JP2008245775A - In-vivo implant - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an in-vivo implant formed by firmly and tightly sticking a bioactive film to a substrate surface and a high-strength in-vivo implant with high bioactivity by using a material with kinetic property close to the bone as the substrate. <P>SOLUTION: This in-vivo implant includes the substrate 1 with a porous surface, and the bioactive film 2 formed of a bioactive material on the surface of the substrate. The material forming the substrate uses engineering plastic. The substrate includes at least one kind of fiber selected from a carbon fiber, a glass fiber, a ceramic fiber, a metal fiber, and an organic fiber. <P>COPYRIGHT: (C)2009,JPO&INPIT

Description

  The present invention relates to a bioimplant, and more particularly to a bioimplant having a bioactive coating adhered to a substrate.

  As a treatment method when a bone is largely lost, autologous bone transplantation in which a part of a patient's own normal bone is cut out and transplanted to an affected part, or an artificial bone transplantation in which an artificial bone made of an artificial material is transplanted is performed. However, autografts limit the amount of bone that can be harvested and damage normal cells, so the burden on the patient is heavy and the bone for autologous bone transplantation used for autologous bone transplantation is normal. Since a new defect part is generated by cutting from a rough bone, it cannot be said to be an essential treatment method when a bone is largely lost. Artificial bone transplantation uses industrially produced artificial bone, so there is no problem like autologous bone transplantation, but the mechanical and biological characteristics of the artificial bone differ from the original bone. There is a problem that the use is limited according to the above-mentioned characteristics. For example, if a titanium alloy metal material is selected as the material for the artificial bone, the metal material is usually high in strength, but has a high modulus of elasticity and lacks toughness. Then, there is a problem that stress shielding occurs due to a difference in mechanical characteristics with surrounding bones, and a problem that it does not directly bond to bones. In addition, when bioceramics such as hydroxyapatite is selected as the material for the artificial bone, bioceramics are usually not only highly biocompatible but also highly bioactive and have excellent bone binding properties, but external Since it is vulnerable to impact, there is a problem that it cannot be used for a part where a large load is applied instantaneously. Furthermore, when a polymer such as ultrahigh molecular weight polyethylene is selected as the material for the artificial bone, the polymer is usually excellent in flexibility, but has a problem that it does not directly bind to bone because it lacks biological activity.

As materials that can solve these problems, development of materials that make up for each other's drawbacks by combining polymers and bioceramics having biological activity has been actively conducted.
For example, among the polymers, polyether ether ketone (PEEK) is close to the original bone and excellent in biocompatibility because of its mechanical properties, so it can be used as an orthopedic material in areas where high strength is required. Application is expected. However, since PEEK itself lacks biological activity, it does not have connectivity with bone. In order to use PEEK as a bioimplant for a site that requires a bond with bone, it is necessary to have bioactivity, so it is an attempt to coat hydroxyapatite with bioactivity on the surface of PEEK. There are several.

  In Patent Document 1, “According to the present invention, an artificial acetabular cup comprises a bearing surface layer made of a composite material comprising PEEK resin and at least 20 to 40% carbon short fibers, and a barrier and / or porous Including a backing layer to provide degree and / or roughness "(see paragraph number 0009 of Patent Document 1)," The backing layer can be coated with a bioactive material if desired. " Reference 1 paragraph number 0010), “The backing layer can be made from a metal such as titanium, tantalum or niobium to create a barrier between the composite material and the bone cell, or it can be made from pure PEEK, for example. (See paragraph number 0013 of Patent Document 1).

  According to the above description, the artificial acetabular cup described in Patent Document 1 has at least a bearing surface layer and a backing layer, and the backing layer can be covered with a bioactive material. The bearing surface layer is composed of a composite material including PEEK resin and at least 20 to 40% carbon short fibers, while the backing layer is composed of metal or pure PEEK, and the bearing surface layer and the backing layer. The material is different.

In Patent Document 2, “especially for medical implants and prostheses,
(A) The variable portion of the surface layer is composed of a calcium phosphate phase,
(B) In the bioactive surface layer in which the layer has a thickness of 0.1 to 50.0 μm, and (C) the surface layer is configured to be porous,
(D) the surface layer contains amorphous or nanocrystalline calcium phosphate;
(E) the Ca / P ratio is in the range of 0.5 to 2.0 over the entire surface layer;
(F) Ca ions and PO ₄ ions deposited in the surface layer are distributed throughout the metal oxide layer,
(G) The surface layer has a pore density of 10 ⁴ to 10 ⁸ pores / mm ² ,
(H) A surface layer, wherein the surface layer contains a metal oxide in a proportion of 25 to 95 atomic percent. (Refer to claim 1 of Patent Document 2)
“The substrate is plastic, mainly polyoxymethylene (POM), polyetheretherketone (PEEK), polyallyletherketone (PAEK), polyetherimide (PEI) or liquid crystal polymer (LCP), polymethylpentene (PMP) , Polysulfone (PSU), polyethersulfone (PESU or PES), polyethylene terephthalate (PETP), polymethyl methacrylate (PMMA) or ultra-high molecular weight polyethylene (UHMW-PE), and the substrate is a metal layer made of valve metal A substrate having a surface layer according to any one of claims 1 to 11, characterized in that the substrate is provided (see claim 15 of Patent Document 2).

  According to the above description, the substrate, the metal layer and the surface layer are laminated, the surface layer is characterized by claim 1, and the substrate and metal layer are characterized by claim 15. For the substrate and metal layer, only the materials are shown.

Japanese Unexamined Patent Publication No. 2006-158953 Special table 2004-531305 gazette

  An object of the present invention is to provide a bioimplant in which a bioactive coating is formed in close contact with a substrate surface. Furthermore, the other subject of this invention is providing the high intensity | strength biological implant which has bioactivity by using the material with a mechanical characteristic close to a bone as a base material.

As means for solving the problems,
Claim 1
A substrate having a porous surface;
A bioactive coating formed of a bioactive substance on the surface of the substrate;
A biological implant characterized by comprising:
Claim 2
A bio-implant characterized in that the material forming the substrate 1 is an engineering plastic,
Claim 3
A material for forming the substrate 1 is a polyetheretherketone, which is a biological implant,
Claim 4
The base material includes at least one fiber selected from carbon fiber, glass fiber, metal fiber, and organic fiber,
Claim 5
A bioimplant characterized in that the bioactive substance is a calcium phosphate compound;
Claim 6
A bioimplant characterized in that the bioactive substance is hydroxyapatite,
Claim 7
A bioimplant characterized in that the bioactive substance is low crystalline,
Claim 8
The bioactive implant is characterized in that the bioactive coating has a thickness of 1 to 100 μm,
Claim 9
The biological implant is characterized in that the porous layer formed on the surface of the substrate has a thickness of 1-1000 μm.

  According to the present invention, since the substrate surface is porous, it is possible to provide a biological implant in which the substrate and the bioactive coating are firmly adhered. Accordingly, it is possible to solve the problem that the bioactive film is peeled off while the living body implant is embedded in the living body. In addition, since the bioimplant according to the present invention uses a material having a mechanical property close to that of bone as the base material, it is necessary to bond to the bone, and a site where a large load is continuously applied for a long period of time. When applied as an artificial bone, stress-shielding does not occur, and a high-strength biological implant having biological activity can be provided. Further, since hydroxyapatite is an inorganic component of actual bone, when it is used as a bioactive coating, it has higher biocompatibility and becomes easier to bind to bone. Furthermore, since the bioactive coating is low crystalline and has the same crystallinity as that of actual bone, the bioactive coating can be quickly combined with the living body.

First, with reference to FIG. 1, the structure of the biological implant which is one Example which concerns on this invention is demonstrated.
As shown in FIG. 1, a biological implant that is an example of the present invention includes a substrate 1 and a bioactive coating 2. The surface of the substrate 1 is porous and forms a porous layer 3. The porous layer 3 has pores opened on the surface. Since the surface area of the porous layer 3 increases due to the presence of the pores, the adhesion area between the porous layer 3 and the bioactive film 2 is increased, and the porous layer 3 and the bioactive film 2 are firmly adhered to each other. . Further, the pores opened on the surface of the porous layer 3 form communication holes formed by a plurality of pores communicating with each other. When this communication hole is formed in the depth direction from the surface of the porous layer, the bioactive substance forming the bioactive coating 2 has penetrated into the porous layer 3 through this communication hole, and the substrate 1 And the bioactive coating 2 are engaged in the porous layer. The substrate 1 and the bioactive film 2 are firmly adhered even in this respect. Thus, since the base material 1 and the bioactive coating 2 are firmly adhered, the problem that the bioactive coating 2 is peeled off while the biological implant is embedded in the living body can be solved. .

  As the base material, it is desirable that the mechanical properties are close to those of bone, that is, the elastic modulus is 10 to 50 GPa and the bending strength is 100 MPa or more.

Examples of the material for forming such a base material include engineering plastics and fiber reinforced plastics. Engineering plastics include, for example, polyamide, polyacetal, polycarbonate, polyphenylene ether, polyester, polyphenylin oxide, polybutylene terephthalate, polyethylene terephthalate, polysulfone, polyethersulfone, polyphenylene sulfide, polyarylate, polyetherimide, polyether Examples include ether ketone, polyamideimide, polyimide, fluorine resin, ethylene vinyl alcohol copolymer, polymethylpentene, phenol resin, epoxy resin, silicone resin, diallyl phthalate resin, polyoxymethylene, polytetrafluoroethylene, 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, polyvinylacetoacetal, polyfluorinated ethylene propylene, polytrifluoroethylene chloride, methacrylic resin, Linol resin, polyallyl ether ketone, polyether sulfone, polyketone sulfide, polystyrene, polyamino bismaleimide, urea resin, melamine resin, xylene resin, isophthalic acid Resins, aniline resins, furan resins, polyurethane, alkylbenzene resin, guanamine resin, poly ether resins.

  Among these materials, polyether ether ketone (PEEK), which has a mechanical property close to that of bone and is biocompatible, is particularly preferable.

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

  In addition, various stabilizers such as antistatic agents, antioxidants, hindered amine compounds, lubricants, anti-blocking agents, ultraviolet absorbers, inorganic fillers, colorants such as pigments, and the like as necessary in the base material. An additive may be contained.

  The surface of the substrate has a porous layer. The surface of the porous layer has a large number of extremely fine pores that open to the surface, and these pores form a network structure in the porous layer. Since the surface of the porous layer is increased in surface area due to the presence of these pores, the adhesion area between the porous layer and the bioactive coating is increased, and the porous layer and the bioactive coating are firmly adhered. Further, the pores opened on the surface of the porous layer form communication holes formed by a plurality of pores communicating with each other. When this communication hole is formed in the depth direction from the surface of the porous layer, the bioactive substance forming the bioactive coating 2 has penetrated into the porous layer 3 through this communication hole, and the substrate 1 And the bioactive coating 2 are engaged in the porous layer. The substrate 1 and the bioactive film 2 are firmly adhered even in this respect.

  The thickness of the porous layer can be selected in the range of 1 to 1000 μm. For example, when the substrate is in a block shape and the length of one side is several mm or more, the thickness of the porous layer is preferably 20 to 200 μm. This is because if the porous layer is too thick, the strength of the biological implant may be reduced, and if the porous layer is too thin, the adhesion between the substrate and the bioactive film may be reduced.

  The pore diameter that opens to the substrate surface of the porous layer, the long diameter of the communication hole formed by communicating the pores with a plurality of pores, and the porosity of the pore that opens to the substrate surface of the porous layer are the usual methods. Can be calculated. For example, it can be determined by a mercury porosimeter. Also, observe the surface and cross-section of the substrate with a scanning electron microscope, and use the photographs of the surface and cross-section of the substrate to measure the pore diameter and the long diameter of the communication hole, and also calculate from the pore area ratio. Thus, the porosity can be obtained.

  The range of the pore diameter when the pore diameter opening on the substrate surface of the porous layer is measured with a mercury porosimeter is preferably 0.01 to 200 μm. In the case of less than 0.01 μm, if the particle size of the bioactive substance is smaller than the bioactive substance, the bioactive substance may enter the pores of the porous layer and cannot be fixed. Therefore, the adhesion between the base material and the bioactive film may be deteriorated. On the other hand, when the thickness exceeds 200 μm, the strength of the biological implant may be lowered, and the surface area of the porous layer is reduced, so that the adhesion area between the porous layer and the bioactive film is reduced. Therefore, the adhesion between the base material and the bioactive film may be reduced.

  The pores opened on the substrate surface of the porous layer are observed with a scanning electron microscope, and the porosity calculated from the pore area ratio is preferably 20 to 80%. If it is less than 20%, the bioactive substance will enter the pores of the porous layer and the space for fixing will be small, so the adhesion between the substrate and the bioactive film will be reduced. This is because if it exceeds 80%, the strength of the biological implant may be lowered.

  The porous layer can be formed on the surface of the substrate by immersing it in a corrosive solution such as concentrated sulfuric acid, concentrated nitric acid or chromic acid. In addition, a porous body can be formed by a known method. For example, a low-molecular water-soluble organic substance such as sucrose or a low-molecular water-soluble inorganic substance such as sodium chloride is dispersed in a polymer and melt-molded. Then, the organic substance or the inorganic substance is eluted from the obtained molded body. A porous body can be formed by immersing in a solvent such as water for a predetermined time. Also, a method using a foaming agent or the like and a method of forming a porous body by welding the surfaces of resin particles can be employed.

  Regarding the thickness, pore diameter, and porosity of the porous layer, when forming pores by immersing in concentrated sulfuric acid, adjust the thickness of the porous layer according to the time and / or temperature of immersing in concentrated sulfuric acid. In addition, the pore diameter and the porosity can be adjusted according to the type and / or temperature of the cleaning solution immersed after the concentrated sulfuric acid immersion. An example of the cleaning solution is pure water.

The bioactive substance forming the bioactive film is not particularly limited as long as it is a ceramic exhibiting bioactivity, and examples thereof include calcium phosphate materials, bioglass, crystallized glass (also referred to as glass ceramics), calcium carbonate, and the like. . Examples of calcium phosphate materials include calcium hydrogen phosphate, calcium hydrogen phosphate hydrate, calcium dihydrogen phosphate, calcium dihydrogen phosphate hydrate, α-type tricalcium phosphate, β-type tricalcium phosphate, Examples thereof include dolomite, tetracalcium phosphate, octacalcium phosphate, hydroxyapatite, fluorapatite, carbonate apatite, and chlorapatite. Examples of the bioglass include SiO ₂ —CaO—Na ₂ O—P ₂ O ₅ glass, SiO ₂ —CaO—Na ₂ O—P ₂ O ₅ —K ₂ O—MgO glass, and SiO ₂ —. Examples include CaO—Al ₂ O ₃ —P ₂ O ₅ glass. Examples of the crystallized glass include SiO ₂ —CaO—MgO—P ₂ O ₅ glass (also referred to as apatite wollastonite crystallized glass), CaO—Al ₂ O ₃ —P ₂ O ₅ glass, and the like. Is mentioned. These calcium phosphate materials, bioglass, and crystallized glass are, 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 Clinic "(edited by Hideki Aoki et al., April 10, 1987, Quintessence Publishing Co., Ltd.).

  Among these, as a bioactive substance that forms a bioactive film, a calcium phosphate-based material is preferable in terms of excellent bioactivity, and furthermore, since it is an inorganic component of actual bone, it has excellent stability in the body environment. Hydroxyapatite is particularly preferred because it does not show significant solubility.

The bioactive film is preferably low crystalline. This is because the bone can be quickly combined with the bone by making the same crystallinity because the bone is low crystalline.
The crystallinity of the bioactive film can be adjusted by, for example, the type and composition ratio of the composition component of the simulated body fluid and / or the immersion temperature when the bioactive film is generated from the bioactive substance by the method of immersing in the simulated body fluid. it can.

  The particle size of the bioactive substance forming the bioactive film is preferably in the range of 0.01 to 100 μm. When the thickness exceeds 100 μm, the bioactive substance cannot enter from the pores opened on the surface of the porous layer. The shape of the bioactive substance is not particularly limited, and examples thereof include a spherical shape, a plate shape, a columnar shape, and a needle shape, and any shape that can easily enter and fix from pores that open on the surface of the porous layer. Good.

  The thickness of the bioactive film is preferably from 0.1 to 100 μm. 0.5-50 micrometers is especially preferable. When the thickness exceeds 100 μm, the bond strength with the bone becomes weaker as the thickness increases, and distortion due to the difference in expansion coefficient between the base material and the bioactive film with respect to temperature and humidity increases, resulting in cracks in the bioactive film layer. This is because it becomes easy to enter, and it becomes easy to peel off using the crack as a nucleus. If the thickness is less than 0.1 μm, it is difficult to uniformly coat industrially.

The bioactive film can be formed on the substrate surface as follows.
A bioactive substance exhibiting bioactivity is dispersed in an organic solvent to prepare a suspension of the bioactive substance. Ethanol, ether, acetone or the like can be used as the organic solvent. The concentration of the suspension of the bioactive substance is preferably 1 to 10% by mass as long as the bioactive substance can be sufficiently penetrated into the pores opened on the surface of the substrate and fixed.

  A substrate having a porous layer on the surface is immersed in the suspension of the bioactive substance while irradiating with ultrasonic waves. By irradiating with ultrasonic waves, the bioactive substance can penetrate into the pores from the pores opened on the surface of the substrate and can be fixed. Furthermore, even when the pores opened on the surface of the base material form a communicating hole formed by communicating with a plurality of pores, by applying vibration by ultrasonic irradiation, the bioactive substance is caused to enter the inside of the communicating hole, It can be fixed.

  Next, the base material on which the bioactive substance is fixed is naturally dried at room temperature, and immersed in a simulated body fluid for 0.5 to 14 days in a 37 ° C. environment. Since this simulated body fluid has an inorganic ion concentration almost equal to that of human plasma, crystals can be precipitated from the bioactive substance fixed in the pores opened on the surface of the base material to form a bioactive film. This immersion period can be appropriately adjusted according to the type of the bioactive substance. For example, when hydroxyapatite is selected as the bioactive substance, it is preferably immersed for 1 to 14 days. When this immersion period is less than one day, the amount of crystals deposited is small and a bioactive film may not be formed. When the substrate is immersed for more than 14 days, the crystals continue to grow as the immersion period becomes longer, so that the bioactive film is formed thicker. As a result, the bond strength with the bone is weakened, and the distortion due to the difference in expansion coefficient between the base material and the bioactive film with respect to temperature and humidity is increased. As a result, the bioactive film layer is liable to crack, It becomes easy to peel as a nucleus. In addition, it is not preferable because it takes a long time to produce a biological implant.

  Next, after washing by immersing several times in pure water and then drying, a bioimplant in which the bioactive coating is firmly adhered to the substrate surface can be obtained.

In this simulated body fluid immersion test, the test body is immersed in a simulated body fluid that has a concentration of inorganic ions almost equal to human plasma and is supersaturated with respect to apatite, and the ability to form apatite on the surface of the specimen is evaluated. For details, see Otsuki et al. “Mechanizm of apatite formation on CaO—SiO ₂ —P ₂ O ₅ glasses in a simulated body fluid”, Journal of Non-Crystal Solid (Vol. 3 of Journal of Non-Cr 84-92, 1992.

  The formation of the bioactive film on the surface of the substrate is not limited to the above-described method, but a chemical vapor deposition method such as a thermal CVD method, a plasma CVD method, a photo CVD method, an epitaxial CVD method, an atomic layer CVD method, or a molecular beam epitaxy method. , Physical vapor deposition methods such as ion plating methods and sputtering methods, or thermal spraying methods such as plasma spraying methods and flame spraying methods, as well as substrate reaction methods, solid phase reaction methods, thermal decomposition methods, alkoxide methods, and silane coupling methods Etc. can also be performed.

  The living body implant according to the present invention is used in various shapes, for example, a particle shape, a fiber shape, a block shape, a film shape, and the like according to the use site in the living body. Preferably, the shape similar to the shape of the bone defect part or the tooth defect part or the like, or the shape corresponding to the shape of the bone defect part or the tooth defect part, etc., to which the living body implant of the present invention is supplemented, for example, a similar shape, Molded, shaped and / or prepared for use.

In the bioimplant according to the present invention, the bioactive film can be formed on the surface of the base material after the base material is formed, shaped and / or prepared into a desired shape, or the bioactive film is formed on the base material. Later, the bioimplant can be shaped, shaped and / or prepared into a desired shape.
The bioactive coating may be formed on the entire surface of the substrate, or may be formed only on the surface that needs to be bonded to the bone.

  As an application object, it can be used for bone filling materials, artificial joints, osteosynthesis materials, artificial vertebral bodies, intervertebral body spacers, vertebral body cages, artificial tooth roots, and the like.

  Next, the present invention will be described with reference to examples and comparative examples, but the present invention is not limited to the following examples and comparative examples.

Example 1
This is an example in which polyether ether ketone (PEEK) is used as a substrate and hydroxyapatite is used as a bioactive substance for forming a bioactive film.
A bioactive implant specimen was prepared according to the following procedure.
The surface of a disk-shaped substrate made of PEEK (diameter 10 mm, thickness 2 mm, Victrex 450G) was polished with sandpaper (# 1000) and immersed in concentrated sulfuric acid for 5 minutes. The base material taken out from the concentrated sulfuric acid was immersed in pure water for 10 minutes, and then repeatedly washed until the pH of the pure water became neutral to obtain a base material having a porous layer on the surface.
5 g of hydroxyapatite (HAP-100 manufactured by Taihei Chemical Industrial Co., Ltd.) and 100 ml of ethanol were mixed to prepare an ethanol suspension of hydroxyapatite.
The base material having a porous layer was immersed in an ethanol suspension of hydroxyapatite for 10 minutes while being irradiated with ultrasonic waves, and naturally dried at room temperature to obtain a base material to which hydroxyapatite was adhered.
The substrate to which hydroxyapatite was adhered was immersed in a simulated body fluid for 7 days in a 37 ° C. environment, and then further immersed in a new simulated body fluid for 7 days (14 days in total). The base material taken out from the simulated body fluid was immersed in pure water for 10 minutes, then repeatedly washed three times in the same manner, and then dried at 120 ° C. for 3 hours to obtain a biological implant.

About the biological implant manufactured as mentioned above, the surface of the base material in each process step was observed with the scanning electron microscope (magnification rate 3000 times).
The surface of the base material after the immersion treatment in concentrated sulfuric acid is shown in FIG. The substrate had a large number of pores on the surface and the inside was a network structure, and the pore diameter found on the outermost surface was almost 2 μm or less and extremely fine. From the pore area ratio, the porosity of the outermost surface portion was estimated to be 43%. Furthermore, when the pore size distribution was measured with a mercury porosimeter (manufactured by Shimadzu Corporation, Autopore IV9510), a clear peak was observed at a position where the pore diameter was 0.1 μm. (Fig. 11)
The surface of the base material after being immersed in the ethanol suspension of hydroxyapatite is shown in FIG. It can be seen that hydroxyapatite particles are attached to the network structure formed on the surface of the substrate.
The surface of the base material after being immersed in the simulated body fluid is shown in FIG. Scaly crystals were uniformly formed on the entire surface of the substrate.
FIG. 5 shows the results of observing the cross-section of the base material immersed in the simulated body fluid, that is, the obtained biological implant with a scanning electron microscope (magnification rate: 1000 times). The biological implant was formed by sequentially laminating a PEEK part (not shown) having no pores, a PEEK part having pores, and a layer considered to be a hydroxyapatite crystal. The PEEK portion having pores was porous, and a plurality of independent pores and fine communication holes formed by communicating a plurality of pores were observed. The pore diameter was 1 to 30 μm. A layer having a thickness of about 15 μm, which seems to be a hydroxyapatite crystal, was formed in close contact with the surface of the PEEK part having the pores.

  FIG. 6 shows the results of measurement of the surface portion of the base material at each processing stage using an X-ray diffractometer. The peak attributed to hydroxyapatite was detected from the base material (after 14 days of SBF immersion) after being immersed in the simulated body fluid. Therefore, it was found that the scaly crystals formed on the entire surface of the substrate were hydroxyapatite. Moreover, since this peak is broad, it was confirmed that the hydroxyapatite has low crystallinity. In the base material (after HAP adhesion treatment) after being immersed in the ethanol suspension of hydroxyapatite, no peak of hydroxyapatite was detected. This is presumably because the amount of hydroxyapatite particles attached was not sufficient to be detected by an X-ray diffractometer.

(Comparative Example 1)
A biological implant was obtained in the same manner as in Example 1 except that the base material composed of PEEK was not treated with concentrated sulfuric acid.

(Evaluation of adhesion between substrate and bioactive film)
By observing the biological implant with a scanning electron microscope, the adhesion between the substrate formed of PEEK and the bioactive film formed of hydroxyapatite was evaluated.
(1) The cross section of the biological implant obtained in Example 1 was observed with a scanning electron microscope (magnification rate 1000 times). The results are shown in FIG. A layer of hydroxyapatite crystal having a thickness of about 15 μm was formed in close contact with the surface of the PEEK part having pores.
(2) The biological implants obtained in Example 1 and Comparative Example 1 were irradiated with ultrasonic waves in pure water for 10 minutes. FIGS. 7 and 8 show the results of observation of the living body implant irradiated with ultrasonic waves with a scanning electron microscope after natural drying at room temperature (magnification rate 100 times). In the bioimplant obtained in Example 1, the hydroxyapatite film was not detached from the surface of the base material of the bioimplant and remained uniformly formed on the entire surface. On the other hand, with respect to the biological implant obtained in Comparative Example 1, it was observed that the hydroxyapatite film was detached from the substrate surface.
(3) The biological implants obtained in Example 1 and Comparative Example 1 were cut into a cross shape with a cutter. The results of observing this living body implant with a scanning electron microscope (magnification rate 100 times) are shown in FIGS. Regarding the biological implant obtained in Example 1, it was not recognized that the hydroxyapatite film was detached around the cutting line by the cutter. On the other hand, with respect to the biological implant obtained in Comparative Example 1, it was recognized that the hydroxyapatite film was detached around the cutting line by the cutter.
In any of the above tests, it was confirmed that when the porous layer was formed on the surface of the base material by performing concentrated sulfuric acid treatment, the base material and the hydroxyapatite film were firmly adhered to each other. .

FIG. 1 is a schematic view of a bioactive implant of the present invention. FIG. 2 is a scanning electron micrograph of the substrate surface after concentrated sulfuric acid treatment in Example 1. FIG. 3 is a scanning electron micrograph of the surface of the substrate after immersion in an ethanol suspension of hydroxyapatite in Example 1. FIG. 4 is a scanning electron micrograph of the substrate surface after immersion in simulated body fluid in Example 1. FIG. 5 is a scanning electron micrograph of the cross section of the substrate after being immersed in the simulated body fluid in Example 1. FIG. 6 is an X-ray diffraction pattern of the substrate surface at each processing stage. FIG. 7 is a scanning electron micrograph of the surface of the living body implant of Example 1 after ultrasonic treatment. FIG. 8 is a scanning electron micrograph of the surface of the biological implant of Comparative Example 1 after ultrasonic treatment. FIG. 9 is a scanning electron micrograph of a location where a cut was made in the biological implant of Example 1. FIG. 10 is a scanning electron micrograph of a portion where the biological implant of Comparative Example 1 has been cut. FIG. 11 shows the pore size distribution measurement results of the base material after the concentrated sulfuric acid treatment in Example 1.

Explanation of symbols

DESCRIPTION OF SYMBOLS 1 Base material 2 Bioactive film 3 Porous layer

Claims (9)

A substrate having a porous surface;
A bioactive coating formed of a bioactive substance on the surface of the substrate;
A living body implant characterized by comprising.   The living body implant according to claim 1, wherein the material forming the base material is an engineering plastic.   The living body implant according to claim 1 or 2, wherein the material forming the substrate is polyetheretherketone.   The biological implant according to any one of claims 1 to 3, wherein the base material includes at least one fiber selected from carbon fiber, glass fiber, ceramic fiber, metal fiber, and organic fiber.   The biological implant according to any one of claims 1 to 4, wherein the bioactive substance is a calcium phosphate compound.   The biological implant according to any one of claims 1 to 5, wherein the bioactive substance is hydroxyapatite.   The biological implant according to any one of claims 1 to 6, wherein the bioactive substance is low crystalline.   The biological implant according to any one of claims 1 to 7, wherein the thickness of the bioactive coating is 1 to 100 µm.   The living body implant according to any one of claims 1 to 8, wherein the porous layer formed on the surface of the substrate has a thickness of 1 to 1000 µm.

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