Implant material and method for manufacturing the implant material

Abstract

The present invention aims to provide an implant material with improved fixation to a living body. The implant material of the present invention is an implant material having a hole in at least one direction, characterized in that a member constituting the hole has a groove. Further, in a preferred embodiment of the implant material of the present invention, characterized in that the member constituting the hole is constituted by a column and / or a plate. Further, in a preferred embodiment of the implant material of the present invention, characterized in that the groove is provided to the column and / or the plate. Furthermore, the manufacturing method of the implant material of the present invention is a method for manufacturing the implant material of the present invention, characterized in that the manufacturing is performed by a 3D shaping method.

Description

Technical Field

[0001] The present invention relates to an implant material and a method for manufacturing the implant material, in particular to an implant material with a groove and a one-way hole and a method for manufacturing the implant material. Background Art

[0002] Various bioimplant materials have been proposed as bone substitutes, including high-strength materials such as stainless steel alloys, titanium or titanium alloys, and bioactive materials such as apatite sintered bodies, bioactive glass, and bioactive crystallized glass.

[0003] Although high-strength materials such as stainless steel alloys or titanium-based metals have the characteristic of high mechanical strength, they cannot be directly fixed to bones if they are intact. Moreover, although bioactive materials such as apatite sinter, bioactive glass, and bioactive crystallized glass are combined with bones in a short period of time, they are insufficient in strength and have the problem that their applicable parts are limited. In order to solve these problems, an implant material (Japanese Patent Application No. 8-357040) is proposed in which a coating composed of bioactive materials is formed on the surface of the high-strength material by plasma spraying or baking paint. In this way, bone implants caused by bone diseases, bone defects, etc. are used more frequently, and it is expected that demand will continue to increase with the progress of an aging society.

[0004] In addition, as an example of bone, for example, if we take the human spine for illustration, the spine plays an important role in supporting the trunk and protecting the nerves (spinal cord) that transmit sensations and movements from the brain to the internal organs and limbs. However, when the vertebrae that make up the spine or the intervertebral discs that support loads and allow movement between vertebrae are deformed due to disease, the deformed vertebrae or intervertebral discs may compress the spinal cord. In this case, the compression of the spinal cord causes symptoms such as numbness or pain in the hands and feet.

[0005] To relieve spinal cord compression, a surgery is performed to insert a spacer (commonly called a fusion cage) into the intervertebral disc between vertebrae. By inserting the fusion cage between vertebrae and mechanically fixing them, the appropriate spacing and position between vertebrae are restored, thereby eliminating spinal cord compression.

[0006] Typically, fusion cages are made of metal or resin with high mechanical strength to support the load caused by body weight. Therefore, they do not directly adhere to the body's bones. Therefore, through-holes are provided in the cage, and bone is guided into these holes, thereby achieving fixation through the anchoring effect. Furthermore, to prevent movement between the vertebrae and the cage, screws or rods are sometimes used to connect the vertebrae.

[0007] While this type of fusion device is highly effective, the fixation between the vertebrae and the device is insufficient. Postoperatively, the device can move and fall out of the vertebrae, or it can move between the vertebrae and damage the vertebrae or surrounding tissues. This can result in renewed spinal cord compression or interference with other parts of the spinal cord, causing numbness or pain, necessitating further surgery.

[0008] Prior art literature

[0009] Patent Literature

[0010] Patent Document 1: Japanese Patent Application Laid-Open No. 8-357040 Summary of the Invention

[0011] Problems to be solved by the invention

[0012] However, most of the above-mentioned previous implant materials focus on the mechanical properties of the material itself, and there are almost no implant materials that recognize the microstructure of the bone itself, which plays a major role in the anchoring effect. Generally speaking, the porous bodies of the prior art are structures that expect bone to enter the pores, and are not structures for forming excellent tissue that prevents the deterioration of bone quantity and bone quality (here, representing bone strength). Therefore, an implant material that takes into account bone quantity and bone quality and achieves high-quality bone entry is desired.

[0013] In addition, in addition to the above-mentioned techniques, in order to allow the bone to quickly enter the through-hole of the implant material such as the fusion device and be firmly fixed, a method of selecting bone from the ilium (the ilium is the pelvic part) and transplanting the selected bone into the through-hole of the fusion device to promote bone induction in the through-hole is also adopted. However, since the skin is additionally increased in addition to the spine as the surgical object, the burden on the patient increases and there is also concern about pain. In addition, even when a bone transplant is used, the fixation of the implant material such as the fusion device is sometimes insufficient. The focus is placed on the situation of introducing bone into the hole of the implant material such as the fusion device. As mentioned above, the quality of the bone amount and bone quality entering the hole has not been fully studied. It is known that there are cases where the bone that has just entered the hole has a high bone density but a weak mechanical strength, and it is considered that the initial fixation of the implant material such as the fusion device is low.

[0014] Moreover, in implant materials such as fusion devices, not only bone induction is performed near the surface like an artificial joint, but also bone filling is required to be deeper in the thickness direction (the thickness direction is equivalent to the direction of the intervertebral space, for example). In order to improve the fixation of implant materials such as fusion devices, the bone quality in the deep part of the fusion device hole also needs to be considered. Although it is known that bone quality is related to mechanical stimulation in the organism based on body weight, since the rigidity of metal or PEEK fusion devices is greater than that of bones, it is difficult to transfer loads to bones, especially in the deep part of the hole where it is difficult to set the external environment such as mechanical stimulation.

[0015] Therefore, an object of the present invention is to provide an implant material having improved fixation to a living body.

[0016] Solutions to Problems

[0017] To achieve the above-mentioned object, the inventors focused on the original hard tissue structure existing in the living body and diligently studied its application to implant materials, resulting in the discovery of the implant material of the present invention.

[0018] The implant material of the present invention is an implant material having a hole in at least one direction, and is characterized in that a member constituting the hole has a groove.

[0019] Furthermore, in a preferred embodiment of the implant material of the present invention, it is characterized in that the member constituting the hole is composed of a column and / or a plate.

[0020] Furthermore, in a preferred embodiment of the implant material of the present invention, the groove is provided in the column and / or plate.

[0021] In a preferred embodiment of the implant material of the present invention, the hole is constituted by a plurality of the pillars and / or plates.

[0022] In a preferred embodiment of the implant material of the present invention, the grooves are alternately arranged on the front and back surfaces of the pillars and / or plates.

[0023] Furthermore, in a preferred embodiment of the implant material of the present invention, the pillars and / or plates are composed of a single body and / or a block.

[0024] Furthermore, in a preferred embodiment of the implant material of the present invention, it is characterized in that the pillars and / or plates are designed to be flexible.

[0025] In a preferred embodiment of the implant material of the present invention, the hole is a structure that does not penetrate the implant material or penetrates the implant material.

[0026] In addition, in a preferred embodiment of the implant material of the present invention, it is characterized in that the implant material is at least one selected from polymer materials, ceramic materials, metal materials, amorphous materials, or mixed materials thereof.

[0027] Furthermore, in a preferred embodiment of the implant material of the present invention, the width of the groove is 0.25 to 500 μm.

[0028] In a preferred embodiment of the implant material of the present invention, the pores, when present in plurality, are interconnected.

[0029] In addition, in a preferred embodiment of the implant material of the present invention, it is characterized in that the columns and / or plates have a telescopic structure by themselves, or the columns and / or plates are designed to bend by changing the thickness, width or height of the columns or the plates.

[0030] Furthermore, in a preferred embodiment of the implant material of the present invention, the implant material is designed to be flexible in at least a portion of its contact surface with the living body.

[0031] In a preferred embodiment of the implant material of the present invention, the hole is formed of a truss structure, and an inscribed circle of the hole is 500 μm to 2000 μm.

[0032] In addition, in a preferred embodiment of the implant material of the present invention, the implant material is characterized in that the implant material has a cage-like structure and has a second hole on a side surface of the cage-like structure.

[0033] Furthermore, the method for producing the implant material of the present invention is a method for producing the implant material of the present invention, characterized in that the implant material is produced by a 3D molding method.

[0034] Effects of the Invention

[0035] The implant material of the present invention can achieve early bone entry and early fixation, thereby reducing adverse effects on surrounding bone. Furthermore, the implant material of the present invention can achieve the advantageous effect of early strong fixation of the organism and the implant material without requiring mechanical stimulation or the setting of an external environment such as a magnetic field.

[0036] Furthermore, according to the method for manufacturing an implant material of the present invention, it is possible to provide an implant material that can achieve early bone entry and early fixation while reducing adverse effects on surrounding bones. BRIEF DESCRIPTION OF THE DRAWINGS

[0037] Figure 1 A cross-sectional view shows an example of a hole-forming member. It can be seen that the hole-forming member has a groove. Although it is a cross-section, it also includes shapes on the opposite side of the cross-section when cut (excluding the internal triangular porous body, which is a truss structure).

[0038] Figure 2 An example of the relationship between a member constituting a hole and the outer periphery of an implant material is shown.

[0039] Figure 3 A perspective view showing an example of a truss structure and a groove.

[0040] Figure 4(a) shows a conventional implant material (evaluation sample C). Figure 4 (b) shows an implant material according to one embodiment of the present invention, showing a state where a unidirectional hole penetrates (evaluation sample D). Figure 4 (c) shows the image viewed from a 90-degree rotation. Figure 4 (b) shows the implant material with holes designed on the side of the cage (Evaluation Sample E).

[0041] Figure 5 The results of the pull-out test in which the maximum load measured was defined as the pull-out strength are shown.

[0042] Figure 6 The results of microscopic observation of the evaluation sample E are shown. Figure 6 (b) shows Figure 6 (a) is an enlarged view of the portion surrounded by a rectangle on the left center.

[0043] Figure 7 An example of use of the implant material according to one embodiment of the present invention is shown.

[0044] Figure 8 This is a schematic diagram showing a case where a cylindrical fusion cage is used in a vertebral body among implant materials according to one embodiment of the present invention. Figure 8 (a) shows the central part of the cylindrical cross section, Figure 8 (b) shows the middle part between the center and the upper part of the cylindrical cross section, Figure 8 (c) shows the upper part of the cylindrical section.

[0045] Figure 9 A schematic diagram showing a case where a box-type fusion cage for intervertebral use is used in a vertebral body among implant materials according to one embodiment of the present invention. Figure 9 (a) is a view showing an example of an implant material of the present invention implanted in a spine, viewed from the lateral direction (a direction perpendicular to the cranio-caudal axis). Figure 9 (b) is a schematic diagram of an example of the implant material of the present invention as viewed from the lateral direction (a direction perpendicular to the cranio-caudal axis). Figure 9 Reference numeral 41 in (b) indicates a ceiling structure of the box-type fusion cage that forms a contact surface with the vertebral body / end plate in the vertical direction. Figure 9 (c) is a cross-sectional view of an example of the implant material of the present invention as viewed from the transverse direction (a direction perpendicular to the cranio-caudal axis direction). Figure 9 (d) is a perspective view (seen from above at an angle) of an example of the implant material of the present invention.

[0046] Figure 10 A schematic diagram of a box-type fusion cage is shown as an implant material according to one embodiment of the present invention. Figure 10 (a) is a cross-sectional view of an example of the implant material of the present invention. Figure 10(b) is a schematic diagram of an example of the implant material of the present invention as viewed from the lateral direction (a direction perpendicular to the cranio-caudal axis). Figure 10 Reference numeral 51 in (b) indicates a ceiling structure of the box-type fusion cage that forms a contact surface with the vertebral body / end plate in the vertical direction. Figure 10 (c) is a perspective view of an example of the implant material of the present invention.

[0047] Figure 11 This means that the height of the box-type cage is 8mm and 11mm, and the Figure 4 (a) Evaluation of Sample C and the equivalent bone graft group of the box fusion cage Figure 4 (b) is a graph showing the results of a comparative extrusion test of a group evaluating the bone orientation induction effect of Sample D. Figure 11 (a) shows the results when the height of the box-type cage is 8 mm and 11 mm. Figure 11 (b) shows the results when the height of the box-type fusion cage is 8 mm. Figure 11 (c) shows the results when the height of the box-type cage is 11 mm. DETAILED DESCRIPTION

[0048] The implant material of the present invention is an implant material having a hole in at least one direction, characterized in that the component constituting the hole has a groove. Through the groove, when the osteoblasts initially enter the inside of the implant material (porous body), the osteoblasts can be stretched and arranged along the depth direction of the hole of the implant material of the osteoblasts (when a fusion device is used as described later, the thickness direction of the fusion device). In the present invention, in addition to the hole, the groove is also provided, whereby the arranged osteoblasts produce a bone matrix that has been oriented in parallel with the direction in which they are stretched and arranged, and therefore have the effect of promoting the orientation of the bone matrix from the initial stage of embedding (bone regeneration) without mechanical stimulation. Moreover, in the present invention, a groove is also provided in addition to the hole, whereby strong fixation can be obtained in advance between the bone and the implant material without setting an external environment such as mechanical stimulation or a magnetic field.

[0049] In the present invention, there are no particular limitations on the grooves; however, for example, grooves can be provided on the surface of a column or plate, as described later. The groove width is not particularly limited, as long as it is suitable for the member forming the hole. However, the groove width is preferably 0.25 μm to 500 μm, more preferably 0.5 to 200 μm. Furthermore, the grooves can be provided at equal intervals along the thickness direction described above.

[0050] In addition, in the preferred embodiment of the implant material of the present application, the member constituting the hole is constituted by a column and / or a plate. In this way, by constituting the member by a column and / or a plate, a porous body can be easily formed inside the implant material. In the present application, without the need for setting an external environment, a porous body for inducing bone ingrowth and bone orientation into the hole inside the implant material such as a fusion cage for obtaining strong fixation in advance between vertebrae can be easily provided. The porous body can be patterned with columns and / or plates at a certain interval in the thickness direction of the fusion cage (in the case of a hole, the long axis direction of the hole. In the case of a vertebra, the cranial-caudal axis direction).

[0051] In this way, by changing the thickness, width, height, etc. of the column or the plate, the rigidity of the column can be adjusted. That is, in the preferred embodiment of the implant material of the present application, from the viewpoint of maintaining good bone quality for a long period of time by applying continuous mechanical stimulation after oriented bone is formed in the porous body, the column and / or the plate are designed to be flexible by having an elastic structure themselves or by changing the thickness, width, or height of the column or the plate. Here, regarding the elastic structure, as long as it is elastic, there is no particular limitation. For example, if the case where it is inserted into a vertebral body is taken as an example, the elastic structure means that it contracts if a load is applied from the superior and inferior vertebral bodies and returns to the original state if the load is not applied.

[0052] In addition, in the preferred embodiment of the implant material of the present application, from the viewpoint of better matching the implant material to the living body, the implant material is designed to be flexible in the contact surface of at least a portion of the implant material that contacts the living body. By being designed to be flexible in this way, for example, in the case where an intervertebral fusion cage is used as the implant material of the present application in a vertebra, as will be described in the examples below, it is expected that the contact surface that contacts the vertebra by being flexible, that is, the surface of the back surface of the intervertebral fusion cage, matches the shape of the bone. By matching the shape of the bone, the surface of the back surface of the fusion cage is closely adhered to the vertebra without gaps, and bone is easily induced into the porous body. This is also clearly known from the fact that, as will be described in the examples below, by burying the intervertebral fusion cage in the intervertebral space of a sheep as well, the results of observing the punch strength and the tissue are that bone is abundantly ingrown into the porous body.

[0053] Further, the thickness of the column or plate is not particularly limited. In the case where the material of the implant is, for example, a metal material, the thickness of the column or plate can be preferably 0.1 to 2 mm, more preferably 0.5 to 1 mm. Although it is also affected by the material used, in this thickness range, the column or plate is deflected in the thickness direction of the implant such as a cage by a load acting on the interosseous space of the vertebrae or the like, whereby load transmission to the bone in the porous body can be more easily performed. Thus, after the formation of the oriented bone inside the porous body, the bone inside the cage receives the principal stress load (i.e., mechanical stimulus) from the upper and lower vertebral bodies to maintain and promote bone orientation, and further deterioration during long-term embedding can be inhibited. Thus, the bone quality in the porous body of the cage is maintained in a good condition for a long period of time after the surgery, and as a result, long-term stable fixation of the vertebrae and the cage from the initial stage can be achieved.

[0054] Further, in the preferred embodiment of the implant of the present application, the column and / or plate is characterized by being composed of a monomer and / or a block. For example, the column and / or plate can be provided as a block or a monomer linked in a radial, cross, zigzag, or the like. The plate can be designed to be rotatable around the column as a center of rotation, or the plate can be rotated at regular intervals and fixed at the position to freely design the size of the hole.

[0055] Further, in the preferred embodiment of the implant of the present application, from the viewpoint of orienting the bone firmly in the entire region where the bone enters, the holes are characterized by being composed of a plurality of columns and / or plates.

[0056] Further, in the preferred embodiment of the implant of the present application, from the viewpoint of orienting the bone in the direction of the column and / or plate, the groove is provided in the column and / or plate. Further, from the viewpoint of promoting the orientation of the bone matrix from the initial stage of embedding (bone regeneration) without mechanical stimulus, the groove can be provided in the depth direction (long axis direction) of the hole.

[0057] Further, in the preferred embodiment of the implant of the present application, from the viewpoint of obtaining firm fixation by thinning the plate thickness to minimize the volume of the artificial material such as metal occupying in the porous body and maximize the space where the bone can enter, the groove is alternately arranged on the front and back surfaces of the column and / or plate. For example, as an example of the reason for alternately providing the groove on the front and back surfaces of the plate, although the plate thickness is thinned to expand the region in the cage where the bone can be filled to increase the amount of bone (to make it flexible), the depth of the groove can not be ensured if it is not alternately arranged.

[0058] In addition, in a preferred embodiment of the implant material of the present invention, it is characterized in that the column and / or plate are designed to be bent. Moreover, in a preferred embodiment, pattern configuration can be performed by a column and a plate. This is because, by pattern configuration, it is possible to easily design according to the size of the hole. That is, it is possible to achieve a constant size of the hole, i.e., the size of the inscribed circle, consisting of the column and the plate. For example, in the embodiment described later, although the optimum value of the inscribed circle of the hole is set to more than 500 μm in the sheep implantation test, in order to easily define the optimum value, a space of a certain size can be made as a pattern configuration. As long as the space above it is provided, it can be random (the size of the inscribed circle is dispersed), and there is no particular limitation.

[0059] In a preferred embodiment of the implant material of the present invention, from the viewpoint of maximizing the space for bone entry and obtaining a strong fixing force, the hole is formed by a truss structure and the inscribed circle of the hole is 500 μm to 2000 μm.

[0060] In addition, as described above, the rigidity of the column can be adjusted by changing the thickness, width, height, etc. of the column or the plate. Moreover, the axis connecting the columns, the plates, the plates and the columns, etc. is assumed to be a beam (including the part of the fusion device that is equivalent to the ceiling (upper and lower sides) when a fusion device is used.), and the beam can be set to a flexible structure or a telescopic structure. The same as the case of the plate telescopic as described above. For example, by configuring the beam in a honeycomb shape or the like to telescope, it can be adjusted so that the contact surface of the box-type fusion device is in close contact with the end plate shape of the vertebral body. From the perspective of the telescopic structure, the thickness of the beam can be set to 0.1mm to 1.5mm, preferably 0.3mm to 1.0mm. For example, the beam can be set to about 0.5mm.

[0061] In addition, in a preferred embodiment of the implant material of the present invention, it is characterized in that the hole is a structure that does not penetrate the implant material or penetrates the implant material. In the present invention, through the groove, when the osteoblasts initially enter the inside of the implant material (porous body), the osteoblasts can be stretched and arranged along the depth direction of the hole of the implant material of the osteoblasts (in the case of using a fusion device as described later, it is the thickness direction of the fusion device), so the hole can be a through hole or a non-through hole. It should be noted that in the case of a through hole, between adjacent vertebrae, the bone tissue passes through the through hole and is continuous between the vertebrae, which can further ensure the fixation strength of the vertebrae and the fusion device.

[0062] The material of the implant material is also not particularly limited. In addition, in a preferred embodiment of the implant material of the present invention, as the implant material, at least one selected from polytetrafluoroethylene ((Teflon (registered trademark)), polymer materials, ceramic materials, metal materials, amorphous materials or their mixed materials can be listed. As the metal material, pure metals, alloys, intermetallic compounds, etc. can be listed. Moreover, the amorphous material can include a portion of crystallized parts. This is because, even if the crystallized part is included, there is a portion called amorphous material. As the amorphous material, for example, bioglass, etc. can be listed.

[0063] For example, as the material of the implant material, hard tissue substitute materials and the like can also be listed. As hard tissue substitute materials, ceramics represented by apatite, inorganic materials such as alumina, zirconium oxide, stainless steel, Co-Cr alloy, titanium, alloy, tantalum and other metal materials can be listed. Ceramics can also be divided into bioactive ceramics, bioinactive ceramics and the like. As bioceramics, calcium phosphate-based ceramics, silica-based glass and crystallized glass and the like can be listed. As calcium phosphate-based ceramics, hydroxyapatite and calcium phosphate are known, which are used in artificial tooth roots, skin terminals (skin terminals), metal coating materials and the like. Materials of the above-mentioned various materials can be used as implant materials.

[0064] In a preferred embodiment of the implant material of the present invention, the groove width may preferably be 0.25 to 500 μm, more preferably 0.5 to 200 μm, from the viewpoint that osteoblasts can detect the orientation direction of collagen and apatite.

[0065] In a preferred embodiment of the implant material of the present invention, the pores are interconnected when there are a plurality of pores. This is because, for example, bone marrow fluid can flow continuously between the pores, further enabling bone to penetrate deeper into the porous body.

[0066] In addition, the manufacturing method of the implant material of the present invention is a method for manufacturing the implant material of the present invention, characterized in that, manufactured by 3D shaping method (AM, Additive Manufacturing). About 3D shaping method, conventional methods can be used, which is not particularly limited. About the processing method of implant material etc., it is widely known in the art that the implant material of the present invention can be applied to manufacture by conventional methods.

[0067] In addition, the column or the plate constituting the porous body described above can be connected to the truss structure. The truss structure can be provided as a structure connected to the upper and lower surfaces of the cage in a triangular, quadrangular, or polygonal shape. By the truss structure, the outer peripheral portion of the cage and the column or the plate constituting the porous body can be integrated. The size of the inscribed circle of the gap formed inside the triangular, quadrangular, or polygonal shape with respect to the truss structure is not particularly limited. For example, from the viewpoint of the size of the bone cell (osteoblast + osteoclast + osteocyte (osteo cyte)), the size of the inscribed circle is preferably 500 μm or more. The column or the plate constituting the porous body can be arranged along the truss of the truss structure. In this case, the inscribed circle of the gap formed by the arranged column and / or plate can be provided to be equivalent to the inscribed circle of the truss porous body. The size of the gap can be provided to be the most suitable size for the bone to enter the inside of the porous body.

[0068] The truss structure itself can also be provided as a groove continuous with the groove provided on the column or the plate constituting the porous body. By the groove of the truss structure, bone orientation is promoted after the bone just enters, and fusion of the cage to the vertebrae can be achieved while exhibiting high bone quality from the initial entry of the bone.

[0069] The column and / or the space between the columns arranged to constitute the porous body can not be connected. In this case, a space can be provided at a certain interval between the columns, the bone marrow fluid can be continuously flowed, and the entry of the bone to the deep portion of the porous body can be achieved. In addition, a hole can be provided to communicate the outside of the outer peripheral portion of the cage with the inside of the porous body. Thus, the bone marrow fluid can be continuously flowed, and the entry of the bone to the deep portion of the porous body can be achieved.

[0070] In addition, in the preferred embodiment of the implant material of the present application, from the viewpoint that the side hole is effective for inducing bone to the porous body, the implant material has a cage structure, and the second hole is provided on the side of the cage structure. This is because, as will be apparent from the data of the cylindrical cage (or box-shaped cage) embedded in the vertebrae to the side hole of the intervertebral cage described in the examples below, it can be determined that the side hole is effective for inducing bone to the porous body.

[0071] Example

[0072] Here, one embodiment of the present application will be described, but the present application is not limited to the following embodiment. Furthermore, of course, appropriate modifications can be made without departing from the spirit of the present application.

[0073] Example 1

[0074] Bone tissue is composed of undifferentiated mesenchymal cells, osteoblasts, osteocytes, and osteoclasts. During the formation of new bone, osteoblasts secrete type I collagen and other proteins, which then form apatite, which is then added to collagen fibers, leading to calcification. As calcification progresses, osteoblasts become osteocytes and become embedded in the bone matrix, completing new bone formation.

[0075] In such a bone formation process, it is known that the direction of travel of type I collagen (Col) is roughly consistent with the crystal orientation of hexagonal apatite crystals (BAp) (here, orientation refers to the directionality of apatite crystals aligned in a certain direction rather than randomly). The complex of Col and BAp determines the strength and softness of the bone matrix, that is, the bone. Hexagonal crystals have a=b≠c as the crystal axis, and show significant mechanical anisotropy along the a-axis and the c-axis. Therefore, it can be seen that the mechanical properties of bone are closely related to the orientation of the bone matrix caused by the orientation of apatite crystals generated by osteoblasts, that is, osteoblasts and the type I collagen and apatite secreted by them are closely related to their orientation. Therefore, in the present invention, in order to orient the bone matrix by stretching and arranging the osteoblasts along the thickness direction of the osteoblast fusion device, a groove structure extending along the orientation direction is adopted for the porous body intended for bone entry.

[0076] In one example of the implant material produced in this trial, the grooves of the porous body are as follows Figure 1 As shown, they are arranged at equal intervals on the surface of the plates and / or pillars constituting the porous body. Figure 1 A cross-sectional view is shown for an example of a member constituting a hole. It can be seen that the member constituting the hole has a groove. Figure 1 In the figure, 1 represents the plate thickness, 2 represents the inscribed circle between the plates, 3 represents the groove width, and 4 represents the groove depth. In this figure, the radial shape equivalent to 120 degrees represents a tetrahedral internal structure connecting three plates. A tetrahedral structure is a structure with three plates and a trident shape, but it can also be a cross shape. A cross shape refers to a structure in which two plates intersect at 90 degrees. Moreover, a column can refer to the central part of a tetrahedral structure or a cylinder or prism standing perpendicular to the paper. The shape illustrated this time is just an example, and the configuration of plates and columns can be considered infinitely. Figure 2 An example of the relationship between a member constituting a hole and the outer periphery of an implant material is shown. Figure 3 A perspective view showing an example of a truss structure and a groove. Figure 2 In the figure, 5 represents the surrounding bone, 6 represents the hole connecting the surrounding bone with the inside of the implant material (the second hole), 7 represents the inside of the implant material (the inside of the porous body), 8 represents the hole connecting the holes inside the implant material (the third hole), 12 represents the groove, 13 represents the plate, 14 represents the column, and 15 represents the hole (the first hole). Figure 3In the figure, 12 represents a groove, 13 represents a plate, 14 represents a column, and 15 represents a hole (first hole). By connecting the hole (second hole) 6 that connects the surrounding bone with the interior of the implant material or connecting the holes (third hole) 8 within the implant material, it is also possible to promote the continuous circulation of bone marrow fluid, for example.

[0077] like Figure 2 As shown in FIG, as an example, the porous body of the fusion device can be formed by connecting three radially extending plates with grooves in the center to form a trident structure. The adjacent trident structures can be formed without being directly connected to each other, and gaps can be provided between the radially extending plates to form a connected porous body ( Figure 2 8). In this way, when the three-pronged structures are arranged with gaps, they exist without any spatial restrictions and fall off. Therefore, the three-pronged structures can be connected to the structures on the periphery of the fusion device through the plate-like structures on the front and back sides of the fusion device to form an integrated structure. Moreover, for example, the three-pronged structures can be connected to form a honeycomb structure, and the honeycomb can have horizontal holes (that is, holes that are horizontally connected perpendicular to the hole direction of the honeycomb, for example, Figure 2 5, 6, etc.).

[0078] The plates and / or columns of limited width constituting the porous body are connected to form radial or cross-shaped blocks or are arranged separately. Osteoblasts enter along the grooves provided in the plates and / or columns, and have the effect of promoting bone orientation from the initial entry of the bone. The arrangement of the plates and / or columns can be any one of zigzag or equally spaced. The plates and / or columns are preferably deflected by the load under the biomechanical environment. The deflection imparts mechanical stimulation in the direction of the principal stress to the bone entering the porous body along the plates and / or columns, which can contribute to continuous bone orientation. Therefore, in order to make the plates and / or columns deflect by the load, their thickness or thickness are preferably, for example, less than 1 mm.

[0079] While the peripheral portion of the fusion device in its outer shape bears the load under the biological internal mechanical environment, the porous body and the bone entering the porous body become one to fix the fusion device and the intervertebral space. That is, the peripheral portion of the fusion device can be structurally integrated with the porous body. As a method of connecting the plates and / or columns that are spatially arranged to form the porous body with the peripheral portion of the fusion device, a truss structure is configured to connect the surface portion of the fusion device (that is, the upper and lower surfaces of the fusion device that are inserted between the vertebrae and the vertebrae) to the peripheral portion of the fusion device. The truss structure is configured in a manner connected to the plates and / or columns that form the porous body. As long as it can be connected to the plates or columns that form the porous body, the truss shape can be any shape of a triangle, a quadrilateral or a polygon. The truss structure on the surface of the fusion device is provided with grooves in a manner continuous with the grooves provided on the plates and / or columns that form the porous body. When the bone begins to enter the porous body of the fusion device, osteoblasts extend from the truss structure equivalent to the outermost surface of the fusion device. Therefore, the grooves of the truss structure can be expected to promote the effect of bone orientation from the initial stage of bone entry. In order to perform bone filling deeper along the thickness direction of the fusion device, the plates that constitute the porous body in a manner that can continuously supply bone marrow fluid containing osteoblasts can be set to a limited width. By setting it to a limited width, an appropriate gap can be set between adjacent plates and / or columns, and the bone marrow fluid containing osteoblasts can be continuously supplied throughout the entire area of ​​the porous body. Through this continuous supply, bone entry into the deep part of the porous body of the fusion device can be achieved. In addition, the porous body can be provided with holes on the side of the fusion device. The holes play a role in suppressing the retention of bone marrow fluid in the deep part of the porous body and promoting the continuous circulation of bone marrow fluid.

[0080] To confirm the functionality of the porous body of the fusion device described above, the porous body was embedded in sheep vertebrae and the bone volume, bone orientation, and bone fixation within the porous body were evaluated by a pull-out test. The results are shown below.

[0081] [Evaluation samples]

[0082] In this evaluation, as a porous body, a sample was prepared in which three finite plates connected in a radial pattern at intervals of 120 degrees were arranged in a zigzag pattern. The width of the grooves provided in the finite plates was 0.2 mm and the depth was 0.15 mm. The plate thickness was set to 0.5 mm, and the grooves were arranged on both sides of the plate in such a manner that the bottoms of the grooves did not overlap with each other. When used for implantation in the vertebrae, the outer shape of the fusion device was set to be cylindrical. As a truss structure, a triangular shape was adopted. The triangular truss structure was connected in a manner consistent with the finite plates arranged in a radial pattern, and its inscribed circle was set to two types: 500 μm (evaluation sample A) or 1000 μm (evaluation sample B). In order to study the influence of the external environment such as the previous bone transplantation method or mechanical stimulation, the following evaluation samples C to E ( Figure 4 ). Figure 4(a) shows a conventional implant material (evaluation sample C). Figure 4 (b) shows an implant material according to one embodiment of the present invention having a one-way hole therethrough (evaluation sample D). Figure 4 (c) shows Figure 4 (b) is a view of the implant material rotated 90 degrees, showing the hole on the side of the cage. (Evaluation Sample E). Figure 4 In the figure, 10 denotes a bone graft, 11 denotes a hole on a side of the fusion cage, 12 denotes a groove, 13 denotes a plate, and 14 denotes a column.

[0083] Sample C: Similar to conventional fusion cages, only through-holes were provided in the fusion cage, and the holes were filled with transplanted bone.

[0084] Sample D: In a fusion device having the porous body, the rostral axis corresponding to the load transmission direction and the groove of the porous body were embedded in parallel.

[0085] Sample E: In this porous body fusion device, the rostral axis and the porous body grooves are embedded perpendicularly. Although the fusion device shape is the same as that of Sample D, the load transmission direction is 90 degrees different from the porous body grooves.

[0086] [Sample preparation]

[0087] The evaluation sample was designed using CAD software and exported in STL (stereolithography) format. This data was then used for integrated fabrication using AM (Additive Manufacturing). The material used was Ti-6Al-4V, a titanium alloy with proven success as an implant material, and the fabrication was performed using a laser metal forming machine (EOS M290, manufactured by EOS). The resulting groove width and thickness were reduced to 0.1-0.5mm (width 0.2mm, depth 0.15mm) compared to the designed values.

[0088] [Sheep implantation]

[0089] Suffolk sheep aged 12 months and older were used as subjects. One specimen was implanted in each of the L1 to L4 lumbar vertebrae. The sheep were slaughtered 8 or 16 weeks after implantation, and the L1 to L4 vertebrae with implanted cages were selected.

[0090] [Bone tissue observation]

[0091] To evaluate the bone induced within the porous structure of the fusion device, Villanueva staining was performed. Non-decalcified thin sections were prepared from the central portion of the cylindrical fusion device along a cross-section parallel to the craniocaudal axis. The ratio of bone (BV) to the void space (TV) within the fusion device was measured. The results are shown in Table 1.

[0092] [Table 1]

[0093]

[0094] Table 1 shows that for samples A and B with an inscribed circle of 500 μm and 1000 μm, the 1000 μm sample has a higher bone mass, indicating that a larger inscribed circle facilitates bone ingress. Furthermore, in a comparison of samples A and D with and without holes on the side of the fusion device at an inscribed circle of 1000 μm, the hole significantly increased bone mass. No significant differences were observed in the effect of the orientation of the porous body (samples D and E).

[0095] [Pulling test]

[0096] Pull-out tests were conducted on evaluation specimen C, which simulated a conventional bone grafting device, and on evaluation specimens D and E, which were equipped with the porous body, to evaluate the adhesion strength between the bone and the device based on the porous body. After thawing the vertebrae with the device embedded in the device, the vertebrae were fixed with bone cement so that the screws provided in the device at the top of the fixture were exposed. A pull-out test of the device was conducted on the fixture using a pull-out tester (manufactured by INSTRON, Model 5965). The test speed was set to 5 mm / min, and the maximum load measured during the test was set as the pull-out strength.

[0097] The results are as follows Figure 5 shown. Figure 5 The results of the pull-out test are shown, in which the maximum load measured during the pull-out test is defined as the pull-out strength. Figure 5 , compared with the evaluation sample C that required bone transplantation in the past, the pull-out strength of the evaluation samples D and E with the porous body increased significantly. At the 8th and 16th weeks, although an increase in pull-out strength was observed in the evaluation sample C, it was not as good as that of the evaluation samples D and E. This is speculated to be the result of the porous body introducing good bone quality into the porous body in advance. Moreover, in the evaluation sample D implanted parallel to the head-tail axis, the pull-out strength tended to increase with the increase in age. This is speculated to be because the mechanical stimulation generated by the load in the direction of the principal stress of the in vivo mechanical environment (for sheep, it is the head-tail axis direction as for humans) can further promote bone orientation.

[0098] [Directivity measurement]

[0099] To evaluate bone orientation, thin sections of the evaluation sample E prepared during bone tissue observation were used to analyze the orientation of collagen fibers related to bone orientation using a birefringence method (WPA-micro: Photonic Lattice). Figure 6 The observation results of evaluation sample E are shown. Figure 6 (b) shows Figure 6 An enlarged view of the portion surrounded by the rectangle on the left side of the center of (a). The results show that the surrounding bones (sheep vertebrae) of the evaluation sample are horizontally oriented relative to the image, but within the porous body, they are vertically oriented from the entrance. This indicates that the porous body itself induces an orientation different from the original orientation of the sheep vertebrae.

[0100] in addition, Figure 7 An example of use of the implant material according to one embodiment of the present invention is shown. Figure 7 In the figure, 15 represents a hole, 30 represents a thickness direction, 31 represents a fusion device of another embodiment of the present invention, and 32 represents the insertion direction of the fusion device. Although not shown in the figure, in this embodiment, a groove is also provided in the hole 15. This implant material is an example of a fusion device for humans, but the thickness direction is the cranio-caudal axis direction of humans as shown in the figure. That is, the thickness direction can be set as the direction of the gap between vertebrae. The evaluation sample this time is cylindrical, so in the evaluation sample D, it becomes the connecting hole direction (cranio-caudal axis direction) shown in the figure.

[0101] Figure 8 A cross section parallel to the long axis of a cylindrical cage is shown when the cylindrical cage is used as an implant material according to one embodiment of the present invention. Figure 8 (a) shows the central part of the cylindrical cross section, Figure 8 (b) shows the middle part between the center and the upper part of the cylindrical cross section, Figure 8 (c) shows the upper part of the cylindrical cross section. These implant materials can also be set as an embodiment of the present invention. That is, Figure 8 The structure is shown cross-sectioned at the upper, middle, and center sections parallel to the long axis of the cylinder. The internal structure can be a triangular arrangement of plates with grooves (center section), connected by a truss structure at the upper and lower parts of the cage (upper section).

[0102] Thus, it is understood that according to the present invention, the geometric pattern structure of the internal structure having grooves (such as the aforementioned trident structure) itself can promote directional new bone formation in the porous body regardless of external environments such as mechanical stimulation.

[0103] The above results clearly demonstrate the relationship between grooves formed in the porous body and bone orientation. In particular, evaluation sample E, in which the grooves were arranged perpendicular to the principal stress direction of the biomechanical environment, achieved high pullout strength, indicating that the geometric pattern of the porous body itself promotes bone orientation, independent of the biomechanical environment. Furthermore, the above results indicate that, considering the ability to detect the orientation of osteoblasts and the size of the cells themselves, the groove width is preferably 0.25 to 500 μm, the inscribed circle of the porous body is preferably 500 μm or greater, and, considering the strength of the porous body and the groove depth, the plate thickness is preferably 0.5 to 1 mm.

[0104] Example 2

[0105] Next, a box-type fusion device was designed as the implant material of the present invention, and the induction effect of bone orientation was studied. Specifically, as a large animal test (sheep), an extrusion test of a box-type fusion device placed between the vertebrae of the sheep was carried out. That is, by using a large animal test on sheep, a box-type fusion device was implanted between the vertebrae in the same manner as in human clinical practice, and an extrusion test of the box-type fusion device was carried out 8 weeks after implantation. Regarding the two types of box-type fusion devices with a height of 8 mm and 11 mm, the same test was carried out. Figure 4 (a) The bone graft group of the box-type fusion cage equivalent to the evaluation sample C (the fusion cage was pre-filled with the bone graft) and Figure 4 (b) Comparative extrusion test of the bone orientation induction group evaluating the equivalence of sample D.

[0106] Figure 9 A schematic diagram showing a case where a box-type fusion cage is used in a vertebral body among implant materials according to one embodiment of the present invention. Figure 9 (a) is a view showing an example of an implant material of the present invention implanted in a spine, viewed from the lateral direction (a direction perpendicular to the cranio-caudal axis). Figure 9 (b) is a schematic diagram of an example of the implant material of the present invention when viewed from the transverse direction (a direction perpendicular to the cranio-caudal axis). Figure 9 In (b), 41 represents a ceiling structure of a box-type fusion device that forms a contact surface with the vertebral body / end plate in the up-down direction (showing a bent state), 42 represents a column structure that forms a directional porous structure, 43 represents a vertebral body, 44 represents a case where the contact surface of the box-type fusion device (an implant material of an example of the present invention) is adapted to the shape of the vertebral end plate, 45 represents a box-type fusion device, and 46 represents an end plate. Figure 9 (c) is a cross-sectional view of an example of the implant material of the present invention as viewed from the transverse direction (a direction perpendicular to the cranio-caudal axis direction). Figure 9 (d) is a perspective view (viewed from above) of an example of the implant material of the present invention. It can be seen that the contact surface of the box-type fusion cage is adapted to the shape of the vertebral endplates, and the directional porous contact of the box-type fusion cage further promotes bone healing. It was also found that a wider contact surface further promotes bone healing.

[0107] Figure 10 In the implant material according to one embodiment of the present invention, a schematic diagram of a box-shaped fusion cage is shown. Figure 10 (a) is a cross-sectional view of an example of the implant material of the present invention. Figure 10 (b) is a schematic diagram of an example of the implant material of the present invention when viewed from the transverse direction (a direction perpendicular to the cranio-caudal axis). Figure 10 In the figure, 51 denotes a ceiling structure of a box-type fusion cage forming a contact surface with the vertebral body / end plate in the vertical direction, and 52 denotes a column structure forming directional porous. Figure 10 (c) is a perspective view of an example of the implant material of the present invention. The ceiling structure of the box-type fusion device, which forms a contact surface with the vertebral body / endplate in the vertical direction, can be any flexible structure and can be in the shape of a disk, plate, column, or the like.

[0108] Figure 11 The graph shows the results of a comparative compression test conducted on a bone transplant group and a bone orientation induction group using two types of box-type cages, 8 mm and 11 mm in height. Figure 11 (a) shows the result when the height of the box-type fusion cage is 8mm and 11mm. Figure 11 (b) shows the result when the height of the box-type fusion cage is 8 mm. Figure 11 (c) shows the results when the height of the box-type cage is 11 mm.

[0109] Based on the above results, paired t-tests were performed for the three cases of 8mm height, 11mm height, and both heights combined, and significant differences were confirmed in all cases. It was determined that the bone-oriented porous body exhibited a higher compressive load than the bone graft, and that the shear strength at the interface between the bone and the bone-oriented porous body was superior to that of the bone graft. In other words, the compressive strength of the box-type fusion cage with the oriented porous body was significantly higher than that of the bone graft.

[0110] In Embodiment 2, as a verification experiment, a box-shaped cage was embedded in a vertebra, in a case of use for humans, a damaged intervertebral disc (between vertebrae) was removed, and the box-shaped cage was able to be embedded and fixed between the vertebrae. The direction of flexion was set to the cranial-caudal axis direction (the vertical direction in which the weight of the body acts on the head (body weight head) when a human stands), and a case in which the trifid structure was compressed and flexed by the vertebrae above and below the cage was assumed to be designed. In the box-shaped cage, the structure that links the trifid structure was designed to be thin (0.5 mm), and an effect in which the contact surface that contacts the vertebrae by flexion of the structure itself, that is, the surface back of the box-shaped cage, matches the shape of the bone was able to be expected. By matching the shape of the bone, the surface back of the cage was tightly attached to the vertebrae without a gap, and bone induction to the porous body was able to be easily induced.

[0111] Industrial applicability

[0112] According to the present application, contribution to the treatment of hard tissue disorders, the field of regenerative medicine dentistry (particularly orthopedics, neurosurgery, dentistry), or basic medicine is able to be expected.

[0113] Explanation of reference numerals

[0114] 1 plate thickness

[0115] 2 incircle between plates

[0116] 3 slot width

[0117] 4 slot depth

[0118] 5 surrounding bone

[0119] 6 hole that communicates the surrounding bone with the inside of the implant material (second hole)

[0120] 7 inside of the implant material (inside of the porous body)

[0121] 8 hole that communicates between the holes in the inside of the implant material

[0122] 10 graft bone

[0123] 11 hole of the cage side surface

[0124] 12 slot

[0125] 13 plate

[0126] 14 column

[0127] 15 hole

[0128] 30 thickness direction

[0129] 31 cage of another aspect of the present application

[0130] 32 insertion direction of the cage

[0131] 41, 51 The roof structure of the box-type fusion cage forms the contact surface with the vertebral body / endplate

[0132] 42, 52 Forming a directional porous column structure

[0133] 43 vertebrae

[0134] 44 The contact surface of the box-type fusion cage (implant material in one embodiment of the present invention) is adapted to the shape of the vertebral endplate

[0135] 45 box-type fusion cage

[0136] 46 endplate

Claims

1. An implant material having holes in at least one direction, wherein the one direction is the thickness direction of the implant material, characterized in that: The member constituting the hole is composed of a column and a plate, the column and the plate are composed of a single body, and the plate is radially connected to the column with the column as the center. The columns and the plate have grooves on their surfaces, the grooves extending in the depth direction of the hole, the grooves not being connected to each other, the grooves having groove bottoms, and the grooves being alternately arranged on the front and back surfaces of the plate. The hole is formed by a truss structure, and an inscribed circle of the hole is 1000 μm to 2000 μm.

2. The implant material according to claim 1, wherein The holes are formed of a plurality of the pillars and the plates.

3. The implant material according to claim 1, wherein The posts and plates are designed to flex.

4. The implant material according to claim 1, wherein The hole is a structure that does not penetrate the implant material or penetrates the implant material.

5. The implant material according to claim 1, wherein The implant material is at least one selected from polymer materials, ceramic materials, metal materials, amorphous materials or mixed materials thereof.

6. The implant material according to claim 1, wherein The width of the groove is 0.25-500 μm.

7. The implant material according to claim 1, wherein When there are a plurality of these holes, they are interconnected.

8. The implant material according to claim 3, wherein The columns and plates are designed to flex by having telescopic structures themselves, or by varying the thickness, width or height of the columns or plates.

9. The implant material according to claim 1, wherein The implant material is designed to bend in at least a portion of its contact surface with the living body.

10. The implant material according to any one of claims 1 to 9, wherein The implant material has a cage-like structure and has a second hole on a side of the cage-like structure.

11. A method for producing an implant material, the method being a method for producing the implant material according to any one of claims 1 to 10, wherein: Produced using 3D modeling.

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