Patent Application
20220054713
The present invention relates to an implant material and a method for manufacturing the implant material, and more particularly to an implant material having grooves and unidirectional holes and a method for manufacturing the implant material.
Conventionally, various bioimplant materials have been proposed as alternative materials for bone. For example, high-strength materials such as stainless alloys, titanium-based metals such as titanium and titanium alloys, and bioactive materials such as apatite sintered bodies, bioactive glass, and bioactive crystallized glass are known.
High-strength materials such as stainless alloys and titanium-based metals have the characteristic of having high mechanical strength, but they do not directly adhere to bone as they are. Further, bioactive materials such as apatite sintered body, bioactive glass, and bioactive crystallized glass bind to bone in a short period of time, but have a problem that they are insufficient in strength and the applicable place is limited. In order to solve these problems, an implant material in which a film made of a bioactive material is formed on the surface of a high-strength material by plasma spraying or baking has been proposed (Japanese Unexamined Patent Publication No. H8-357040). In this way, bone implants caused by bone diseases, bone defects, etc. are frequently used, and it is expected that demand will increase with the progress of an aging society.
Further, taking the human spine as an example of bones, for example, the spine plays an important role in supporting the trunk and protecting the nerves (spinal cord) that transmit the sensations and movements of the internal organs and limbs from the brain. However, if the vertebrae that make up the spine or the intervertebral discs that support load and move between the vertebrae are deformed due to a disease, there are possibilities that the deformed vertebrae or intervertebral discs may press the spinal cord. In this case, the compression of the spinal cord causes symptoms such as numbness and pain in the limbs.
Surgery to insert a spacer (generally called a cage) into a portion of the intervertebral disc between the vertebrae is performed for the purpose of relieving the compression of the spinal cord. By inserting a cage between the vertebrae and mechanically immobilizing it, it is intended to reproduce the appropriate spacing and position between the vertebrae and to relieve the compression of the spinal cord.
In general, this cage has a role of supporting the load caused by the weight, and since it is made of metal or resin having high mechanical strength, it does not directly adhere to the bone of the living body. Therefore, a method is adopted in which a through hole is provided in the cage, and a bone is guided into the hole to be fixed by an anchoring effect. In addition, screws and rods may be used to connect the vertebrae to prevent them from moving.
Although the cage is highly useful in this way, the fixation between the vertebrae and the cage is not sufficient, and the cage moves and falls out from between the vertebral bodies after surgery, or the cage moves between the vertebral bodies, damaging the vertebrae and surrounding tissues. As a result, the spinal cord is compressed again, and the cage interferes with other parts to induce numbness and pain, which requires surgery again.
Patent literature 1: JP-A1-H8-357040
However, many of the above-mentioned conventional implant materials pay attention to the mechanical properties of the material itself, and there are few materials that are conscious of the fine structure of the bone itself, which plays a leading role in the anchoring effect. The porous body of the prior art is intended to vaguely expect bone invasion into the pores (holes, or opening), and is not intended to form an excellent tissue that prevents deterioration of bone mass and bone quality (here, which represents bone strength). Therefore, an implant material that realizes high-quality bone invasion in consideration of bone mass and bone quality has been desired.
Further, in addition to the above method, a method has been adopted in which bone is separately collected from the ilium (the ilium is a part of the pelvic) so that the bone can quickly enter the through hole of the implant material such as the cage and be firmly fixed, and then the collected bone is transplanted into the through hole of the cage to promote the induction of the bone into the through hole. Since additional skin incisions will be added in addition to the back, which is the target of surgery, the burden on the patient will increase and there will be concerns about pain. In addition, even when transplanted bone is used, there is possibility that the implant material such as a cage may not be sufficiently fixed. Emphasis was placed on attracting bone into the hole of the implant material such as a cage, and the quality of the bone mass and the quality of the bone that invaded the hole were not sufficiently examined as described above. In particular, it is known that the bone that has just invaded 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 a cage is low.
In addition, it is required that implant materials such as cages not only guide bone near the surface like artificial joints, but also deeply invade and fill bone in the thickness direction (the thickness direction corresponds to, for example, the intervertebral space direction). In order to improve the fixation of implant materials such as cages, it is necessary to consider the bone quality in the deep part of the cage hole. It is well known that bone quality is related to mechanical stimulation in vivo due to weight, etc., but since the rigidity of cages made by metal or PEEK is larger than that of bone, it is difficult for the load to be transmitted to the bone. Especially it becomes difficult to set the external environment such as mechanical stimulation in the deep part of the hole.
Therefore, an object of the present invention is to provide an implant material having improved fixation with a living body.
In order to achieve the above object, the inventors focused on the structure of the original hard tissue existing in the living body, and as a result of diligent research on its application to the implant material. As a result, the inventors discovered the implant material of the present invention.
An implant material according to the present invention, is characterized by comprising hole in at least one direction, and a member constituting the hole comprising grooves.
Further, in a preferred embodiment of the implant material according to the present invention, it is characterized in that the member constituting the hole is composed of pillar and/or plate.
Further, in a preferred embodiment of the implant material according to the present invention, it is characterized in that the grooves are provided in the pillars and/or the plates.
Further, in a preferred embodiment of the implant material according to the present invention, it is characterized in that the multiple holes are composed of pillars and/or plates.
Further, in a preferred embodiment of the implant material according to the present invention, it is characterized in that the grooves are alternately arranged on the front and back surfaces of the pillar and/or the plate.
Further, in a preferred embodiment of the implant material according to the present invention, it is characterized in that the pillar and/or the plate are composed of a simple unit and/or a block.
Further, in a preferred embodiment of the implant material according to the present invention, it is characterized in that the pillar and/or plate are designed to bend.
Further, in a preferred embodiment of the implant material according to the present invention, it is characterized in that the hole is designed not to penetrate the implant material or is designed to penetrate the implant material.
Further, in a preferred embodiment of the implant material according to the present invention, it is characterized in that the implant material is at least one selected from a polymer material, a ceramic material, a metal material, an amorphous material, or a mixed material thereof.
Further, in a preferred embodiment of the implant material according to the present invention, it is characterized in that a width of the groove is 0.25 to 500 μm.
Further, in a preferred embodiment of the implant material according to the present invention, it is characterized in that the holes are in communication with each other when there are a plurality of holes.
Further, in a preferred embodiment of the implant material according to the present invention, it is characterized in that pillars and/or plates are designed so that the pillars and/or plates are bend by having a stretchable structure by themselves, or by varying the thickness, width, or height of the pillars or plates.
Further, in a preferred embodiment of the implant material according to the present invention, it is characterized in that the implant material is designed to bend at least a part of the contact surface where the implant material and a living body come into contact with each other.
Further, in a preferred embodiment of the implant material according to the present invention, it is characterized in that the hole is formed of a truss structure body and the inscribed circle of the hole is 500 μm to 2000 μm.
Further, in a preferred embodiment of the implant material according to the present invention, it 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.
Further, a method of manufacturing the implant material according to the present invention, is characterized by being a method for manufacturing the implant material of the present invention, and is characterized by being produced by a 3D modeling method.
According to the implant material of the present invention, it has advantageous effects that early bone entry and early fixation are possible, and an adverse effect on surrounding bone is reduced. Further, the implant material according to the present invention has advantageous effects that strong immobilization between the living body and the implant material can be realized at an early stage without requiring setting of an external environment such as a mechanical stimulus or a magnetic field.
Further, according to the method of manufacturing an implant material of the present invention, it is possible to provide an implant material capable of early bone entry and early fixation and reducing adverse effects on surrounding bone.
An implant material according to the present invention, is characterized by comprising hole in at least one direction, and a member constituting the hole comprising grooves. The groove makes it possible to extend and arrange osteoblasts in the depth direction (the thickness direction of the cage when a cage is used as described later) of the holes (pores or opening) of the implant material when the osteoblasts first invade the inside of the implant material (porous body). In the present invention, by having the groove in addition to the pore, the arranged osteoblasts produce a bone matrix oriented in parallel with the extension/arrangement direction, so that it has the effect of promoting bone matrix orientation from the beginning that the osteoblasts are implanted without mechanical stimulation (bone regeneration). Further, in the present invention, by setting a groove other than the hole, it is possible to obtain strong fixation at an early stage between the bone and the implant material without setting an external environment such as a mechanical stimulus or a magnetic field.
In the present invention, the groove is not particularly limited, but for example, a groove can be set on the surface of a pillar (or a column) or a plate described later. The width of the groove is also not particularly limited as long as it is set for the member constituting the hole, but the width of the groove can be preferably 0.25 μm to 500 μm, and more preferably 0.5 to 200 μm. Further, the grooves can be provided at equal intervals in the thickness direction described above.
Further, in a preferred embodiment of the implant material of the present invention, the member constituting the hole is characterized by being composed of a pillar and/or a plate. As described above, the structure of the pillar and/or the plate makes it possible to easily form a porous body inside the implant material. The present invention can easily provide a porous body that induces bone invasion and bone orientation in a hole inside an implant material such as a cage in order to obtain strong fixation between vertebrae at an early stage without requiring setting of an external environment. In the porous body, pillars or/and plates can be arranged in a pattern at regular intervals in the thickness direction of the cage (in the case of forming a hole, the direction of the major axis of the hole; in the case of a vertebra, the direction of the cranio-caudal axis).
In this way, the rigidity of the pillar can be adjusted by changing the thickness, width, height, etc. of the pillar or the plate. That is, in a preferred embodiment of the implant material of the present invention, from the viewpoint of maintaining good bone quality for a long period of time by applying continuous mechanical stimulation after forming oriented bone in the porous body, it is characterized in that the pillar and/or the plate are designed to bend (flex) by having a stretchable structure itself or by changing the thickness, width, or height of the pillar or the plate. Here, the stretchable structure is not particularly limited as long as the stretchable structure expands and contracts. For example, in the case of insertion into a vertebral body, the stretchable structure can mean that it contracts when a load is received from the upper and lower vertebral bodies and returns to its original state when a load is not applied.
Further, in a preferred embodiment of the implant material of the present invention, from the viewpoint that the living body and the implant material are more compatible with each other, it is characterized that the implant material is designed to bend (or flex) at least a part of the contact surface where the implant material and the living body come into contact with each other. By designing to bend in this way, for example, when the implant material of the present invention is used as a facet cage for the vertebra, as will be clear in the examples described later, by bending, it can be expected that the contact surface with the vertebra, that is, front and back surfaces of the facet cage will fit into the shape of the bone. By fitting into the shape of the bone, the front and back surfaces of the cage are in close contact with the vertebrae, making it easier to guide the bone into the porous body. This is also clear from the fact that the bone is vigorously invaded into the porous body as a result of implanting the intervertebral cage in the intervertebral space of the sheep in the same way and observing the punching strength and tissue as in the examples described later.
Further, the thickness of the pillar or plate is not particularly limited. When the material of the implant material is, for example, a metal material, the thickness of the pillar or plate can be preferably 0.1 to 2 mm, more preferably 0.5 to 1 mm. although it depends on the material used, within this thickness range, the pillar or plate can easily flex in the thickness direction of the implant material such as the cage due to the load acting between the bones such as the vertebrae, thereby transmitting the load to the bone in the porous body. After the bone is oriented inside the porous body in this way, by receiving the main stress load (that is, mechanical stimulation) from the upper and lower vertebral bodies, the bone inside the cage can maintain and promote bone orientation, and it is possible to further suppress deterioration during long-term implantation. This makes it possible to maintain good bone quality in the porous body of the cage for a long period of time immediately after surgery, and as a result, to achieve stable fixation of the vertebrae and cage for a long period of time from the initial stage.
Further, in a preferred embodiment of the implant material according to the present invention, it is characterized in that the pillar and/or the plate are composed of a simple unit and/or a block. For example, the pillar and/or plate can be a block or a single unit connected in a radial, cross-shaped, staggered shape. The plate may be rotatable with the pillar as the center of rotation, and the size of the hole can be freely designed by rotating the plate and fixing the position at regular intervals.
Further, in a preferred embodiment of the implant material according to the present invention, from the viewpoint that bone orientation attains in the entire region where the bone penetrates to obtain strong fixation, it is characterized in that the multiple holes are composed of pillars and/or plates.
Further, in a preferred embodiment of the implant material according to the present invention, from the viewpoint that the pillar or/and plate defines the hole direction and orients the bone in that direction, it is characterized in that the grooves are provided in the pillars and/or the plates. Further, from the viewpoint of promoting bone matrix orientation from the initial stage of implantation (bone regeneration) without mechanical stimulation, the groove can be provided along the depth direction (major axis direction) of the hole.
Further, in a preferred embodiment of the implant material according to the present invention, from the view point that strong fixation is obtained by reducing the plate thickness to minimize the volume of the artificial material such as metal occupying the porous body and maximizing the space where bone can penetrate, it is characterized in that the grooves are alternately arranged on the front and back surfaces of the pillar and/or the plate. For example, as an example of the reason why the grooves are provided alternately on the front and back of the plate, although the metal part is thinned to widen the area inside the cage that can be filled with bone and the plate thickness is reduced to increase the bone mass (to give flexibility), this is because there is possibility that the depth of the groove may not be secured unless the grooves are arranged alternately.
Further, in a preferred embodiment of the implant material according to the present invention, it is characterized in that the pillar and/or plate are designed to bend. Further, in a preferred embodiment, the pattern may be arranged by the pillars and the boards. This is because the pattern arrangement makes it possible to easily design according to the size of the holes. That is, it is possible to make the size of the hole composed of the pillar and the plate, that is, the size of the inscribed circle constant. For example, in the examples described later, although the optimum value of the inscribed circle of the hole is set to 500 μm or more in the sheep implantation test, but in order to easily define this optimum value, a space of a certain size can be created as a pattern arrangement. Since it is sufficient to provide a space larger than that, it may be random (there is no problem that the size of the inscribed circle is different) and is not particularly limited.
In a preferred embodiment of the implant material according to the present invention, from the viewpoint of maximizing the space in which the bone penetrates and obtaining a strong fixing force, it is characterized in that the hole is formed of a truss structure body and the inscribed circle of the hole is 500 μm to 2000 μm.
Further, as described above, the rigidity of the pillar can be adjusted by changing the thickness, width, height, etc. of the pillar or the plate. Further, assuming that the shaft connecting between the pillars, the plates (boards), the plates and the plillars, etc. is a beam (girder) (when a cage is used, the portion corresponding to the ceiling (upper and lower sides) of the cage is included), the beam may be a flexible structure or a stretchable structure. It is similar to the expansion and contraction of the plate as described above. For example, by expanding and contracting the beams arranged in a honeycomb shape or the like, it is possible to adjust so that the contact surface of the box-shaped cage is in perfect contact with the shape of the end plate of the vertebral body. The thickness of the beam can be 0.1 mm to 1.5 mm, preferably 0.3 mm to 1.0 mm, and for example, the beam can be about 0.5 mm, from the viewpoint of the flexible structure.
Further, in a preferred embodiment of the implant material of the present invention, it is characterized in that the hole is designed not to penetrate the implant material or is designed to penetrate the implant material. In the present invention, when the osteoblasts first invade the implant material (porous body), the groove makes it possible to extend and arrange osteoblasts in the depth direction of the holes of the implant material for osteoblast (when a cage is used as described later, in the thickness direction of the cage), so that the hole may be a through hole or a non-penetrating hole. In the case the hole is designed to penetrate the implant material, the bone tissue is continuous between the adjacent vertebrae through a penetrating hole, so that the fixation strength between the vertebrae and the cage can be further secured.
The material of the implant material is not particularly limited. Further, in a preferred embodiment of the implant material of the present invention, as the implant material mention may be made of at least one selected from polytetrafluoroethylene ((Teflon (registered trademark)), polymer material, ceramic material, metal material, amorphous material, or a mixture thereof. As the metal material, mention may be made of pure metals, alloys, intermetal compounds and the like. Further, the amorphous material can include a partially crystallized portion. This is because there is a material called an amorphous material even if it contains a crystallized portion. As the amorphous material, for example mention may be made of bioglass and the like.
For example, as the material of the implant material, a hard tissue substitute material or the like can be mentioned. As the hard tissue substitute material, mention may be made of inorganic materials such as ceramics typified by apatite, alumina and zirconia, and metal materials such as stainless steel, Co—Cr alloy, titanium, alloy and tantalum. Ceramics can be further divided into bioactive ceramics, bioinactive ceramics and the like. As bioceramics, mention may be made of calcium phosphate-based ceramics, silica-based glass, and crystallized glass. Hydroxyapatite and tricalcium phosphate are well known as calcium phosphate-based ceramics, and these are used for artificial tooth roots, skin terminals, metal coating materials, and the like. These various materials can be used as the implant material.
Further, in a preferred embodiment of the implant material according to the present invention, from the viewpoint of the width at which osteoblasts can detect the orientation direction of collagen and apatite, a width of the groove can be preferably 0.25 to 500 μm, more preferably 0.5 to 200 μm.
Further, in a preferred embodiment of the implant material according to the present invention, it is characterized in that the holes are in communication with each other when there are a plurality of holes. This is because, for example, continuous inflow of bone marrow fluid is possible between the holes, and it is possible to realize bone invasion into the deep part of the porous body.
Further, a method of manufacturing the implant material according to the present invention, is characterized by being a method for manufacturing the implant material of the present invention, and is characterized by being produced by a 3D modeling method (AM, Additive Manufacturing). As for the 3D modeling method, a conventional method can be used and is not particularly limited. The processing method of the implant material and the like are widely known in the art, and the implant material can be produced by applying to the implant material of the present invention by a conventional method.
Further, the pillars or plates constituting the above-mentioned porous body can be connected to the truss structure body. The truss structure body may be a structure body connected to a triangular, square or polygonal shape on the upper and lower surfaces of the cage continuous with the structure body on the outer periphery of the cage. With this truss structure, the outer periphery of the cage and the pillars or plates constituting the porous body can be integrated. The size of the inscribed circle with respect to the void formed inside the triangular, square or polygonal shape of the truss structure body is also not particularly limited. For example, from the viewpoint of the size of bone lineage cells (osteoblast+osteoclast+osteosite), the size of the inscribed circle is preferably 500 μm or more. The pillars or plates constituting the porous body can be arranged along the truss of the truss structure body. In this case, the inscribed circle of the void formed by the arranged pillars and/or plates can also be equivalent to the inscribed circle of the truss porous body. The size of this void can be the optimum size for bone invasion into the porous body.
The truss structure itself may also be provided so that the same grooves as those provided in the pillars or plates constituting the porous body are continuous. The groove of this truss structure body makes it possible to promote bone orientation immediately after bone invasion, to develop high bone quality from the initial stage of bone invasion, and to realize cage fixation with vertebrae.
The pillars and/or pillars arranged to form the porous body may not be connected each other. In this case, spaces at regular intervals can be provided between the pillars, allowing continuous inflow of bone marrow fluid and realizing bone invasion into the deep part of the porous body. Further, a hole may be provided so as to communicate the outside of the outer periphery of the cage with the inside of the porous body. As a result, continuous inflow of bone marrow fluid is possible, and bone invasion into the deep part of the porous body can be realized.
Further, in a preferred embodiment of the implant material according to the present invention, from the viewpoint that the side holes are effective for guiding the bone into the porous body. it 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. This is because it turned out to be effective for the hole on a side surface to guide the bone into the porous body from the data of the cylindrical cage (or box-shaped cage) embedded in the vertebrae regarding the hole on a side surface of the facet cage, as will be apparent in the examples described later.
Here, an embodiment of the present invention will be described, but the present invention is not construed as being limited to the following examples. Further, needless to say, it can be appropriately changed without departing from the scope of the present invention.
Bone tissue is composed of undifferentiated mesenchymal cells, osteogenic cells, osteoblasts, bone cells (osteocytes) and osteoclasts and the like. In the process of newborn bone formation, osteoblasts secrete type I collagen and the like, and additively produce apatite to collagen fibers to promote calcification. As calcification progresses, it becomes bone cells and is embedded in the bone matrix to complete newborn bone formation.
In such a bone formation process, it is known that the traveling direction of type I collagen (Col) and the crystal orientation of hexagonal apatite crystals (BAp) are almost the same (here, the orientation means that the orientation of the apatite crystals is not random but they are aligned in the same direction). This Col and BAp complex determines the bone matrix, that is, the strength and flexibility of the bone. Hexagonal crystals have a=b # c as the crystal axis and show remarkable mechanical anisotropy along the a and c axes. Therefore, it can be seen that the mechanical properties of bone are closely related to the orientation of the bone matrix due to the orientation of the apatite crystals produced from the osteoblasts. In other words, it can be seen that osteoblasts and type I collagen and apatite secreted from them are closely related to their orientation. Therefore, in the present invention, in order to orient the bone matrix by extending and arranging the osteoblasts in the cage thickness direction of the osteoblasts, a groove structure extending in the orientation direction with respect to the porous body intended for bone invasion can be adopted.
In an example of the implant material prototyped this time, the grooves of the porous body are provided at equal intervals on the surface of the plate or/and the pillar constituting the porous body as shown in FIG.
As shown in
The finite width plates or/and pillars that make up the porous body are arranged in blocks that are connected in a radial or cross shape, or alone. Osteoblasts invade along the groove provided in this plate or/and pillar, and have a role of promoting bone orientation from the initial stage of bone invasion. The arrangement of the plates and/or pillars may be either staggered or evenly spaced. It is desirable that this plate or/and pillar bend or flex under load in a biomechanical environment. This deflection can provide mechanical stimulation in the direction of principal stress to the bone that has invaded the porous body along the plate or/and pillar, and can contribute to continuous bone orientation. Therefore, it is desirable that the thickness or thickness of the plate or/and the pillar be, for example, 1 mm or less so that the plate or the pillar can be bent or flexed by a load.
The outer peripheral part of the cage that forms the outer shape shares the load support in the in vivo mechanical environment, and at the same time, the porous body and the bone invading the porous body are integrated and the cage and the intervertebral space are fixed. That is, the outer peripheral portion of the cage and the porous body can be structurally integrated. As a method of connecting the space-arranged plate or/and the pillar and the outer circumference of the cage to form the porous body, a truss structure that connects the surface of the cage (that is, the upper and lower surfaces of the cage where the cage inserted between the intervertebral space contacts the vertebrae) and the outer circumference of the cage is arranged. This truss structure body is arranged so as to be connected to a plate or/and a pillar constituting the porous body. The truss shape may be any triangle, quadrangle, or polygon as long as it can be connected to a plate or a pillar constituting the porous body. The truss structure body on the surface of the cage is provided with a groove so as to be continuous with the groove provided on the plate or/and the pillar constituting the porous body. When bone begins to invade the cage porous body, osteoblasts grow from the truss structure body corresponding to the outermost surface of the cage, so the groove of the truss structure body can be expected to have the effect of promoting bone orientation from the initial stage of bone invasion. In order to fill the bone deeply in the thickness direction of the cage, the plate constituting the porous body can have a finite width so that the bone marrow fluid containing osteoblasts can be continuously supplied. With such a finite width, an appropriate gap can be provided between adjacent plates or/and pillars, and bone marrow fluid containing osteoblasts can be continuously supplied over the entire porous body. By this continuous supply, it is possible to realize bone invasion deep into the cage porous body. In addition, the porous body can be provided with holes on the side surface of the cage. These holes play a role in suppressing the retention of bone marrow fluid in the deep part of the porous body and promoting continuous circulation of bone marrow fluid.
In order to confirm the functionality of the above cage porous body, the porous body was implanted in the vertebrae of sheep, and the bone mass, bone orientation, and bone fixation in the porous body were evaluated by a pull out test. The results are shown below.
In this evaluation, a sample was prepared in which three finite plates connected radially every 120 degrees as a porous body were arranged in a staggered pattern. The groove provided on the finite plate has a width of 0.2 mm and a depth of 0.15 mm. The plate thickness was 0.5 mm, and the grooves were arranged on both sides of the plate so that the bottoms of the grooves did not overlap each other. The outer shape of the cage was cylindrical for vertebra implantation. A triangular shape was adopted as the truss structure. The triangular truss structure communicated with the finite plates arranged in a radial pattern, and two kinds of the inscribed circles were set to 500 μm (Evaluation sample A) or 1000 μm (evaluation sample B). In order to investigate the influence of the external environment such as the conventional bone graft method and mechanical stimulation, the following evaluation samples C to E with holes on the side surface of the cage were prepared (
Sample C: Similar to a conventional cage, the cage is provided with only a through hole, and the hole is filled with a bone implant.
Sample D: In the cage having the porous body, the sheep head tail axis corresponding to the load transmission direction and the groove of the porous body are embedded in parallel.
Sample E: A cage having the porous body, which is embedded so that the head tail axis of the sheep and the groove of the porous body are perpendicular to each other. The cage shape is the same as sample D, but the load transfer direction is 90 degrees different from the groove of the porous body.
[Sample Preparation]
The above evaluation sample was designed with CAD software, output in STL format (Stereolithography), and integrally modeled by AM (Additive Manufacturing) using the data. The material used was Ti-6A1-4V alloy, which is a titanium-based alloy that has a proven track record as an implant material, and was modeled with a laser metal molding machine (EOS M290, manufactured by EOS). The groove width and thickness after modeling were 0.1 to 0.5 mm in width and 0.1 to 0.2 mm in depth with respect to the design values (width 0.2 mm, depth 0.15 mm).
[Sheep Burial]
Sample one by one was implanted in each of L1 to L4 of the lumbar vertebrae of Suffolk sheep 12 months or older. L1 to L4 vertebrae in which the cage was implanted were collected.
[Observation of Bone Tissue]
In order to evaluate the bone induced inside the porous body of the cage, Vilanueva staining was performed, and a non-decalcified thin sections were prepared with a cross section parallel to the cranio-caudal axis with respect to the central part. The ratio of bone (BV: Bone Volume) to the space (TV: Total Volume) inside the cage was measured. The results are shown in Table 1.
From Table 1, in the inscribed circles of 500 μm and 1000 μm (evaluation samples A and B), 1000 μm has more bone mass, and the larger inscribed circle is more advantageous for bone invasion. In addition, in the comparison with/without holes on the side surface of the cage with an inscribed circle of 1000 μm (evaluation samples A and D), the bone mass was significantly larger with holes on the side surface of the cage. No significant difference was observed in the influence of the direction of the porous body (evaluation samples D and E).
[Pull-Out Test]
A pull-out test was carried out with the evaluation sample C simulating a cage for conventional bone grafting and the evaluation samples D and E with the porous body, and the adhesion strength between the bone and the cage by the porous body was evaluated. After thawing the vertebra in which the cage was implanted, the vertebra was fixed with bone cement so that the screws provided in the cage part at the top of the jig are exposed. For the jig, a pull-out test of the cage was carried out with a tensile tester (manufactured by INSTRON, model number 5965). The crosshead speed was 5 mm/min, and the maximum load measured during the test was taken as the pull-out strength.
The results are shown in
[Orientation Measurement]
In order to evaluate bone orientation, sliced sections of evaluation sample E prepared by bone tissue observation were used, and the orientation of collagen fibers related to bone orientation was analyzed by birefringence technique (WPA-micro: Photonic Lattice).
Further,
As described above, according to the present invention, it can be seen that the geometric pattern structure itself of the internal structure having a groove (such as the above-mentioned tetra structure) can promote the formation of oriented new bone into the porous body regardless of the external environment such as mechanical stimulation.
From the above results, the relationship between the groove provided in the porous body and the bone orientation is clear. In particular, high pull-out strength was obtained in the evaluation sample E arranged so that the groove of the porous body was perpendicular to the principal stress direction in the biomechanical environment. This indicates that the geometric pattern of the porous body itself promotes bone orientation, independent of the biomechanical environment. Further, from the above, it was found that the groove width of 0.25 to 500 μm can be preferably used in consideration of the detectability of the osteoblast orientation direction and the size of the cell itself, the inscribed circle of the porous body can be 500 μm or more, and the plate thickness of 0.5 to 1 mm can be preferably used in consideration of the strength of the porous body and the groove depth.
Next, a box-shaped cage was designed as the implant material of the present invention, and the effect of inducing bone orientation was investigated. Specifically, as a large animal test (sheep), an extrusion test of a box-type cage placed between the sheep's vertebrae was performed. That is, in a large animal test using sheep, a box-type cage was implanted in the intervertebral space as in human clinical practice, and an extrusion test of the box-type cage was performed 8 weeks after implantation. For two types of box-shaped cage having heights of 8 mm and 11 mm, a comparative extrusion test was performed between the transplanted bone group of the box-shaped cage equivalent to the evaluation sample C of
From these results, the Paired T-test was performed for the three cases of height 8 mm, height 11 mm, and both cases, and significant differences were observed in all cases. It was found that the extrusion load of the bone orientation-induced porous body was higher than that of the transplanted bone, and the shear strength at the joint surface between the bone and the bone orientation derivative was significantly higher than that of the transplanted bone. That is, it was found that the extrusion strength of the box-shaped cage having the oriented porous material was significantly higher than that of the transplanted bone.
In Example 2, a box-shaped cage can be implanted in the vertebrae as a verification experiment, and when used in humans, the damaged intervertebral disc (between the vertebrae) can be removed, and the box-shaped cage can be implanted and fixed between the vertebrae. The direction of deflection is the cranio-caudal direction (the vertical direction in which the weight head is applied when the human is standing), and the design can be based on the assumption that the tetra-shaped structure body is compressed by the vertebrae above and below the cage and bends by compression. In the box-shaped cage, the structure body connecting the tetra-shaped structures body is thinly designed (0.5 mm), and the structure body itself bends of flexs so that the contact surface with the vertebrae, that is, the effect that the front and back surfaces of the box-shaped cage fit into the shape of the bone can be expected. By adapting to the shape of the bone, the front and back surfaces of the cage are in close contact with the vertebrae, making it easier to guide the bone into the porous body.
According to the present invention, it can be expected to contribute to the fields of treatment of hard tissue diseases, regenerative medicine and dentistry (particularly orthopedics, neurosurgery, dentistry) and basic medicine.
| Number | Date | Country | Kind |
|---|---|---|---|
| 2018-199592 | Oct 2018 | JP | national |
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/JP2019/041360 | 10/21/2019 | WO | 00 |
