JP2018015043A - Vertebral body spacer - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a vertebral body spacer excellent in initial fixation property when disposed between vertebral bodies, which can maintain a stable fixed state for a long period of time.SOLUTION: A vertebral body spacer interposed between a first vertebral body and a second vertebral body adjacent to the first vertebral body includes a first surface facing the first vertebral body and a second surface facing the second vertebral body located on a side opposite to the first surface. There is a protrusion on the first surface, and the protrusion includes a base containing a high polymer material, a dense part present at the apex of the base and containing the high polymer material and a bioactive material, and a porous part that covers the surface of the base other than the apex, containing the high polymer material and the bioactive material.SELECTED DRAWING: Figure 5

Description

  The present invention relates to a vertebral body spacer, and more particularly to a vertebral body spacer that has good initial fixation between vertebral bodies when placed between vertebral bodies and that is stably maintained for a long period of time. .

Patent Document 1 states that “a bioimplant that is made of plastic and includes a dense substantial portion and a porous surface layer formed on the surface of the substantial portion,
The substantial part has an uneven structure on the outermost surface,
The surface layer is formed by connecting pores three-dimensionally,
There is disclosed a “biological implant” characterized in that the thickness of the surface layer formed in the concave portion of the concavo-convex structure is at least twice the thickness of the surface layer formed in the convex portion of the concavo-convex structure (Patent Document) 1), and the biological implant is “applicable to artificial vertebral bodies, interbody spacers, vertebral body cages,...” (Paragraph number 0124 of Patent Document 1). Column).

  Patent Document 2 states that “a surface foam comprising a substantial part and a surface layer having a small diameter pore and a large diameter pore formed on the surface thereof, and the surface layer forms the substantial part. It is obtained by making the surface portion of the base material made of engineering plastic into a porous structure, and the small pores and a part of the large pores form open pores that open on the surface of the surface layer, and the open pores Has a small diameter open pore with an average open pore diameter of 5 μm or less and a large diameter open pore with an average open pore diameter of 10 to 200 μm. The large diameter open pore that opens on the surface of the surface layer has a small diameter on its inner wall surface. Disclosed is a biological implant characterized in that a communicating hole communicating with a pore and a large-diameter pore is formed (Claim 1 of Cited Document 2), and the biological implant is “artificial vertebral body, interbody spacer, Applicable to vertebral body cage, ... Can be made "(paragraph number 0083 column of Patent Document 2).

In Patent Document 3, “a bioimplant manufacturing method for manufacturing a bioimplant in which a bioactive substance is immobilized on the surface of a base material made of a thermoplastic resin,
Disclosed is a method for producing a biological implant, comprising a step of heating a base material on which the bioactive substance is disposed on a glass transition temperature of the thermoplastic resin to a heating temperature of −30 ° C. or higher and lower than a melting point ”. (Claim 1 of Patent Document 3), and the biological implant manufactured by the manufacturing method can be suitably used as an artificial vertebral body, interbody spacer, vertebral body cage,... (Patent Document 3, paragraph number 0117).

  As conventionally known, the interbody spacer is a vertebral body in the spine (hereinafter sometimes referred to as “first vertebral body”) and a vertebral body adjacent to the vertebral body (hereinafter referred to as “second vertebral body”). A medical member interposed between the vertebral body and the vertebral body. Conventionally disclosed intervertebral spacers have a substantially rectangular parallelepiped shape, and are surfaces facing the first vertebral body (hereinafter referred to as “first surface”) when inserted between the first vertebral body and the second vertebral body. Is formed on the uneven surface, and the surface opposite to the first surface (hereinafter sometimes referred to as the “second surface”) toward the second vertebral body is the uneven surface. The length (height) from the first surface to the second surface is about 5 to 13 mm, the lateral width of the first surface and the second surface is about 7 to 12 mm, and the first surface and the first surface are formed. The length from the front end portion to the rear end portion is formed to have a dimension of about 20 to 25 mm.

  This interbody spacer is inserted and placed between the first vertebral body and the second vertebral body by a surgical operation called lumbar fusion (sometimes referred to as spinal fusion).

Japanese Patent No. 5404165 Japanese Patent No. 5372788 Japanese Patent No. 5728321

  It is assumed that the surface layer disclosed in Patent Documents 1 to 3 is formed on the surface of the interbody spacer formed in the shape disclosed in Non-Patent Document 1. This assumed surface layer-containing interbody spacer uses the interbody spacer formed in the shape disclosed in Non-Patent Document 1 as a spacer base, and the surface disclosed in Patent Documents 1 to 3 It can be thought of as comprising a layer.

  However, when this assumed surface layer-containing interbody spacer is inserted into the gap between the first vertebral body and the second vertebral body, it is formed on the first and second surfaces of the surface layer-containing interbody spacer. It is inevitable that the surface layer at the top of the convex portion in the concavo-convex portion is damaged by the first vertebral body or the second vertebral body, which makes it difficult to maintain the porous structure included in the surface layer. If the porous structure included in the top surface layer in the uneven portion is not maintained, the osteoblasts cannot be satisfactorily entered from the first vertebral body or the second vertebral body to the convex portion of the spacer base, and therefore The connection between the first vertebral body or the second vertebral body and the surface layer-containing interbody spacer may be insufficient, and the surface layer-containing interbody spacer may be interposed between the first vertebral body and the second vertebral body. There is a risk that the spinal fusion procedure that inserts into and fixes the vertebrae and the surface layer-containing interbody spacer will fail.

  Further, when a surface layer covering the convex portion is missing when the surface layer-containing interbody spacer is inserted between vertebral bodies, the surface layer-containing interbody spacer is located at a good position between the vertebral bodies. Even if the first vertebral body or the second vertebral body and the surface layer-containing interbody spacer are insufficiently bonded, the movement of the patient's body after the operation causes the surface layer-containing vertebrae It is assumed that the interbody spacer is detached from the vertebral bodies or causes a positional shift between the vertebral bodies.

  An object of the present invention is to provide a vertebral body spacer that has good initial fixation when placed between vertebral bodies and can maintain a stable fixed state for a long period of time, and a method for manufacturing the vertebral body spacer. .

Means for solving the problems are as follows:
(1) A vertebral body spacer interposed between a first vertebral body and a second vertebral body adjacent to the first vertebral body, the first surface facing the first vertebral body, and the second vertebral body A vertebral body spacer having a second surface facing the vertebral body and opposite to the first surface,
A protrusion is present on the first surface, and the protrusion is present on a base containing a polymer material, on a top of the base, and a dense part containing the polymer material and a bioactive substance, The vertebral body spacer is characterized in that it covers a surface other than the top of the base and includes a porous portion containing the polymer material and a bioactive substance.

A preferred aspect of the means for solving the above problems is as follows:
(2) The vertebral body spacer according to (1) above, wherein the vertebral body spacer has a through space penetrating the first surface and the second surface,
(3) The vertebral body spacer according to (2), wherein each of the first surface and the second surface is linked to a side wall, and the side wall includes a communication space communicating with the through space. And
(4) The dense portion is the vertebral body spacer according to any one of (1) to (3), characterized in that the porosity is smaller than the porosity of the porous portion.
(5) The porous part is the vertebral body spacer according to any one of (1) to (4), wherein the porosity is 30% or more,
(6) The porous part has a small diameter pore and a large diameter pore,
The vertebral body according to any one of (1) to (5), wherein a part of the small-diameter pore and the large-diameter pore form an open pore that opens on a surface of the porous portion. Spacer,
(7) The vertebral body spacer according to any one of (1) to (6), wherein a height from the first surface of the projecting portion is 300 μm or more and 2000 μm or less,
(8) The protruding portion according to any one of (1) to (7), including at least one fiber selected from the group consisting of carbon fiber, glass fiber, ceramic fiber, metal fiber, and organic fiber. Vertebral body spacer as described,
(9) The vertebral body spacer according to any one of (1) to (8), wherein the polymer material is polyetheretherketone,
(10) The vertebral body spacer according to any one of (1) to (9), wherein the vertebral body spacer has a bioactive substance on at least one of an inner wall surface of an open pore in the porous portion and a surface of the porous portion. Yes,
(11) The vertebral body spacer according to any one of (1) to (10), wherein the bioactive substance is calcium phosphate,
(12) The vertebral body spacer according to (11), wherein the calcium phosphate is hydroxyapatite.

According to the present invention, the dense portion is present at the top of the base portion formed so as to protrude from the first surface. Therefore, when the dense portion is inserted between the first vertebral body and the second vertebral body, the dense portion is the vertebral body. No part of the dense part is peeled off. Immediately after being interposed between the first vertebral body and the second vertebral body, the dense part formed at the top of the convex part is recessed into the first vertebral body, and the dense part contains a bioactive substance. This facilitates chemical bonding with the vertebral body, so that there is no misalignment of the vertebral body spacer after insertion and placement of the vertebral body spacer between the vertebrae. Vertebral body spacers can be provided.
Furthermore, after being inserted between the first vertebral body and the second vertebral body, the osteoblasts can smoothly enter the pores existing in the porous portion, and the entry of osteoblasts Provides a vertebral body spacer that is firmly connected to the vertebral bodies by the bone formed by the, and that is not easily displaced between the vertebral bodies over a long period of time due to the strong connection, and that the detachment from the vertebral bodies is unlikely to occur. can do.

  According to the present invention, in addition to the above technical effect, osteoblasts that have entered the formed through space are fixedly interposed between vertebral bodies by mature bones, and are not easily displaced due to the movement of the spine. Also, it is possible to provide a vertebral body spacer that is difficult to separate from between vertebral bodies.

  According to the present invention, in addition to the above technical effect, osteoblasts that have entered the formed communication gap are fixedly interposed between vertebral bodies by mature bones, and are not easily displaced due to the movement of the spine. Also, it is possible to provide a vertebral body spacer that is difficult to separate from between vertebral bodies. In particular, when a through space and a communication space are provided, bones formed by maturation of osteoblasts that have entered the through space and the communication space are fixedly interposed between vertebral bodies in the longitudinal and lateral directions of the spinal column. Thus, it is possible to provide a vertebral body spacer that is mounted and hardly displaced due to the movement of the spinal column and that is difficult to be separated from between vertebral bodies.

  According to the present invention, in addition to the above technical effect, it is possible to provide a vertebral body spacer in which the dense portion can be distinguished from the porous portion by the porosity.

  According to this invention, in addition to the above technical effect, the porous part has small diameter pores and large diameter pores, and the open pores are formed on the surface of the porous part. It is possible to provide a vertebral body spacer that is firmly fixed between vertebral bodies by bones in which blast cells have grown and hardened.

  According to the present invention, since the protrusion from the first surface is within the predetermined range, the protrusion is appropriately recessed into the first vertebral body or the second vertebral body, and the vertebral body spacer is It is possible to provide a vertebral body spacer having an excellent function of being able to reduce the risk of displacement of the vertebral body spacer, particularly in the initial stage after the placement, after being inserted and placed between the bodies.

  According to the present invention, since the protruding portion contains at least one kind of fiber mixed with high-strength fibers such as carbon fibers, the strength of the protruding portion is increased by the fiber, and therefore the protruding portion is inserted between the vertebral bodies. It is possible to provide a vertebral body spacer capable of exhibiting an excellent technical effect that the protrusion is sometimes abraded by the vertebral body and the shape of the protrusion is not lost or deformed.

  According to the present invention, when the polymer material that is one element constituting the base portion and the dense portion is an engineering plastic, particularly a polyether ether ketone, a vertebral body spacer having high strength and high durability can be provided. The technical effect of is produced.

  According to this invention, since at least one of the inner wall surface of the open pores in the porous portion and the surface of the porous portion contains a bioactive substance, particularly calcium phosphate, especially hydroxyapatite, osteoblasts enter the pores. Therefore, it is difficult to cause a living body rejection reaction. Therefore, for example, it is possible to provide a vertebral body spacer that does not cause inflammation in the living body even if a long period of time elapses after the completion of spinal fusion. The

FIG. 1 is a perspective view showing a vertebral body spacer showing an example of the present invention. FIG. 2 is a front view showing a vertebral body spacer which is an example of the present invention. FIG. 3 is a plan view showing a vertebral body spacer which is an example of the present invention. FIG. 4 is an explanatory view showing various modifications of the protrusions in the vertebral body spacer which is an example of the present invention. FIG. 5 is a cross-sectional explanatory view showing a cross section of a protruding portion in a vertebral body spacer which is an example of the present invention. FIG. 6 is a cross-sectional explanatory view showing a cross section of a porous portion in a vertebral body spacer which is an example of the present invention.

  As shown in FIG. 1, a vertebral body spacer 1 which is an example of the present invention includes a vertebral body (this may be referred to as a first vertebral body) and a vertebral body adjacent to this vertebral body (which is referred to as a first vertebral body). 2) (which may be referred to as two vertebral bodies).

  The vertebral body spacer 1 shown in FIG. 1 faces a first surface 2 facing the first vertebral body and a second vertebral body when inserted between the first vertebral body and the second vertebral body. And a second surface 3 located on the opposite side of the first surface 2. Each of the first surface 2 and the second surface 3 has a protrusion 4 that protrudes in a direction toward the vertebral body.

  The first surface 2 and the second surface 3 may have planes that appear when the protrusions 4 are removed, or may not be parallel to each other. When not parallel, the first surface 2 is slightly inclined with respect to the second surface 3 so that the height H1 on the distal end side inserted between the vertebrae is smaller than the height H2 on the rear end side. Alternatively, the first surface 2 may be slightly inclined with respect to the second surface 3 such that the height H2 on the rear end side is smaller than the height H1 on the front end side. When the height H1 of the distal end portion of the vertebral body spacer 1, that is, the distal end portion inserted when inserted between the vertebrae is smaller than the height H2 of the rear end portion, the vertebral body spacer 1 is smoothly inserted between the vertebrae. be able to. If the height H2 on the rear end side is smaller than the height H1 on the front end side, after inserting the vertebral body spacer 1 into the intervertebral space, the vertebral body spacer 1 moves from the intervertebral space to the opposite side in the insertion direction. The risk of falling out can be reduced.

  As shown in FIG. 1, the vertebral body spacer 1 may have a tip 5a and a rear end 5b formed in a triangular prism shape, and as shown in FIG. 2, the tip 6a and The rear end portion 6b may be a hemisphere obtained by halving a sphere, or a halved ellipsoid obtained by halving an ellipsoid. The shape of the front end portion and the rear end portion of the vertebral body spacer 1 can be appropriately determined according to the state or state of the spine in the patient into which the vertebral body spacer 1 is to be inserted.

  The vertebral body spacer 1 may have the same lateral width of the first surface 2 and the second surface 3, that is, the length in the direction perpendicular to the direction in which the vertebral body spacer 1 is inserted between the vertebral bodies, Any of the lateral widths of the first surface 2 and the second surface 3 may be large. Also, the vertebral body spacer 1 may have the same width W1 at the front end and the horizontal width W2 at the rear end, and either the width W1 or the width W2 may be slightly larger.

  The protrusion 4 may be formed on one of the first surface 2 and the second surface 3, or may be formed on both. In the preferred vertebral body spacer 1, there are protrusions 4 on both the first surface 2 and the second surface 3. When the protrusions 4 are formed on both surfaces, the connection between the first surface 2 and the vertebral body and the connection between the second surface 3 and the vertebral body are realized, whereby the connection between the vertebral body and the vertebral body spacer 1 is achieved. Or bone fusion will be certain.

  As shown in FIG. 1, the protrusion 4 can employ an aggregate having a structure in which a plurality of triangular prisms that are tilted sideways when viewed from the width direction are arranged. The protruding portion 4 is not limited to an assembly having a structure in which the plurality of triangular prisms are laid down side by side and arranged in parallel. Aggregates having an arrayed structure can also be adopted. Furthermore, as shown in FIG. 4 (a), each protrusion 4a has a conical shape, and the conical protrusions are arranged at random or in a matrix. An assembly having an array structure can also be adopted, and as shown in FIG. 4B, each protrusion 4b has a truncated cone shape, and each protrusion of the truncated cone shape is randomly Alternatively, an assembly having an array structure arranged in a matrix can be adopted. As shown in FIG. 4C, each protrusion 4c has a cylindrical shape, and each protrusion having the cylindrical shape is formed. It is also possible to adopt an aggregate having an arrangement structure in which the portions are arranged randomly or in a matrix, and furthermore, the conical protrusions 4a shown in FIGS. 4 (a) to 4 (c), The frustoconical protrusions 4b and the cylindrical protrusions 4c are randomly or in a matrix. It may be arranged assemblage. In addition, in this invention, although the protrusion part means the individual protrusion part in an aggregate | assembly, the aggregate | assembly of a "protrusion part" may be called a "protrusion part." Protrusions as aggregates and individual protrusions can be easily distinguished by the context in which the term is used.

  As shown in FIG. 3, the vertebral body spacer 1 preferably also has a through space 7 that penetrates from the first surface 2 toward the first vertebral body to the second surface 3 toward the second vertebral body. When the vertebral body spacer 1 provided with the through space 7 is interposed between the first vertebral body and the second vertebral body, blood flows into the through space 7 and the invasion of osteoblasts is promoted. Bone formation is quickly realized in the through space 7, and as a result, the bone fusion between the first vertebral body and the second vertebral body and the vertebral body spacer 1 is realized early.

  As shown in FIG. 2, the vertebral body spacer 1 is formed on the front surface 8 of the vertebral body spacer 1 that is continuous with the first surface 2 toward the first vertebral body and is continuous with the second surface 3 toward the second vertebral body. One or a plurality of communication gaps 9 may be formed. When the vertebral body spacer 1 in which the communication space 9 is formed is interposed between the first vertebral body and the second vertebral body, blood flows into the communication space 9 and the invasion of osteoblasts is promoted, Bone formation is realized in the communication gap 9, and as a result, bone fusion between the first vertebral body and the second vertebral body and the vertebral body spacer 1 is realized.

  In FIG. 2, the front surface 8 is also a side wall linked to the first surface 2 and the third surface 3 of the vertebral body spacer 1. Further, the first surface 2 in FIG. 3 can also be referred to as a plane in the vertebral body spacer 1.

  As shown in FIG. 2, the vertebral body spacer 1 according to the present invention generally has a total length L in the direction of insertion between the vertebral bodies of the vertebral body spacer 1 of 20 to 25 mm. As shown in FIG. 2, The distance between the first surface 2 and the second surface 3, that is, the height H is usually 7 to 14 mm, and is linked to or continuous with the first surface 2 and the second surface 3 as shown in FIG. The distance between one side wall and the other side wall, that is, the width W is usually 8 to 11 mm. Moreover, the height from the 1st surface 2 or the 2nd surface 3 of the protrusion part 4 is 300 micrometers or more normally and 2000 micrometers or less.

  As shown in FIG. 5, the protruding portion 4 includes a base portion 10, a dense portion 11, and a porous portion 12.

  The base 10 is the main body of the vertebral body spacer 1. The base 10 can be formed of a polymeric material, preferably a polymeric material having mechanical properties that are similar to or close to vertebrae. Examples of the mechanical properties include an elastic modulus of 1 to 50 GPa and a bending strength of 100 MPa or more.

  Examples of the plastic whose mechanical properties are close to bone include engineering plastic and fiber reinforced plastic. Engineering plastics include, for example, polyamide, polyacetal, polycarbonate, polyphenylene ether, polyester, polyphenylin oxide, polybutylene terephthalate, polyethylene terephthalate, polysulfone, polyethersulfone, polyphenylene sulfide, polyarylate, polyetherimide, polyetherether Examples include ketones, polyamideimides, polyimides, fluororesins, ethylene vinyl alcohol copolymers, polymethylpentene, phenol resins, epoxy resins, silicone resins, diallyl phthalate resins, polyoxymethylenes, polytetrafluoroethylenes, and the like.

  Examples of plastics that serve as a matrix of fiber reinforced plastic include, in addition to the engineering plastics, polyethylene, polyvinyl chloride, polypropylene, EVA resin, EEA resin, 4-methylpentene-1 resin, ABS resin, AS resin, ACS resin, and the like. , Methyl methacrylate resin, ethylene vinyl chloride copolymer, propylene vinyl chloride copolymer, vinylidene chloride resin, polyvinyl alcohol, polyvinyl formal, polyvinyl acetoacetal, polyfluorinated ethylene propylene, polytrifluoroethylene chloride, methacrylic resin, renor Resin, polyallyl ether ketone, polyether sulfone, polyketone sulfide, polystyrene, polyamino bismaleimide, urea resin, melamine resin, xylene resin, isophthalic acid series Fat, aniline resins, furan resins, polyurethane, alkylbenzene resin, guanamine resin, poly ether resins.

  Polyether ether ketone (PEEK) is particularly preferable as the material forming the base of the vertebral body spacer according to the present invention. PEEK is biocompatible and has mechanical properties close to bone. Therefore, when PEEK is adopted as a material for forming the base of the vertebral body spacer, stress shielding, that is, stress applied to the bone when the vertebral body spacer is embedded between the vertebral bodies where a large load is continuously applied for a long period of time. It is possible to obtain a high-strength vertebral body spacer that does not cause bone loss or bone density reduction that may occur due to shielding.

  Examples of the fiber in the fiber reinforced plastic include carbon fiber, glass fiber, ceramic fiber, metal fiber, and organic fiber. For carbon fibers, carbon nanotubes are also included here. Glass fibers include fibers such as borosilicate glass (E glass), high-strength glass (S glass), and high elasticity glass (YM-31A glass), and ceramic fibers include silicon carbide, silicon nitride, alumina, and potassium titanate. Boron carbide, magnesium oxide, zinc oxide, aluminum borate, boron and other fibers, metal fibers are tungsten, molybdenum, stainless steel, steel, tantalum fibers, etc., organic fibers are polyvinyl alcohol, polyamide, polyethylene terephthalate, Fibers such as polyester and aramid, or a mixture thereof can be used.

  Further, in the material forming the base of the vertebral body spacer according to the present invention, if necessary, a light stabilizer such as an antistatic agent, an antioxidant, a hindered amine compound, a lubricant, an antiblocking agent, an ultraviolet absorber, an inorganic Various additives such as fillers and colorants such as pigments may be contained.

  The base of the vertebral body spacer according to the present invention can be molded by a general plastic molding method, for example, an injection molding method, an extrusion molding method or the like.

  The porous portion is a layer that covers the surface of the protruding portion other than the portion where the dense portion is formed. The porous part can contain the same polymer material as that constituting the base part, in particular engineering plastics, polyether ether ketone and the like, and a bioactive substance.

The bioactive substance is preferably fixed to the surface of the porous part. The bioactive substance is not particularly limited as long as it has a high affinity with a living body and has a property of chemically reacting with bone tissue including living bones. For example, calcium phosphate compound, bioactive glass, calcium carbonate, etc. Is mentioned. Examples of calcium phosphate compounds include calcium hydrogen phosphate, calcium hydrogen phosphate hydrate, calcium dihydrogen phosphate, calcium dihydrogen phosphate hydrate, α-type tricalcium phosphate, β-type tricalcium phosphate, dolomite , Tetracalcium phosphate, octacalcium phosphate, hydroxyapatite, fluorapatite, carbonate apatite, and chlorapatite. Bioactive glass comprises bioglass, crystallized glass (also called glass-ceramics.), Etc., as a bioglass, for _{example, SiO 2 -CaO-Na 2 O} -P 2 O 5 based _glass, SiO 2 -CaO- Na ₂ O—P ₂ O ₅ —K ₂ O—MgO-based glass, SiO ₂ —CaO—Al ₂ O ₃ —P ₂ O ₅ -based glass, and the like can be mentioned. Examples of crystallized glass include SiO _{2. -CaO-MgO-P} 2 _{O 5} based glass (also called apatite wollastonite crystallized glass.), _{and, CaO-Al 2 O 3 -P} 2 O 5 based glass. These calcium phosphate compounds, bioglass, and crystallized glass are described in, for example, “Chemical Handbook Applied Chemistry 6th Edition” (The Chemical Society of Japan, published on January 30, 2003, Maruzen Co., Ltd.), “Development of Bioceramics and Clinical ”(edited by Hideki Aoki et al., April 10, 1987, Quintessence Publishing Co., Ltd.).

  Among these, the bioactive substance is preferably at least one of a calcium phosphate compound and bioactive glass from the viewpoint of excellent bioactivity. Furthermore, the bioactive substance is similar in composition, structure and properties to the living bone, and is stable in the body environment. Hydroxyapatite or tricalcium phosphate is particularly preferable in that it is excellent and does not show remarkable solubility in the body.

  This bioactive substance may be highly crystalline, low crystalline or non-crystalline, and may have a plurality of crystallinity. The solubility of the bioactive substance, that is, the biobinding property can be adjusted by the crystallinity of the bioactive substance immobilized on the surface of the porous layer. For example, if the crystallinity of the bioactive substance is made highly crystalline, the biological bone can be formed even in a part where the bioactive substance has a low dissolution rate and is fixed to the porous layer for a long period of time, and it is difficult to form a living bone. On the other hand, when the crystallinity of the bioactive substance is amorphous, the dissolution rate of the bioactive substance is high, and the vertebral body spacer and the vertebra are quickly combined. Therefore, according to the present invention, the crystallinity of the bioactive substance can be appropriately selected according to the bone formation rate by osteoblasts that bone fuse the vertebra and the vertebral body spacer.

  Here, the low crystallinity means a state in which the degree of crystal development is low. Taking hydroxyapatite as an example, in powder X-ray diffraction measurement, 2θ = 25.878 ° and interplanar spacing (d value) = 3.44 mm. A half-width in a diffraction line is 0.2 ° or more, and high crystallinity means a state in which the degree of crystal growth is high. In the case of hydroxyapatite, the half-width is less than 0.2 °. Means things. Since the hydroxyapatite of living bone has low crystallinity (half-value width under the above conditions: about 0.4 °), the same crystallinity (half-value width under the same conditions: 0.2 to 1.0) °) or by making it non-crystalline, the living implant and the living bone are quickly bonded. Further, the non-crystalline property means that a broad peak is observed in the vicinity of 2θ = 30 ° in powder X-ray diffraction measurement, and it has a characteristic of becoming hydroxyapatite by firing at a temperature of 500 ° C. or higher.

  The crystallinity of the bioactive substance can be appropriately adjusted by the “method for fixing the bioactive substance” described later. For example, when a method of immersing the vertebral body spacer body in the suspension of the bioactive substance is employed. Depends on the crystallinity of the bioactive substance to be suspended. On the other hand, when a method of alternately immersing the vertebral body spacer body in a solution containing calcium ions and a solution containing phosphate ions is adopted. It can adjust with the kind of composition component of a solution, a composition ratio, and / or immersion temperature.

The shape of the highly crystalline or low crystalline bioactive substance is granular, granular, or dispersed in or dispersed on the surface of the porous polymer material layer formed on the surface of the base. It may be in the form of a powder or may be an aggregate, and examples thereof include a spherical shape, an elliptical spherical shape, a needle shape, a columnar shape, a rod shape, a plate shape, and a polygonal shape. The particle diameter of the bioactive substance immobilized as an element constituting the porous portion is not particularly limited as long as it is smaller than an observation region (100 μm ² ) described later. In terms of being more firmly fixed to the surface of the molecular material layer, for example, the thickness is preferably 0.001 to 10 μm, and particularly preferably 0.01 to 5 μm. In the present specification, “particle” and “particle diameter” refer to “primary particle” and “primary particle diameter”, respectively, unless otherwise specified. When the active substance is an agglomerate, it is the primary particle that is the minimum unit constituting the agglomerate and the diameter thereof. The particle diameter can be calculated by the intercept method. Specifically, a photograph can be taken with a scanning electron microscope, a straight line intersecting at least 15 particles can be drawn, and the average value of the length of the portion where the straight line and the particle intersect can be calculated. If the shape is other than spherical particles, the area-converted diameter is calculated.

  In the porous portion of the vertebral body spacer according to the present invention, the particles of the bioactive substance are immobilized in a dispersed or scattered state on the surface of the porous polymer material film covering the surface of the base portion. The surface on which the particles of the bioactive substance are immobilized is the outer surface of the porous polymer material film. The particles of the bioactive substance are immobilized in a dispersed or scattered state on the surface of the porous polymer material film. Therefore, since the particles of the bioactive substance are scattered and dispersed on the surface forming the outline of the porous polymer material film, most of the scattered particles are porous. It is exposed without being completely buried in the polymer material film. When the particles of the bioactive substance, most or part of which are exposed, are fixed in a dispersed or scattered state, the vertebral body spacer and the vertebral body are rapidly and uniformly bone-unioned and bonded. The bioactive substance particles are in a dispersed or dispersed state. However, this does not completely exclude the dispersion or dispersion of the aggregates of the plurality of particles, as long as most of the bioactive substance particles are dispersed or scattered. Well, some of them may be agglomerated.

  In the vertebral body spacer of the present invention, since the particles of the bioactive substance are fixed in a dispersed or scattered state and do not form a film, the particles cover the outer surface of the vertebral body spacer body, particularly the base surface. It is sufficient that the coverage ratio to be applied is less than 100%.

  As shown in FIG. 6, the porous portion 12 in the vertebral body spacer 1 according to the present invention is a surface foam formed of a surface layer 16 having a large number of small diameter pores 14 and large diameter pores 15 formed on the surface of the base portion 10. Is a layer. The surface foam layer includes a polymer material, particularly engineering plastic, and a bioactive substance, and a part of the small-diameter pores 14 and the large-diameter pores 15 form open pores 17 that open on the surface of the surface layer 16. doing. The open pores 17 include small open pores 18 having an average open pore size A of 5 μm or less and large open pores 19 having an average open pore size B of 10 to 200 μm, and a large diameter that opens on the surface of the surface layer 16. The open hole 19 is formed with a communication hole 20 communicating with the small diameter hole 14 and the large diameter hole 15 on the inner wall surface thereof.

The surface layer 16 has a plurality of small-diameter pores 14 and large-diameter pores 15 having different sizes, and these pores are formed by independent pores 21 and two or more independent pores communicating with each other. The formed continuous air holes 22 are formed.
Some of the small-diameter pores 14 and large-diameter pores 15 form open pores 17 that open on the surface of the surface layer 16, and the open pores 17 have an average open pore diameter A of 5 μm or less, preferably 3 μm or less. It has pores 18 and large-diameter open pores 19 having an average open pore size B of 10 to 200 μm, preferably 30 to 150 μm. On the inner wall surface of the large diameter open hole 19, a communication hole 20 formed so as to communicate with the small diameter hole 14 and the large diameter hole 15 is formed. The communication hole 20 is preferably formed with a plurality of communication holes 20 with respect to one open hole 17, and the small diameter communication hole diameter C formed in communication with the small diameter hole 14 is 5 μm or less, preferably 3 μm or less. The small-diameter communication hole 23 and the large-diameter communication hole 24 formed in communication with the large-diameter pore 15 are 10 to 200 μm, preferably 30 to 150 μm. The small diameter pores 14 and the large diameter pores 15 have a spherical shape and / or an oblate shape and / or an oblong shape and / or a shape formed by combining these shapes. By using the surface layer 16 having such pores, for example, in the vertebral body spacer having a porous portion in the present invention, when the vertebral body spacer is inserted and arranged between the vertebral bodies, the surface layer 16 has a surface. Bone through a large number of open pores 17 that are open and communication holes 20 formed by communicating the open pores 17 with the small-diameter pores 14 and the large-diameter pores 15 formed inside the surface layer. Bone tissues such as blasts and osteoclasts can enter the surface layer 16. As a result, since new bone is formed so as to fill the space existing in the surface layer 16, a vertebral body spacer that can be firmly bonded to the bone can be provided. Further, the more the communication holes 20, especially the large diameter communication holes 24, are formed on the inner wall surface of the large diameter open hole 19 formed by the large diameter pores 15, the bone tissue is moved from the surface of the surface layer 16 to the deep part. Since it can be reached and new bone can be formed in the deep part of the surface layer 16, the bone and the vertebral body spacer can be firmly bonded.

  The average open pore diameter of the small-diameter open pores 18 opening on the surface of the surface layer 16 and the average open-pore diameter of the large open pores 19 are determined by observing the surface of the surface layer 16 with a scanning electron microscope. It can obtain | require as follows using the image to show.

  First, an SEM image in which the surface of the surface layer 16 is set to a predetermined magnification, for example, 300 times, is obtained by a scanning electron microscope. Next, the major and minor diameters of the open pores in the outermost part of the relatively large surface in the entire field of view of the SEM image, for example, open pores having an average diameter of about 10 μm or more are measured. Subsequently, the average open pore diameter of the large-diameter open pores 19 can be obtained by calculating the arithmetic average of these measured values.

  The small-diameter open pores 18 usually exist in a skeleton portion between the large-diameter open pores 19 and the large-diameter open pores 19. When measuring the average open pore diameter of the small-diameter open pores 18, it is preferable to further increase the magnification of the scanning electron microscope in order to reduce the measurement error. For example, an SEM image in which the scanning electron microscope is set to 3000 times is obtained. Next, the major axis and minor axis of the open pores formed in the skeleton portion are measured. That is, the major and minor diameters of all open pores except the large-diameter open pores 19 previously measured are measured. Subsequently, the average open pore diameter of the small-diameter open pores 18 can be obtained by calculating the arithmetic average of these measured values.

  When there are a large number of large-diameter open pores 19 or small-diameter open pores 18 on the SEM image, for example, 50 or more, five straight lines are drawn at random so as to cross the SEM image, The diameter opening hole 19 or the small diameter opening hole 18 is selected according to the above-mentioned criteria, and the major axis and the minor axis are measured. Next, by calculating the arithmetic average of these measured values, the average open pore diameter of the large-diameter open pores 19 and the small-diameter open pores 18 can be obtained.

  The hole diameter of the communication hole 20 in which the small-diameter hole 14 and the large-diameter hole 15 are formed so as to communicate with the open hole 17 opened on the surface of the surface layer 16 is obtained from an SEM image taken at a predetermined magnification as described above. Alternatively, it can be determined using a mercury porosimeter.

  The area ratio of the large-diameter open pores 19 when the outermost surface of the surface layer 16 is projected is not particularly limited, but is preferably 10 to 95%, and particularly preferably 20 to 85%. When the area ratio of the large-diameter open pores 19 is within the above range, the bone tissue can be infiltrated into the surface layer 16, so that new bone is formed inside the surface layer 16, and as a result, the bone It is possible to provide a vertebral body spacer that can be firmly coupled to the body.

  The area ratio of the large-diameter open pores 19 when the outermost surface of the surface layer 16 is projected is obtained by using image analysis software (for example, Scion Image manufactured by Scion) obtained by photographing the surface of the surface layer 16 with a scanning electron microscope. Then, it is obtained by binarizing the large-diameter open pores 19 formed by the large-diameter pores 15 and other portions, and then calculating the area ratio of the large-diameter open pores with respect to the area of the entire photograph. it can.

  The porosity of the small diameter pores 14 and the large diameter pores 15 in the surface layer 16 is not particularly limited, but is a range in which the total porosity of the small diameter pores 14 and the large diameter pores 15 is 99% or less. The porosity is preferably 5 to 50%, particularly preferably 10 to 40%, and the porosity of the large-diameter pore 15 is preferably 20 to 90%, and preferably 30 to 80%. Particularly preferred. If the porosity of the small-diameter pores 14 is within the above range, a large amount of scaffolds to which proteins and cells involved in bone formation adhere can be secured, so that new bone is easily formed in the surface layer 16, and vertebra spacer And bone can be firmly bonded. When the porosity of the large-diameter pore 15 is in the above range, the bone tissue is easily retained after entering the inside of the surface layer 16, and a space for forming new bone is sufficiently secured. Since new bone is formed so as to be buried, the bone and the vertebral body spacer can be combined more firmly.

  The porosity of the small-diameter pores 14 and the porosity of the large-diameter pores 15 of the surface layer 16 are obtained by image analysis software (for example, Scion manufactured by Scion, Inc.) obtained by photographing a cross section perpendicular to the surface of the surface layer 16 with a scanning electron microscope. Image) can be used to calculate the areas of the large pores 15 and the small pores 14 respectively. As in the case of calculating the average open pores described above, the scanning electron microscope image is displayed at an appropriate magnification for measuring the areas of the large pores 15 and the small pores 14. The porosity (a × 100 (%)) of the large diameter pores is calculated from the area ratio (a) of the large diameter pores to the area of the entire image. The porosity ((1−a) × b × 100 (%)) of the small-diameter pores is calculated from the area ratio (b) of the small-diameter pores to the area excluding the large-diameter pores from the entire image.

  The thickness of the surface layer 16 is, for example, preferably 10 to 1000 μm, and particularly preferably 20 to 200 μm. Within the above range, after the vertebral body spacer is inserted and arranged between the vertebral bodies, a large number of open pores 17 opened on the surface of the surface layer 16 and inside the open pores 17 and the surface layer 16 are formed. The bone tissue can enter the inside of the surface layer 16 through the communication hole 20 formed by the communication between the small diameter pores 14 and the large diameter pores 15. As a result, new bone is formed inside the surface layer 16, and thus a vertebral body spacer that can be combined with living bone can be provided.

  In the porous portion 12 according to the present invention, particles of a bioactive substance are fixed to the surface of the open pores 17 and the surface of the surface layer 16. A method for fixing bioactive substance particles on the surface of the open pores 17 and the surface of the surface layer 16 will be described later.

  The dense portion 11 in the present invention exists at the top of the protruding portion 4. The dense portion 11 is composed of a polymer material that is a constituent element of the base portion or a polymer material that is the same as the polymer material that is a constituent element of the porous portion, particularly an engineering plastic, and polyether ether ketone. It may be formed of the same or different kind of bioactive substance as the bioactive substance constituting the part.

  A suitable dense portion 11 may be dense without voids or may be porous. However, the porous dense portion 11 does not need to have a complicated porous structure as in the porous portion, and can be easily cut or peeled even when contacting the vertebral body as described later. Any structure that does not have to be provided.

  The porosity of the dense portion 11 which is porous is smaller than the porosity of the porous portion 12 (surface layer 16), and is usually less than 30%, preferably 1% or more and 25% or less. This porosity is calculated from the image of a cross section orthogonal to the surface of the dense part 11 or the porous part 12 taken with a scanning electron microscope using image analysis software (for example, Scion Image manufactured by Scion). By doing so, it can be measured. The scanning electron microscope image is displayed at an appropriate magnification for measuring the area of the gap. The void ratio (c × 100 (%)) is calculated from the area ratio (c) of the void to the area of the entire image. When the dense portion 11 is within the range of the porosity, even when the dense portion 11 contacts the vertebral body when the vertebral body spacer is inserted between the vertebral bodies, it is not easily cut or peeled off.

  It is preferable that the dense part 11 has a thickness of 5 to 50 μm, preferably 10 to 40 μm from the top of the protruding part 4. If the thickness and the area of the dense portion 11 are within the above ranges, the bioactive substance is appropriately contained, which contributes to bonding or fusion with the bone. Well, since the thickness is not too large, the entire vertebral body spacer 1 This is preferable because the influence on the mechanical characteristics, particularly the compression characteristics, can be reduced as much as possible.

  The dense portion 11 and the porous portion 12 in the vertebral body spacer according to the present invention can be formed as follows.

  First, a vertebral body spacer main body having the protruding portion 4 is manufactured, although the dense portion 11 and the porous portion 12 are not formed.

  As a method for forming micropores on the surface of the vertebral body spacer main body, particularly on the surface of the protrusion, a known method can be adopted. For example, as the first step, the vertebral body spacer main body made of a polymer material And a method of immersing the vertebral body spacer body in a cleaning solution that does not elute the polymer material, such as pure water, for a predetermined period of time in a corrosive solution such as concentrated sulfuric acid, concentrated nitric acid, or chromic acid. Can do. When, for example, polyether ether ketone (PEEK) is used as the polymer material, the vertebral body spacer body made of PEEK is immersed in concentrated sulfuric acid for a predetermined time, and then immersed in pure water on the surface of the protruding portion. Micropores can be formed.

  The pore size of the micropores formed on the surface of the vertebral body spacer body made of the polymer material is determined by applying the foaming agent used in the next step to the surface of the vertebral body spacer body body made of the polymer material, particularly the surface of the protrusion. As long as it has a pore diameter that can be penetrated into the resin, it can be appropriately selected depending on the type of foaming agent. For example, when sodium carbonate is employed as the foaming agent, the pore diameter of the micropores is preferably 0.1 to 200 μm. The porosity of the micropores formed on the surface of the vertebral body spacer body made of a polymer material, particularly the porosity of the micropores formed on the surface of the protruding portion, is used in the next step (second step). For example, when sodium carbonate is used as the foaming agent, it is formed on the surface of the vertebral body spacer body made of a polymer material, particularly on the surface of the protruding portion. It is preferable that the porosity of the layer having s is 10 to 90%. When the porosity is in the low range within the porosity range, for example, the pores are formed in communication from the surface of the vertebral body spacer body made of a polymer material to the inside, or made of the polymer material. A hole is formed so that the foaming agent is held at a desired depth from the surface of the vertebral body spacer body made of a polymer material, such as a columnar hole formed perpendicularly from the surface of the vertebral body spacer body to the inside. Preferably it is formed. The thickness of the porous layer in which a large number of micropores are formed is preferably 10 to 1000 μm. The thickness, pore diameter, and porosity of the porous layer having a large number of micropores are determined depending on the time and / or temperature at which PEEK is immersed in concentrated sulfuric acid when, for example, concentrated sulfuric acid is used as the PEEK corrosive solution. The thickness of the layer can be adjusted. In addition, the pore diameter and the porosity can be adjusted by the type and / or temperature of the cleaning solution that is subsequently immersed in concentrated sulfuric acid.

  Next, as a second step, the vertebral body spacer body formed with the porous layer having micropores obtained in the first step is immersed in a solution containing a foaming agent for a predetermined time to have a large number of micropores. A foaming agent holding base material is produced in which a foaming agent is held on the surface of the vertebral spacer main body. The foaming agent may be any substance that can form a desired porous structure on the surface of the vertebral body spacer body made of a polymer material, particularly on the surface of the protruding portion, and as such a foaming agent, carbonate, Examples thereof include inorganic foaming agents such as aluminum powder, and organic foaming agents such as azo compounds and isocyanate compounds. When producing the vertebral body spacer according to the present invention, the foaming agent is preferably a substance that does not adversely affect the living body, and as such a foaming agent, carbonates are preferred, for example, sodium bicarbonate, sodium carbonate, carbonate Mention may be made of potassium.

  Next, as a third step, the foaming agent holding substrate obtained in the second step is immersed in a foaming solution for swelling the polymer material and foaming the foaming agent for a predetermined time, and the swelling of the polymer material is performed. A foamed substrate formed by simultaneously proceeding with foaming of the foaming agent is produced. Examples of the foaming solution include acidic solutions such as concentrated sulfuric acid, hydrochloric acid, and nitric acid. When the material for forming the foaming agent holding substrate is PEEK and the foaming agent is carbonate, the foaming solution is preferably concentrated sulfuric acid having a concentration of 90% or more.

  Next, as the fourth step, the foamed base material obtained in the third step is immersed in a coagulation solution that solidifies the swollen polymer material, thereby producing a surface foam. Examples of the coagulation solution, that is, a solution from which the polymer material does not elute, include aqueous solutions such as water, acetone, and ethanol. When the material for forming the foamed substrate is PEEK, in addition to the above, there are aqueous solutions of inorganic acids such as sulfuric acid, nitric acid, phosphoric acid, hydrochloric acid and the like, water-soluble organic solvents having a concentration of less than 90%. Examples of the water-soluble organic solvent include N-methyl-2-pyrrolidone, dimethylformamide, dimethylacetamide, dimethyl sulfoxide, tetrahydrofuran, ethylene glycol, diethylene glycol, trietylene glycol, propylene glycol, diester. Alcohols such as propylene glycol, glycerin ethanol, propanol, butanol, pentanol, hexanole and their aqueous solutions, liquids such as polyethylene glycol, polypropylene glycol, polyvinylpyrrolidone, etc. Mention may be made of polymers or their aqueous solutions and mixtures thereof.

  In the fourth step, the foamed substrate obtained in the third step may be immersed in at least one solution selected from a plurality of types of solutions that can be used as a coagulation solution. good. Further, a mixture of at least two kinds of solutions may be used.

  After the fourth step, it is preferable to wash the foaming agent and coagulation solution remaining on the surface foam with pure water.

  Porous structure formed on the surface of vertebral body spacer body made of polymer material, that is, large diameter pore diameter, small diameter pore diameter, communication hole diameter, porosity, etc. that define the porous structure of the surface layer of the surface foam Is adjusted by appropriately selecting the type and concentration of the foaming agent, the type and concentration of the foaming solution, the immersion time in the foaming solution, the type and concentration of the coagulation solution, the immersion time in the coagulation solution, the temperature in each step, etc. be able to.

  Among these, a surface foam in which the surface layer has a desired porous structure by changing at least one selected from the type of coagulation solution, the concentration of the coagulation solution, and the immersion time in the coagulation solution. Can be easily obtained. As the type and concentration of the coagulation solution, it is preferable to appropriately select at least one of water and a low coagulation solution that requires a longer time than water to coagulate the swollen plastic. When the material forming the foamed substrate is PEEK, sulfuric acid having a concentration of less than 90% can be used as the low coagulation solution.

  For example, when a foamed base material formed by PEEK is immersed in sulfuric acid having a concentration of 86% as a low coagulation solution, PEEK solidifies more slowly than when immersed in water. That is, the coagulation rate becomes slow. Therefore, the porous structure on the surface of the foamed substrate changes as time elapses when the foamed substrate is immersed in the low coagulation solution.

  In the following, the change in the structure of the surface of the foamed base material caused by the difference in the immersion time for immersing the foamed base material in the low coagulation solution will be described with reference to the large diameter pores 15 and the large diameter pores 15 in the porous portion 12 shown in FIG. A description will be given separately for the large-diameter communication holes 24 and the small-diameter pores 14 formed in communication.

  The hole diameters of the large-diameter open holes 19 and the large-diameter communication holes 24 where the large-diameter holes 15 open on the surface gradually increase as the immersion time elapses. When a predetermined time or more elapses, these pore sizes become smaller. Further, the number of large-diameter open holes 19 and large-diameter communication holes 24 gradually decreases as the immersion time elapses. It is understood that the pore diameter increases as the immersion time elapses, and a plurality of pores formed by the foaming agent are connected and enlarged while the swollen PEEK is gradually solidified. On the other hand, when the predetermined time or more elapses, the pore diameter becomes small because the foaming agent is weakened while the swollen PEEK is slowly solidified, and all the pores including the pores that are connected and enlarged are included. Is considered to be reduced in diameter. In addition, the number of large-diameter open pores 19 and large-diameter communication holes 24 decreases as the immersion time elapses because a plurality of large-diameter open pores 19 and large-diameter communication holes are formed while the swollen PEEK is slowly solidified. It is understood that 24 is connected and integrated.

  The pore diameter and the porosity of the small-diameter open pore 18 where the small-diameter pore 14 opens on the surface gradually decrease as the immersion time elapses. The large pores are formed by the action of the foaming agent, whereas the small pores 14 are considered to be formed based on the phase separation phenomenon of the swollen PEEK. The swollen PEEK is less likely to cause phase separation with a low-coagulation solution that gradually solidifies, and the longer the dipping time of the low-coagulation solution, the more the coagulation proceeds while the swollen PEEK and the low-coagulation solution are homogenized. For this reason, it is considered that the number and the diameter of the small-diameter open pores 18 are reduced and the porosity is also lowered.

  As described above, the porous polymer material that becomes the predecessor of the porous portion in the vertebral body spacer in which the porous structure of the surface layer 16 in the porous portion 12 differs due to the difference in the immersion time of the foamed base material in the low coagulation solution A layer can be obtained. In particular, if the solidification is quickly completed by immersing in water or the like at a time when the diameters of the large-diameter open pores 19 and the large-diameter communication holes 24 are maximized, a porous material having good communication to the inside of the surface layer 16 is obtained. A polymeric material layer can be obtained.

  In the above description, the sulfuric acid having a concentration of 86% has been described as an example of the low coagulation solution. The situation is different. For example, when sulfuric acid having a lower concentration is used, PEEK swollen in a shorter time than when sulfuric acid having a concentration of 86% is solidified, so that the large pores 15 are solidified before the effectiveness of the blowing agent is weakened. Sometimes. In that case, even if the foamed base material is immersed in the low coagulation solution for a long time, the diameters of the large-diameter open pores 19 and the large-diameter communication holes 24 are not reduced or the number is not reduced.

  Depending on the type and concentration of the low coagulation solution, as described above, the method of changing the structure of the surface of the foamed substrate with the passage of the immersion time is different. Therefore, select the desired low coagulation solution, immerse the foam substrate for a predetermined time, and when the surface structure of the foam substrate has the desired porous structure, soak in water and quickly swell Since the plastic can be solidified, a surface foam having a desired porous structure in the surface layer can be obtained. In order to solidify the swollen plastic, in addition to immersing the foamed substrate in water, the swollen plastic may be dipped in a low coagulation solution for a sufficient time to solidify.

  As described above, a surface foamed vertebral body spacer body in which a polymer foam layer formed by foaming a polymer material is formed over the entire surface of the vertebral body spacer body. The surface foamed vertebral body spacer body has a polymer foam layer also formed on the surface of the base portion present on the first surface.

  About this surface foam vertebral body spacer body, a bioactive substance is fixed to the polymer foam layer as follows.

  As a method for fixing the bioactive substance to the polymer foam layer, for example, a method of spraying the bioactive substance on the surface of the surface foamed vertebral body spacer body, the surface foamed vertebral body spacer body is immersed in the bioactive substance forming liquid, and the surface Examples include a method of fixing a bioactive substance to the surface of the foamed vertebral body spacer body, particularly a polymer foam layer formed on the surface of the base, a method of immersing the surface foamed vertebral body spacer body in a suspension of the bioactive substance, etc. It is done.

  Among these methods, in the vertebral body spacer having a complex shape on the first surface having an assembly of a plurality of protrusions, the bioactive substance is uniformly dispersed on the surface having the complex shape, Alternatively, a method of immersing the surface foamed vertebral body spacer main body in a suspension containing a bioactive substance is preferable in that it can be easily fixed in a uniformly dispersed state. A method of immersing the surface foamed vertebral body spacer body in a suspension containing a bioactive substance to fix the bioactive substance includes a step of immersing the surface foamed vertebral body spacer body in a suspension containing a bioactive substance. In addition, if desired, a sub-step of preparing a suspension containing a bioactive substance, a sub-step of washing the surface foamed vertebral body spacer body after removing it from the suspension, and the surface foamed vertebral body after washing It is preferable to have a sub-process for drying the spacer body.

  In order to carry out this soaking step, first, a sub-step of preparing a suspension of the bioactive substance is carried out. The liquid medium for suspending the bioactive substance is not particularly limited as long as it is a liquid medium that does not dissolve the surface foamed vertebral body spacer body and the bioactive substance. For example, alcohol such as methanol, ethanol, propanol, water, acetone, etc. And an aqueous medium, hexane and the like. The bioactive substance is preferably a particle having a particle diameter in the above range and the above shape. The prepared bioactive substance is put into a liquid medium and stirred by a stirrer or the like, for example, by irradiating an ultrasonic wave with an output of 200 W at a frequency of 38 kHz as desired, or by homogenizing with an ultrasonic homogenizer, etc. The bioactive substance can be uniformly suspended in the liquid medium. The amount of the bioactive substance input at this time may be appropriately adjusted according to the surface area of the surface foamed vertebral body spacer main body and the amount of the bioactive substance disposed on the surface thereof. It can be set to 01 to 100 g. Moreover, the irradiation time of ultrasonic waves is adjusted to a time during which the bioactive substance can be uniformly dispersed, and can be, for example, 5 to 180 minutes.

Next, a step of immersing the surface foamed vertebral body spacer body in the suspension thus prepared is performed. This step of immersing is performed by immersing the surface foamed vertebral body spacer body in the suspension and stirring the suspension as desired. The liquid temperature of the suspension at this time, that is, the immersion temperature and the immersion time are not particularly limited, and may be appropriately adjusted according to the amount of the bioactive substance to be fixed to the surface of the surface foamed vertebral body spacer body. The immersion temperature is lower than the glass transition temperature of the polymer material forming the surface foamed vertebral spacer body, particularly the engineering plastic, specifically, the temperature below the boiling point of the solvent, and the immersion time is 1 minute to 24 hours. it can. The volume of the surface foamed vertebral body spacer body immersed in the suspension is not particularly limited, but the amount of the bioactive substance to be arranged may be reduced if the amount of the suspension is not sufficient. It can be set as 0.001-50 cm < ³ > with respect to 100 mL of liquids.

  In the step of immersing, if desired, a sub-step of washing after removing the surface foamed vertebral body spacer body from the suspension is performed. The cleaning liquid for cleaning the surface foamed vertebral body spacer body is not particularly limited as long as it is a liquid medium that does not dissolve the surface foamed vertebral body spacer body and the bioactive substance. For example, the same liquid medium as the liquid medium of water or suspension And is preferably water or pure water. In the step of immersing, if desired, a sub-step of drying the surface foamed vertebral body spacer body after washing is performed. As the drying method, a known drying method can be adopted without any particular limitation, and examples thereof include air drying, air drying, and heat drying. The heating temperature when heating in the drying sub-process is lower than the glass transition temperature of the polymer material forming the surface foamed vertebral body spacer main body, particularly the engineering plastic.

  In this way, the step of immersing the surface foamed vertebral body spacer body in the suspension containing the bioactive substance is performed. Most of the bioactive substance fixed to the surface of the surface foamed vertebral body spacer body, particularly the surface of the protrusion on the first surface, in the submerging process and the drying subprocess in the dipping process. Does not fall off the surface of the foam vertebral body spacer body.

  In the method of manufacturing the vertebral body spacer according to the present invention, the surface foaming in which the bioactive substance is fixed to the surfaces of the top and the peripheral side surfaces of the base in the projecting portion, following the fixing step performed in this way. A step of heating the vertebral body spacer body to a heating temperature that is at least 30 ° C. lower than the glass transition temperature of the polymer material that is an element constituting the vertebral body spacer body and less than the melting point is performed. For convenience of explanation, the surface foam vertebral body spacer body with the bioactive substance fixed on the surface may be referred to as “bioactive substance-fixed vertebral body spacer body” below. The heating temperature for heating the life-active substance-fixed vertebral body spacer body is 30 ° C. lower than the glass transition temperature (Tg) of the polymer material forming the life-active substance-fixed vertebral body spacer body (Tg-30 °) or more. However, it is appropriately selected from the temperature range that is lower than the melting point of the polymer material. When the bioactive substance-fixed vertebral body spacer body is heated to this temperature range, a part of the surface of the bioactive substance-fixed vertebral body spacer body is softened, and a part of the bioactivity that has been simply attached until then The substance can be firmly fixed and fixed to the surface of the bioactive substance-fixing vertebral body spacer body, particularly the surface of the base. The lower limit of the heating temperature is (Tg-30) ° C., which is equal to or higher than the glass transition temperature (Tg) in that the bioactive substance-fixed vertebral body spacer body and the bioactive substance can be more firmly adhered to each other. The upper limit of the heating temperature is less than the melting point of the polymer material, and the bioactive substance-fixed vertebral body spacer body and the bioactive substance are preferably higher than the glass transition temperature (Tg). It is preferable that the temperature is 80 ° C. or higher than the glass transition temperature (Tg) in that it can be firmly adhered to each other. In the present invention, the glass transition temperature (Tg) of the polymer material is referred to as “blend polymer material” when the “polymer material” includes two or more polymer materials. In this case, the heating temperature can be determined using the lowest glass transition temperature of each polymer material constituting the blend polymer material as an index.

  In this heating step, the time for heating the bioactive substance-fixed vertebral body spacer body, that is, the time for maintaining the heating temperature may be a time that allows the vicinity of the surface of the bioactive substance-fixed vertebral body spacer body to be softened. The active substance-fixing vertebral body spacer main body and the bioactive substance are preferably 1 hour or longer, and particularly preferably 3 hours or longer, in that the active substance-fixing vertebral body spacer body and the bioactive substance can be more firmly adhered to each other. The upper limit value of the heating time is not particularly limited, and even if it is considerably long, improvement in the degree of adhesion of the bioactive substance to the base material cannot be expected. be able to. As a heating method for the bioactive substance-fixed vertebral body spacer body, a known heating method can be appropriately employed. In this way, the bioactive substance placed on the surface of the bioactive substance-fixing vertebral body spacer body can be immobilized.

  In the bioactive substance-fixed vertebral body spacer body in which the bioactive substance is thus immobilized, the outer surface of the vertebral body spacer body is covered with a porous layer containing a polymer material and a bioactive substance. Therefore, the top of the base and the peripheral side surface of the base are covered with the porous layer. For convenience of explanation, the bioactive substance-fixed vertebral body spacer body in which the top part of the base part and the peripheral side surface of the base part are covered with the porous layer will be referred to as a “porous layer-covered vertebral body spacer body” hereinafter. There is.

  Next, the porous layer-covered vertebral body spacer body is subjected to a step of forming a dense portion.

  The dense portion compresses the porous layer containing the polymer material and the bioactive substance that covers the top of the protruding portion formed on the first surface of the porous layer-covered vertebral body spacer body. Thus, it can be formed.

  As the compression device, the porous layer-covered vertebral body spacer main body is arranged so that the second surface of the porous layer-covered vertebral body spacer main body is in contact with the horizontal base surface, and then the porous layer-covered vertebral body spacer main body It is possible to employ a pressing device that includes a pressing portion that is disposed above and includes a pressing surface that can be lowered toward the porous layer-covered vertebral body spacer main body.

  By pressing the porous layer that covers the top of the base of the protruding portion of the porous layer-covered vertebral body spacer body with the pressing surface of the pressing device, the dense portion is compressed by compressing the porous layer. Can be formed.

  It is preferable to appropriately set the pressing conditions such as the pressing force when pressing with the pressing surface in the pressing device so that the porosity in the layer as a result of compressing the porous layer is less than 30%. .

  The vertebral body spacer thus obtained has a protruding portion on the first surface, more precisely, an aggregate of protruding portions. In each protruding portion, a dense portion is present at the top of the base, and on the outer peripheral surface of the base. Since there is a porous part with a larger porosity than the dense part, when this vertebral body spacer is inserted between vertebral bodies and placed, the protruding part is easy to sink into the vertebra with the dense part at the tip as the tip, and the vertebrae This results in an increase in the amount of protrusions that pierce, and this results in improved fixation of the vertebral body spacers between the vertebral bodies. That is, when this vertebral body spacer is inserted / placed between vertebral bodies, the vertebral body spacers do not shift in position between the vertebral bodies. In addition, if the dense part is porous, osteoblasts can easily enter the pores in the dense part, thereby forming bone by the osteoblasts. As a result, the vertebral body spacer and the vertebrae are joined. Thorough bone fusion. Therefore, the vertebral body spacer according to the present invention causes the vertebral body spacer to be displaced between the vertebral bodies or to be detached from the vertebral bodies even after a long time has passed since the insertion and placement between the vertebral bodies. Long-term fixing stability can be realized.

DESCRIPTION OF SYMBOLS 1 Vertebral body spacer 2 1st surface 3 2nd surface 4 Protrusion part 4a Protrusion part 4b Protrusion part 4c Protrusion part 5a Front end part 5b Term end part 6a Front end part 6b Rear end part 7 Through space 8 Front surface 9 Communication space 10 Base 11 Dense Part 12 Porous part 14 Small diameter pore 15 Large diameter pore 16 Surface layer 17 Open hole 18 Small diameter open hole 19 Large diameter open hole 20 Communication hole 21 Independent hole 22 Communication hole 23 Small diameter communication hole 24 Large diameter communication hole

Claims (12)

A vertebral body spacer interposed between a first vertebral body and a second vertebral body adjacent to the first vertebral body, the first vertebral body facing the first vertebral body, and the second vertebral body A vertebral body spacer having a second surface facing and opposite to the first surface,
A protrusion is present on the first surface, and the protrusion is present on a base containing a polymer material, on a top of the base, and a dense part containing the polymer material and a bioactive substance, A vertebral body spacer characterized by covering a surface other than the top of the base and including a porous portion containing the polymer material and a bioactive substance.   The vertebral body spacer according to claim 1, wherein the vertebral body spacer has a through gap penetrating the first surface and the second surface.   The vertebral body spacer according to claim 2, wherein each of the first surface and the second surface is linked to a side wall, and the side wall includes a communication space communicating with the through space.   The vertebral body spacer according to any one of claims 1 to 3, wherein the dense portion has a porosity smaller than that of the porous portion.   The vertebral body spacer according to any one of claims 1 to 4, wherein the porous portion has a porosity of 30% or more. The porous part has small diameter pores and large diameter pores;
The vertebral body spacer according to any one of claims 1 to 5, wherein a part of the small-diameter pores and the large-diameter pores form open pores that open on a surface of the porous portion.   The vertebral body spacer according to any one of claims 1 to 6, wherein a height of the protruding portion from the first surface is not less than 300 µm and not more than 2000 µm.   The vertebral body spacer according to any one of claims 1 to 7, wherein the protrusion includes at least one fiber selected from the group consisting of carbon fiber, glass fiber, ceramic fiber, metal fiber, and organic fiber.   The vertebral body spacer according to any one of claims 1 to 8, wherein the polymer material is polyetheretherketone.   The vertebral body spacer according to any one of claims 1 to 9, further comprising a bioactive substance on at least one of an inner wall surface of an open pore in the porous portion and a surface of the porous portion.   The vertebral body spacer according to any one of claims 1 to 10, wherein the bioactive substance is calcium phosphate. The vertebral body spacer according to claim 11, wherein the calcium phosphate is hydroxyapatite.