JP4327432B2 - Implant material - Google Patents

Description

[0001]
BACKGROUND OF THE INVENTION
The present invention relates to a bioactive and degradable absorbable implant material used as a substitute for allograft bone or autograft bone.
[0002]
[Prior art]
Conventionally, ceramic bone implant materials such as hydroxyapatite (HA) and tricalcium phosphate (TCP), which are bioactive, have been used as bone substitutes. In addition, recently, in order to compensate for large bone defects, surgical methods that use allografts obtained by cutting and processing cadaver bones, and the pelvis, which can be regenerated and healed without any problems in strength after removal of small bones. Surgical methods for extracting and using autograft bone fragments from large bone sites such as ribs are routinely performed.
[0003]
[Problems to be solved by the invention]
However, when ceramic implant material is embedded in a bone defect site, there is a problem that the cortical bone part and the cancellous bone part of the bone defect site are uniformly filled with hard ceramics. There is a problem that the bone defect part cannot be reconstructed with its own bone tissue because it remains (it is said that it is replaced with bone, but there is a fear that it will remain for 20 years or more very late) .
[0004]
On the other hand, allograft bone fragments are block-shaped with cortical bone on a part of the surface of cancellous bone, and the cortical bone portion at the bone defect site can be compensated by the cortical bone of the bone fragment. The cancellous bone portion of the bone defect site can be supplemented by the cancellous bone of the bone fragment. However, since this allograft is obtained by cutting and processing a cadaver bone, there is a problem that it is not easy to obtain a large amount of cadaver bone as a raw material and provide a necessary and sufficient amount of the graft bone. In addition, there is a problem that the shape that can be processed is greatly limited. In addition, even if it is an allograft bone fragment, the transplanted bone fragment is a bone tissue different from its own bone tissue, and depending on the implantation conditions, it may be naturally absorbed and disappear, or there is a risk of lack of strength or a decrease in strength. . In addition, since it is a cadaver bone of another person, sterilization treatment is necessary. However, depending on the condition, degeneration of the cadaver bone occurs, and thus it is necessary to sufficiently control the sterilization condition. However, sometimes it is inadequate, so it can be informed of the occurrence of a serious accident that leads to death after implantation. Autografted bone fragments removed during the operation are immune to this type of accident, but they cannot be denied in any way.
[0005]
An object of the present invention is to provide an in vivo active and totally in vivo resorbable implant material that can solve the above-mentioned problems, as a substitute for a living bone composed of an integral body of cortical bone and cancellous bone.
[0006]
[Means for Solving the Problems]
To achieve the above object, the implant material of the present invention, a bioactive bioceramics powder into the porous matrix of the biodegradable absorbable polymers pore size therein to have a continuous pores of 100-400 60 to 90 A dense skin layer made of biodegradable absorbable polymer containing bioactive bioceramics powder is formed on a part of the surface of the block-shaped porous body containing% by weight. And is intended to replace living bones made of an integral body of cortical bone and cancellous bone.
[0007]
In this implant material, the block-shaped porous body plays the role of cancellous bone, and the high-strength epidermis layer plays the role of cortical bone. Therefore, the implant material can be used as a substitute for allografts or autografts. Embedding in the defect part and filling the cancellous bone part of the bone defect part with a block-like porous body, and filling the cortical bone part of the bone defect part with the epidermis layer, it is as if the cancellous bone part of the bone defect part Is filled with cancellous bone, and the cortical bone part is filled with cortical bone.
[0008]
As described above, when the bone defect site is filled with the implant material of the present invention, the bodily fluid penetrates into the block-like porous body through the continuous pores, the hydrolysis proceeds rapidly, and the bone conduction of the bioceramic powder. Since the osteoblasts enter the inside of the porous body due to the ability and the bone tissue is conductively formed, the block-like porous body is replaced with the bone tissue within a relatively short period of time. On the other hand, the epidermis layer is gradually delayed from the surface of the block-like porous body, and the hydrolysis gradually proceeds from the surface, maintaining sufficient strength until the block-like porous body is replaced with bone tissue to some extent. Disappears by replacing bone tissue. As described above, the implant material of the present invention does not have a specific biological reaction, and can become an autologous bone by invasion and replacement of surrounding living bone while being non-specifically decomposed, absorbed and discharged. In other words, both the block-shaped porous body and the epidermis layer are decomposed and absorbed and replaced with bone tissue, and do not remain in the living body as foreign materials. Because of the long-term survival, it is possible to dispel the fear of the occurrence of harmfulness, and it is possible to repair and reconstruct the bone defect site with the replaced bone tissue.
[0009]
In addition, since the implant material of the present invention is made from a biodegradable absorbable polymer as a raw material, there is no worry of insufficient acquisition of the raw material, unlike conventional allograft bones made from cadaveric bone. A large amount of implant material can be mass-produced without limitation, and a desired shape and size can be produced by molding or cutting.
[0010]
Further, the skin layer in the implant material of the present invention contains bioceramic powder, but is composed of a biodegradable and absorbable polymer, so it is too hard and brittle like a fired ceramic implant material. In other words, it has toughness and does not easily crack, and can be heated and deformed if necessary. The block-shaped porous body also contains a large amount of bioceramic powder, but it is a porous body made from biodegradable and absorbable polymer, so that even if the porosity is high, It is very brittle and does not drop off when it is embedded, so it can be deformed by heating if necessary. Thus, the implant material of the present invention is not brittle, has a sufficient practical strength, can be deformed by heating, and has excellent handleability.
[0011]
The porous porous body in the implant material of the present invention has a porosity of 50 to 90%, continuous pores account for 50 to 90% of the total pores, and the pore size of the continuous pores is about 100 to about 400 μm. Some are desirable from the standpoints of resorbability and conduction substitution of bone tissue. And it is desirable that the content of the bioceramic powder in the block-shaped porous body is 60 to 90% by weight, and when such a content is obtained, the osteoconductivity is more sufficient than the porous body having a lower content. The porous body is replaced with bone tissue within a relatively short period of time. Further, the foreign body reaction around the strip caused by hydrolysis of the resorbable polymer having no osteoconductivity is further avoided.
[0012]
In the implant material of the present invention, it is desirable that the content of the bioceramic powder in the epidermis layer is 10 to 60% by weight, and when the content is such, sufficient osteoconductivity is obtained without the epidermis layer becoming brittle. It can be demonstrated.
[0013]
DETAILED DESCRIPTION OF THE INVENTION
Hereinafter, specific embodiments of the present invention will be described with reference to the drawings.
[0014]
FIG. 1 is a perspective view of an implant material according to an embodiment of the present invention.
[0015]
In this implant material, a skin layer 2 is overlapped and integrally provided on a convexly curved side surface of a block-shaped porous body 1. Block-shaped porous body 1, there is internal to what pore size containing bioactive bioceramic powder 60-90% by weight in the porous matrix of the biodegradable absorbable polymers which have the continuous pores of 100~400μm Thus, part of the bioceramic powder is exposed on the surface of the porous body 1 and the inner surface of the continuous pores of the porous matrix .
[0016]
This block-shaped porous body 1 is produced by the following method. First, the biodegradable absorbent polymer is dissolved in a volatile solvent and a bioceramic powder is mixed to prepare a suspension. The suspension is fiberized by means of spraying or the like, and a fiber assembly in which fibers are intertwined Form the body. Next, the fiber assembly is heated and pressurized to form a block-like porous fiber fusion assembly as shown in FIG. 1, and by immersing the fiber fusion assembly in a volatile solvent, While the fibers are contracted and fused, the substantially fibrous form is lost to form a matrix, and the shape is changed to a porous body in which the inter-fiber voids are rounded continuous pores. The shape of the porous body 1 is not particularly limited as long as it is a block shape, and is produced in various shapes according to the bone defect site to be compensated.
[0017]
In consideration of physical strength, invasion and stabilization of osteoblasts, the porous body 1 has a porosity of 50 to 90% (preferably 60 to 80%), and continuous pores are 50% of the total pores. It is desirable to occupy ˜90% (preferably 70 to 90%) and the pore diameter of the continuous pores is about 100 to about 400 μm (preferably 150 to 350 μm). When the porosity exceeds 90% and the pore diameter is larger than 400 μm, the physical strength of the porous body 1 is lowered and becomes brittle. On the other hand, when the porosity is less than 50%, the continuous pores are less than 50% of the total pores, and the pore diameter is smaller than 100 μm, it becomes difficult for the body fluid and osteoblasts to enter, and the porous body 1 is hydrolyzed and bone tissue. The growth time of the porous body 1 becomes slow, and the time required for the porous body 1 to replace bone cells becomes long.
[0018]
The porous body 1 plays the role of cancellous bone, does not require the strength as the epidermal layer 2 that plays the role of cortical bone, is decomposed relatively quickly, and is conductively formed by the bioceramic powder. It is necessary to replace bone tissue. Therefore, the biodegradable and absorbable polymer used as the raw material of the porous body 1 is safe, relatively quick to decompose, not very brittle, amorphous or a mixture of crystal and amorphous poly-D, L-lactic acid, L-lactic acid and D, L-lactic acid copolymer, lactic acid and glycolic acid copolymer, lactic acid and caprolactone copolymer, lactic acid and ethylene glycol copolymer, lactic acid and para-dioxanone copolymer, etc. These are used alone or in admixture of two or more. Among these polymers, those having a viscosity average molecular weight of about 50,000 to 1,000,000 are preferably used in consideration of the ease of forming a fiber aggregate by fiberization and the period of decomposition and absorption in vivo.
[0019]
The bioceramic powder to be contained in the biodegradable absorbable polymer of the porous body 1 is bioactive, has good osteoconductivity and good biocompatibility, and has not been calcined, unfired hydroxyapatite, di Powders such as calcium phosphate, tricalcium phosphate, tetracalcium phosphate, octacalcium phosphate, calcite, serabital, diopsite, and smallpox are used, but among them, they are totally absorbed in vivo and completely replaced with bone tissue. In vivo bioabsorbable bioceramics powders are preferred, especially uncalcined and uncalcined hydroxyapatite, tricalcium phosphate, and octacalcium phosphate, which have extremely high bioactivity, excellent osteoconductivity, and harmfulness. It is optimal because it is low and is absorbed by the living body in a short period of time. These bioceramic powders having a particle size of 10 μm or less are preferably used. Particularly, those having a particle size of about 0.2 to 5 μm are fibrillated by means such as spraying to form a fiber aggregate. In this case, the fibers are used very preferably because they are not cut short.
[0020]
The content of the bioceramic powder in the porous body 1 is desirably 60 to 90% by weight, and if it exceeds 90% by weight, the fibers are short when forming a fiber aggregate by means of spraying or the like. On the other hand, if it is less than 60% by weight, the formation of conduction in the bone tissue is delayed, and it takes too much time for the porous body 1 to replace the bone tissue. The more preferable content rate of bioceramics powder is 60 to 80 weight%.
[0021]
The porous body 1 preferably contains appropriate amounts of various bone forming factors, growth factors, drugs and the like. BMP as the main osteogenic factor, monokines and lymphokines such as IL-1, TNF-α, TNF-β, IFN-γ, colony stimulating factor, or TGF-α as the main growth factors , TGF-β, IGF-1, PDGF, FGF and so-called growth differentiation factors. In addition, as a drug, a drug related to bone growth (such as vitamin D, prostaglandins or anti-cancer drugs), an antibacterial agent and the like can be arbitrarily selected. When the above-described growth factor is contained in the porous body 1, bone formation is remarkably promoted inside the porous body 1, and the porous body 1 is replaced with bone tissue at an early stage, so that most of the bone defects are quickly repaired. It will be rebuilt. And when said chemical | medical agent is contained, a chemical | medical agent will be fully absorbed and a chemical | medical effect will be exhibited.
[0022]
Further, the surface of the porous body 1 (the surface on which the skin layer 2 is not provided) may be subjected to an oxidation treatment such as corona discharge, plasma treatment, hydrogen peroxide treatment, etc. Since the wettability of the biodegradable polymer on the surface of the body 1 is improved and osteoblasts penetrate and grow more effectively inside the porous body 1, the replacement with bone tissue is further promoted There are advantages to being. Further, the skin layer 2 may be subjected to the same oxidation treatment.
[0023]
On the other hand, the epidermis layer 2 that plays the role of cortical bone is a dense layer composed of a biodegradable and absorbable polymer containing bioactive bioceramics powder. In the implant material shown in FIG. 1, the skin layer 2 is integrally provided so as to overlap with the convex curved side surface of the block-shaped porous body 1, and any one of the other side surface, top surface, and bottom surface of the porous body 1 is provided. It may be provided so as to overlap with each other, or may be provided so as to overlap with two side surfaces of the porous body 1 like the implant material shown in FIG. 2, or may be provided so as to overlap with other two surfaces or three or more surfaces. In short, the skin layer 2 may be provided so as to overlap a part of the surface of the block-shaped porous body 1.
[0024]
The thickness of the skin layer 2 is not particularly limited, but is preferably set as appropriate within a range of 1.0 to 5.0 mm in consideration of a bone defect site in which the implant material is embedded. If the thickness is less than 1.0 mm, the strength of the epidermis layer 2 may be insufficient. If the thickness is greater than 5.0 mm, it takes a long time for the epidermis layer 2 to be decomposed and absorbed to replace bone tissue.
[0025]
Since the skin layer 2 is required to have a strength higher than that of the block-shaped porous body 1, crystalline poly-L-lactic acid or polyglycolic acid is preferably used as the biodegradable absorbent polymer. Particularly, the high-strength skin layer 2 using poly-L-lactic acid having a viscosity average molecular weight of 150,000 or more, preferably about 200,000 to 600,000 is suitable.
[0026]
The bioceramic powder contained in the skin layer 2 is the same as the bioceramic powder contained in the porous body 1 described above, but the content is preferably in the range of 10 to 60% by weight. . If it exceeds 60% by weight, the skin layer 2 becomes brittle, and if it is less than 10% by weight, the formation of bone conduction by the bioceramic powder becomes insufficient.
[0027]
The skin layer 2 is formed by injection-molding a biodegradable absorbent polymer containing bioceramic powder, or cutting a biodegradable absorbent polymer-molded block containing bioceramic powder. In the latter method, the molding block is made into a block in which polymer molecules and crystals are oriented by means of compression molding or forging molding, and the skin layer 2 obtained by cutting this is a dense layer. It is very suitable because the polymer molecules and crystals are oriented three-dimensionally and the strength is further improved. In addition, a skin layer obtained by cutting a stretched molded block can also be used.
[0028]
This implant material is obtained by superimposing the skin layer 2 produced by the above method on one convex curved side surface of the block-like porous body 1 produced by the above method and making it unseparable by means such as heat welding. It is what The means for integrating the skin layer 2 and the porous body 1 is not limited to heat welding. For example, the skin layer 2 and the porous body 1 may be integrated by bonding, or a dovetail groove may be provided on one of the contact surfaces of the skin layer 2 and the porous body 1. Alternatively, an ant may be formed on the other side, and the ant may be integrated by a means such as fitting in the ant groove.
[0029]
The implant material having the above-described configuration is embedded in the bone defect portion, the cancellous bone portion of the bone defect portion is filled with the block-shaped porous body 1, and the cortical bone portion of the bone defect portion is replaced by the epidermis layer 1. When supplemented, the block-shaped porous body 1 plays the role of cancellous bone, and the high-strength epidermal layer 2 plays the role of cortical bone. The part is filled with cortical bone.
[0030]
When the bone defect site is filled with the implant material of the present invention as described above, the body fluid penetrates into the block-like porous body 1 through the continuous pores, the hydrolysis proceeds rapidly, and the bone of the bioceramic powder is obtained. Due to the conductivity, osteoblasts enter the porous body, and bone tissue is conductively formed. Therefore, the block-shaped porous body 1 is replaced with bone tissue within a relatively short period of time. On the other hand, the skin layer 2 maintains sufficient strength for a period until the block-like porous body 1 is replaced with the bone tissue to some extent by the hydrolysis gradually progressing from the surface later than the block-like porous body 1. Eventually, the bone tissue replaces and disappears. As described above, the implant material of the present invention decomposes and absorbs both the block-like porous body 1 and the epidermis layer 2 and is replaced with bone tissue, and does not remain in the living body as a foreign body. It is possible to dispel the fear of expression of harmfulness due to long-term survival in the living body, which is concerned about the material, and it is possible to repair and reconstruct the bone defect site with the replaced bone tissue.
[0031]
The implant material of the present invention comprising a composite of a block-like porous body 1 and an outer skin layer 2 can be used for various purposes as a surgical substitute, but has come to be used especially now. However, it is effective as a prosthetic material and spacer for the vertebral bodies of the cervical vertebrae and lumbar vertebrae, which have been clarified in several problems.
[0032]
FIG. 2 is a perspective view of an implant material according to another embodiment of the present invention.
[0033]
In this implant material, skin layers 2 and 2 are integrally provided on both side surfaces of a substantially rectangular parallelepiped porous body 1 whose vertical dimension gradually decreases. Since the porous body 1 and the skin layer 2 are the same as those already described, description thereof is omitted. Such an implant material is inserted between vertebral bodies as, for example, an intervertebral body spacer, and the porous body 1 quickly replaces the bone tissue as described above while receiving the pressure of the upper and lower vertebral bodies. The upper and lower vertebral bodies are fused and fixed, and the epidermal layer 2 is finally replaced with bone tissue.
[0034]
FIG. 3 is a perspective view of an implant material according to still another embodiment of the present invention.
[0035]
This implant material is used as an iliac spacer, and is formed by integrally superposing the skin layer 2 on one surface of a curved substantially square plate-like porous body 1. Since the porous body 1 and the skin layer 2 are the same as those already described, description thereof is omitted.
[0036]
【The invention's effect】
As can be seen from the above description, the implant material of the present invention is used as a bone substitute material, intervertebral body spacer, and other applications as a substitute for living bone consisting of a single body of cortical bone and cancellous bone, and is used for bone filling. When used as a material, the cancellous bone part of the bone defect is covered by a block-like porous body that acts as a cancellous bone, and the cortical bone of the bone defect part is covered by a strong epidermal layer that acts as a cortical bone. Part can be compensated. And since the porous body is quickly decomposed and absorbed and replaced with bone tissue in a relatively short period of time, the epidermis layer that is slow to total decomposition and absorption is finally decomposed and absorbed and replaced with bone tissue. As with bone substitutes made of ceramics, it is possible to reliably eliminate the fear of the occurrence of harmful effects due to long-term survival in the body as a foreign body, and repair and rebuild the bone defect part with its own bone tissue replaced be able to. When used as an interbody spacer, the upper and lower vertebral bodies can be fused and fixed by replacing the porous body and the epidermis layer with bone tissue.
[0037]
Moreover, since the implant material of the present invention is made from a biodegradable absorbable polymer as a raw material, it can be made of a raw material such as a conventional allograft bone piece made of cadaver bone or a graft bone piece extracted from autologous bone. There is no fear of insufficient acquisition, and a necessary and sufficient amount of implant material can be mass-produced. A desired shape and size can be produced by molding or cutting.
[Brief description of the drawings]
FIG. 1 is a perspective view of an implant material according to an embodiment of the present invention.
FIG. 2 is a perspective view of an implant material according to another embodiment of the present invention.
FIG. 3 is a perspective view of an implant material according to yet another embodiment of the present invention.
[Explanation of symbols]
1 Block-shaped porous body 2 Skin layer

Claims (4)

Part of the surface of the internal pore size comprised from 60 to 90 wt% of bioactive bioceramics powder into the porous matrix of the biodegradable absorbable polymers which have the continuous pores of 100~400μm block-shaped porous body An implant material comprising a skin layer made of a biodegradable absorbable polymer containing a bioactive bioceramic powder and integrally provided thereon. A porosity of the porous body 50-90%, implant material according to claim 1 which continuous pores accounts for 50-90% of the total pores. The porous body dissolves the biodegradable absorbent polymer and mixes the bioceramics powder to prepare a suspension. The suspension is fiberized to form a fiber assembly in which fibers are intertwined. The aggregate is heated and pressurized to form a block-like porous fiber fusion aggregate. The fiber fusion aggregate disappears by immersing this fiber fusion aggregate in a volatile solvent to shrink and fuse the fibers. The implant material according to claim 1 or 2, wherein the implant material is obtained by forming a matrix and making the interfiber spaces into round pores .   The implant material according to any one of claims 1 to 3, wherein the content of the bioceramic powder in the skin layer is 10 to 60% by weight.

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