JP4281996B2 - Biomaterial - Google Patents

Description

[0001]
BACKGROUND OF THE INVENTION
The present invention relates to a biomedical member, and more particularly to a biomedical member that can be suitably used for a large artificial bone or the like that requires time for regeneration.
[0002]
[Prior art]
Ceramics are used for biomedical members such as artificial bones from the viewpoints of excellent strength characteristics and low biological harm.
In particular, among the biomedical members, the artificial bone is preferably compatible with autologous bone and the like, and preferably has characteristics such as being fixed by absorption into living tissue over time. Therefore, ceramics composed of calcium phosphate compounds, which are the main constituents of bone, have come into practical use as a more suitable material.
[0003]
Examples of the calcium phosphate compound include tricalcium phosphate, tetracalcium phosphate, and hydroxyapatite. Ceramics made of these materials are dense bodies that support loads, and cells are introduced into pores to integrate with bone. It is used in the form of a porous body to be transformed, or a composite of both.
[0004]
Among the porous ceramics, in particular, cells that form bones easily intrude into the inside, and since nutrients and the like can be sufficiently supplied to the cells, the porosity is high and each pore is entirely present. A proposal has been made that a ceramic porous body having a communicating structure is suitable (see, for example, Patent Documents 1 and 2).
[0005]
In addition, pores in the porous body communicate with each other 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 the like, which are burned off during firing, and hydroxyapatite Thus, a method of making a continuous two-dimensional porous structure is disclosed (for example, see Patent Documents 3 and 4).
[0006]
[Patent Document 1]
JP 2000-302567 A [Patent Document 2]
JP 2002-17846 A [Patent Document 3]
Japanese Patent Laid-Open No. 7-23994 [Patent Document 4]
Japanese Patent Application Laid-Open No. 62-295666
[Problems to be solved by the invention]
Currently, research is being conducted on the issue of how to achieve early recovery of the affected area using biomaterials made of ceramics as described above.
As one of them, it has been studied to secure blood flow in the central part (inside) of the artificial bone and promote bone regeneration by introducing blood vessels into the artificial 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 was very difficult to integrate the blood vessel and integrate it later.
[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 central portion of the member, and the formation of the blood vessel is promoted. Accordingly, it is an object of the present invention to provide a biological member that can promote bone regeneration and can be easily manufactured.
[0010]
[Means for Solving the Problems]
Biological member according to the present invention is integrated ceramic rod-shaped body is suitable for entering embedding at least three of a living body, at least one rod-shaped body made of a ceramic porous body having pores communicating with each other inside the ceramic rod-shaped body And at least one of the ceramic rod-like bodies is a rod-like body made of a ceramic dense body , and at least one rod-like body existing on the outer periphery of the bundle of ceramic rod-like bodies is made of the ceramic porous body The ceramic porous body is exposed at least at a part of the outer periphery of the bundle of ceramic rod-shaped bodies.
Such a biomedical member is easy to manufacture, and can easily introduce blood vessels to the central part of the member. When used as an artificial bone or the like, it can promote bone regeneration. it can.
[0011]
In addition, with the above-described configuration, it is possible to ensure the invasion and adhesion of cells into the biomedical member, and to introduce and introduce blood vessels from the outer peripheral surface of the ceramic rod-shaped body.
[0012]
The ceramic rod-shaped body is preferably a cylindrical rod-shaped body having a circular cross section with a diameter of 1 mm to 10 mm.
From the viewpoint of ensuring a sufficient gap for introducing blood vessels between the ceramic rod-shaped bodies and ensuring the strength, the biological member according to the present invention is constituted by a cylindrical rod-shaped body having the above thickness. It is preferable.
[0013]
Further, the ceramic porous body preferably 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 ensuring the entry of cells into the living body member, ease of attachment, and appropriate strength, and according to stirring foaming, high porosity suitable as a living body member The rate, porosity, etc. can be controlled homogeneously and easily.
[0014]
Furthermore, it is preferable that the ceramic rod-like body is bound and integrated.
By binding using a material such as a titanium belt or a polylactic acid thread that is not harmful to the living body, it is possible to prevent the ceramic rod-like body that is firmly integrated and composed of a combination of rod-like bodies from being decomposed. .
[0015]
Alternatively, the ceramic rod-shaped body can be firmly integrated by sintering and joining a hydroxyapatite slurry or the like.
[0016]
DETAILED DESCRIPTION OF THE INVENTION
Hereinafter, the present invention will be described in more detail with reference to the drawings.
FIG. 1 shows a first embodiment of a biological member according to the present invention.
The biomedical member shown in FIG. 1 is obtained by uniting ceramic rod-like bodies 1 made of a large number of cylindrical rod-like bodies by binding them with a titanium belt 2.
The titanium belt 2 is for tightening the outer periphery so that the bundle of ceramic rods 1 is not disassembled. Instead, for example, a belt made of a material that is not harmful to the living body, such as polylactic acid yarn. It can also be bundled using the shape or thread.
[0017]
FIG. 2 shows a partially enlarged view of three ceramic rod-shaped bodies 1 adjacent to each other in the bundle of ceramic rod-shaped bodies 1. A tubular gap 3 is formed between the integrated ceramic rods 1. The tubular gap 3 can be used as a space for blood vessel introduction.
[0018]
As shown in FIGS. 1 and 2, when the ceramic rod-shaped body 1 is a cylindrical rod-shaped body, the diameter of the circular cross section is preferably 1 mm or more and 10 mm or less.
In the case where the diameter is less than 1 mm, when the ceramic rod-shaped body 1 is made of a porous body, the strength is extremely lowered and the processing becomes difficult.
On the other hand, when the diameter exceeds 10 mm, the gap 3 between the ceramic rod-shaped bodies 1 becomes too large, and bone regeneration is not sufficiently performed.
The diameter is preferably 2 mm or more and 5 mm or less.
Even when the cross-sectional shape of the ceramic rod-shaped body is not circular, the size of the ceramic rod-shaped body is preferably approximately 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 porous body constituting the ceramic rod-like body 1 preferably has a structure in which substantially spherical pores communicate with each other.
Furthermore, the porous body is described in, for example, Patent Document 1 (Japanese Patent Application Laid-Open No. 2000-302567) from the viewpoint of ensuring the entry of cells into the living body member, ease of attachment, and appropriate strength. It is preferable to have an average pore diameter, a porosity, an average opening diameter of the communication 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%, cells enter the central part of the ceramic rod-like body, and it becomes difficult to spread and adhere.
On the other hand, when the porosity exceeds 85%, sufficient strength of the ceramic rod-like body cannot be obtained, and breakage easily occurs.
[0021]
The average pore diameter of the porous body is preferably 50 μm or more and 800 μm or less, and more preferably 80 μm or more and 300 μm or less.
Further, the average opening diameter of the communication part of each pore having a substantially spherical shape is 3 μm or more, more preferably 10 μm or more from the viewpoint of promoting the cell absorption rate, the culture rate, etc., and the pores communicating with the outside However, it preferably occupies 40% or more of the volume of the porous body, more preferably 55% or more.
In addition, the volume of this continuous ventilation hole can be measured with a mercury porosimeter.
[0022]
Moreover, it is preferable that the ceramic rod-shaped body which consists of the above porous bodies is formed by stirring foaming.
Stirring bubbles are preferable because high porosity, porosity properties, and the like suitable for the above-described biomedical member can be controlled homogeneously and easily.
[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 in the case of 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 mixed by stirring to prepare a raw material slurry.
Furthermore, a foaming agent such as polyoxyethylene lauryl ether is added and foamed with stirring to homogenize and stabilize the bubbles to prepare 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 the porous body.
[0024]
The material of the ceramic rod-like body may be either a porous body or a dense body, which is hydroxyapatite (Ca ₅ (PO ₄ ) ₃ OH) or hydroxyapatite and calcium triphosphate (hereinafter referred to as TCP), which is a calcium phosphate ceramic. ).
Hydroxyapatite is a main composition component of bone, is relatively excellent in mechanical properties such as strength, and is a suitable material without any harm to living body. Further, when the biomedical member according to the present invention is used as an artificial bone, it has an advantage that it is gradually absorbed into a living tissue with time and is excellent in substituting with a living bone.
The hydroxyapatite may be one in which a part of the hydroxyl group or a part of the 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 rod-like bodies 1 is large, the ceramic porous body 1a and the ceramic dense body 1b are combined, and the defect portion 4 is formed in the middle of the ceramic porous body 1a in the longitudinal direction. Also good.
As described above, even if the defect 4 is formed in the middle of the rod-shaped body 1, the ceramic porous body 1a is combined with the ceramic dense body 1b. Sufficient strength can be maintained.
[0026]
For example, as shown in FIG. 4, the chipped portion 4 formed in the ceramic porous body 1 a was partially scraped while the rod-shaped body itself remained continuous even when the rod-shaped body was divided. It may be in such a state.
In this way, not only the gap 3 between the adjacent ceramic rod-like bodies 1 but also the defect portions 4 as described above are formed in some places, so that these many defect portions 4 promote blood vessel introduction. do.
In addition, the said defect | deletion part 3 can also be formed by eluting only TCP from the composite body of a hydroxyapatite and TCP other than grinding, for example.
[0027]
As shown in FIG. 3, the ceramic rod-shaped body 1 is mixed with a ceramic dense body 1b in a part, and the ceramic porous body 1a and the ceramic dense body 1b are combined. The improved structure can improve the strength of the entire ceramic rod-like body.
Thus, a living body member of any size can be easily obtained by appropriately arranging and combining the ceramic porous body 1a and the ceramic dense body 1b according to the required strength.
[0028]
At this time, it is preferable that the outer peripheral surface of the bundle of ceramic rod-shaped bodies is not limited to the ceramic dense body 1b. The porous ceramic body 1a is exposed at least at a part of the outer circumference of the bundle of ceramic rod-like bodies, preferably at two or more so that cells and the like can enter the living body member. It is preferable that the continuous air holes of the body 1a communicate with the outside.
[0029]
The ceramic dense body 1b may be obtained by a normal method for producing a ceramic material.
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 hydroxyapatite powder and stirring and mixing it. What was obtained by molding and firing the dense slurry thus obtained can be used as the ceramic dense body.
[0030]
FIG. 5 shows another embodiment of a bundle of ceramic rods. The ceramic rod-shaped body 1 shown in FIG. 5 is a combination of cylindrical rod-shaped bodies 1c and prismatic rod-shaped bodies 1d alternately.
Thus, the ceramic rods may have the same or different cross-sectional shapes.
Therefore, the ceramic rod-like body according to the present invention is not limited to a combination of a plurality of cylindrical rod-like bodies having the same circular cross section, but a combination of columnar rods having different circular cross-section diameters, as shown in FIG. Further, a combination of the cylindrical rod-shaped body 1c and the 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 obtained by binding the titanium rods 5 so that the surroundings are covered with the ceramic rods 1.
Even if the ceramic rod-shaped body 1 is composed of either a porous body or a dense body, for example, when the biological member according to the present invention is used as an artificial bone, the longitudinal direction of the ceramic rod-shaped body and the artificial bone It is important to match the axial directions of these so that sufficient strength can be obtained in the axial direction.
Therefore, when strength is particularly required, as shown in FIG. 6, the strength is improved by incorporating a titanium rod in the ceramic rod-like body 1 instead of or together with the ceramic dense body. You can also plan.
[0032]
FIG. 7 shows a second embodiment of the biomedical member according to the present invention. The biomedical member shown in FIG. 7 is obtained by fixing each ceramic rod-shaped body 1 using a slurry 6 of hydroxyapatite, and then sintering and integrating them.
As described above, as a method of integrating the ceramic rod-shaped body 1, as shown in FIG. 1, in addition to binding using a titanium belt (wire) or the like, the same material as that of the ceramic rod-shaped body is used. Each ceramic rod-shaped body may be joined using an adhesive or the like.
Whichever method is used, it is sufficient that the ceramic rod-shaped bodies are integrated without being separated.
[0033]
The biological member according to the present invention having the above-described configuration is easy to invade blood vessels such as capillaries not only from both ends in the longitudinal direction but also from the side peripheral surface, and the center of the biological member Since a sufficient space for the blood vessel to extend is secured also in the portion (inside), the blood vessel is easily formed on the entire living body member, and as a result, the formation of bone can be promoted.
[0034]
【Example】
EXAMPLES Hereinafter, although this invention is demonstrated more concretely based on an Example, this invention is not restrict | limited by the following Example.
[ Reference Example 1]
A hydroxyapatite slurry was prepared, stirred and foamed, and then formed into a plate having a thickness of 20 mm. The molded body was solidified by cross-linking polymerization, dried and fired. The obtained sintered body was cut and polished to process a large number of cylindrical rod-shaped bodies having a diameter of 3 mm and a length of 25 mm.
These cylindrical rod-like bodies were bundled with titanium wires at intervals of 5 mm at four locations to produce a biological member having a diameter of about 30 mm and a length of 25 mm as shown in FIG.
After aligning both end faces of the obtained biomedical member, a load was applied in the axial direction, and the biomedical member was not changed even at a load of 50 kg.
When the biomedical member was observed with a microscope, the average pore diameter was 150 μm, and the opening diameter of the communicating holes between the pores was about 50 μm on average.
In addition, when the biomedical member was colored and submerged in water for 1 minute, then taken out and cut, it was found that the colored water had penetrated to the center of the biomedical member.
[0035]
[ Reference Example 2]
A hydroxyapatite slurry was prepared, stirred and foamed, and then formed into a plate having a thickness of 20 mm. The molded body was solidified by cross-linking polymerization, dried and fired. The obtained sintered body was cut and polished, and a large number of cylindrical rods having a diameter of 3 mm and a length of 25 mm and prismatic rods having a size of 3 mm × 3 mm × 25 mm were processed.
As shown in FIG. 5, the cylindrical rod-shaped body and the prismatic rod-shaped body are alternately arranged as much as possible, and are bound by titanium wires at intervals of 5 mm at four locations, and a substantially cylindrical living body having a diameter of about 30 mm and a length of 25 mm. The member for manufacture was produced.
After aligning both end faces of the obtained biomedical member, a load was applied in the axial direction, and the biomedical member was not changed even at a load of 50 kg.
When the biomedical member was observed with a microscope, the average pore diameter was 150 μm, and the opening diameter of the communicating holes between the pores was about 50 μm on average.
In addition, when the biomedical member was colored and submerged in water for 1 minute, then taken out and cut, it was found that the colored water had penetrated to the center of the biomedical member.
[0036]
[Example 1 ]
A hydroxyapatite slurry was prepared and formed into a plate-like body having a thickness of 20 mm without stirring and foaming. The molded body was solidified by cross-linking polymerization, 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 Reference Example 1 are arranged in an evenly mixed manner, and are bound by titanium wires at intervals of 5 mm at a diameter of about 30 mm. A substantially cylindrical member for living body having a length of 25 mm was produced.
In addition, the cylindrical rod-shaped body (porous body) was processed so that one piece was divided into two to three pieces in the longitudinal direction and a defect portion existed in the middle of the single piece. And as shown in FIG. 3, each defect | deletion part was made equal to the whole.
After aligning both end faces of the obtained biomedical member, a load was applied in the axial direction, and the biomedical member was not changed even at a load of 50 kg.
In addition, when the biomedical member was colored and submerged in water for 1 minute, then taken out and cut, it was found that the colored water had penetrated to the center of the biomedical member.
[0037]
[Example 2 ]
A hydroxyapatite slurry prepared without stirring and foaming is applied and bundled near both ends and the center of a plurality of cylindrical rod-like bodies (porous bodies) produced in the same manner as in Reference Example 1, and then fired. A biological member as shown in FIG. 7 having a diameter of about 30 mm and a length of 25 mm was prepared.
After aligning both end faces of the obtained biomedical member, a load was applied in the axial direction, and the biomedical member was not changed even at a load of 50 kg.
In addition, when the biomedical member was colored and submerged in water for 1 minute, then taken out and cut, it was found that the colored water had penetrated to the center of the biomedical member.
[0038]
The biomedical members obtained in the above Reference Examples and Examples each had a structure suitable for blood vessel formation because there was a gap of 100 μm or more not only on both end surfaces but also on the side peripheral surface. In addition, it was recognized that all of them had a homogeneous structure as a whole, and there was sufficient space for blood vessels to be formed inside each living body member.
Furthermore, since a sufficient load can be supported in the axial direction, it was confirmed that it can 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, when the biomedical member according to the present invention is used as an artificial bone or the like, a blood vessel can be easily introduced to the central part of the member, and by promoting the formation of the blood vessel, Regeneration can be promoted.
Moreover, since the biomedical member according to the present invention can be formed by combining a plurality of ceramic rod-shaped bodies, it can be easily manufactured and has excellent strength in the axial direction.
Therefore, the biomedical member according to the present invention is suitable as an artificial bone, and can be particularly suitably used for an artificial bone corresponding to a large bone such as a tibia or a femur that requires time for regeneration.
[Brief description of the drawings]
FIG. 1 is a perspective view showing a first embodiment of a biomedical member according to the present invention.
FIG. 2 is an enlarged perspective view of a part of a bundle of ceramic rod-like bodies.
FIG. 3 is a perspective view showing another embodiment of a bundle of ceramic rod-like bodies.
FIG. 4 is an enlarged perspective view of a defect portion 4;
FIG. 5 is a perspective view showing another embodiment of a bundle of ceramic rod-like bodies.
FIG. 6 is a perspective view showing another embodiment of a bundle of ceramic rod-like bodies.
FIG. 7 is a perspective view showing a second embodiment of the biomedical member according to the present invention.
[Explanation of symbols]
DESCRIPTION OF SYMBOLS 1 Ceramic rod-shaped body 1a Ceramic porous body 1b Ceramic dense body 1c Cylindrical rod-shaped body 1d Rectangular columnar rod-shaped body 2 Titanium belt (wire)
3 Clearance 4 Defect 5 Titanium rod 6 Hydroxyapatite slurry

Claims (5)

Is ceramic rod-shaped body is integrally suitable for entering embedding at least three of a living body, at least one of said ceramic rod-shaped body is a rod-like member made of a ceramic porous body having pores communicating with each other therein, at least of the ceramic rod-shaped body One is a rod-shaped body made of a ceramic dense body , and at least one rod-shaped body existing on the outer periphery of the bundle of ceramic rod-shaped bodies is made of the ceramic porous body, and the bundle of ceramic rod-shaped bodies A biomaterial, wherein the ceramic porous body is exposed at least at a part of an outer periphery of the body.   The biological member according to claim 1, wherein the ceramic rod-shaped body is a cylindrical rod-shaped body having a circular cross section with a diameter of 1 mm to 10 mm.   The biological member according to claim 1 or 2, wherein the ceramic porous body 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 3, wherein the ceramic rod-shaped body is bound and integrated.   The biological member according to any one of claims 1 to 4, wherein the ceramic rod-shaped body is integrated by sintering.

Images