JP2004298565A - Member for living body - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a member for the living bodies which achieves an easier guiding of the blood vessels into the center part of the member when used as an artificial bone or the like to promote the regeneration of the bone and moreover, the easier production thereof. <P>SOLUTION: The member for the living bodies to be used as the artificial bone or the like has at least three ceramics bar-like bodies 1 each with the cross section of 1 mm or more to 10 mm or less in diameter which each comprises a ceramics porous element having pores communicating with each other inside and are bundled at several points with a titanium belt 2 to be integrated. <P>COPYRIGHT: (C)2005,JPO&NCIPI

Description

[0001]
TECHNICAL FIELD OF THE INVENTION
The present invention relates to a living body member, and more particularly, to a living body member that can be suitably used for large artificial bones and the like that require time for regeneration.
[0002]
[Prior art]
Ceramics are used in biological members such as artificial bones from the viewpoint of excellent strength characteristics and low harm to living organisms.
In particular, among the living body members, the artificial bone preferably has compatibility with autologous bone and the like, and preferably has characteristics such as being fixed by absorption into living tissue over time. Accordingly, ceramics comprising a calcium phosphate compound, which is a main component of bone, have come into practical use as a more suitable material.
[0003]
Examples of the calcium phosphate-based compound include tricalcium phosphate, tetracalcium phosphate, and hydroxyapatite.Ceramics made of these materials are integrated with bone by introducing cells into a dense body that supports a load, pores, and the like. It is used in the form of a porous body or a composite of both.
[0004]
Among the ceramic porous bodies, in particular, cells that form bone are easy to penetrate into the inside, and since nutrients and the like can be sufficiently supplied to the cells, the porosity is high, and each pore is formed throughout. It has already been proposed that a ceramic porous body having a communicating configuration is suitable (for example, see Patent Documents 1 and 2).
[0005]
Further, the pores in the porous body are communicated in a certain direction, and a porous bone filling material excellent in strength and workability in a certain direction, or a laminated molded body of hydroxyapatite and a network fiber or the like which is burned out during firing are fired. Thus, a method of forming a continuous two-dimensional porous structure has been disclosed (for example, see Patent Documents 3 and 4).
[0006]
[Patent Document 1]
Japanese Patent Application Laid-Open No. 2000-302567 [Patent Document 2]
JP 2002-17846 A [Patent Document 3]
JP-A-7-23994 [Patent Document 4]
Japanese Patent Application Laid-Open No. 62-295666
[Problems to be solved by the invention]
At present, studies are being made on the problem of how to achieve early recovery of an affected part using the above-mentioned biomaterial made of ceramics.
As one of them, it has been studied to introduce a blood vessel into the artificial bone to secure a blood flow in the central part (inside) of the artificial bone and to promote the regeneration of the bone.
[0008]
However, the process of introducing an artificial blood vessel into ceramics hardened by sintering is time-consuming, and requires research and development of the artificial blood vessel itself. It has been very difficult to integrate the blood vessels later by integrating them.
[0009]
The present invention has been made to solve the above technical problem, and when used as an artificial bone or the like, a blood vessel can be easily introduced to the center of the member, and the formation of a blood vessel is promoted. Accordingly, it is an object of the present invention to provide a biological member that can promote the regeneration of bone and can be easily manufactured.
[0010]
[Means for Solving the Problems]
The biological member according to the present invention is characterized in that at least three ceramic rods suitable for biological implantation are integrated.
Such a biological member is easy to manufacture, and can easily introduce blood vessels to the center of the member, and when used as an artificial bone or the like, promotes bone regeneration. it can.
[0011]
It is preferable that the ceramic rod is made of a ceramic porous body having pores communicating with each other.
With the porous body as described above, it is possible to ensure the invasion and attachment of cells into the living body member, and to introduce and form blood vessels from the outer peripheral surface of the ceramic rod.
[0012]
In addition, it is preferable that the ceramic rod is a cylindrical rod having a circular cross section having a diameter of 1 mm or more and 10 mm or less.
From the viewpoint of securing a sufficient space for introducing blood vessels between the ceramic rods and securing the strength, the living body member according to the present invention is formed of a cylindrical rod having the above-described thickness. Is preferred.
[0013]
Further, it is preferable that the ceramic rod has a porosity of 65% or more and 85% or less and is formed by stirring and foaming.
The porosity is defined from the viewpoint of infiltration of cells into the living body member, ease of attachment and appropriate strength, and, according to stirring and foaming, high porosity suitable as a living body member The ratio, the porosity, etc. can be controlled uniformly and easily.
[0014]
Furthermore, it is preferable that the ceramic rods are bound and integrated.
By binding using a titanium belt or a polylactic acid thread or the like that is not harmful to living organisms, it is possible to prevent the ceramic rod composed of a combination of rods from being decomposed firmly. .
[0015]
Alternatively, the ceramic rods can be strongly integrated by sintering and bonding a hydroxyapatite slurry or the like.
[0016]
BEST MODE FOR CARRYING OUT THE INVENTION
Hereinafter, the present invention will be described in more detail with reference to the drawings.
FIG. 1 shows a first embodiment of the biological member according to the present invention.
The biomedical member shown in FIG. 1 is obtained by binding ceramic rods 1 made of a large number of cylindrical rods by a titanium belt 2 and integrating them.
The titanium belt 2 is for tightening the outer periphery so that the bundle of the ceramic rods 1 is not decomposed. Instead, for example, a belt made of a material that is not harmful to the living body such as a polylactic acid thread is used. It can also be bound using a shape or thread.
[0017]
FIG. 2 is a partially enlarged view of three ceramic rods 1 adjacent to each other in the bundle of the ceramic rods 1. A tubular gap 3 is formed between the integrated ceramic rods 1. This tubular gap 3 can be used as a space for introducing blood vessels.
[0018]
As shown in FIGS. 1 and 2, when the ceramic rod 1 is a cylindrical rod, the diameter of the circular cross section thereof is preferably 1 mm or more and 10 mm or less.
When the diameter is less than 1 mm, when the ceramic rod 1 is made of a porous material, the strength is extremely reduced and processing becomes difficult.
On the other hand, when the diameter exceeds 10 mm, the gap 3 between the ceramic rods 1 becomes too large, and the bone is not sufficiently regenerated.
The diameter is preferably 2 mm or more and 5 mm or less.
In addition, even when the cross-sectional shape of the ceramic rod is not circular, the size of the ceramic rod is preferably substantially the same. For example, in the case of a rectangular cross section, the length of one side is preferably about 1 mm or more and 10 mm or less.
[0019]
The ceramic rod 1 is preferably made of a ceramic porous body, and the porous body preferably has a structure in which substantially spherical pores communicate with each other.
Further, the porous body is described in, for example, Patent Document 1 (Japanese Patent Application Laid-Open No. 2000-302567) from the viewpoint of ensuring penetration of cells into a living body member, easy attachment, and appropriate strength. It is preferable to have an average pore diameter, a porosity, an average opening diameter of the communicating portion, and the like.
[0020]
In the present invention, the porosity of the porous body is more preferably 65% or more and 85% or less.
When the porosity is less than 65%, it is difficult for the cells to enter the central portion of the ceramic rod, spread sufficiently, and adhere.
On the other hand, when the porosity exceeds 85%, the ceramic rod-shaped body does not have sufficient strength, and is likely to be damaged.
[0021]
The average pore diameter of the porous body is preferably 50 μm or more and 800 μm or less, more preferably 80 μm or more and 300 μm or less.
Furthermore, the average opening diameter of the communicating portion of each of the substantially spherical pores is 3 μm or more, and more preferably 10 μm or more, from the viewpoint of promoting the cell absorption rate, culture rate, and the like, and the pores communicating with the outside. Occupies preferably at least 40% of the volume of the porous body, more preferably at least 55%.
In addition, the volume of the continuous vent can be measured by a mercury porosimeter.
[0022]
In addition, it is preferable that the ceramic rod-shaped body made of the porous body as described above is formed by stirring and foaming.
The use of the stirring bubble is preferable because the high porosity, the porosity, and the like suitable for the above-mentioned living body member can be uniformly and easily controlled.
[0023]
As a method for producing a ceramic rod-shaped body made of a porous body by stirring and foaming, for example, a method as described in Patent Document 1 can be used.
A specific production method using hydroxyapatite is shown below.
First, a hydroxyapatite powder and a crosslinkable resin such as polyethyleneimine are added to water to which a dispersant has been added, and the mixture is stirred and mixed to prepare a raw material slurry.
Further, a foaming agent such as polyoxyethylene lauryl ether is added, and the mixture is stirred and foamed to homogenize and stabilize the foam, thereby preparing a foam slurry.
Next, a crosslinking agent (gelling agent) such as sorbitol polyglycidyl ether is added to the foam slurry, and the mixture is stirred and mixed to prepare a porous slurry.
Then, the porous slurry is cast and molded to form a porous gelled body (crosslinked body) in a state where the foam structure is maintained, and then fired to obtain a ceramic rod-shaped body made of a porous body.
[0024]
Regardless of whether the ceramic rod-shaped body is a porous body or a dense body, hydroxyapatite (Ca ₅ (PO ₄ ) ₃ OH), which is a calcium phosphate-based ceramic, or hydroxyapatite and calcium triphosphate (hereinafter, referred to as TCP) )).
Hydroxyapatite is a main component of bone, has relatively excellent mechanical properties such as strength, and is a suitable material without harm to living organisms. Further, when the living body member according to the present invention is used as an artificial bone, it has an advantage that it is gradually absorbed into living tissue over time, and is excellent in substitutability for living bone.
The hydroxyapatite may be one in which a part of a hydroxyl group or a part of a phosphate group is substituted with a carbonate group.
[0025]
FIG. 3 shows another embodiment of a bundle of ceramic rods. As shown in FIG. 3, when the number of the ceramic rods 1 is large, the ceramic porous body 1a and the ceramic dense body 1b are combined, and the defective portion 4 is formed in the longitudinal direction of the ceramic porous body 1a. Is also good.
As described above, even if the defective portion 4 is formed in the middle of the rod-shaped body 1, since the porous ceramic body 1 a is combined with the dense ceramic body 1 b, the whole body member for living body formed by integrating these is integrated. , Sufficient strength can be maintained.
[0026]
For example, as shown in FIG. 4, the defective portion 4 formed in the ceramic porous body 1 a was partially scraped off while the rod itself remained continuous even when the rod was divided. It may be in such a state.
As described above, not only the gaps 3 between the adjacent ceramic rods 1 but also the above-described defective portions 4 are formed in places, so that a large number of these defective portions 4 promote the introduction of blood vessels. do.
In addition to the grinding process, the defective portion 3 can be formed by, for example, eluting only TCP from a composite of hydroxyapatite and TCP.
[0027]
As shown in FIG. 3, the ceramic rod-shaped body 1 has a ceramic dense body 1b partially mixed therein, and is composed of the ceramic porous body 1a and the ceramic dense body 1b. With such a configuration, the strength of the entire ceramic rod can be improved.
Thus, by appropriately arranging and combining the ceramic porous body 1a and the ceramic dense body 1b according to the required strength, a living body member of any size can be easily obtained.
[0028]
At this time, it is preferable that the outer peripheral surface of the bundle of the ceramic rods does not include only the dense ceramic body 1b. The ceramic porous body 1a is formed such that the ceramic porous body 1a is exposed at least at a part, preferably at two or more, of the outer periphery of the bundle of ceramic rods so that cells and the like can enter the inside of the living body member. It is preferable that the continuous ventilation hole of the body 1a be in a state communicating with the outside.
[0029]
The ceramic dense body 1b may be obtained by a normal ceramics material manufacturing method.
For example, in the above-described method for producing a ceramic rod-shaped body made of a porous body, it is obtained by adding only a crosslinking agent (gelling agent) to a slurry of a hydroxyapatite powder without adding a foaming agent, and stirring and mixing. A compact obtained by molding and firing the dense slurry can be used as the ceramic dense body.
[0030]
FIG. 5 shows another embodiment of a bundle of ceramic rods. The ceramic rod 1 shown in FIG. 5 is obtained by alternately combining cylindrical rods 1c and prismatic rods 1d.
As described above, the ceramic rods may have the same or different cross-sectional shapes.
Therefore, the ceramic rod according to the present invention is not limited to a combination of a plurality of cylindrical rods having a circular cross section of the same diameter, but may be a combination of cylindrical rods having different diameters of a circular cross section, as shown in FIG. Alternatively, a combination of a cylindrical rod-shaped body 1c and a prismatic rod-shaped body 1d may be used.
[0031]
FIG. 6 shows another embodiment of a bundle of ceramic rods. The bundle of ceramic rods shown in FIG. 6 is formed by binding a titanium rod 5 as a core so that the periphery thereof is covered with the ceramic rod 1.
Regardless of whether the ceramic rod 1 is made of a porous body or a dense body, for example, when the living body member according to the present invention is used as an artificial bone, the longitudinal direction of the ceramic rod and the artificial bone It is important that the axial directions are aligned so that sufficient strength can be obtained in the axial direction.
Therefore, when the strength is particularly required, as shown in FIG. 6, the strength is improved by incorporating a titanium rod into the ceramic rod 1 instead of or together with the ceramic dense body. You can also plan.
[0032]
FIG. 7 shows a second embodiment of the biological member according to the present invention. In the biological member shown in FIG. 7, each ceramic rod 1 is fixed using a slurry 6 of hydroxyapatite, and then sintered to be integrated.
As described above, as a method of integrating the ceramic rod 1, as shown in FIG. 1, in addition to binding using a titanium belt (wire) or the like, a material similar to the ceramic rod is used. The ceramic rods may be joined using an adhesive or the like.
In any case, the ceramic rods may be integrated without being separated.
[0033]
The living body member according to the present invention having the above-described configuration can easily penetrate blood vessels such as capillaries not only from both ends in the longitudinal direction, but also from the side peripheral surface. In the part (inside), a sufficient space for the blood vessel to expand is ensured, so that the blood vessel is easily formed on the whole body member, and as a result, the formation of bone can be promoted.
[0034]
【Example】
Hereinafter, the present invention will be described more specifically based on examples, but the present invention is not limited to the following examples.
[Example 1]
A hydroxyapatite slurry was prepared, stirred and foamed, and then formed into a plate having a thickness of 20 mm. After the molded body was solidified by crosslinking polymerization, it was dried and fired. The obtained sintered body was cut and polished to process a large number of cylindrical rods having a diameter of 3 mm and a length of 25 mm.
These cylindrical rods were bound at four locations with titanium wires at intervals of 5 mm to produce a substantially cylindrical biological member as shown in FIG. 1 having a diameter of about 30 mm and a length of 25 mm.
After aligning both end surfaces of the obtained living body member, when a load was applied from the axial direction, the living body member did not change even with a load of 50 kg.
Microscopic observation of the living body member revealed that the pore diameter was 150 μm on average, and the opening diameter of the communicating hole between the pores was about 50 μm on average.
When the living body member was colored and submerged in water for 1 minute, taken out and cut, it was confirmed that the colored water had penetrated to the center of the living body member.
[0035]
[Example 2]
A hydroxyapatite slurry was prepared, stirred and foamed, and then formed into a plate having a thickness of 20 mm. After the molded body was solidified by crosslinking polymerization, it was dried and fired. The obtained sintered body was cut and polished to form a large number of cylindrical rods having a diameter of 3 mm and a length of 25 mm and rectangular rods having a size of 3 mm × 3 mm × 25 mm.
As shown in FIG. 5, the columnar rods and the prismatic rods are arranged alternately as possible, bound at four locations by titanium wires at intervals of 5 mm, and formed into a substantially cylindrical living body having a diameter of about 30 mm and a length of 25 mm. A member for use was produced.
After aligning both end surfaces of the obtained living body member, when a load was applied from the axial direction, the living body member did not change even with a load of 50 kg.
Microscopic observation of the living body member revealed that the pore diameter was 150 μm on average, and the opening diameter of the communicating hole between the pores was about 50 μm on average.
When the living body member was colored and submerged in water for 1 minute, taken out and cut, it was confirmed that the colored water had penetrated to the center of the living body member.
[0036]
[Example 3]
A hydroxyapatite slurry was prepared and formed into a 20 mm thick plate without stirring and foaming. After the molded body was solidified by crosslinking polymerization, it was dried and fired. The obtained sintered body was cut and polished to obtain a cylindrical rod-shaped body (dense body) having a diameter of 3 mm and a length of 25 mm.
The cylindrical rod-shaped body (dense body) and the same cylindrical rod-shaped body (porous body) as in Example 1 are uniformly mixed and arranged, bound at four places by titanium wires at intervals of 5 mm, and have a diameter of about 30 mm. And a substantially cylindrical living body member having a length of 25 mm.
In addition, one cylindrical rod-shaped body (porous body) was divided into two or three pieces in the longitudinal direction, and was processed so that there was a defective part in the middle of one piece. Then, as shown in FIG. 3, each defective portion was made to be uniform throughout.
After aligning both end surfaces of the obtained living body member, when a load was applied from the axial direction, the living body member did not change even with a load of 50 kg.
When the living body member was colored and submerged in water for 1 minute, taken out and cut, it was confirmed that the colored water had penetrated to the center of the living body member.
[0037]
[Example 4]
A hydroxyapatite slurry prepared without stirring and foaming was applied to the ends and near the center of a plurality of cylindrical rod-shaped bodies (porous bodies) produced in the same manner as in Example 1, bundled and fired. A substantially cylindrical body member having a diameter of about 30 mm and a length of 25 mm as shown in FIG. 7 was produced.
After aligning both end surfaces of the obtained living body member, when a load was applied from the axial direction, the living body member did not change even with a load of 50 kg.
When the living body member was colored and submerged in water for 1 minute, taken out and cut, it was confirmed that the colored water had penetrated to the center of the living body member.
[0038]
Each of the biological members obtained in Examples 1 to 4 had a gap of 100 μm or more not only on both end faces but also on the peripheral side face, and thus had a structure suitable for angiogenesis. In addition, all of them had a uniform structure as a whole, and it was recognized that there was sufficient space inside each living body member to form blood vessels.
Furthermore, since it was possible to support a sufficient load in the axial direction, it was confirmed that it could be used as an artificial bone corresponding to a large bone such as a tibia or a femur.
[0039]
【The invention's effect】
As described above, the biological member according to the present invention, when used as an artificial bone or the like, can easily introduce a blood vessel to the central portion of the member, and promotes the formation of a blood vessel, thereby promoting bone formation. Reproduction can be promoted.
Further, since the biological member according to the present invention can be formed by combining a plurality of ceramic rods, it can be easily manufactured and has excellent strength in the axial direction.
Therefore, the biological member according to the present invention is suitable as an artificial bone, and can be particularly preferably used as an artificial bone corresponding to a large bone such as a tibia or a femur which requires a long time for regeneration.
[Brief description of the drawings]
FIG. 1 is a perspective view showing a first embodiment of a biological member according to the present invention.
FIG. 2 is an enlarged perspective view of a part of a bundle of ceramic rods.
FIG. 3 is a perspective view showing another embodiment of a bundle of ceramic rods.
FIG. 4 is an enlarged perspective view of a defective portion 4;
FIG. 5 is a perspective view showing another embodiment of a bundle of ceramic rods.
FIG. 6 is a perspective view showing another embodiment of a bundle of ceramic rods.
FIG. 7 is a perspective view showing a second embodiment of the biological member according to the present invention.
[Explanation of symbols]
Reference Signs List 1 ceramic rod 1a ceramic porous body 1b ceramic dense body 1c cylindrical rod 1d prismatic rod 2 titanium belt (wire)
3 Gap 4 Defect 5 Titanium rod 6 Hydroxyapatite slurry

Claims (6)

A biological member, wherein at least three ceramic rods suitable for implanting a living body are integrated. The living body member according to claim 1, wherein the ceramic rod-shaped body is formed of a ceramic porous body having pores communicating with each other. The biological member according to claim 1 or 2, wherein the ceramic rod is a cylindrical rod having a circular cross section having a diameter of 1 mm or more and 10 mm or less. The living body member according to any one of claims 1 to 3, wherein the ceramic rod has a porosity of 65% or more and 85% or less and is formed by stirring and foaming. . The living body member according to any one of claims 1 to 4, wherein the ceramic rods are bound and integrated. The biomaterial according to any one of claims 1 to 5, wherein the ceramic rods are integrated by sintering.

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