JP2019154598A - Biocompatible member - Google Patents

Abstract

To provide a biocompatible member in which the adhesion of a hydroxyapatite formed on a metal substrate is enhanced.SOLUTION: A biocompatible member 1 comprises a metal substrate 3 and a hydroxyapatite layer 5 that is directly or indirectly coated on the metal substrate 3. The coated surface 7 of the metal substrate 3 on which the hydroxyapatite layer 5 is coated has an arithmetic average height Sa of 0.2 μm or more and 1.0 μm or less and a surface roughness Str of 0.2 or more and 1.0 or less. The biocompatible member 1 has a high adhesion of the hydroxyapatite layer 5 to the metal substrate 3 without using an intermediate layer.SELECTED DRAWING: Figure 1

Description

  The present invention relates to a biocompatible member.

Development of biocompatible members that can be implanted in a living body is underway.
For example, Patent Document 1 discloses the following biocompatible member. That is, a biocompatible member is disclosed in which an intermediate layer made of CaTiO ₃ is formed on the surface of a titanium base material using hydrothermal treatment, and hydroxyapatite crystals are further deposited thereon. In this biocompatible member, the titanium base material and the hydroxyapatite layer are firmly adhered to each other by the intermediate layer made of CaTiO ₃ . This biocompatible member is chemically bonded to living bone by a hydroxyapatite layer.
Patent Document 2 discloses the following biocompatible member. That is, a biocompatible member in which the surface of a titanium base material or a titanium alloy base material (hereinafter also referred to as “titanium base material”) is coated with β-TCP and hydroxyapatite with a thickness of 10 μm or less is disclosed. In this biocompatible member, it is described that the surface roughness Ra of the titanium base material or the like is preferably 1.5 μm or more, or Rz is preferably 10 μm or more.

Special table 2013-508262 gazette JP 2001-340445 A

However, in the biocompatible members of Patent Document 1 and Patent Document 2, the adhesion of hydroxyapatite to a titanium substrate or the like was not always good. For this reason, the further improvement of adhesiveness was desired.
This invention is made | formed in view of the said situation, and it aims at providing the biocompatible member which improved the adhesiveness of the hydroxyapatite with respect to metal base materials, such as a titanium base material. The present invention can be realized as the following forms.

[1]
A biocompatible member comprising a metal substrate and a hydroxyapatite layer coated directly or indirectly on the metal substrate,
The surface of the metal substrate on which the hydroxyapatite layer is coated has an arithmetic average height Sa of 0.2 μm to 1.0 μm and a surface texture aspect ratio Str of 0.2 to 1.0. A biocompatible member characterized by being.

[2]
The biocompatible member according to [1], wherein the metal base material is titanium or a titanium alloy.

[3]
The biocompatible member according to [1] or [2], wherein the hydroxyapatite layer includes a hexagonal hydroxyapatite crystal aggregate.

The biocompatible member of the present invention has high adhesion of the hydroxyapatite layer to the metal substrate.
When the metal substrate is titanium or a titanium alloy, biocompatibility is increased.
When the hydroxyapatite layer contains a hexagonal hydroxyapatite crystal aggregate, in vivo stability is enhanced.

It is sectional drawing of a biocompatible member. It is sectional drawing of a biocompatible member. It is a figure which shows the scanning operation | movement of the nozzle in sandblasting. It is a figure which shows the scanning operation | movement of the nozzle in sandblasting. It is a photograph which shows the sample of Experimental example 1 after an adhesive evaluation test. It is a photograph which shows the sample of Experimental example 2 after an adhesive evaluation test. It is a photograph which shows the sample of Experimental example 3 after an adhesive evaluation test. It is a photograph which shows the sample of Experimental example 4 after an adhesive evaluation test. It is a photograph which shows the sample of Experimental example 5 after an adhesive evaluation test. It is a photograph which shows the sample of Experimental example 6 after an adhesive evaluation test.

  The present invention will be described in detail below. In addition, in this specification, in the description using "-" about a numerical range, unless there is particular notice, a lower limit and an upper limit shall be included. For example, the description “10 to 20” includes both “10” as the lower limit and “20” as the upper limit. That is, “10 to 20” has the same meaning as “10 to 20”.

1. Biocompatible member As shown in FIG. 1 or FIG. 2, the biocompatible member 1 of the present embodiment includes a metal base 3, a hydroxyapatite layer 5 directly or indirectly coated on the metal base 3, and Is provided. Here, indirect coating means the coating | cover provided with the intermediate | middle layer 6 between the metal base material 3 and the hydroxyapatite layer 5 (refer FIG. 2). The coated surface 7 of the metal substrate 3 covered with the hydroxyapatite layer 5 has an arithmetic average height Sa of 0.2 μm or more and 1.0 μm or less, and a surface texture aspect ratio Str of 0.2 or more and 1 0.0 or less. In addition, as far as the present inventors know, there was no biocompatible member that satisfies the above requirements.

(1) Metal base material Although the material of the metal base material 3 is not specifically limited, From a viewpoint of ensuring high biocompatibility, it is preferable that it is titanium or a titanium alloy.
Although titanium is not specifically limited, Pure titanium JIS 1-4 types are illustrated.
The titanium alloy is not particularly limited, but Nb (niobium), Ta (tantalum), W (tungsten), Zr (zirconium), P (phosphorus), Au (gold), Ca (calcium), Ag (silver), Pt (Platinum), Al (aluminum), V (vanadium), Si (silicon), B (boron), N (nitrogen), C (carbon), Pd (palladium), Y (yttrium), Hf (hafnium), Ir (Iridium), Mo (molybdenum), Fe (iron), Mg (magnesium), Na (sodium), and one or more elements selected from the group consisting of K (potassium), with the balance being Ti (titanium) and The titanium alloy which is an unavoidable impurity is illustrated.
The size, thickness, shape, etc. of the metal substrate are appropriately selected depending on the use of the biocompatible member.

(2) Intermediate layer The intermediate layer 6 is a layer formed between the metal substrate 3 and the hydroxyapatite layer 5. The material of the intermediate layer is preferably CaTiO ₃ from the viewpoint of chemically bonding the metal substrate 3 and the hydroxyapatite layer 5 and improving the adhesion.

(3) Hydroxyapatite layer The hydroxyapatite layer 5 is composed of hydroxyapatite (hydroxyapatite, Ca ₁₀ (PO ₄ ) ₆ (OH) ₂ , HAp). Hydroxyapatite is the main constituent of human bones and teeth. Hydroxyapatite has high biocompatibility and is widely used as an implant material for artificial bones, artificial tooth roots, and the like.
The shape of hydroxyapatite may be any of hexagonal columnar shape, needle shape, plate shape, and spherical shape. From the viewpoint of increasing the in vivo stability, it is preferable that the hydroxyapatite layer 5 includes a hexagonal hydroxyapatite crystal aggregate. When a hexagonal hydroxyapatite crystal aggregate is included, the crystallinity is high, and it is stable without being immediately dissolved in a living body. Therefore, in this case, it is estimated that good bone fixation characteristics can be secured.

(4) Surface roughness of metal substrate The coated surface 7 of the metal substrate 3 on which the hydroxyapatite layer 5 is coated has an arithmetic average height Sa of 0.2 μm or more and 1.0 μm or less, and has a surface property. The aspect ratio Str is 0.2 or more and 1.0 or less. The aspect ratio Str of the surface property represents the isotropic / anisotropy of the surface property. The closer to 0, the streaks are on the surface, and the closer to 1.0, the surface is independent of direction, in other words, there is no directionality. For this reason, the surface property can be quantitatively confirmed from the value of Str.
Sa and Str are both values measured according to ISO25178. When Sa and Str are within these ranges, the roughening on the coated surface 7 is isotropic, the anchoring of the hydroxyapatite layer 5 to the metal substrate 3 becomes homogeneous, and the adhesion between them is improved. When Sa is larger than 1.0 μm, the metal strength is lowered, so that it is preferably 1.0 μm or less. Even when Sa is 1.0 μm or less, the adhesiveness can be secured by setting Str within the range.
The arithmetic average height Sa is preferably 0.2 μm or more and 0.85 μm or less, and more preferably 0.2 μm or more and 0.7 μm or less.
The aspect ratio Str of the surface property is preferably 0.4 or more and 1.0 or less, and more preferably 0.6 or more and 1.0 or less.
In addition, the measurement of Sa of the metal base material 3 with which the hydroxyapatite layer 5 was coat | covered is performed in the following procedures.
An adhesive (FM1000 ADHESIVE FILM manufactured by Solvay) is applied on the hydroxyapatite layer 5 of the metal substrate 3 coated with the hydroxyapatite layer 5, and a tensile test jig is adhered. After the adhesive is cured at 176 ° C. for 3 hours, a tensile test is performed in accordance with ASTM F 1147-05: 2011. After the tensile test is performed, Sa and Str are measured according to ISO25178 at locations where the hydroxyapatite layer and the intermediate layer are peeled off and the metal substrate is exposed.

2. Manufacturing method of biocompatible member The manufacturing method of the biocompatible member 1 is not specifically limited. For example, the hydroxyapatite layer 5 may be formed on the surface of the metal substrate 3 by thermal spraying or the like. Here, a preferred example of the method for manufacturing the biocompatible member 1 will be described. In this example, the surface of the metal substrate 3 is roughened, and then the hydroxyapatite layer 5 is formed.
(1) Roughening treatment of the surface of the metal base material In the roughening treatment, the arithmetic average height Sa of the coated surface 7 of the metal base material 3 is finally 0.2 μm or more and 1.0 μm or less, and the surface properties If it can process so that aspect ratio Str may be 0.2 or more and 1.0 or less, it will not specifically limit. For example, blasting, etching and the like can be mentioned, and these can be used alone or in combination of two or more.
Examples of the blasting include sand blasting and wet blasting. From the viewpoint that the operation is simple, sandblasting can be mentioned as a suitable example. The type and particle size of the abrasive used for the sandblast treatment are not particularly limited.
As the abrasive, for example, alumina, cinnabar sand, gold sand, glass, silicon carbide, titanium oxide, zirconia, diamond and the like can be suitably used.

As long as the etching can be performed so that the arithmetic average height Sa and the surface texture aspect ratio Str are within the above-described ranges, the type of the treatment liquid and the treatment conditions are not particularly limited.
Here, a suitable example of etching will be described. In the first aspect of etching, a treatment liquid A having the following composition can be used. A procedure for performing alkali degreasing, washing with water, etching, washing with water, and drying in this order on the surface of the metal substrate 3 is a suitable treatment procedure. In the case of the treatment liquid A, the treatment time is not particularly limited, but is preferably 10 to 30 seconds, more preferably 15 to 25 seconds, and further preferably 18 to 22 seconds.

<Composition of Treatment Solution A> (The following composition is based on weight. The following component may be contained as an essential component, and may contain other components. Treatment Solution A is an aqueous solution. .)
Nitric acid: 55-60%
Hydrogen fluoride: 13.0 to 14.0%
Ammonium monofluoride: 1.0-1.4%

In the second aspect of etching, a treatment liquid B having the following composition can be used. A procedure in which the surface of the metal base 3 is degreased, etched, washed with water, pickled, washed with water, and dried in this order is a suitable processing procedure. In the case of the treatment liquid B, the treatment time is not particularly limited, but is preferably 70 to 170 seconds, more preferably 90 to 150 seconds, and further preferably 110 to 130 seconds.

<Composition of Processing Solution B> (The following composition is based on weight. The following component may be included as an essential component, and other components may be included. Processing Solution B is an aqueous solution. .)
Hydrogen peroxide: 18-22%
Ammonium monofluoride: 8-12%
Sulfuric acid: less than 5%

(2) Formation of Hydroxyapatite Layer A known method can be employed to form the hydroxyapatite layer 5.
The synthetic solution used for forming the hydroxyapatite layer 5 contains calcium ions, hydroxide ions, organic phosphate esters, chelating agents, and water from the viewpoint of producing highly crystalline hexagonal hydroxyapatite. Is preferred.
The calcium ion source is not particularly limited. For example, at least one selected from the group consisting of calcium nitrate, calcium hydroxide, calcium carbonate, calcium acetate, calcium halide, calcium oxide, and calcium phosphate is preferably used. Can do.
The hydroxide ion source is not particularly limited. For example, the hydroxide ion source is a hydroxide-containing compound such as potassium hydroxide, ammonium hydroxide, calcium hydroxide or sodium hydroxide, or in an aqueous solution such as ammonia or calcium oxide. At least one selected from compounds that generate physical ions can be suitably used.
The organic phosphate ester is not particularly limited, and for example, at least one selected from the group consisting of triethyl phosphate, trimethyl phosphate, tributyl phosphate, and triphenyl phosphate can be suitably used.
Although a chelating agent is not specifically limited, For example, EDTA (ethylenediaminetetraacetic acid) can be used conveniently.

Here, a preferable blending ratio of various components in the synthesis solution will be described. It is preferable that each component is added in the following range with respect to 1000 g of water.
The addition amount of the calcium ion source is preferably 30 to 80 g, more preferably 40 to 70 g, and still more preferably 50 to 60 g as a hydrate.
The addition amount of the hydroxide ion source is preferably 80 to 130 g, more preferably 90 to 120 g, and still more preferably 100 to 110 g.
The addition amount of the organic phosphate is preferably 10 to 60 g, more preferably 20 to 50 g, and still more preferably 30 to 40 g.
The addition amount of a chelating agent becomes like this. Preferably it is 40-90g, More preferably, it is 50-80g, More preferably, it is 60-70g.

Note that a preliminary solution (1) containing hydroxide ions and a preliminary solution (2) containing calcium ions, a chelating agent, and an organic phosphate ester are prepared in advance, and both may be mixed to form a synthetic solution. Moreover, you may prepare the synthesis solution which added all the components from the beginning.
From the viewpoint of the homogeneity of the synthesis solution, it is preferable to prepare the preliminary solution (1) and the preliminary solution (2) in advance and mix them to obtain a synthetic solution.

In the formation of the hydroxyapatite layer 5, the synthetic solution is brought into contact with the roughened surface (coating surface 7) of the metal substrate 3 and heated. Although heating temperature is not specifically limited, Preferably it is 160-250 degreeC, More preferably, it is 170-230 degreeC, More preferably, it is 180-220 degreeC.
Moreover, when heating, it is preferable to apply a pressure larger than atmospheric pressure. For this purpose, it is preferable to use a pressure-resistant reaction vessel.
The reaction time is not particularly limited, but is preferably 4 to 12 hours, more preferably 6 to 10 hours, and still more preferably from the viewpoint of covering the entire surface of the substrate and forming a homogeneous hydroxyapatite film. Is 7-9 hours.

The present invention will be described more specifically with reference to examples.
Experimental examples 3 to 5 correspond to examples, and experimental examples 1, 2, and 6 are comparative examples.

1. Production of Biocompatible Member As the metal substrate 3, a Ti-6Al-4V 15 mm square substrate was used.
In Experimental Examples 2 to 6, each sample was prepared by sequentially performing a cleaning process, a roughening process, and a hydrothermal treatment on the metal substrate 3.
In Experimental Example 1, the metal substrate 3 was subjected to washing treatment and hydrothermal treatment in order to produce a sample. That is, in Experimental Example 1, the roughening process is not performed.
The details of the washing treatment, roughening treatment, and hydrothermal treatment are as follows.

<Cleaning process>
Ultrasonic cleaning was performed for 5 minutes each with acetone, ethanol, and pure water.

<Roughening treatment>
(Experimental example 1)
Roughening is not performed.
(Experimental example 2)
For the roughening treatment, sandpaper # 100 was used.
(Experimental example 3)
Sand blasting was performed under the conditions shown in Table 1 below. The arrows in FIGS. 3 and 4 indicate the movement of the nozzle on the metal substrate 3. After scanning the nozzle as shown in FIG. 3, the operation of scanning the nozzle as shown in FIG. 4 was repeated alternately. At this time, the nozzle was scanned at approximately the same speed. By scanning in this way, the entire surface of the metal substrate 3 could be roughened to the same extent.
In Table 1, the particle size is “F220”, which is an index of the particle size of the abrasive according to JIS R6001-1998.

(Experimental example 4)
As the roughening treatment, chemical etching described in Table 2 below was performed. “%” In the liquid type is based on weight.

(Experimental example 5)
As the roughening treatment, chemical etching described in Table 3 below was performed. “%” In the liquid type is based on weight.

(Experimental example 6)
As roughening treatment, buffing was performed.

<Measurement of surface roughness of metal substrate>
The surface roughness of each metal substrate 3 of Experimental Examples 1 to 6 was measured according to the description in Table 4 below.

<Hydrothermal treatment>
Hydrothermal treatment was performed as follows. Calcium nitrate, triethyl phosphate, EDTA, and potassium hydroxide were dissolved in pure water to prepare a synthesis solution.
The synthetic solution and the metal substrate 3 were put into a pressure resistant reaction vessel equipped with an inner cylinder made of Teflon (registered trademark), and hydrothermal treatment was performed.
Details of the hydrothermal treatment will be described.

(Preparation of solution A)
A solution A was prepared by dissolving 207.84 g of potassium hydroxide in 300 g of pure water.
(Preparation of solution B)
Solution B was prepared by mixing 109.58 g of calcium nitrate tetrahydrate, 135.60 g of EDTA, 68.12 g of triethyl phosphate, and 1700 g of pure water.
(Preparation of synthesis solution)
Solution A was slowly added to Solution B to prepare a synthesis solution.

(Synthesis method)
The metal substrate 3 and the synthesis solution were placed in the inner cylinder container, and the metal substrate 3 was immersed in the synthesis solution. After sealing the pressure resistant reactor, the temperature was raised to 200 ° C. over 8 hours and maintained at 200 ° C. for 8 hours.

2. Adhesion Evaluation Method The adhesion of the hydroxyapatite layer 5 to the metal substrate 3 was evaluated using ASTM number D3359-09. The number of samples was 3 (n = 3).

3. Adhesion evaluation results Table 5 shows the adhesion evaluation results. Moreover, the state after the evaluation test of each sample is shown in FIGS. FIG. 5 shows a sample of Experimental Example 1. FIG. 6 shows a sample of Experimental Example 2. FIG. 7 shows a sample of Experimental Example 3. FIG. 8 shows a sample of Experimental Example 4. FIG. 9 shows a sample of Experimental Example 5. FIG. 10 shows a sample of Experimental Example 6. Each experimental example has three samples, but FIGS. 5 to 10 show representative examples of the three samples.

In Table 5, “# 100” means processing using sandpaper # 100. “S-22” means chemical etching using ESTRAIN S-22. “TCP-09” means chemical etching using clean etch TCP-09.
“XXX” indicates that all three samples have poor adhesion evaluation.
“◯◯◯” indicates that the adhesion evaluation is good in all three samples.

From the results of Table 5, Experimental Examples 3 to 5 in which the arithmetic average height Sa is 0.2 μm to 10 μm and the surface texture aspect ratio Str is 0.2 to 1.0 are based on the metal substrate 3. It was found that the adhesion of the hydroxyapatite layer 5 was high. On the other hand, in Experimental Example 6 in which the arithmetic average height Sa was less than 0.2 μm, the adhesion of the hydroxyapatite layer 5 to the metal substrate 3 was low. Further, in Experimental Examples 1 and 2 having a surface texture aspect ratio Str of less than 0.2, the adhesion of the hydroxyapatite layer 5 to the metal substrate 3 was low.
As shown in FIGS. 7, 8, and 9, in Experimental Examples 3 to 5, the portion where the hydroxyapatite layer 5 is formed is scratched with a cutter in accordance with ASTM number D3359-09, and the tape is attached. Even after peeling, the hydroxyapatite layer 5 hardly peeled off. On the other hand, as shown in FIGS. 5, 6, and 10, in Examples 1, 2, and 6, the hydroxyapatite layer 5 was considerably peeled after the same test.
From the above results, in the biocompatible member 1, when the arithmetic average height Sa and the surface property aspect ratio Str of the coated surface 7 on which the hydroxyapatite layer 5 of the metal substrate 3 is coated are in a specific range, the metal It was confirmed that the adhesion of the hydroxyapatite layer 5 to the substrate 3 was high.

<Other Embodiment (Modification)>
In addition, this invention is not restricted to said Example and embodiment, In the range which does not deviate from the summary, it is possible to implement in various aspects.

DESCRIPTION OF SYMBOLS 1 ... Biocompatible member 3 ... Metal base material 5 ... Hydroxyapatite layer 6 ... Intermediate | middle layer 7 ... The surface (coating surface) by which the hydroxyapatite layer is coat | covered

Claims (3)

A biocompatible member comprising a metal substrate and a hydroxyapatite layer coated directly or indirectly on the metal substrate,
The surface of the metal substrate on which the hydroxyapatite layer is coated has an arithmetic average height Sa of 0.2 μm to 1.0 μm and a surface texture aspect ratio Str of 0.2 to 1.0. A biocompatible member characterized by being.   The biocompatible member according to claim 1, wherein the metal base material is titanium or a titanium alloy.   The biocompatible member according to claim 1, wherein the hydroxyapatite layer includes a hexagonal hydroxyapatite crystal aggregate.