JP2000210313A - Bone substitutive material having excellent bioaffinity - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a bone substitutive material which is uniformly formed with a layer exhibiting good bioaffinity in the rugged portions of a base material by a simple method and exhibits a sufficient shearing strength. SOLUTION: This bone substitutive material is formed with ruggedness on the surface of the base material made of titanium or titanium alloy which is a bonding surface to the vital tissue. The root diameter W of the projecting parts of the ruggedness is >=40 zmm in average. An alkali titanate layer 21 having >=35 atm.% in oxygen concentration is formed across a depth of 0.5 to 2 μm in the ruggedness. The layer 21 has the good bioaffinity. The core portions of the projecting parts are titanium or titanium alloy portions 12 and, therefore, thin film the strength of the projecting parts is sufficiently assured and, then, the possibility that the projecting parts are dislodged is extremely little in spite of the exertion of external force.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a bone substitute material such as an artificial bone, an artificial joint or an artificial tooth root, and more particularly to a bone substitute material having excellent biocompatibility.

[0002]

2. Description of the Related Art In repairing damaged or missing bones, joints, dental roots, and the like, bone substitute materials such as artificial bones, artificial joints, and artificial roots are sometimes used. Such a bone substitute material is required to have sufficient strength and good biocompatibility. Therefore, the material of the bone substitute material is selected, and various measures are taken for the surface condition. ing.

For example, a bone substitute material having irregularities formed on the surface of a substrate has been proposed (conventional example). In the conventional bone substitute material, after being implanted in the body, a new living bone tissue penetrates and grows in the concave portion of the bone substitute material, and exerts a strong fixing force by the anchor effect of the new bone.

[0004] As a method of forming the irregularities, there are a method by sandblasting and a method by thermal spraying of fine powders (arc spraying, plasma spraying).

[0005] As an improvement of the above conventional example,
After forming irregularities on the surface of the base material as described above, a bioactive substance (for example, bioglass, biocrystallized glass, A
Bone substitute materials coated with W glass, hydroxyapatite, tricalcium phosphate) have been proposed. (Conventional example: JP-A-6-154257).
This conventional bone substitute material is more excellent in biocompatibility than the above-mentioned conventional one, has good penetration and growth of a new living tissue, and has an effect that the bone substitute material can be securely fixed to living bone. .

On the other hand, there has been proposed a bone substitute material in which the surface of a substrate is chemically changed to improve biocompatibility (conventional example: Patent No. 2775523). The bone substitute material of the conventional example is obtained by immersing a substrate made of titanium (or a titanium alloy) in an alkali solution and then heating (hereinafter, this treatment may be referred to as an alkali treatment) to oxidize the surface of the substrate. A film (alkali titanate layer) containing a titanium phase and an amorphous phase of an alkali titanate is formed.

[0007]

By the way, although the bone substitute material of the above-mentioned conventional example has an improved fixing force as compared with the conventional example, the bioactive substance such as the bioglass has a relatively high viscosity. For this reason, it is difficult to uniformly cover the inside of the concave portion with the bioactive substance. Therefore, there is an uncovered portion, and it is not expected to improve the fixing force by that amount.

On the other hand, as a method of coating the bioactive substance all over the recess, a method has been proposed in which a substrate having irregularities is exposed to a vacuum environment and immersed in a suspension of the bioactive substance ( Conventional Example: JP-A-4-2341).

[0009] However, since this method requires a complicated process, it is desired to form a layer having good biocompatibility by a simpler method.

In view of the above, a method is conceivable in which an alkali titanate layer is formed on an uneven portion by applying the above-mentioned alkali treatment to the substrate having the unevenness formed on the substrate surface (conventional example) as in the conventional example. The alkali treatment in the above-mentioned conventional example can be expected to be performed to the inside of the concave portion because the viscosity of the alkaline solution used is low.

However, if the conventional example is simply applied to the conventional example, a problem may occur in the bonding strength between the bone substitute material and the living bone.

That is, for example, when the convex portion is thin or the alkali titanate layer is formed deep, the entire convex portion becomes the alkali titanate layer 11 (FIG. 7: sectional view of the bone substitute material surface), Since the alkali titanate layer is weak in strength, the above-mentioned projections easily fall off. In FIG. 7, 1
Reference numeral 2 denotes a portion of the base material which remains titanium or a titanium alloy (a portion which has not been chemically changed by the alkali treatment).

In other words, even if new bone invades and grows on the irregularities of such a bone substitute material and the bone substitute material and the living bone are combined, when a strong external force is applied, the above-mentioned projections together with the invaded new bone form the bone substitute. The problem of falling off from the material main body arises. That is, sufficient shear strength cannot be obtained. In particular, when a bone substitute material (for example, a bone substitute material for a femur) is used in a place where a load is large, such as a hip joint, a strong force is applied, so that there is a high risk that the bone substitute material is separated from the living bone.

It is to be noted that a bioglass or the like is applied to the uneven surface of the base material.
In the formed bone substitute material of the above-mentioned conventional example, a coating is formed on the surface of the base material, and the base material (for example, titanium) itself does not change, so that the projections have sufficient strength. Therefore, there is no possibility that a problem such as dropout of the convex portion occurs as described above.

Therefore, in the present invention, in a simple manner,
It is an object of the present invention to provide a bone substitute material in which layers exhibiting good biocompatibility are uniformly formed on uneven portions of a substrate and exhibit sufficient shear strength.

[0016]

Means for Solving the Problems The bone substitute material having excellent biocompatibility according to the present invention is a bone substitute having irregularities formed on the surface of a substrate made of titanium or a titanium alloy and having a joint surface with a living tissue. In the material, the root diameter of the convex portions of the irregularities is 40 on average.
The gist is that the alkali titanate layer having an oxygen concentration of 35 atomic% or more is formed over a depth of 0.5 to 2 μm.

FIG. 1 is a schematic sectional view showing a surface portion of a bone substitute material according to the present invention. As shown in FIG. 1, the bone substitute material of the present invention has an alkali titanate layer 21 having an oxygen concentration of 35 atomic% or more (hereinafter, may be referred to as a high-concentration alkaline titanate layer) 21 formed on the surface. However, since the core portion of the convex portion is a base material made of titanium or a titanium alloy (titanium or titanium alloy portion 12), the strength of the convex portion is sufficiently ensured, and therefore, even if an external force is applied, the convex portion is convex. The risk of the part falling off is extremely small.

In FIG. 1, reference numeral 22 denotes an alkali titanate layer having an oxygen concentration of less than 35 atomic% (hereinafter sometimes referred to as a low-concentration alkaline titanate layer). In other words, the outermost surface of the alkali titanate layer has the highest oxygen concentration and gradually decreases toward the deep portion, but the low-concentration alkali titanate layer 22 separates the high-concentration alkali titanate layer 21 from titanium or titanium alloy. This is the transition to the part 12.

Although the alkali titanate layer has relatively good biocompatibility, an alkali titanate layer having an oxygen concentration of 35 atomic% or more is formed on the outermost surface in order to exhibit extremely good biocompatibility. Need to be done. The high-concentration alkali titanate layer has a good affinity for living bone chemically and, in addition, the outermost surface of the high-concentration alkali titanate layer has a three-dimensional network structure (FIG. 2: the present invention). An electron micrograph showing the outermost surface of such a bone substitute material [5000]
Fold]), the contact area with the new bone is very large, and therefore, the bone can be bonded very well. Therefore, living bone tissue penetrates and grows well in the recess of the bone substitute material,
The living bone and the bone substitute material adhere strongly.

However, if the thickness of the high-concentration alkali titanate layer is more than 2 μm, the alkali titanate layer may fall off and sufficient mechanical strength cannot be secured.
When the thickness is less than 0.5 μm, the affinity with the living body is not sufficient, and for example, when immersed in a simulated body fluid, formation of hydroxyapatite is not recognized. Therefore, as described above, the thickness (depth from the outermost surface) of the high-concentration alkaline titanate layer is set to 0.5 to 2 μm. More preferably, it is 0.7 μm or more and 1.7 μm or less.

In addition, since the above alkali titanate layer is produced by changing the layer on the surface of the substrate, it differs from the conventional example in which a bioactive substance is applied to the surface of the substrate, unlike the conventional example. The uneven shape of the material can be left as it is, that is, without smoothing by filling the unevenness, a good anchoring effect can be exhibited. In addition, the alkali liquid used for forming the alkali titanate layer has a low viscosity and can penetrate well into the inside of the concave portion, so that the alkali titanate layer can be uniformly formed on the surface of the base material, and therefore an improvement in the fixing force can be expected. .

As described above, the root diameter of the projections (W in FIG. 1) of the projections and depressions needs to be 40 μm or more on average, and thus most of the projections have a sufficient thickness. Therefore, as described above, there is a sufficient amount of protrusions in which the core portion remains titanium (or titanium alloy), and therefore, a good shear strength is exhibited. The variation of the root diameter of the convex portion of each convex portion formed on the base material has a substantially normal distribution, and the average of the root diameter of the convex portion generally indicates the maximum frequent value of the root diameter of the convex portion.

In the case where the projection has a constricted shape, the diameter of the neck portion is used as the root diameter of the projection. If the diameter of the neck portion is small, the neck portion may be broken.

Further, it is preferable that the root diameter of the convex portion is 50 μm or more on average. On the other hand, the average is preferably not more than 300 μm. If the projections are too large, the anchor effect due to the invasion of the new bone into the irregularities cannot be expected.

The substrate of the bone substitute material of the present invention is made of titanium or a titanium alloy as described above, and such a substrate can exhibit sufficient strength. Examples of the titanium alloy include a titanium alloy containing at least one of aluminum, vanadium, molybdenum, zirconium, niobium, tantalum, and the like.

Further, in the present invention, it is preferable that the concave portion in the unevenness satisfies the following expression (1).

(Number of concave portions having a size of 200 to 300 μm) / (number of concave portions having a size of 100 to 500 μm) ≧ 0.3 (1)

That is, three concave portions having a concave portion diameter of 200 to 300 μm
If it is formed with a frequency of occurrence of 0% or more, the new bone penetrates and grows in the concave portion to exhibit a good anchoring effect.
If the diameter of the recess is more than 300 μm, it takes a long time for the new bone to grow in the recess, which is not preferable. On the other hand, if the diameter of the recess is less than 200 μm, the new bone grows in the recess. However, the anchor effect is not sufficient because it is small.

As described above, a concave portion having an average root diameter of the convex portion of 40 μm or more and a concave portion diameter of 200 to 300 μm as described above is assumed to be a concave and convex shape capable of exhibiting a sufficient anchor effect and not causing the convex portion to fall off. Is more preferable, the combination of which is 30% or more and the high concentration alkali titanate layer is 0.5 to 2 μm.

[0030]

Next, a method for producing a bone substitute material according to the present invention will be described. First, a method for forming irregularities on the surface of a titanium or titanium alloy substrate will be described.

Titanium or titanium alloy powder / granules are fused to a titanium or titanium alloy base material by a plasma spraying method. Specifically, for example, a plasma gun having two powder ports is prepared, and a particle size of 100 is obtained from one port.
~ 500μm titanium (or titanium alloy) powder is ejected, titanium (or titanium alloy) powder having a particle size of 50μm or less is ejected from another port, and plasma is alternately directed toward the substrate surface from each port. By performing the thermal spraying, a concave / convex layer having an average root diameter of the convex portion of 40 μm or more and a concave portion having a diameter of 200 to 300 μm of 30% is formed on the surface of the base material.

The irregularities formed in this way are irregular in size and arrangement, and the inside of the concave portion has a complicated cave shape. When the new bone tissue penetrates into the unevenness of such a structure, it is hard to come out, and thus an extremely strong fixing force is achieved.

In addition to the above thermal spraying method, the irregularities can also be formed by sandblasting the surface of a titanium or titanium alloy base material. Next, a method of forming an alkali titanate layer will be described.

The titanium or titanium alloy substrate provided with the irregularities as described above is immersed in an aqueous alkali solution to form a hydrated gel layer of sodium titanate, and then fired to obtain a dense amorphous material. An alkali titanate layer can be formed. Specifically, for example, 2 at 50 to 80 ° C.
It is immersed in a 5N alkaline aqueous solution for about 24 to 48 hours, and then heat-treated at around 600 ° C. Since the alkaline aqueous solution has low viscosity, it can spread all the way inside the recess,
Therefore, uneven portions can be uniformly processed without forming a non-alkali treated portion.

As a result, an alkali titanate layer having an oxygen concentration of 35 atomic% or more is uniformly formed at a depth of 0.5 to 2 μm from the outermost surface.

The high-concentration alkali titanate layer has good biocompatibility, and for example, forms hydroxyapatite when immersed in a simulated body fluid. The hydroxyapatite is composed of almost the same components as living bone, and these strongly bind. That is, the high-concentration alkaline titanate layer is bonded to living bone via hydroxyapatite.

For example, when sodium hydroxide is used as the alkaline aqueous solution, a sodium titanate layer is formed as the alkali titanate layer, and when potassium hydroxide is used as the alkaline aqueous solution, the alkali titanate layer is formed. A potassium titanate layer is formed.

The bone substitute material thus obtained exhibits a very strong fixation force to living bone due to the good affinity of the surface and the anchor effect based on the irregularities.

When a high-temperature heat treatment is performed in the production of the bone substitute material, the shear strength is reduced. However, in the production of the bone substitute material according to the present invention, the heat treatment is performed at about 600 ° C. as described above. And the temperature is lower than the transformation point of the titanium alloy, so that the shear strength is not significantly reduced. For example, the shear strength of the uneven part after treatment is 90 to
Since the strength of the bone substitute material of the present invention is 110 MPa and does not lower than that before the treatment with the aqueous alkali solution, the bone substitute material of the present invention can be used favorably even in a large-sized and heavy-load portion such as a hip joint.

In the case of a substrate in which a bioactive substance such as bioglass is coated on the uneven surface of the substrate as in the conventional example, a heat treatment generally exceeding 1000 ° C. is required for the production thereof, and this heat treatment causes There is a problem that the shear strength of the base portion and the uneven layer is reduced. For example, while the shear strength before coating the bioactive substance is around 100 MPa, the shear strength after coating is 30 to 50 MPa (300 to 500 kgf / cm ^2). ).

The surface of the uneven portion was cut in a direction perpendicular to the surface, and this cross section was photographed with a scanning electron microscope (SEM), and the image was analyzed based on the obtained image. Preferably, it is 70%. The porosity is 30
%, The amount of new bone invading into the recesses (voids) is small, and it is difficult to obtain a sufficient fixation force, while the porosity is 70%.
This is because, in the case of exceeding, although the amount of bone that penetrates into the concave part increases, the strength of the concave and convex part is insufficient and the convex part may fall off. More preferably, the porosity is 45% or more and 65% or less.

It is preferable that the concaves and convexes have a wide inside of the concave portion or that the concave portion is bent inside, so that a stronger anchor effect can be expected.

[0043]

EXAMPLES Hereinafter, the bone substitute material according to the present invention will be described in detail with reference to examples, but the present invention is not limited to the examples, and may be adapted to the above and following points. The present invention can be implemented with appropriate modifications within the scope, and all of them are included in the technical scope of the present invention.

<Experiment 1> Pure titanium powder and pure titanium powder were plasma-sprayed on a titanium alloy (Ti.6Al.2Nb.1Ta) cylindrical base material having a diameter of 4 mm and a length of 10 mm.
An unevenness of 0.7 mm was formed. Sample Nos. 1 to 8 were immersed in aqueous sodium hydroxide solutions having various concentrations shown in Table 1 for 48 hours, and then washed in pure water using an ultrasonic cleaner. Then, after drying, 600-
Heat treatment was performed at 650 ° C. for 1 hour. Sample No. 9 was left as it was without alkali treatment.

As an example, a scanning electron micrograph (× 1000) of the surface of sample No. 4 is shown in FIG.

The thicknesses of the high-concentration alkali titanate layers of Sample Nos. 1 to 8 are as shown in Table 1 below. The thickness of the high-concentration alkali titanate layer was determined by Auger electron spectroscopy.

FIG. 3 shows the result of Auger electron spectroscopy of Sample No. 4 as an example. As can be seen from FIG. 3, the alkali titanate layer having an oxygen concentration of 35 atomic% or more is 0.83 μm.
m is formed.

Sample No. 9 not subjected to alkali treatment
The layer having an oxygen concentration of 35 atomic% or more was less than several tens nm.

[0049]

[Table 1]

For Samples 1 to 8, the concave diameter was 200 to 30.
When the frequency of occurrence of 0 μm concave portions was examined, it was 43%. The frequency of occurrence of the concave portions was determined by observing the concave and convex portions by vertically cutting the surface of the base material, setting the number of concave portions of 100 to 500 μm as the total number of concave portions, and setting the ratio to the total number.

As an example, FIG. 4 shows the frequency of occurrence of concave portions of each size for sample No. 4. From FIG.
It can be seen that the frequency of occurrence of 300 μm concave portions is 43%.

Next, each of the above sample Nos. 1 to 9 was immersed in a simulated body fluid, and the formation state of the hydroxyapatite layer was examined. The results are shown in Table 1.

FIG. 6 shows a scanning electron micrograph (× 1000) of the surface of Sample No. 4 as an example. FIG.
As shown in Fig. 5, a hydroxyapatite layer is formed on the uneven surface of the bone substitute material.

As can be seen from Table 1, for example, sample Nos. 1 and 2
When the high-concentration alkali titanate layer is thin as in the above, it can be seen that the ability to form hydroxyapatite is inferior and the biocompatibility is relatively poor. On the other hand, when the high-concentration alkali titanate layer was as thick as 2.5 μm or more as in Sample Nos. 7 and 8, cracks were generated on the bone substitute material surface. On the other hand, it can be seen that the samples of Sample Nos. 3 to 6 had good hydroxyapatite formation without cracks in the bone substitute material and good biocompatibility.

The thickness of the high concentration alkali titanate layer is
It can be adjusted by changing the concentration of the alkaline aqueous solution as described above, and by changing the temperature and the immersion time of the alkaline aqueous solution.

<Experiment 2> A disk-shaped substrate made of a titanium alloy (Ti.6Al.2Nb.1Ta) having a diameter of 20 mm and a length of 13 mm was prepared.
Pure titanium powder and pure titanium powder were plasma-sprayed to form irregularities having a thickness of 0.7 mm. Sample No. 10-1
7 was immersed in aqueous sodium hydroxide solutions having various concentrations shown in Table 2 for 48 hours, and then washed with pure water using an ultrasonic cleaner. Then, after drying, heat treatment was performed at 600 to 650 ° C. for 1 hour using a firing furnace. Sample No. 18
Was not subjected to alkali treatment, and was left as it was. Sample No. 19 was also not subjected to the alkali treatment, and after forming the irregularities as described above, AW glass was applied to the irregular surface of the substrate and heat-treated at 1000 ° C.

The thicknesses of the high-concentration alkali titanate layers of Sample Nos. 10 to 17 are as shown in Table 2 below.

The shear strength of each of Samples 10 to 19 was measured. As a measuring method, an opposing test piece made of a titanium alloy (Ti · 6Al · 2Nb · 1Ta) having no unevenness and each of the above sample Nos. 10 to 19 were respectively bonded to a bonding agent (Ti ·
(15Ni.15Cu), and a force was applied so as to shift the joint surface between the opposing test piece and the sample, and the shear strength of the uneven portion was measured. The results are shown in Table 2.

[0059]

[Table 2]

As can be seen from Table 2, the bone substitute materials of Sample Nos. 10 to 15 exhibited a good shear strength of 80 MPa or more.

[0061]

As described above, the bone substitute material according to the present invention is
By a simple method, layers exhibiting good biocompatibility are uniformly formed on the uneven surface of the base material, thereby exhibiting excellent biocompatibility and having sufficient shear strength.

[Brief description of the drawings]

FIG. 1 is a schematic sectional view showing a surface portion of a bone substitute material according to the present invention.

FIG. 2 is an electron micrograph [5000 times] showing an example of the outermost surface of a bone replacement material according to the present invention (fine network structure of uneven portions treated with an alkaline aqueous solution).

FIG. 3 shows a sample N which is an embodiment of the bone substitute material according to the present invention.
o. Graph showing the results of Auger electron spectroscopy analysis for o.

FIG. 4 shows a sample N which is an embodiment of the bone substitute material according to the present invention.
o. Graph showing the frequency of occurrence of concave portions of each size for o.

FIG. 5 shows a sample N which is an embodiment of the bone substitute material according to the present invention.
o. Scanning electron micrograph of the surface for 4 [1000
Times] (Surface structure of uneven portion treated with alkaline aqueous solution).

FIG. 6 is a scanning electron micrograph (× 1000) of the surface of sample No. 4 on which hydroxyapatite was formed.

FIG. 7 is a cross-sectional view of a bone replacement material surface for explaining a problem.

[Explanation of symbols]

 11 Alkali titanate layer 12 Titanium or titanium alloy part 21 High concentration alkaline titanate layer 22 Low concentration alkaline titanate layer

 ──────────────────────────────────────────────────続 き Continuing on the front page (72) Inventor Yoshio Sasaki 1-3-18 Wakihama-cho, Chuo-ku, Kobe Kobe Steel, Ltd. No. 3-18 Kobe Steel Ltd. Kobe Head Office F-term (reference) 4C081 AB03 AB05 AB06 BA13 CG02 CG03 DB07 DC03 DC04 DC05 DC06 4C097 AA01 AA03 AA30 BB10 CC02 CC03 DD10

Claims (2)

[Claims] 1. A bone substitute material having a surface of a titanium or titanium alloy substrate having irregularities formed on a bonding surface with a living tissue, wherein the irregularities have an average root diameter of 40 μm or more; Has an oxygen concentration of 3-2 over a depth of 0.5-2 μm.
A bone substitute material having excellent biocompatibility, characterized in that an alkali titanate layer of 5 atomic% or more is formed. 2. The bone substitute material having excellent biocompatibility according to claim 1, wherein the concave portions in the concave and convex portions satisfy the following expression (1). (The number of concave portions having a size of 200 to 300 μm) / (the number of concave portions having a size of 100 to 500 μm) ≧ 0.3 (1)