WO2020031933A1

WO2020031933A1 - Bone repair implant and method for manufacturing same

Info

Publication number: WO2020031933A1
Application number: PCT/JP2019/030631
Authority: WO
Inventors: 高章植野; 世市郎中島; 山口　誠二; 松下　富春; 壽北垣; 重雄森
Original assignee: 学校法人大阪医科薬科大学; 学校法人中部大学; 大阪冶金興業株式会社
Priority date: 2018-08-08
Filing date: 2019-08-05
Publication date: 2020-02-13
Also published as: JPWO2020031933A1

Abstract

The bone repair implant 10 according to the present invention is a bone repair implant, comprising titanium or a titanium alloy, for being installed at a bone injury site A of a patient, wherein the implant is characterized by: comprising a plate-shaped part 11 at least partially having a surface morphology that corresponds to the surface morphology of the bone having the bone injury site A; and the plate-shaped part 11 being provided with a through-hole 14 through which a fastener, for fastening the plate-shaped part 11 to a section of bone at the periphery of the bone injury site A, can pass.

Description

Bone repair implant and method of manufacturing the same

The present invention relates to a bone repair implant to be installed at a bone damage site.

Conventionally, when a bone is partially lost due to various diseases or accidents, bone other than the own bone defect is transplanted in place of the lost bone, and further fixed with a metal fixture or the like. Have been done.

For example, in the case of a jaw bone, as shown in FIG. 14, a bone 101 obtained from another site is implanted into a bone defect A of the jaw bone 100, and a metal fixing tool 102 processed so as to conform to the shape of the jaw bone 100. Thus, the jawbone 100 and the transplant bone 101 are connected. Specifically, the metal fixture 102 is provided with a plurality of holes 103 along the longitudinal direction, and the metal fixture 102 is connected to the jaw bone 100 and the transplanted bone by a fastener such as a screw passing through the hole 103. It is fastened to 101. Thus, the implanted bone 101 is fixed to the jawbone 100. When such a conventional method is adopted, the patient loses bones other than the bone defect A, and the surgeon removes the bone from the bone defect A and fixes the fixture 102 along the jaw bone shape. In order to perform the operation, the operation time is long and the burden is large.

Therefore, in recent years, it has been studied to install an implant having an ability to induce osteogenesis in a bone defect. By using such a method, it is not necessary to transplant bone at another site to the bone defect, and the burden on the patient and the operator can be reduced. Such an implant is disclosed, for example, in Patent Document 1. The implant of Patent Literature 1 achieves bone formation induction by compounding a bone formation factor (BMP) with a three-dimensional mesh structure formed by using an electron beam using titanium as a material. Since the implant is manufactured based on the three-dimensional coordinate data of the shape of the bone defect, it is easy to control the shape, and further includes BMP, so that bone formation can be induced by placing the implant in the bone defect. it can.

Patent Document 2 discloses a technique for producing a bone repair material by osteoconduction by performing a simple bioactivation treatment on a titanium material without using an osteogenesis-inducing factor such as the BMP. . Specifically, Patent Literature 2 discloses that an apatite layer that is advantageous for bonding with living bone can be formed on the surface of a titanium substrate by performing an acid treatment and a heat treatment on the substrate. .

JP 2013-188419 A International Publication No. 2010/087427

In the implant of Patent Literature 1, BMP is used to add the ability to induce bone formation. However, since it is usually difficult to directly attach BMP to titanium as a base material, surface treatment of the base material is performed. In addition, various processes are performed, such as applying a dextrin solution after BMP is attached. For this reason, the manufacturing process becomes complicated, and even if the above-described treatment is performed, there is a possibility that an amount of BMP capable of exhibiting sufficient osteogenesis-inducing ability cannot be provided to the implant. In addition, BMP itself is presently inexpensive and cannot be mass-produced, so that there remains a problem in clinical use. Furthermore, the implant of Patent Literature 1 is manufactured based on three-dimensional coordinate data of the shape of the bone defect, but the shape is merely a prosthesis for the bone defect, and the bone defect is It is not configured to be able to fix and support the bone itself where the part has formed. Therefore, actually, the above-mentioned fixing tool is separately required.

Further, the technology disclosed in Patent Document 2 (see also Non-Patent Documents 1 to 3) does not require the treatment as in Patent Document 1, and provides simple treatment such as acid treatment and heat treatment for the base material. There have been reports of animal experiments on the possibility of osteointegration (osteoconductivity) in titanium plates and porous titanium bodies and the induction of new bone even in an environment where there is no surrounding bone. However, none of the above-mentioned patent documents and non-patent documents discloses a method of utilizing the method for repairing a bone defect. Furthermore, Patent Document 2 does not disclose an implant having a configuration capable of fixing the bone itself in which a bone defect has occurred, similarly to Patent Document 1.

The present invention has been made in view of the above problems, and an object of the present invention is to provide a bone repair implant capable of supporting and fixing a bone itself having a bone damaged portion by a simple method, and having excellent bone forming ability. To get.

In order to achieve the above-mentioned object, conventionally, by forming an implant having a surface shape corresponding to the surface shape of the bone having the bone defect using three-dimensional coordinate data of the bone having the bone damaged part of the patient, Thus, a bone repair implant that can be easily installed on a bone having a bone damaged portion and that can support and fix the bone without the need for an operator to perform shape processing has been completed.

A bone repair implant according to the present invention is a bone repair implant made of titanium or a titanium alloy for installation at a bone damaged part of a patient, and has at least a part of a surface shape corresponding to the surface shape of the bone having the bone damaged part. The plate-shaped part is provided with a through-hole through which a fastener for fastening the plate-shaped part to a bone part around the bone damaged part can pass. It is characterized by.

According to the bone repair implant according to the present invention, since the bone shape is formed in a surface shape corresponding to the surface shape of the bone having the bone damaged portion, it is not necessary to mold the implant to fit the bone during the operation, which is relatively easy. Can be installed in In particular, by placing the surface shape of the surface of the implant of the present invention in contact with the bone at least partially so as to correspond to the surface shape of the bone, placing the implant at least partially in close contact with the bone. Can be. In addition to this, the implant of the present invention is provided with a through hole through which the fastener passes, so that the fastener is used to fasten to the bone portion around the bone damaged portion, so that the periphery of the bone damaged portion is The located bone can be easily fixed integrally. As a result, it is not necessary to perform processing by the operator as in the related art, and the burden can be reduced.

において In the bone repair implant according to the present invention, the plate-shaped portion may be formed in a shape having a tissue setting portion forming a space for setting a transplanted tissue.

In this way, an important transplant tissue for bone repair can be installed on the plate-like portion in the tissue installation section, that is, a tissue installation as a space in which tissues such as blood vessels and skin necessary for promoting bone repair can be arranged. Since the parts are formed, they can be easily arranged, and the burden on the operator can be reduced.

In the bone repair implant according to the present invention, the plate-shaped portion is configured to be installed at a position capable of supporting the bone having the bone damaged portion, and has a surface shape corresponding to the surface shape of the bone at the installation site. It is preferable to have For example, the plate portion has a surface shape corresponding to a surface shape of a lower portion of the bone having the bone damaged portion, and the plate portion covers a lower portion of the bone damaged portion and has the bone damaged portion. It may be configured to be installed on a bone having the bone damaged portion so as to support the bone from below.

With this configuration, the plate-shaped portion covers the lower portion of the bone damaged portion and supports the bone having the bone damaged portion from below, so that the stability when the bone having the bone damaged portion is fixed by the implant can be improved. . In addition, since the bone having the damaged bone can be supported from below even during the installation operation before fixation, the operation for installing the implant can be facilitated, and the burden on the operator can be reduced.

In the bone repair implant according to the present invention, the plate-shaped portion may be integrally formed with an artificial bone portion for at least partially filling the bone damaged portion in the bone damaged portion.

において In the bone repair implant according to the present invention, it is preferable that the plate-like portion and the artificial bone portion have mechanical properties corresponding to a bone portion around the bone damaged portion.

In this way, the discontinuity of the mechanical properties between the bone damage and the surrounding bone can be reduced, and the plate-like portion normally cooperates with the movement of the bone around the bone damage. As a result, the burden on the patient can be reduced, and functional failure of the relevant portion can be prevented.

In addition, in the bone repair implant according to the present invention, it is preferable that the surface in contact with the bone damaged portion has bioactivity. The portion provided with the bioactivity may be composed of titanium oxide. In the bone repair implant according to the present invention, it is preferable that at least a part of the implant has a porous structure.

すると In the above manner, the bioactivity of the surface in contact with the bone damage promotes the bonding with the bone, so that the integration of the bone and the implant is promoted after the operation. In particular, if an artificial bone part capable of filling the above bone damaged part is provided and subjected to bioactivity treatment, the bone damaged part can be repaired several months after the operation. Therefore, there is no need to implant bones at other parts of the patient or to use a separate metal fixture. Furthermore, the implant of the present invention is made of a biocompatible metal such as titanium or a titanium alloy, and has a porous structure that easily fuses with the bone around the bone damage, so that it is not necessary to remove the implant from the patient after installation. Therefore, according to the bone repair implant according to the present invention, the burden on the patient and the operator can be reduced.

In addition, in the bone repair implant according to the present invention, it is preferable that at least a part of the plate-shaped portion and the artificial bone portion have antibacterial properties. In this way, it is possible to prevent an infection or the like from occurring in the patient due to the installation of the bone repair implant.

The method for manufacturing a bone repair implant according to the present invention includes the steps of obtaining three-dimensional coordinate data of a bone having a bone damaged part of a patient, and using the titanium or titanium alloy as a material based on the three-dimensional coordinate data, Shaping a plate-like portion having a surface shape corresponding to the surface shape of the bone having the portion at least partially and having a through hole.

According to the manufacturing method of the bone repair implant according to the present invention, since it is manufactured based on the three-dimensional coordinate data of the bone having the bone damaged part of the patient, according to the shape of various bones having the bone damaged part of the patient, Implants of various shapes can be easily manufactured. In particular, the implant according to the present invention having the above characteristics can be easily manufactured.

において In the method for manufacturing a bone repair implant according to the present invention, it is preferable that the shaping step uses an additive manufacturing technique. In this way, it is possible to accurately and easily form the shape corresponding to the shape of various bones having a bone damaged portion, and to make the internal structure a porous structure.

は In the method of manufacturing a bone repair implant according to the present invention, in the forming step, the plate-shaped portion may be formed into a shape having a tissue setting portion forming a space for setting a transplanted tissue.

In the method of manufacturing a bone repair implant according to the present invention, in the shaping step, the surface shape corresponding to the surface shape of the bone at a position suitable for setting the plate-shaped portion capable of supporting the bone having the bone damaged portion is provided. It is preferable to shape the plate-shaped portion, and for example, the plate-shaped portion having a surface shape corresponding to the surface shape of the lower part of the bone having the above-mentioned bone damaged portion may be formed.

In the method for manufacturing a bone repair implant according to the present invention, an artificial bone part for at least partially filling a bone defect part in the bone damaged part may be formed integrally with the plate-shaped part. Preferably, after the step of shaping, the method further comprises a step of subjecting at least a part of the surface of the plate-shaped part and the artificial bone part to a bioactive treatment. And heat treating the implant.

すると In this way, a surface layer that promotes osteogenic ability can be formed on the implant, so that excellent osteogenic ability can be imparted to the implant.

骨 Preferably, the method for manufacturing a bone repair implant according to the present invention further includes a step of performing an antimicrobial treatment on at least a part of the plate-like portion and the artificial bone portion after the shaping step.

According to the bone repair implant and the method for manufacturing the same according to the present invention, a bone repair implant capable of supporting and fixing surrounding bone by a simple method and having excellent bone formation inducing ability can be obtained.

(A)-(c) is a figure which shows the bone repair implant which concerns on one Embodiment of this invention, (a) shows the state which installed the bone repair implant in the jawbone which has a bone damage part, (b) It is a perspective view of a bone repair implant, (c) is a perspective view of another direction. (A)-(c) is a figure which shows the bone repair implant which concerns on one modification of one Embodiment of this invention, (a) shows the state which installed the bone repair implant in the jawbone which has a bone damage part, (B) is a perspective view of the bone repair implant, and (c) is a perspective view in another direction. FIGS. 3A and 3B are views showing a cross section taken along line III-III of FIG. (A)-(c) is a figure which shows the bone repair implant which concerns on another modification of one Embodiment of this invention, and shows the state which installed the bone repair implant in the jawbone which has a bone damage part. (B) is a perspective view of a bone repair implant, and (c) is a perspective view of another embodiment. FIG. 4 shows a bone repair implant according to another modified example of the embodiment of the present invention, in which (a) shows a state in which the bone repair implant is installed on a jawbone having a bone damage part, and (b) to (d) show the state. FIG. 4 is a diagram showing a right side surface, a front side, and a left side surface of the bone repair implant, respectively. 9 is a photograph showing a bone repair implant manufactured by an additive manufacturing technique according to another modified example of the embodiment of the present invention. (A)-(d) is a figure which shows the bone repair implant manufactured by the additive manufacturing technology which concerns on another modification of one Embodiment of this invention, (a) shows a side surface, (b) It is a sectional view showing the state where the front was shown, (c) showed the lower surface, and the implant was fastened to the bone with the fastener. (A) to (d) are photographs for explaining a method for installing a bone repair implant in a bone defect part of a rat in Example 1 of the present invention. 2 is a photograph of a micro-CT and a photograph of a non-demineralized polished specimen at a bone defect part two weeks after installation of a rat on which a bone repair implant is installed in Example 1 of the present invention. 4 is a graph showing the amount of new bone 2 weeks and 7 weeks after the rat in which the bone repair implant was placed in Example 1 of the present invention. FIG. 9 is a diagram for explaining conditions for stress simulation according to a third embodiment of the present invention. FIG. 9 is a diagram for explaining conditions for stress simulation according to a third embodiment of the present invention. FIG. 14 is a diagram illustrating a part of the result of the stress simulation of the third embodiment of the present invention. FIG. 2 is a view showing a conventional bone repair implant.

Hereinafter, embodiments for carrying out the present invention will be described with reference to the drawings. The description of the preferred embodiments below is merely exemplary in nature and is not intended to limit the invention, its application, or uses.

骨 The bone repair implant according to the present invention is a bone repair implant made of titanium or a titanium alloy to be installed on a bone damaged part of a patient. Titanium is a biocompatible metal, which is extremely advantageous for use as an implant material. In the present invention, the bone damaged part is a part where a part of the bone is lost or broken due to surgery or the like, or a bone part where various morphological abnormalities have occurred, and includes a bone part that is not in perfect condition.

生体 It is preferable that the surface of the bone repair implant of the present invention has been subjected to a bioactive treatment. The bioactive treatment is not particularly limited as long as it is a treatment capable of strengthening the bond between the implant surface and the bone. For example, it is preferable to form a surface layer made of titanium oxide that promotes bone formation composed of titanium oxide on the implant surface. . The surface layer is formed by oxidizing titanium on the surface of the implant by performing the heat treatment. Further, it is preferable that the surface layer has an osteogenic ability by being subjected to an acid treatment before being subjected to the heat treatment. The bone repair implant of the present invention exhibits excellent bone formation ability by the acid treatment and the heat treatment. In particular, it is preferable to use a mixed acid solution containing at least two or more of hydrochloric acid, sulfuric acid, nitric acid, and hydrofluoric acid in order to impart excellent osteogenic ability to the implant. The temperature in the heat treatment is preferably from 500 ° C. to 750 ° C.

骨 In addition, the bone repair implant of the present invention is preferably subjected to an antibacterial treatment in addition to the bioactive treatment. The antibacterial treatment is not particularly limited as long as it is a treatment capable of imparting antibacterial properties to the surface of the implant. . Thereby, ions such as silver, gallium, or iodine having an antibacterial action can be released from the surface of the implant. Further, before the antibacterial treatment, a treatment of immersing the implant in an aqueous solution containing calcium ions may be performed in order to improve the apatite-forming ability, which is known to improve osteointegration. Before performing these treatments, a treatment may be performed in which the implants are immersed in an aqueous alkali solution such as sodium hydroxide in order to keep the ions at a high concentration in the implants. This antibacterial treatment can also be performed together with the above-mentioned bioactivity treatment. For example, after the above-mentioned mixed acid treatment and heat treatment, the above-mentioned treatment with an aqueous alkali solution such as sodium hydroxide, and the treatment with an aqueous solution containing calcium ions, and then an aqueous silver nitrate solution Or an aqueous solution containing iodine ions such as an aqueous solution containing silver ions such as iodine or an aqueous solution of iodine trichloride.

Further, the bone repair implant according to the present invention is constituted by a plate-like portion having at least partially a shape corresponding to a surface shape of a bone having a bone damaged portion of a patient, and has a structure having a through hole. It is characterized by the following. In the present invention, the plate-shaped portion is not limited to a flat plate, and may be a curved plate having a curved portion, and is preferably curved so as to conform to the shape of the portion to be installed. In particular, it is preferable to have a cross-sectional shape such as a substantially U shape or a substantially J shape from the viewpoint of bending strength. In addition, in order that the surface shape of the plate-like portion is at least partially a shape corresponding to the surface shape of the bone having the bone damaged portion of the patient, the bone repair implant according to the present invention provides the bone damaged portion of the patient with the bone damaged portion. It is formed based on the three-dimensional coordinate data of the bone having. The forming method is not particularly limited, but, for example, a lamination molding technique can be used. In particular, by using a 3D printer using an SLM method with a small lamination pitch, it is possible to accurately and easily form a shape corresponding to various bone shapes having a bone damaged portion, and to make the internal structure a porous structure. You can also. The lamination pitch is, for example, 0.01 mm to 0.05 mm. By using a porous structure, the weight of the implant can be reduced, and the structure can be easily fused with bone. The porous structure is, for example, a spongy structure. Further, the implant of the present invention will be described later. From the viewpoint of reducing stress generated in the implant after installation and preventing damage, the implant of the present invention is formed in such a form as to cover the widest possible area of the bone having the bone damaged part of the patient. Preferably, there is.

As described above, since the bone repair implant according to the present invention is formed by using, for example, a 3D printer, it can be formed into various shapes according to the installation site on the patient, and has various design properties, and further has various designs. It can correspond to the usage form. For example, when an implant having a cross-sectional shape such as a substantially U-shape or a substantially J-shape is employed as described above, the implant can be used in a form such as a tray for supporting a bone damaged portion from below. Then, a material that promotes bone repair, such as crushed cancellous bone, can be placed on the tray-shaped implant, which is preferable. However, it is naturally possible to use without placing anything on the implant. . In addition, when a plate-shaped implant instead of a tray-shaped implant is employed, for example, an osteomuscular flap with a vascular handle may be fixed to one surface of the implant, and the implant may be used in such a manner as to be placed at a bone injury site. . In addition, the implanted bone such as the fibula may be fixed to the implant and placed on the damaged bone of the patient. In this case, the implanted bone may be divided and fixed according to the shape of the implant.

The bone repair implant according to the present invention, as described above, is configured of a plate-shaped portion having at least partially a shape corresponding to the surface shape of the bone having the bone damaged portion of the patient. A tissue setting part which forms a space for setting the transplanted tissue may be formed. In this way, the shape portion corresponding to the surface shape of the bone having the patient's bone damaged portion in the plate-shaped portion comes into contact with the tissue such as the patient's bone, and the plate-shaped portion and the patient's bone are connected to the tissue such as the screw in this portion. While the connection can be made with the fastener, the transplanted tissue such as a blood vessel or skin important for bone repair can be set in the plate-shaped portion in the tissue setting portion. The tissue setting section is formed in such a manner that the transplanted tissue can be set on the plate-like portion, and is not limited to the following configuration. For example, a slight depression is provided in the plate-like portion, or a transplanted tissue is provided. It may be configured to be slightly curved to the side opposite to the side so that the implanted tissue can be easily installed. Since the space for placing the transplanted tissue on the plate-like portion is sufficiently obtained by the tissue setting section, the work load on the operator for arranging the blood vessels and the like can be reduced.

Hereinafter, as one embodiment of the present invention, a case where the bone repair implant according to the present invention is installed at a site having a bone defect as a bone damaged portion of the mandible will be described with reference to FIG. Specifically, FIG. 1A shows a state in which a bone repair implant 10 according to the present invention is installed in a bone defect A in which a part of the mandible is lost, and FIGS. 1B and 1C respectively. FIG. 3 is a perspective view showing another direction of the bone repair implant 10. As shown in FIG. 1, the bone repair implant 10 is formed in a curved plate shape so as to correspond to the surface shape of a bone (mandible) having a bone defect A. Specifically, the bone repair implant 10 is composed of a plate-like portion 11 placed on a bone having a bone defect A, and the plate-like portion 11 penetrates through connection portions 13 located on both sides of the central portion 12. A hole 14 is provided. The bone repair implant 10 is installed so that the central part 12 covers a part of the bone defect part A. In particular, in the present embodiment, the bone repair implant 10 is mounted so that the central portion 12 covers the lower part of the bone defect A, and the bone repair implant 10 supports the bone having the bone defect A from below. As described above, the connecting portions 13 are arranged on both sides of the central portion 12, and the connecting portion 13 has a surface shape corresponding to the surface shape of the bone portion B located on both sides of the bone defect portion A. And is formed to be in contact with, preferably close to, that portion. Also, as described above, since the through-hole 14 is provided in the connection portion 13, a fastener such as a screw is passed through the through-hole 14 when the bone repair implant 10 is installed, and both sides of the connection portion 13 and the bone defect portion A are provided. And the bone part B located at As a result, the bone repair implant 10 is installed on the bone having the bone defect A, and the bone having the bone defect A is supported and fixed. In the bone repair implant 10 according to the present embodiment, the surface of the plate-like portion 11 on the side in contact with the bone is subjected to a bioactive treatment for strengthening the bond with the bone. As described above, the biological activity treatment is not particularly limited as long as the treatment can impart the above-mentioned effect, but a mixed acid heating treatment is particularly preferable.

の一 Further, a modified example of the above embodiment will be described with reference to FIG. As shown in FIG. 2, this modified example is characterized in that an artificial bone portion 25 is protruded from a central portion 22 of a plate-shaped portion 21 as compared with the bone repair implant according to the above embodiment. The artificial bone part 25 is formed in a shape that matches the shape of the bone defect part A. Therefore, by installing the bone repair implant 20, the bone defect A can be filled with the artificial bone 25. Like the plate-like portion 21, such an artificial bone portion 25 can be formed based on three-dimensional coordinate data of a patient's bone, and for example, an additive manufacturing technique can be used. For this reason, the artificial bone part 25 can be formed integrally with the plate-shaped part 21. Further, the artificial bone portion 25 has a porous structure, and a surface in contact with the bone is subjected to a bioactive treatment for strengthening the bond with the bone, similarly to the plate-like portion 21. As in the above embodiment, the bioactivity treatment is not particularly limited as long as it can impart the above-mentioned effect, but a mixed acid heating treatment is particularly preferable. With such a configuration, it becomes possible to promote the integration of the artificial bone portion 25 and the surrounding bone, and it is possible to promote the bone repair at the bone defect portion.

The artificial bone portion 25 may be formed separately from the plate-like portion 21 as described above, or may be formed as a separate body. In this case, the artificial bone portion 25 and the plate-like portion 21 are connected to each other by a fastener such as a screw. Connected by In this case, titanium or a titanium alloy can be used as the material of the artificial bone portion 25 as in the case of the plate-like portion 21, and it is preferable that the surface of the artificial bone portion 25 be subjected to bioactivity treatment. In addition, a portion of the surface of the artificial bone portion 25 that comes into contact with the patient's bone is preferably made of porous titanium or roughened titanium, and the other surface may be smooth. The internal structure of the artificial bone portion 25 is not particularly limited, but may be hollow or porous. As a material of the artificial bone portion 25, for example, a bioactive ceramic such as hydroxyapatite may be used in addition to titanium as described above. By using the artificial bone part 25 having a bioactive ability on the surface, the bonding of the artificial bone part 25 to the bone part B around the bone defect part A in which the artificial bone part 25 is implanted can be promoted.

In the present embodiment, the plate-like portion 21 and the artificial bone portion 25 preferably have mechanical properties corresponding to the bone portion B around the bone defect portion A. In this way, it is possible to reduce the discontinuity of the mechanical properties between the bone defect B and the surrounding bone B, and the plate-like portion can prevent the movement of the bone B around the bone defect A. It is possible to cooperate normally and reduce the burden on the patient.

In the present embodiment, the artificial bone portion 25 may be provided directly on, for example, a substantially J-shaped (inverted J-shaped) plate-like portion 21 as shown in FIG. Alternatively, as shown in FIG. 3B, it may be provided on a pedestal portion 21 a provided on the plate portion 21 and made of, for example, the same material as the plate portion 21.

As another modified example of the present embodiment, as shown in FIG. 4, the plate-shaped portion 31 has a mesh-shaped portion 36 in addition to at least a part, for example, a portion provided with a through hole into which a fastener is inserted. Is also good. When setting the plate-shaped portion 31 in the bone defect portion of the patient, the transplanted bone 40 is placed on the plate-shaped portion 31 as shown in FIG. There are cases. In this case, when the rigidity of the plate-shaped portion 31 is high, the load applied to the bone around the bone defect portion A is supported by the plate-shaped portion 31, and stress shielding in which no load acts on the transplant bone 40 occurs. The stress shielding is a phenomenon in which a load is concentrated on the implant side instead of the implanted bone, so that the implanted bone is not loaded and causes the implanted bone to atrophy due to bone resorption. As shown in FIG. 4, it is preferable to form a mesh-shaped portion of the plate-shaped portion 31 on which the transplant bone 40 is placed, since the rigidity of the plate-shaped portion 31 can be reduced and the above-mentioned stress shielding can be prevented.

Further, in the above embodiments and modifications, the implant provided in the mandible is illustrated, but as shown in FIG. 5, the implant may extend to the mandibular branch. In this case, it is preferable that a through hole is also provided in a portion of the implant that extends to the mandibular branch, so that the implant can be fastened to the mandibular branch with a fastener.

Further, as another modified example of the present embodiment, as shown in FIG. 6, the bone repair implant may have an outer shape having a plurality of through holes. Such an implant is not limited to a configuration in which the implant is installed from above the mandible as shown in FIG. 6, but may be a configuration in which it is installed from below the mandible as shown in FIG. In the case of these shapes, the degree of freedom of the position where the implant can be fastened to the bone by the fastener can be improved, and even when the implant is installed in the bone defect, the bone defect can be removed through the plurality of through holes. Since the part can be easily observed, the work load on the operator can be reduced. In particular, in the case of the implant 50 installed from below the mandible shown in FIG. 7, since a plurality of through holes 54 are formed over the entire surface of the implant 50, the upper, lower, side, oblique, and the like are excluded. Can be fixed to the bone with the fastener 60 such as a screw from the optimal direction, and it is extremely advantageous for securing the fixing force. Note that, as described above, the bone repair implant according to the present invention is formed based on the three-dimensional coordinate data of the bone damaged part of the patient using, for example, an additive manufacturing technique. It can be applied to the bone damage part of the bone.

Next, a method for manufacturing the bone repair implant according to the present invention will be described. The method for manufacturing a bone repair implant according to the present invention includes a step of obtaining three-dimensional coordinate data of a bone having a bone damaged part of a patient, and a technique such as an additive manufacturing technique or a cutting method based on the three-dimensional coordinate data. The method includes a step of shaping a plate-like portion having a surface shape corresponding to the surface shape of the bone having the bone damage portion at least partially and having a through hole.

In the step of obtaining the three-dimensional coordinate data of the bone having the bone damaged part of the patient, first, the bone having the bone damaged part of the patient is photographed by using an X-ray imaging technique such as an X-ray CT scan. Then, three-dimensional data is designed on the photographed image by a computer using image analysis software, and the three-dimensional data is sliced at a fixed pitch to obtain three-dimensional coordinate data such as STL data.

Next, based on the obtained three-dimensional coordinate data, an implant is formed using a titanium or titanium alloy particle as a material by using a layered manufacturing apparatus or the like. When a 3D printer is used, it is preferable to use a small laminating pitch using an SLM (selective laser melting) method. For example, the pitch is 0.01 mm to 0.05 mm, and particularly the pitch is 0.02 mm to 0.03 mm. It is preferred that By doing so, an implant having a surface shape corresponding to the surface shape of the bone having the bone damaged portion of the patient can be accurately and easily manufactured. In addition, the implant can be formed into a porous structure by being formed with a small pitch, so that the bone and the implant can be integrally fused, and the bonding between them can be strengthened.

インプラント It is preferable to subject the implant obtained thereafter to a bioactive treatment, particularly to the surface in contact with the patient's bone. The bioactive treatment is not particularly limited as long as it can strengthen the bond between the implant and the patient's bone, but it is particularly preferable to perform a mixed acid heating treatment as the bioactive treatment. As the acid to be used, it is preferable to use a mixed acid solution containing at least two of hydrochloric acid, sulfuric acid, nitric acid and hydrofluoric acid. By using these mixed acid solutions, it is possible to form a surface layer capable of exhibiting excellent bone forming ability on the implant. In the acid treatment method, it is convenient and convenient to immerse the implant in the mixed acid solution, and the immersion time is preferably about 1 hour. However, the method is not limited to the above method as long as the mixed acid solution can be brought into contact with the implant. Further, it is more preferable to perform the acid treatment only on a part of the implant where bone formation is desired.

Next, heat treatment is applied to the implant. The temperature is preferably from 500 ° C. to 750 ° C., and the time is preferably about 1 hour.

Furthermore, the manufacturing method according to the present invention may include a step of subjecting the implant to an antibacterial treatment as described above. The treatment method is not particularly limited, and examples thereof include a method of immersing the implant in an aqueous solution containing ions such as silver, gallium, or iodine.

により By the above steps, a bone repair implant according to the present invention having excellent bone formation ability can be obtained by a simple method.

Examples of the bone repair implant according to the present invention and a method for manufacturing the same will be described below in detail. In this example, it is described that the bone repair implant obtained by the above method has more excellent bone formation ability by being subjected to an acid treatment or a heat treatment.

(Example 1)
First, five titanium implants obtained by the above method were prepared, and each of them was subjected to acid treatment and heat treatment under different conditions. Specifically, in Group 1, an acid treatment was performed using a mixed acid solution of hydrochloric acid and sulfuric acid, and a heat treatment was performed at 600 ° C. for 1 hour. In Group 2, alkali treatment with NaOH was performed, and heat treatment was performed at 600 ° C. for 1 hour. In Group 3, a treatment with NaOH · 50 mM HCl was performed, and a heat treatment was performed at 600 ° C. for 1 hour. In Group 4, a treatment with NaOH.CaCl 2 was performed, followed by a heat treatment at 600 ° C. for 1 hour and a hot water treatment at 80 ° C. for 24 hours. Group 5 was untreated.

Next, bone-deficient rats were created. In this method, as shown in FIG. 8, first, the head of an anesthetized rat was incised, the periosteum was opened, and a bone defect was created using a round bar (photograph in FIG. 8 (a)). Subsequently, the implant (SLM mesh) prepared as described above was fitted to a bone defect and fixed with a KLs Martin 1.0 × 8 mm micro screw (FIGS. 8B and 8C). Thereafter, the incision was sutured (photograph (d) of FIG. 8).

Two weeks and seven weeks after placing the implant, an X-ray photograph of the installation site was taken using an X-ray micro-CT scanner, and a non-decalcified polished specimen of the installation site was prepared and stained with Trizine blue. A photograph of the specimen was taken. FIG. 9 shows the result. As shown in FIG. 9, two weeks after the placement of the implant, in all of Groups 1 to 5, although varying in degree, a new portion was formed below the implant placed in the bone defect (the area surrounded by the broken line in the figure). Bone formation was observed. In particular, excellent ability to form new bone was observed in Group 1 (the dark gray part indicated by the arrow in the non-demineralized polished sample). The same thing was observed 7 weeks after the placement of the implant. In Group 1, particularly excellent new bone formation ability was observed.

FIG. 10 shows the results of measuring the amount of new bone 2 weeks and 7 weeks after placing the implant in each Group. The amount of new bone was calculated based on the area ratio in the CT photograph. As shown in FIG. 10, the amount of new bone was increased at 2 weeks and 7 weeks after the installation in all the Groups. In particular, in the rat in which the Group 1 implant was installed, the amount of new bone was increased. It was found to be higher than rats with Group implants.

From the above results, it is clear that bone formation can be promoted by using the implant according to the present invention, and in particular, the implants subjected to the acid treatment and the heat treatment show excellent bone forming ability. .

(Example 2)
Next, it will be described that excellent antibacterial properties can be imparted by performing antibacterial treatment on an implant made of titanium. In this embodiment, an antibacterial treatment by iodine treatment will be described as an example of the antibacterial treatment.

First, a substrate made of pure titanium is polished using a # 400 diamond pad, ultrasonically washed with acetone, 2-propanol and ultrapure water for 30 minutes each, and then added to 5 ml of a 5M aqueous sodium hydroxide solution at 60 ° C. It was immersed for 24 hours (alkali treatment) and washed with ultrapure water for 30 seconds. This titanium plate was immersed in 10 ml of a 100 mM calcium chloride aqueous solution at 40 ° C. for 24 hours (calcium treatment), and washed with ultrapure water for 30 seconds. Next, the temperature of the titanium plate was raised from room temperature to 600 ° C. at a rate of 5 ° C./min in an electric furnace, kept at 600 ° C. in the atmosphere for 1 hour, and allowed to cool in the furnace. Thereafter, Sample A was manufactured by immersing in 10 ml of a 10 mM aqueous solution of iodine trichloride at 80 ° C. for 24 hours (treatment with iodine) and washing with ultrapure water for 30 seconds. In the iodine treatment, a 100 mM aqueous solution of iodine trichloride was used instead of the 10 mM aqueous solution of iodine trichloride, the immersion temperature was changed to 60 ° C., and the other conditions were the same as in the case of sample A above. Was manufactured. In addition, a titanium plate which was not subjected to any of the above processes was used as Sample C.

抗菌 The samples A to C were subjected to an antibacterial test against methicillin-resistant Staphylococcus aureus in accordance with JIS Z 2801: 2012. The test was repeated twice each, and the average number of colonies was calculated twice. The initial average number of colonies was 4.2 × 104 / cm 2. Table 1 shows the results. In addition, in order to examine the stability of the antibacterial effect, the samples A and B were subjected to a humidity resistance test in which the samples were kept at 80 ° C. and a relative humidity of 95% for one week, and 36. A water resistance test was performed in which the sample was held at 5 ° C. for one week while rocking at a speed of 50 strokes / minute. Table 1 shows the results.

示す As shown in Table 1, the viable cell count of sample A and sample B which had been subjected to the antibacterial treatment by iodine treatment was 0 as compared with untreated sample C, indicating strong antibacterial activity. In particular, Sample A exhibited strong antibacterial properties even after the moisture resistance test and the water resistance test, and was found to be excellent in antibacterial stability.

(4) Next, the antibacterial test against Escherichia coli was carried out on the samples A and C in accordance with JIS Z 2801: 2012. The initial average number of colonies was 4.1 × 10 3 / cm 2. For the sample A, the above moisture resistance test and water resistance test were also performed. Table 2 shows the results.

As shown in Table 2, in this test, as compared with the untreated sample C, the sample A showed a strong antibacterial property, further showed a strong antibacterial property even after the moisture resistance test and the water resistance test, and was excellent in antibacterial stability. I understood that.

(Example 3)
Next, with respect to the implant according to the present invention, the load carrying capacity when the shape (the installation range with respect to the bone) was changed was compared and examined using existing numerical simulation software. As shown in FIG. 11, the mandible model was a U-shape in plan view having a diameter of 20 mm and had a partially defective portion, and a plate-like implant was placed in the defective portion. The implant was made of pure titanium, had a thickness of 1.8 mm, and had two through holes with a diameter of 3.1 mm at both ends. The bolts for fastening the implant were also made of pure titanium, the nominal length was 12 mm, the nominal diameter was 3.0 mm, and four bolts were used. As shown in FIG. 11, a hard sphere was used to apply a load to the mandible. Further, as the constraint conditions at the time of the simulation, the constraint conditions shown in FIG. 11 were employed. Furthermore, in this simulation, we compared the model where the part where the implant and the bone are in contact with each other is combined with the model where the part is not combined, and examined the superiority of applying the bioactive treatment to the implant. did. In addition, the range of the implant covering the bone was changed, and the increase and decrease of the generated stress were examined. Specifically, as shown in FIG. 12, the ranges where the implant covers the bone were set to 40 °, 90 °, 135 °, and 180 °, and the respective stresses were compared and examined. FIG. 13 shows a stress simulation result when the range where the implant covers the bone is 40 ° and the implant and the bone are not connected. As shown in FIG. 13, in this case, a maximum stress of 301 MPa was generated on the front side (opposite to the bone) of the implant, a maximum of 300 MPa on the inner side (bone side) of the implant, and a maximum of 290 MPa on the bolt. Similarly, in a stress simulation performed under other conditions, the generated maximum stress is shown in Table 3 below.

As shown in Table 3, as a result of the numerical simulation, it was revealed that the stress generated in the implant can be reduced as the range of the implant covering the bone is increased. Furthermore, it has been clarified that the stress generated in the implant can be reduced by bonding the implant surface and the bone surface. This stress is significantly reduced by increasing the area covered. From this result, it is preferable that the implant has a form that covers the bone as much as possible. By applying bioactive treatment to the surface of the implant that contacts the bone, it is possible to promote the connection between the implant and the bone. Also proved beneficial.

Claims

A bone repair implant comprising titanium or a titanium alloy for installation at a bone injury site of a patient,
A plate-like portion having at least partially a surface shape corresponding to the surface shape of the bone having the bone damaged portion,
The plate-shaped portion is provided with a through hole through which a fastener for fastening the plate-shaped portion to a bone portion around the bone-damaged portion is provided.
The bone repair implant according to claim 1, wherein the plate-shaped portion has a tissue setting portion forming a space for setting a transplanted tissue.
The plate-shaped portion is configured to be installed at a position that can support the bone having the bone damaged portion, and has a surface shape corresponding to the surface shape of the bone at the installation site. The bone repair implant according to claim 1, wherein
The plate-shaped portion has a surface shape corresponding to a surface shape of a lower portion of the bone having the bone damaged portion,
The plate-shaped portion covers a lower portion of the bone damaged portion, and is configured to be installed on the bone having the bone damaged portion so as to support the bone having the bone damaged portion from below. The bone repair implant according to claim 3, wherein
5. The plate-like portion according to claim 1, wherein an artificial bone portion for at least partially filling a bone defect portion in the bone damaged portion is integrally formed. Bone repair implant.
The bone repair implant according to any one of claims 1 to 5, wherein the plate-shaped portion and the artificial bone portion have mechanical characteristics corresponding to a bone portion around the bone damaged portion.
The bone repair implant according to any one of claims 1 to 6, wherein the surface in contact with the bone damaged portion has bioactivity.
The bone restoration implant according to claim 7, wherein the portion provided with the bioactivity has titanium oxide.
The bone repair implant according to any one of claims 1 to 8, wherein at least a part of the plate-like portion and the artificial bone portion is provided with an antibacterial property.
The bone repair implant according to any one of claims 1 to 9, wherein the bone repair implant has a porous structure at least in part.
Obtaining three-dimensional coordinate data of a bone having a bone lesion of the patient;
Based on the three-dimensional coordinate data, using titanium or a titanium alloy as a material, at least partially having a surface shape corresponding to the surface shape of the bone having the bone damaged portion, and forming a plate-shaped portion having a through hole. And a method for producing a bone repair implant.
The method according to claim 11, wherein the shaping step uses an additive manufacturing technique.
The method for manufacturing a bone repair implant according to claim 11 or 12, wherein in the shaping step, the plate-shaped portion is shaped into a shape having a tissue setting portion forming a space for setting a transplanted tissue.
The method according to claim 1, wherein, in the forming step, the plate-shaped portion having a surface shape corresponding to a surface shape of the bone at a position suitable for setting the plate-shaped portion capable of supporting the bone having the bone damaged portion is formed. Item 13. The method for producing a bone repair implant according to item 11 or 12.
The method for manufacturing a bone repair implant according to claim 14, wherein, in the shaping step, the plate-shaped portion having a surface shape corresponding to a surface shape of a lower portion of the bone having the bone damaged portion is shaped.
The artificial bone part for at least partially filling a bone defect part in the bone damaged part in the bone damaged part is integrally formed with the plate-shaped part. Method of manufacturing bone repair implant.
The bone according to any one of claims 11 to 16, further comprising a step of subjecting at least a part of the surface of the plate-like portion and the artificial bone portion to a bioactive treatment after the modeling step. How to make a restoration implant.
18. The method for manufacturing a bone repair implant according to claim 17, wherein the step of performing the bioactive treatment includes a step of performing an acid treatment on the implant and a step of performing a heat treatment on the implant.
The bone repair implant according to any one of claims 11 to 18, further comprising a step of performing an antibacterial treatment on at least a part of the plate-like portion and the artificial bone portion after the shaping step. Production method.