS ₂ ) is observed in the examples than the comparative examples, as can be seen in Figure 4 and Table 2 below, the corrosion process It can be seen that rough surface roughness of Example 2 is the largest and the surface area is the widest.

Remarks R _a (nm) R _q (nm) R _max (nm) Surface area difference (%) division Ti 1.54 ± 0.37 2.51 ± 0.34 53 ± 12 0.12 ± 0.01 Comparative Example 1 MS-Ti 1.87 ± 0.31 2.74 ± 0.37 82 ± 18 0.22 ± 0.04 Comparative Example 2 MS-ECAP 4.04 ± 0.94 5.38 ± 1.33 71 ± 27 0.51 ± 0.06 Example 1 MS-eECAP 241 ± 116 333 ± 114 1786 ± 655 23.63 ± 2.32 Example 2

(Detection of Mo and S)

5, the amounts of Mo and S detected on the surfaces of Example 1, Example 2, Comparative Example 1, and Comparative Example 2 can be confirmed. This was detected using X-ray photoelectron spectroscopy (XPS). As can be seen in Figure 5, it was found that a greater amount of Mo and S was detected on the surface of the examples than the comparative examples, the highest detection amount of Mo and S in Example 2 subjected to the corrosion process.

(Wetability Analysis of Coating Layer Surface)

6, the degree of wettability at the surface of the coating layer of Example 1, Example 2, Comparative Example 1 and Comparative Example 2 can be confirmed. The degree of wettability can be confirmed through the contact angle and the surface energy. The smaller the contact angle, the greater the surface energy, the better the wettability.

As can be seen in Figure 6, the wettability of the examples were superior to the comparative examples, it can be seen that the most excellent wettability in Example 2 subjected to the corrosion process.

(Biocompatibility analysis of metal biomaterials)

The biocompatibility of Example 1, Example 2, Comparative Example 1 and Comparative Example 2 can be confirmed through FIG. Biocompatibility experiments were performed by incubating in each specimen for 7 days using pre-osteoblast cells. One, four, and seven days after culturing the cells, quantitative cell amounts were obtained using a microplate reader.

The greater the Cell Proliferation Ratio, the better the biocompatibility.

As can be seen in FIG. 7, the biocompatibility of the examples was superior to the comparative examples since the seventh day passed, and the biocompatibility of Example 2 which had undergone the corrosion process was the best. It can be seen that the cell proliferation tends to be similar to the wetting tendency. Wetting can affect cell activity because the more hydrophilic the surface, the better the extracellular matrix (ECM) protein, which is a medium that allows cells to deposit on metal surfaces. That is, cell deposition can be achieved on a more hydrophilic surface, which causes the cell proliferation tendency to be similar to the wettability.

(Antibacterial analysis of the coating layer surface)

8, the degree of antimicrobial activity of Example 1, Example 2, Comparative Example 1 and Comparative Example 2 can be confirmed. Antimicrobial experiments were carried out using Eschericia coli (E. Coli) bacteria for 6 hours in each specimen at 37 ℃ environment.

As can be seen in Figure 8, the antimicrobial properties of the examples were superior to the comparative examples, it can be seen that the most excellent antibacterial in Example 2 subjected to the corrosion process. ROS is a substance that helps kill bacteria and is an indicator of antimicrobial activity. In the case of ROS that can be detected through SOSG, it can be seen that it is generated in a similar trend to that of the coated amount of MoS ₂ as shown in FIG. 5.

(Continuity Analysis of Coating Layer Surface)

In the case of Figures 9 and 10, the coating on the implant specimens and then inserted into the artificial bone, it was confirmed the persistence of the coating layer containing MoS ₂ through the surface analysis. By confirming that the coating layer before the artificial bone insertion persists even after the insertion, it was confirmed that the long-term stability in the human body can be improved as a coating material for medical devices of MoS ₂ .

Therefore, when forming a coating layer containing MoS ₂ on the surface of the metal material containing titanium, it can have an antimicrobial effect while maintaining biocompatibility, it is possible to improve the antimicrobial properties of existing medical devices.

The present invention is not limited to the above embodiments and / or embodiments, but may be manufactured in various forms, and a person of ordinary skill in the art to which the present invention pertains may change the technical spirit or essential features of the present invention. It will be appreciated that it can be practiced in other specific forms without doing so. Therefore, it is to be understood that the embodiments and / or embodiments described above are illustrative in all respects and not restrictive.

Claims (12)

Rigidly deforming the metal material including titanium; And
And forming a coating layer including molybdenum disulfide (MoS ₂ ) on the surface of the plastically deformed metal material.
The rigid deformation of the metal material,
Providing a titanium material having a purity of 90% by weight or more and having a rod shape;
Compressing the metal material in an isopath angle; And
And drawing out the compressed metal material. delete The method of claim 1,
In the step of compressing the metal material in the constant channel angle,
A method of manufacturing a metal biomaterial, which is repeatedly compressed a plurality of times so that the average grain size of the metal material is 100 nm or less. The method of claim 1,
In the step of compressing the metal material in the constant channel angle,
Metal biomaterial manufacturing method for processing the metal material at 100 ℃ or more. The method of claim 1,
In the step of forming the coating layer,
Method of producing a metal biomaterial using the 3-APTES (3-aminopropyltriethoxysilane) to form the coating layer on the surface of the metal material. The method of claim 1,
After the rigid deformation of the metal material,
Corroding the surface of the plastically deformed metal material; metal biomaterial manufacturing method further comprising. The method of claim 6,
In the step of corroding the surface of the metal material,
Etch the metal material using a corrosion solution,
The corrosion solution comprises a 1 to 15 parts by weight of hydrofluoric acid solution, nitric acid solution and 100 parts by weight of the nitric acid solution. The method of claim 7, wherein
In the step of corroding the surface of the metal material,
Method for producing a metal biomaterial by etching the metal material in the corrosion solution for 1 to 30 minutes. A metal material having a titanium purity of 90% by weight or more and an average grain size of 100 nm or less; And
And a coating layer disposed on the surface of the metal material and including molybdenum disulfide (MoS ₂ ). The method of claim 9,
The coating layer has a thickness of 1 to 100 nm metal biomaterial. The method of claim 9,
The tensile strength of the metal material is 1000MPa or more metal biomaterial. The method of claim 9,
The contact angle of the surface of the metal biomaterial is 45 ° or less, the surface energy is 55 mJ / m ² or more metal biomaterial.

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