JP2004159971A - Bone-forming member and manufacturing method therefor - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a bone-forming member that can effectively, safely, and sufficiently form a homogeneous bone by suppressing the using amount of an osteogenic inductive factor, or the like, by using a porous ceramic material having a specific structure, and to provide a method for manufacturing the member. <P>SOLUTION: The bone-forming member uses the porous ceramic material formed by stirring frothing which has linked sphere-like opened pores formed in a state where a plurality of adjacent pores is three-dimensionally communicating with each other through communicative holes so that the volume of pores having diameters of ≥5 μm may become ≥85% of the volume of all pores in a pore diameter distribution measured with a mercury porosimeter. On the internal surface of each pore, a biogenic absorptive member and the osteogenic inductive factor are equally carried in a thickness of ≤2 μm. <P>COPYRIGHT: (C)2004,JPO

Description

[0001]
TECHNICAL FIELD OF THE INVENTION
The present invention relates to a bone forming member and a method for manufacturing the same, and more particularly, to a member using a porous ceramic body that can be suitably used for forming bone at a bone defect site, and a method for manufacturing the same.
[0002]
[Prior art]
2. Description of the Related Art Artificial bones made of ceramics and metals have been conventionally developed for the purpose of filling bone loss sites due to injury or the like.
Among the above ceramics, artificial bones such as alumina and zirconia have already been put into practical use from the viewpoint of lack of strength and harmfulness to living bodies.
Artificial bone further preferably has excellent compatibility with autologous bone and the like, and preferably has characteristics such as being absorbed and fixed in living tissue over time. Ceramics composed of a calcium phosphate compound as a main component have come into practical use as more suitable materials.
[0003]
Examples of the calcium phosphate-based compound include tricalcium phosphate, tetracalcium phosphate, and hydroxyapatite. Among ceramics made of these materials, particularly, the porosity is high, and each pore communicates throughout. It has already been proposed that a ceramic porous body having the above configuration is suitable (for example, see Patent Documents 1 and 2).
[0004]
In addition, various proposals have been made with respect to a bone formation technique. For example, Patent Literature 3 discloses that bone can be formed by an implant using a porous hydroxyapatite.
[0005]
On the other hand, as a material using a metal, for example, using titanium which is considered to be non-toxic to living organisms, by using a member made of an osteogenesis-inducing factor, a polymer and a titanium mesh as a biocompatible support, It is also disclosed that a bone defect can be repaired (for example, see Non-Patent Document 1).
[0006]
[Patent Document 1]
JP-A-2000-302567
[Patent Document 2]
JP 2002-17846 A
[Patent Document 3]
JP-A-7-88174
[Non-patent document 1]
"Journal of Biomedical Materials Research" (USA), 2002, Vol. 62, p. 169-174
[0007]
[Problems to be solved by the invention]
In the formation of a bone using a porous ceramic body, after the treatment, the living bone tissue adheres to the porous ceramic body and is fixed in the living tissue. For this reason, the porous structure of the ceramic porous body is such that cells forming bones can easily penetrate into the cells, and nutrients and the like can be sufficiently supplied to the cells, and the strength is relatively large. It is important that the properties can be exhibited.
[0008]
However, in the implant using the hydroxyapatite porous body in the above-mentioned conventional technique, although bone can be formed in a part of the implant, it is hard to say that bone is uniformly formed throughout the implant. there were.
[0009]
In addition, as described above, when titanium mesh is used as a bone forming member, titanium itself is not absorbed in the living body, and a foreign substance remains in the living body. The effect is feared.
In addition, the titanium mesh is inferior in the propagation of cells and the like as compared with the porous ceramic body, so that a large amount of an osteogenesis-inducing factor and a biocompatible support must be used.
[0010]
The bone formation-inducing factors such as bone morphogenetic factors (BMP) and biocompatible support materials such as block copolymers of polylactic acid and polyethylene glycol (PLA-PEG) used here are still not suitable for medical use. It is not commercially available.
Further, the bone formation-inducing factor is very expensive, and a small amount thereof cannot provide a sufficient effect, particularly in primates such as humans. For this reason, bone repair using an osteogenesis-inducing factor is not only expensive but also sometimes makes it difficult to achieve sufficient osteogenesis.
Therefore, it is preferable from the viewpoint of economy and safety to suppress the amount of the bone formation inducing factor used for bone repair to be as small as possible and to enhance the action of the bone formation inducing factor.
[0011]
The present invention has been made in order to solve the above technical problems, by using a ceramic porous body having a specific structure, to suppress the amount of bone formation induction factors and the like, more effectively and safely, An object of the present invention is to provide a bone forming member capable of sufficiently forming a homogeneous bone and a method for producing the same.
[0012]
[Means for Solving the Problems]
The bone forming member according to the present invention is a bone forming member in which a bioabsorbable member and an osteogenesis-inducing factor are carried on the inner surface of pores of a ceramic porous body, and the ceramic porous body has a plurality of adjacent porous bodies. The open pores in which substantially spherical pores are three-dimensionally communicated with each other through the communicating holes are formed, and the pore volume having a pore diameter of 5 μm or more in the pore diameter distribution measured by a mercury porosimeter is 85% or more of the total pore volume, and stirring is started. It is characterized by being formed by foam.
The bone forming member having the above-described structure has a good balance between the penetration rate of cells and the like into the pores of the porous ceramic body and the release rate of the bone formation inducing factor, and efficiently forms bone uniformly and uniformly. can do.
[0013]
The bone formation inducing factor includes bone morphogenic protein (BMP), transforming growth factor (TGF-β), and cartilage-derived morphogenetic (CDMP) derived cartilage. (OIF: osteoinductive factor), insulin-like growth factor (IGF), platelet-derived growth factor (PDGF), and fibroblast growth factor (FGF: selected from FGF). Any one or more of them are preferable. No.
[0014]
In order to apply the bone formation member to a human body, the bone formation induction factor should be a recombinant human osteoinduction factor (rhBMP) -2 obtained by a genetic recombination technique, among BMPs. Is more preferred.
[0015]
It is preferable that the bone formation inducing factor is uniformly mixed in the bioabsorbable member, and the bioabsorbable member is almost uniformly supported on the inner surface of the pores of the porous ceramic body at a thickness of 2 μm or less.
[0016]
The ceramic porous body has a porosity of 50% or more and 90% or less, an average pore diameter of 100 μm or more and 600 μm or less, and an average pore diameter of a communication hole of 20 μm or more. The material is alumina, zirconia, or silica. , Mullite, diopside, wollastonite, alite, belite, arcelmanite, monticerite, living body glass and calcium phosphate ceramics.
[0017]
The porous ceramic body is preferably made of hydroxyapatite among calcium phosphate-based ceramics, and the bioabsorbable member preferably has a sustained release property of an osteogenesis-inducing factor.
[0018]
Examples of the bioabsorbable member having the above characteristics include a polymer of lactic acid and / or glycolic acid, a block copolymer of a polymer of lactic acid and / or glycolic acid and polyethylene glycol, lactic acid and / or glycolic acid And at least one selected from a copolymer of p-dioxanone and polyethylene glycol, and atelocollagen are preferably used.
[0019]
Among the above-mentioned bioabsorbable members, a block copolymer of polylactic acid and polyethylene glycol (PLA-PEG) is more preferable, and in particular, the number average molecular weight is 5,000 or more and 1,000,000 or less, and the molar ratio of the polylactic acid and polyethylene glycol is Those having a ratio of 25:75 to 75:25 are preferred.
[0020]
Further, the bioabsorbable member may be a copolymer of lactic acid and / or glycolic acid, p-dioxanone and polyethylene glycol (PLA-DX-PEG).
[0021]
In addition, the method for producing a bone forming member according to the present invention includes a step of adding a bioabsorbable material composed of an organic compound to acetone, and then mixing the mixture with an osteogenesis-inducing factor to prepare a mixed solution; A step of infiltrating the mixed solution into a ceramic porous body having a plurality of adjacent substantially spherical pores formed into continuous spherical open pores which are three-dimensionally communicated with each other through communication holes; Removing the acetone and causing the bioabsorbable member and the bone formation inducing factor to be supported on the inner surface of the pores of the porous ceramic body to obtain a bone formation member.
According to the above manufacturing method, the bone forming member according to the present invention can be obtained easily and efficiently.
[0022]
In the above-described manufacturing method, it is preferable that the bioabsorbable member is supported substantially uniformly on the inner surface of the pores of the porous ceramic body at a thickness of 2 μm or less.
In this way, by coating the bioabsorbable member thinly, the communication holes of the ceramic porous body are not closed, the open pore state is maintained, and cells having the ability to form bone are inserted into the pores in advance. It is also possible to put.
[0023]
BEST MODE FOR CARRYING OUT THE INVENTION
Hereinafter, the present invention will be described in more detail.
The bone forming member according to the present invention has a structure in which a bioabsorbable member and an osteogenesis-inducing factor are carried on the pore inner surface of a porous ceramic body.
The ceramic porous body has a plurality of adjacent substantially spherical pores formed into continuous spherical open pores which are three-dimensionally communicated with each other through a communication hole. It is 85% or more of the total pore volume and is formed by stirring and foaming.
According to the bone forming member configured as described above, in the surface layer portion of the porous ceramic body, the invasion rate of cells is large, and the formation of bone is promoted. On the other hand, inside the porous ceramic body, bone is formed. The formation-inducing factor is gradually released, and bone formation shifts from the surface layer toward the center, so that bone can be uniformly formed as a whole.
[0024]
Further, as the bone formation inducing factor carried by the bone formation member, various bone formation-related proteins which are components extracted from bone tissue can be used. For example, bone morphogenetic protein (BMP), transforming growth factor (TGF-β), cartilage-derived protein (CDMP), bone morphogenetic protein (IFMP), and induction factor (CDMP). Insulin-like growth factor (IGF), platelet-derived growth factor (PDGF), fibroblast growth factor (FGF), and connective tissue growth factor (CTGFtgrowth factor). fac or), vascular endothelial cell growth factor (VEGF), hepatocyte growth factor (HGF), placenta-derived growth factor (PIGF), hepatocyte growth factor (HGF), hepatocyte growth factor (HGF), hepatocyte growth factor (HGF), and hepatocyte growth factor (HGF). Bisphosphonates, mevalonate pathway inhibitors, signal transduction agonists and the like can be mentioned.
[0025]
Among these osteogenic factors, bone morphogenetic factor (BMP), transforming growth factor (TGF-β), cartilage derived morphogenetic factor (CDMP), osteoinductive factor (OIF), insulin-like growth factor (IGF), platelets It is preferable to use one or more selected from derived growth factor (PDGF) and fibroblast growth factor (FGF). Further, in order to apply the bone forming member to a human body, it is necessary to use a human-derived material. More preferably, it is human bone morphogenetic protein (hBMP) substantially free of other proteins.
In particular, the recombinant human bone morphogenetic factor (rhBMP) obtained by the genetic recombination technique is considered to be capable of obtaining a large amount of materials with stable clinical safety such as immunity and the like and quality. preferable. That is, a transformant such as a cell or a microorganism containing a recombinant DNA containing a nucleotide sequence encoding a human bone morphogen is cultured, and rhBMP produced by the transformant is isolated and purified to prepare. is there.
[0026]
Examples of the rhBMP include rhBMP-2, rhBMP-3, rhBMP-4 (also referred to as rhBMP-2B), rhBMP-5 or rhBMP-6, rhBMP-7, rhBMP-8, and a heterodimer of rhBMP or rhBMP. Modified and partially damaged bodies can be mentioned, and these can be used alone or as a mixture of two or more. Among them, rhBMP-2 or rhBMP-7 is preferable for the formation or regeneration of bone because rhBMP-2 or rhBMP-7 has a large effect, and rhBMP-2 is particularly preferable.
[0027]
Further, the bone formation inducing factor is uniformly mixed in the bioabsorbable member from the viewpoint of forming bone uniformly even in the central portion of the bone formation member, and is uniformly supported on the pore inner surface of the porous ceramic body. Is preferred.
[0028]
In order for the above-mentioned osteogenesis-inducing factor to exert an osteogenic effect, a substrate on which it is carried is required. As the base material, in the present invention, a number of substantially spherical pores are included, and a plurality of adjacent pores form open spherical pores three-dimensionally communicated with each other by the communicating holes opened at the contact portion. The pore volume of 5 μm or more in the pore size distribution measured by a mercury porosimeter is 85% or more of the total pore volume, and a ceramic porous body formed by stirring and foaming is used.
The porous ceramic body having such a structure has a dense skeleton portion, has sufficient strength as a whole, can stably support the bioabsorbable member for a long time, and has an average pore size. Thus, cells and bodily fluids can move and circulate quickly and efficiently through the large-diameter communicating portion formed between the pores.
In addition, in the porous ceramic body, the shape of each pore is substantially spherical, and despite the large porosity, the shape is maintained without collapse. The sexual member and the bone formation inducing factor can be carried on the inner surface of the stoma at a high density without closing the stoma and the communicating hole.
[0029]
The porous ceramic body has a porosity of 50% or more and 90% or less, preferably 65% or more and 85% or less, from the viewpoint that cells and nutrients from the inside of the bone are easily introduced and the whole is easily reached. is there. Further, the average pore diameter is preferably 100 μm or more and 600 μm or less.
The average pore diameter can be measured by a method using resin embedding.
The average diameter of the communicating holes of the open spherical pores of the ceramic porous body is preferably 20 μm or more, and more preferably 40 μm or more. The average diameter of the communication holes can be measured by a mercury porosimeter (mercury porosimetry).
FIG. 1 shows a pore distribution of a ceramic porous body made of hydroxyapatite measured by a mercury porosimeter (mercury porosimetry).
[0030]
The porous ceramic body having pores as described above can be easily manufactured by stirring and foaming. The porous ceramic body formed by stirring and foaming is preferable because the skeleton itself defining the pores is dense, the pores are substantially spherical, and high strength can be obtained.
Specifically, for example, the above-described porous ceramic body can be obtained by the following manufacturing method. The case where the material is hydroxyapatite will be described as an example.
First, polyethyleneimine or the like is added to the hydroxyapatite powder as a crosslinkable polymerizable resin, and mixed and crushed using water as a dispersion medium to prepare a slurry.
Next, polyoxyethylene lauryl ether or the like is added as a foaming agent to the slurry, and the slurry is foamed by stirring.
Further, sorbitol glycidyl ether or the like is added as a cross-linking agent, and the obtained foam slurry is cast, dried with the foam structure fixed, and then sintered at about 1100 to 1300 ° C., A hydroxyapatite porous body is obtained.
[0031]
The porous ceramic body is preferably a ceramic material having no mechanical harm and a material having sufficient mechanical strength. Specifically, alumina, zirconia, silica, mullite, diopside, and ceramic It is preferable to be made of at least one selected from lastnite, alite, belite, arcermanite, monticerite, living body glass and calcium phosphate ceramics.
Among them, calcium phosphate-based ceramics are preferred because of their excellent biocompatibility, and examples of the calcium phosphate-based ceramics include hydroxyapatite, tricalcium phosphate, and fluorapatite. From the viewpoints of assimilation, adhesion, strength, and the like, it is preferable to be composed of hydroxyapatite, which is a main component of bone.
[0032]
In order to gradually release the bone formation inducing factor within a period of several weeks to more than 10 weeks for bone regeneration or formation, a bioabsorbable member to be combined with the bone formation inducing factor is used. It is essential. When an osteogenesis-inducing factor is directly applied to a portion where a bone is to be formed, the osteogenesis-inducing factor immediately flows out, and it is difficult to form bone uniformly.
Therefore, as a bioabsorbable material that is complexed with an osteogenesis-inducing factor, it has sustained release of the osteogenesis-inducing factor, is not harmful to the living body, and is gradually absorbed by tissues in the body while simultaneously forming bone. Those that release the inducer gradually are preferred.
[0033]
As a material having such characteristics, an inorganic material such as tricalcium phosphate can be used, but it is preferable to use an organic compound from the viewpoint of easy control of the time of bioabsorption.
Specifically, a polymer material having both hydrophobic and hydrophilic properties is suitably used. For example, a polymer of lactic acid and / or glycolic acid, a block copolymer of lactic acid and / or glycolic acid and polyethylene glycol, and a copolymer of lactic acid and / or glycolic acid, p-dioxanone and polyethylene glycol ( PLA-DX-PEG), atelocollagen and the like.
[0034]
Among these, polylactic acid-polyethylene glycol copolymer (PLA-PEG) is particularly preferred from the viewpoints of the rate of absorption into tissues in the body and the rate of release of bone formation inducing factors, adhesion to the ceramic porous body, elasticity, and the like. Preferably, the number average molecular weight of the polylactic acid is 5,000 or more and 1,000,000 or less, and the molar ratio of the polylactic acid (PLA) to polyethylene glycol (PEG) is preferably 25:75 to 75:25. In particular, the number average molecular weight as a whole is preferably from 9000 to 9700 and the molar ratio is more preferably from 60:40 to 70:30.
If necessary, the same ceramic component as the material of the ceramic porous body may be added.
[0035]
Similarly, a copolymer of lactic acid and / or glycolic acid, p-dioxanone and polyethylene glycol (PLA-DX-PEG) having a number average molecular weight of 5,000 or more and 20,000 or less, preferably 8,000 or more and 10,000 or less, is also a bio-based compound. It is suitable as an absorbent member. The number average molecular weight is more preferably from 8900 to 9400.
This PLA-DX-PEG preferably has a molar ratio of lactic acid and / or glycolic acid, p-dioxanone and polyethylene glycol of 26 to 60: 4 to 25:25 to 70 in the copolymer.
As a specific method for producing PLA-DX-PEG, for example, a method described in JP-A-2000-237297 can be used.
[0036]
The bioabsorbable member, the communication holes of the ceramic porous body is not closed, from the viewpoint of maintaining the open pore state, not to prevent the insertion of cells and the like having the ability to form bone such as osteoblasts, It is preferred that the ceramic porous body is almost uniformly supported on the inner surface of the pores with a thickness of 2 μm or less.
[0037]
The amount of the bioabsorbable member and the bone formation inducing factor used in the present invention is, for example, 10% when PLA-PEG is used as the bioabsorbable member and BMP-2 is used as the bone formation inducing factor in rabbits. ~ 200mg / cm ³ Degree, preferably 20 to 120 mg / cm ³ About 10 to 120 μg / cm for BMP-2 ³ Degree, preferably 20 to 50 μg / cm ³ To the extent possible, homogeneous bone formation is possible.
As described above, in the present invention, the amount of BMP-2 used was 10 to 29 μg / cm, which was conventionally difficult. ³ Sufficient effects can be obtained with a small amount.
[0038]
Since the bioabsorbable member as described above has water absorbability and swells due to water absorption, when used in a large amount, it protrudes from the bone forming member or flows out, and the shape of the member is reduced. Irrespective of this, bone will form in excess or in parts other than bone.
It is not preferable to use the bone formation inducing factor in excess of the above range from the viewpoint of medical economy and prevention of abnormal bone formation.
Therefore, the amount of the bioabsorbable member and the bone formation inducing factor used can be suppressed to about 1/10 or less of that of the related art, so that the bone formation member according to the present invention is safe and economical. It is excellent.
[0039]
The bone forming member as described above is a manufacturing method according to the present invention, that is, after adding a bioabsorbable material comprising an organic compound to acetone, mixing with an osteogenesis-inducing factor, and preparing a mixed solution. Infiltrating the mixed liquid into a ceramic porous body formed by stirring and foaming and forming a plurality of adjacent substantially spherical pores three-dimensionally communicating with each other through communicating pores. Removing the acetone in the porous ceramic body and supporting the bioabsorbable member and the bone formation inducing factor on the inner surface of the pores of the porous ceramic body.
[0040]
In the step of supporting the bioabsorbable member and the bone formation inducing factor, the mixed solution containing the bioabsorbable member and the bone formation inducing factor is uniformly supported on the pore inner surface of the porous ceramic body, and thereafter, the bone formation is performed. It is necessary to remove by volatilization, freeze-drying, drying under reduced pressure, or the like so as not to remain in the member for use.
[0041]
FIG. 2 shows an electron micrograph of a ceramic porous body used in the present invention and made of hydroxyapatite. FIG. 2A shows an enlargement magnification of 5000 times, and FIG. 2B shows an enlargement magnification of 100 times.
FIG. 3 shows an electron micrograph of the bone forming member in which the porous ceramic body shown in FIG. 2 carries PLA-PEG by the manufacturing method according to the present invention. FIG. 3A shows a case where the magnification is 5000 times, and FIG. 3B shows a case where the magnification is 100 times.
In the bone forming member shown in FIG. 3, the surface of the porous ceramic body is uniformly coated with PLA-PEG, as can be seen by comparing FIG. 2 (a) and FIG. 3 (a). Moreover, as can be seen by comparing FIGS. 2B and 3B, the communication holes of the ceramic porous body are not closed, and the open pore state is maintained.
[0042]
In the bone formation member, for the purpose of further promoting bone formation, it is also possible to insert cells having the ability to form bone such as osteoblasts, mesenchymal stem cells, etc. into the pores in advance. For this purpose, as described above, it is preferable that the bone forming member is configured such that the communication hole of the ceramic porous body is not closed, the open pore state is maintained, and the insertion of cells or the like is not hindered.
For this reason, in the supporting step of the bioabsorbable member and the bone formation inducing factor, it is preferable that the bioabsorbable member is supported almost uniformly at a thickness of 2 μm or less on the pore inner surface of the porous ceramic body.
[0043]
【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]
20 mg of PLA-PEG (PLA: PEG = 68: 38 (molar ratio)) composed of a copolymer having a number average molecular weight of 9300 composed of DL-lactide and polyethylene glycol, and 20 μg of rhBMP-2 were mixed and diluted with acetone. Thus, a gel-like mixture was prepared.
The gel-like mixture was infiltrated into a hydroxyapatite porous body (diameter: 4 mm, length: 15 mm, porosity: 75%, average pore diameter: 150 μm) produced by stirring and foaming, and then left for a while to evaporate acetone. Thus, a bone forming member was obtained in which the bioabsorbable member and the bone formation inducing factor were uniformly carried on the pore inner surface of the porous apatite.
The obtained bone forming member was inserted into a bone defect (15 mm) formed in the radial shaft of the forearm of a rabbit.
Five weeks later, the inserted portion of the member was subjected to X-ray photography and histological examination.
As a result, on X-ray photography, it was confirmed that the entire member showed a hardened image, and that the boundary between the member and the bone stump was completely fused with the bone.
Histologically, it was confirmed that mature bone tissue was formed in all pores of the member. Further, cortical bone was observed on the surface of the member.
[0044]
[Example 2]
As in Example 1, PLA-PEG (20 mg) and rhBMP-2 (5 μg) were mixed and diluted with acetone to prepare a gel-like mixture.
Then, in the same manner as in Example 1, a bone forming member was obtained in which the bioabsorbable member and the bone formation inducing factor were uniformly carried on the pore inner surface of the hydroxyapatite porous body.
The obtained bone forming member was inserted into a bone defect (15 mm) formed in the radial shaft of the forearm of a rabbit.
Five weeks later, the inserted portion of the member was subjected to X-ray photography and histological examination.
As a result, as in Example 1, in X-ray photography, it was confirmed that the entire member showed a hardened image, and that the boundary between the member and the bone stump was completely fused with the bone.
Histologically, it was confirmed that mature bone tissue was formed in all pores of the member. Further, cortical bone was observed on the surface of the member.
[0045]
[Comparative Example 1]
Five weeks later, the bone insertion portion (15 mm) of the radial shaft of the forearm of the rabbit formed in the same manner as in Example 1 was not replaced, and after 5 weeks, an X-ray photograph of the inserted portion of the member was performed, and histological examination was performed. Was.
As a result, a radiograph showed a clear bone defect state, and histologically, the bone defect was filled with fibrous connective tissue, and the bone was not repaired.
[0046]
[Comparative Example 2]
The same hydroxyapatite porous body as in Example 1 was used, without forming a mixed layer of a bioabsorbable member and an osteogenesis-inducing factor, as it was, in the same manner as in Example 1 to form a rabbit forearm radial diaphysis. It was inserted into a bone defect (15 mm).
Five weeks later, the inserted portion of the porous body was subjected to X-ray photography and histological examination.
As a result, it was confirmed by X-ray photography that the X-ray permeability was reduced at both ends of the porous body, and that new bone was formed at the boundary between the porous body and the bone stump.
However, although fibrous connective tissue was found in the pores at the center of the porous body, bone formation was not found.
[0047]
【The invention's effect】
As described above, the use of the bone forming member according to the present invention makes it possible to form a homogeneous bone more effectively, safely and sufficiently due to the excellent characteristics of the ceramic porous body having a specific structure.
In addition, since the bone formation member can reduce the amount of the bone formation inducing factor or the like to about 1/10 or less of the conventional practical amount, it is advantageous from the viewpoint of economy and safety. Things.
Further, according to the method for manufacturing a bone forming member according to the present invention, the bone forming member can be obtained easily and efficiently.
[Brief description of the drawings]
FIG. 1 shows a pore distribution of the porous ceramic body shown in FIG. 1 measured by a mercury porosimeter.
FIGS. 2A and 2B show electron micrographs of a ceramic porous body made of hydroxyapatite according to the present invention, wherein FIG. 2A is an enlargement magnification of 5000 times and FIG. 2B is an enlargement magnification of 100 times.
3 shows electron micrographs of a bone forming member in which PLA-PEG is supported on the porous ceramic body shown in FIG. 2, (a) showing a magnification of 5000 times, and (b) showing a magnification of 100. It is twice.

Claims (12)

A bone forming member in which a bioabsorbable member and an osteogenesis-inducing factor are carried on the pore inner surface of the porous ceramic body,
In the porous ceramic body, a plurality of adjacent substantially spherical pores are connected to each other to form three-dimensionally connected open spherical open pores, and a pore volume having a pore diameter of 5 μm or more in a pore diameter distribution measured by a mercury porosimeter has a total pore volume. An osteogenic member characterized by being 85% or more in volume and formed by stirring and foaming. The osteoinductive factors include bone morphogenetic factor (BMP), transforming growth factor (TGF-β), cartilage-derived morphogenetic factor (CDMP), osteoinductive factor (OIF), insulin-like growth factor (IGF), and platelet-derived growth factor. The osteogenic member according to claim 1, wherein the member is at least one selected from a factor (PDGF) and a fibroblast growth factor (FGF). The bone forming member according to claim 2, wherein the BMP is recombinant human BMP-2. The bone formation inducing factor is uniformly mixed in the bioabsorbable member, and the bioabsorbable member is almost uniformly supported on the inner surface of the pores of the porous ceramic body with a thickness of 2 μm or less. The bone forming member according to any one of claims 1 to 3. The porous ceramic body has a porosity of 50% or more and 90% or less, an average pore diameter of 100 μm or more and 600 μm or less, an average pore diameter of communication holes of 20 μm or more, and is made of alumina, zirconia, silica, mullite, diopside, and wollast. The method according to any one of claims 1 to 4, comprising at least one selected from the group consisting of knight, alite, belite, arcermanite, monticerite, living body glass and calcium phosphate-based ceramics. Bone forming member. The calcium phosphate-based ceramic is made of hydroxyapatite, and the bioabsorbable member is provided with a sustained release of an osteogenesis-inducing factor. Bone forming member. The bioabsorbable member includes a polymer of lactic acid and / or glycolic acid, a block copolymer of a polymer of lactic acid and / or glycolic acid and polyethylene glycol, a copolymer of lactic acid and / or glycolic acid, p-dioxanone and polyethylene glycol. The bone forming member according to any one of claims 1 to 6, comprising at least one member selected from the group consisting of: The bone forming member according to any one of claims 1 to 7, wherein the bioabsorbable member is a block copolymer of polylactic acid and polyethylene glycol. The block copolymer of polylactic acid and polyethylene glycol has a number average molecular weight of 5,000 to 1,000,000 and a molar ratio of the polylactic acid to polyethylene glycol of 25:75 to 75:25. Item 10. The bone forming member according to Item 8. The bone forming member according to any one of claims 1 to 9, wherein the bioabsorbable member is a copolymer of lactic acid and / or glycolic acid, p-dioxanone, and polyethylene glycol. . After adding a bioabsorbable material composed of an organic compound to acetone, mixing with an osteogenesis-inducing factor, and preparing a mixed solution,
A step of infiltrating the mixed liquid into a ceramic porous body formed by stirring and foaming and forming a plurality of adjacent substantially spherical pores three-dimensionally communicating with each other through communicating pores;
Removing acetone in the ceramic porous body, supporting a bioabsorbable member and an osteogenesis-inducing factor on the inner surface of the pores of the ceramic porous body, and obtaining a bone forming member. A method for producing a bone forming member. 12. The method for manufacturing a bone forming member according to claim 11, wherein the bioabsorbable member is substantially uniformly supported on the inner surface of the pores of the porous ceramic body at a thickness of 2 μm or less.

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