JP2006198276A - Biomedical ceramic member, and its manufacturing method - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a manufacturing method for easily obtaining a biomedical member constituted of a composite ceramic material where porous parts and dense parts uniformly exist, and to provide a biomedical ceramic member which has an excellently strong characteristic like a dense body together with the inward enterable property of a cell being the characteristic of the porous parts and, in particular, is suitably used for promoting the formation of a autogenous bone. <P>SOLUTION: Porosity is ≥65% and ≤85% and an average porous diameter is ≥50μm and ≤800μm in porous calcium phosphate-based ceramic, having communication holes between adjacent pores. The granules with a particle size being ≥0.5mm and ≤10mm of the ceramic are mixed with calcium phosphate slurry. The mixture is molded, so as to allow the granules to be mutually brought into contact, and then, calcined. Thus, the biomedical ceramic member is manufactured. <P>COPYRIGHT: (C)2006,JPO&NCIPI

Description

  The present invention is a member that is used in an in vivo manner to join bones, and in particular, when a bone is lost due to a wound or the like, it is compensated for the site to promote regeneration of autologous bone. The present invention relates to a biological ceramic member suitably used for the manufacturing method and a manufacturing method thereof.

For the treatment of bone defects due to wounds and diseases, research has been conducted on artificial bones and joints using metals, ceramics, and the like.
Of the materials such as artificial bones, ceramics such as alumina and zirconia, and metals such as titanium have been put to practical use because of their relatively high strength and almost no biological harm.

However, artificial bone made of alumina, zirconia, titanium, etc., is said to have replaced the bone with a member that has little harm to the living body as much as possible, even if it says that there is little harm for the living body, Even after a long period of time, it remains an inorganic tissue that does not fit in the living body, that is, a dead tissue. Such dead tissue does not change with the aging of patients such as the growth period and the old age.
Therefore, artificial bones, artificial joints, and the like made of the above materials do not grow even when applied to patients in the growing period. The patient may feel pain because it does not deform to fit the bone.
Furthermore, even if it is not harmful for living organisms, it is expected that ions will be released after many years of use, and the anxiety factor could not be eliminated.

Since then, due to further progress in research and development, calcium phosphate ceramics that are close to the original bone composition have been put to practical use as materials suitable for artificial bones.
This calcium phosphate-based ceramic is not harmful to the living body, is excellent in biocompatibility, gradually binds to the self tissue, or after being eroded by osteoclasts, autologous bone is formed in the eroded part. It is recognized that it has properties. That is, it has an excellent feature that it is possible to replace it with autologous bone only after it is once buried in the bone defect part in the operation.

The calcium phosphate ceramics as described above need to be a dense body in order to obtain sufficient strength for application to an artificial bone, but a dense body that does not contain pores is less likely to invade cells and the like. The problem is that it takes a very long time to adapt to the living body.
In some cases, it may remain in the body as it is, and it has been difficult for the dense body to make full use of the original characteristics of the calcium phosphate ceramic as described above.

  Therefore, in an artificial bone made of calcium phosphate ceramics, in order to replace the ceramics with autologous bone, it is necessary to have a certain degree of strength, while a structure in which cells can easily enter the inside. It was also sought to have.

As a ceramic member having a configuration suitable for an artificial bone as described above, for example, a composite ceramic member formed by combining and integrating a member that becomes a dense portion and a member that becomes a porous portion after firing in a molding process The applicant has proposed (see Patent Document 1).
JP 2004-43243 A

However, the ceramic member described in Patent Document 1 is a composite in which a dense gelled body and a porous gelled body are brought into contact with each other, and it cannot always be said that molding is easy. .
Moreover, it has been difficult for the composite member as described above to obtain the entire ceramic member as a homogeneous material.

The present invention has been made to solve the above technical problem, and provides a production method capable of easily obtaining a biomedical member made of a composite ceramic material in which a dense portion and a porous portion are present uniformly. It is for the purpose.
In addition, the present invention combines the excellent strength characteristics such as a dense body and the ease of cell entry into the inside, which is a characteristic of a porous body, and is particularly suitable for promoting the formation of autologous bone by the above production method. An object of the present invention is to provide a living body ceramic member.

The method for producing a biological ceramic member according to the present invention comprises a porous calcium phosphate ceramic particle having a porosity of 65% to 85% and an average pore diameter of 50 μm to 800 μm and having communication holes between adjacent pores. A granule having a diameter of 0.5 mm or more and 10 mm or less is mixed with a calcium phosphate-based slurry, shaped so that the granules are in contact with each other, and then fired.
According to the manufacturing method described above, a biological ceramic member made of a composite material of a dense body and a porous body of phosphate calcium ceramics can be easily manufactured.

The porous calcium phosphate ceramic granules are preferably surface-treated with an organic polymer.
The organic polymer can prevent the slurry from flowing into the porous body of the granules, and the granules can easily form contacts, and the voids of the surface treatment layer disappearance trace after firing are between the granules. It serves as a path for living tissue.

The biological ceramic member according to the present invention is a biological ceramic member manufactured by the above-described manufacturing method, and has an initial compressive strength of 50 MPa or more.
An initial strength in the above range is preferable because it can be easily handled without being damaged when inserted into a living body.

As described above, according to the manufacturing method according to the present invention, a biological ceramic member having both excellent strength characteristics such as a dense body and ease of entry of cells into the interior, which is a characteristic of a porous body, can be easily obtained. It can be manufactured by the method.
In addition, the biological ceramic member obtained by the above manufacturing method has a dense portion and a porous portion, so that even when processed into any shape, excellent biocompatibility is maintained while maintaining the initial strength. Therefore, it can be suitably used as an auxiliary member for connecting bones.

Hereinafter, the present invention will be described in more detail.
The method for producing a biological ceramic member according to the present invention is characterized in that porous calcium phosphate ceramic granules are molded and fired in a calcium phosphate slurry so as to contact each other.
That is, the biological ceramic member according to the present invention is a composite material of a dense body and a porous body made of phosphate calcium ceramics. According to the manufacturing method as described above, such a composite ceramic material can be easily obtained. be able to.

The porous calcium phosphate ceramic granules have a porosity of 65% or more and 85% or less and an average pore diameter of 50 μm or more from the viewpoints of the surface area and permeability of the granules, the invasion and adhesion of cells into the pores, and the like. 800 μm or less.
When the average pore diameter is less than 50 μm, the cells hardly penetrate into the pores.
On the other hand, when the average pore diameter exceeds 800 μm, the cells that have entered the pores are not easily anchored and do not sufficiently settle.

In addition, the granule is not particularly limited in shape, but a granule having a particle size of 0.5 mm or more and 10 mm or less is used, and more preferably a particle having a particle size of 0.5 mm or more and 2 mm or less.
When the particle size of the granule is less than 0.5 mm, it is too fine and inconvenient to handle.
On the other hand, when the particle diameter exceeds 10 mm, it becomes difficult to uniformly disperse the slurry in the slurry at the time of molding.

The porous calcium phosphate ceramic granule has a structure having communication holes between adjacent pores.
By using a granule in which pores communicate with each other, invasion of cells into the pores of the granule is promoted, and replacement of the entire member with autologous bone can be promoted.

In the forming step, the porous calcium phosphate-based ceramic granules are arranged in the calcium phosphate slurry so that the granules are in contact with each other.
By configuring in this way, not only the pores in the granules communicate but also the granules communicate with each other, so that cells can more easily enter the living body ceramic member.

Therefore, it is preferable that the granules have one or more points of contact, and it is necessary to add a necessary amount of granules to the slurry.
In addition, the shape of the granule is not particularly limited, and may be all the same shape or different shapes. For example, all the granules may be formed into a cubic shape, regularly arranged so that adjacent granules are in contact with each other, and the periphery thereof may be filled with slurry.

The porous calcium phosphate ceramic granules are preferably surface-treated with an organic polymer.
Due to the organic polymer on the granule surface, the slurry is prevented from flowing into the porous body of the granule during slurry mixing, and the porosity is prevented from lowering.
In addition, it becomes easy for the surface-treated granules to form a contact via the organic polymer, and further, by firing this, voids are formed in the disappearance trace of the surface treatment layer, and the living tissue between the granules is It has the advantage that it can be a path.

  Examples of the organic polymer used for the surface treatment include an epoxy resin and a silane coupling agent. Epoxy resins are particularly preferred because they are completely burned off after firing.

Hydroxyapatite, β-tricalcium phosphate, and the like are suitably used for the porous calcium phosphate ceramic granules and the calcium phosphate slurry. The granule and the slurry may be the same material or different materials.
Hydroxyapatite is the main component of bone and has already been applied to the human body, and is preferable from the viewpoints of assimilation with bone, adhesion, early recovery, and relatively high strength. It is also suitable as a cell scaffold.
Similarly, β-tricalcium phosphate is a suitable material excellent in biocompatibility and biocompatibility.

In the case of hydroxyapatite, the porous ceramic as described above can be easily produced by stirring and foaming a slurry containing hydroxyapatite and firing. And the desired granule for using for the manufacturing method which concerns on this invention can be obtained by refine | pulverizing this by grinding | pulverization etc.
In addition, the porous hydroxyapatite ceramics manufactured as described above are commercially available under the product name NEOBONE (registered trademark).
The porous body in which pores are formed by stirring and foaming has a dense skeleton that defines the pores, the pores are almost spherical, and high strength can be obtained, and cells, blood, etc. penetrate through capillarity. Easy to handle. Furthermore, it has excellent characteristics such as a large surface area per unit volume and a suitable property as a scaffold for invading cells.

In addition, in order to promote the formation of bone, cells forming bone or an activating substance may be introduced into the porous granule. For example, chondrocytes, osteoblasts, fibroblasts, endothelial cells, epithelial cells, myoblasts, adipocytes, hepatocytes, nerve cells, or precursors thereof, mesenchymal stem cells or embryonic stem cells (ES cells) ) Etc. can be introduced.
Thereby, about the biomedical ceramic member which concerns on this invention, the function as a bone grafting material can be improved more.

In FIG. 1, the structure of the ceramic member for biological bodies obtained by the manufacturing method which concerns on this invention is shown.
In the biological ceramic member shown in FIG. 1, adjacent porous calcium phosphate ceramic granules 2 are in contact with each other, and the organic polymer used for the surface treatment of the granules 2 disappears in the vicinity of the contact by firing. The trace that has been made becomes a neck-shaped gap 3. The remaining portion is a dense portion 1 formed by firing a calcium phosphate slurry.

The living body ceramic member obtained by the manufacturing method according to the present invention as described above has higher strength than a ceramic member made of only a normal porous body, and moreover, a living tissue is formed in a porous portion that exists in large numbers on the surface of the ceramic member. Can be used suitably for a living body site where initial strength is required.
In particular, the biomaterial ceramic member according to the present invention has such a sufficient strength that it can be directly compensated in the case where a bone is lost due to a wound or the like. Can be suitably used.
The initial strength of the biological ceramic member is preferably 50 MPa or more in terms of compressive strength in order to facilitate handling without being damaged when inserted into the living body.

  In addition, the porous ceramic member according to the present invention has porous granules uniformly in the member, so that it does not impair the homogeneous state as a dense material and a composite material of the porous material, and has any shape. It is possible to process.

EXAMPLES Hereinafter, although this invention is demonstrated more concretely based on an Example, this invention is not restrict | limited by the following Example.
Porous granules made of hydroxyapatite ceramics with a porosity of 75% and an average pore diameter of 150 μm are surface-treated with a resin (p-resin made by Nihon Geoscience), and the surface-treated granules have one or more contacts. Was placed in the mold to have
The mold was filled with a slurry of hydroxyapatite, dried, and fired at 1200 ° C. to obtain a biological ceramic member.
The obtained biological ceramic member was processed into a cylindrical shape having a diameter of 10 mm and a height of 10 mm, and the compression strength was measured for the five cylindrical samples. The maximum value was 527.63 MPa, the minimum value was 233.97 MPa, The average value was 380.62 MPa.
Moreover, it was recognized that the porous part was uniformly introduced into each sample.

1 is a schematic cross-sectional view of a biological ceramic member according to the present invention.

Explanation of symbols

DESCRIPTION OF SYMBOLS 1 Dense part 2 Porous calcium phosphate ceramic granule 3 Void

Claims (3)

  A granule having a particle size of 0.5 mm or more and 10 mm or less of porous calcium phosphate ceramics having a porosity of 65% or more and 85% or less and an average pore diameter of 50 μm or more and 800 μm or less and having communication holes between adjacent pores is obtained. A method for producing a biological ceramic member, comprising mixing with a slurry, forming the granules so that they are in contact with each other, and then firing.   The method for producing a biological ceramic member according to claim 1, wherein the porous calcium phosphate ceramic granules are surface-treated with an organic polymer.   A biological ceramic member manufactured by the manufacturing method according to claim 1 or 2, wherein the initial compressive strength is 50 MPa or more.

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