JP5484030B2 - Biological implant - Google Patents

Description

  The present invention relates to a bioimplant, and more particularly to a bioimplant that has mechanical properties close to bone and can form a strong bond with the bone in a short time.

  Conventionally, materials that can be implanted into a living body, for example, living body implants have been developed. As specific materials, ceramic materials, metal materials such as titanium, engineering plastics, and the like are employed. In particular, recently, engineering plastics have attracted attention because they are close to the characteristics of living bones.

  For example, Patent Document 1 employs engineering plastics such as polyetheretherketone as a main material, and a part of the surface has a surface roughness of at least 2 μm for the purpose of obtaining bonding with living bones. An intervertebral implant is disclosed.

  Patent Document 2 discloses an orthopedic composition in which bioactive fine particle ceramics are mixed for the purpose of obtaining bonding with living bones by employing engineering plastics such as polyetheretherketone as an artificial bone main material. doing.

  However, in any of the prior arts, since the hydrophilicity of the engineering plastic was not sufficient, there was room for improvement in affinity with a living body. Furthermore, in the prior art, it takes a long time to bond with a living bone.

Japanese Patent No. 4331481 Japanese translation of PCT publication No. 2004-521685

  The problem to be solved by the present invention is a biological implant that has a high hydrophilicity on the surface of the base material and has a mechanical property close to that of bone so that it can be firmly bonded to bone in a short time. Is to provide.

As means for solving the above-mentioned problems,
(1) A biological implant formed of engineering plastic,
Having a hydrophilic surface provided with at least one hydrophilic functional group;
The ratio of at least one of the hydrophilic functional groups on the hydrophilic surface corresponds to the hydrophilic functional group when the peak obtained by X-ray photoelectron spectroscopy measurement for the central atom in the hydrophilic functional group is separated by waveform. A biological implant characterized in that the area ratio of the peak is 30% or more,
(2) The biological implant according to (1), wherein the engineering plastic is polyetheretherketone,
(3) The biological implant according to (1) or (2), wherein the hydrophilic surface is formed by atmospheric pressure plasma treatment,
(4) The bioimplant according to any one of (1) to (3), wherein a bioactive substance is supported on the hydrophilic surface.
(5) The biological implant according to (4), wherein the bioactive substance is a calcium phosphate compound, and
(6) The living body implant according to (5), wherein the calcium phosphate compound is hydroxyapatite.

  According to the present invention, it is possible to provide a biological implant that has a high hydrophilicity on the surface of the base material and has mechanical properties close to those of bone so that it can be firmly bonded to bone in a short time. . In other words, according to the present invention, by imparting high hydrophilicity to the base material surface of the biological implant, the affinity between the body fluid in the living body and the base material surface is increased. It becomes easy to adhere to the substrate surface, and as a result, it can be bonded to bone in a short time. In addition, the hydrophilic functional group attracts calcium ions in the body fluid to the substrate surface, and then the attracted calcium ions attract phosphate ions, thereby inducing the formation of apatite nuclei that are the origin of bone formation. And can be firmly bonded to the bone in a short time.

FIG. 1 is a schematic view showing a biological implant which is one embodiment of the present invention. FIG. 2 is a schematic view showing the biological implant, calcium ions, and cells shown in FIG. FIG. 3 is a schematic view showing the biological implant, calcium ions, cells, and phosphate ions shown in FIG. FIG. 4 is a schematic view showing the biological implant, cells, and apatite nucleus shown in FIG. FIG. 5 is a waveform separation result of the C1s peak and the O1s peak of the first embodiment.

  The bioimplant according to the present invention is a bioimplant formed of an engineering plastic, having a hydrophilic surface to which at least one hydrophilic functional group is added, and at least one hydrophilic property on the hydrophilic surface. The ratio of the functional group is 30% or more as the area ratio of the peak corresponding to the hydrophilic functional group when the peak obtained by X-ray photoelectron spectroscopy measurement for the central atom in the hydrophilic functional group is separated by waveform. .

  A biological implant that can be implanted in a living body is usually formed by molding various metals, ceramics, resin compounds, or mixtures thereof. The shape of the living body implant may be determined according to the place where the living body is implanted, and for example, a lump shape, a rod shape, a granular shape, or the like can be adopted.

  The living body implant according to the present invention is made of engineering plastic, preferably polyether ether ketone (hereinafter sometimes abbreviated as “PEEK”). PEEK has high biocompatibility, the mechanical properties of PEEK are close to those of human bone, PEEK has resistance to radiation, heat resistance to autoclaves, and various chemicals In view of having chemical resistance to the above, and that there are few eluates from PEEK with respect to body fluids and the like of the living body, PEEK is optimal as a material for living body implants. Examples of a method for forming a living body implant by PEEK include injection molding, extrusion molding, compression molding, transfer molding, blow molding, and cast molding. A molded body formed into a desired shape using PEEK may be used as a biological implant, and a granular body formed by pulverizing the molded body may be used as a biological implant.

  In the living body implant according to the present invention, the mechanical strength of PEEK can be improved by mixing PEEK and various fibers. Examples of the fiber include carbon fiber, glass fiber, ceramic fiber, metal fiber, and organic fiber. Examples of carbon fibers include carbon nanotubes. Examples of the glass fiber include fibers such as borosilicate glass, high-strength glass, and high-elasticity glass. Examples of the ceramic fiber include silicon carbide, silicon nitride, alumina, potassium titanate, boron carbide, magnesium oxide, zinc oxide, aluminum borate, and boron. Examples of metal fibers include tungsten, molybdenum, stainless steel, steel, and tantalum fibers. Examples of the organic fiber include fibers such as polyvinyl alcohol, polyamide, polyethylene terephthalate, polyester, and aramid. Various fibers may be mixed and used.

  The biological implant according to the present invention has a hydrophilic surface formed by imparting a hydrophilic functional group to the surface thereof. The hydrophilic surface is improved in hydrophilicity by the hydrophilic functional group as compared with the surface of the biological implant to which the hydrophilic functional group is not imparted. Therefore, a biological implant having a hydrophilic surface is also suitable for implantation in a living body because it has an affinity for biological fluids in the living body and has a high affinity for cells and proteins involved in bone formation. . Examples of the method for forming a hydrophilic surface include low-pressure plasma treatment, UV ozone treatment, and atmospheric pressure plasma treatment. Details of the method for forming the hydrophilic surface will be described later.

  The hydrophilic functional group may be a functional group having any of anionic and cationic properties as long as it has hydrophilicity. In the biological implant according to the present invention, if the hydrophilic functional group is an anionic functional group, the surface is charged in vivo in the living body to attract calcium ions in the body fluid to the substrate surface, Since calcium ions in the body fluid attract phosphate ions, it is possible to induce the formation of apatite nuclei that are the starting point of bone formation, which is particularly preferable. Examples of the hydrophilic and anionic functional group include a hydroxyl group, a carboxyl group, a phosphate group, and a sulfo group.

  In the biological implant according to the present invention, the hydrophilic functional group, for example, a hydroxyl group, a carboxyl group, a phosphate group, and a sulfo group may be added to the surface of PEEK, and the hydrophilic functional group is a salt. It may be in a state.

  Examples of methods for confirming that the hydrophilic functional group has been added and identifying the type and amount of the hydrophilic functional group include, for example, X-ray photoelectron spectroscopy, Fourier transform infrared absorption spectroscopy, and A water contact angle measurement etc. can be mentioned. In particular, X-ray photoelectron spectroscopy (hereinafter sometimes referred to as “XPS”) is preferable because it facilitates identification of bonding states of various atoms.

  By measuring the hydrophilic surface of the biological implant according to the present invention by XPS, a peak derived from the hydrophilic functional group can be detected. More specifically, the peak area ratio corresponding to the carboxyl group that is a hydrophilic functional group is calculated after waveform separation of the peak obtained by XPS measurement for the carbon atom of the central atom in the hydrophilic functional group, for example, the carboxyl group. Thereby, the ratio of the carboxyl group which is a hydrophilic functional group in the said hydrophilic surface is computable. The central atom is an atom directly bonded to the main chain of PEEK among atoms contained in the hydrophilic functional group. Examples of the central atom include an oxygen atom when the hydrophilic functional group is a hydroxyl group, a carbon atom as described above when the hydrophilic functional group is a carboxyl group, a phosphorus atom when the hydrophilic functional group is a phosphate group, and a sulfo group. When it is a group, it is a sulfur atom. Thus, according to the kind of hydrophilic functional group, each ratio can be calculated.

  For example, in the XPS measurement, when the hydrophilic functional group is a carboxyl group, as shown in FIG. 5, first, only the peak relating to the 1s orbital electron of the carbon atom which is the central atom of the carboxyl group, that is, the C1s waveform only. To extract. Next, the peak of the carboxyl group is specified by performing C1s waveform separation. Subsequently, the sum of the areas of all the peaks excluding the π bond peak obtained by the C1s waveform separation is obtained, and the ratio of the peak area of the carboxyl group to the sum is calculated. The ratio of the calculated peak area is the ratio of hydrophilic functional groups such as carboxyl groups on the hydrophilic surface.

  When the hydrophilic functional group is a hydroxyl group, the central primitive is an oxygen atom, and the area ratio of the peak corresponding to the hydroxyl group is determined by separating the waveform of the O1s waveform. In the case of the O1s waveform, the peak of the carboxyl group and the hydroxyl group appear at the same location, and it is difficult to separate the peak corresponding to the carboxyl group and the peak corresponding to the hydroxyl group. The area ratio of the peak corresponding to the hydroxyl group in the O1s waveform can be obtained.

  First, a peak in which a peak corresponding to a carboxyl group and a peak corresponding to a hydroxyl group overlap is regarded as a single peak (hereinafter sometimes referred to as peak A), and each peak obtained by O1s waveform separation is obtained. The area ratio of peak A to the total area (hereinafter sometimes referred to as area ratio a) and the area ratio of peaks corresponding to ketone bonds (hereinafter sometimes referred to as peak B) (hereinafter referred to as area ratio). b)).

  Next, an area ratio (hereinafter referred to as an area ratio c) of a peak corresponding to a carboxyl group (hereinafter sometimes referred to as a peak C) obtained by performing waveform separation of the C1s waveform on the same object. ) And the area ratio (hereinafter sometimes referred to as area ratio d) of the peak corresponding to the ketone bond (hereinafter sometimes referred to as peak D).

  By using the obtained area ratios a, b, c, and d and the following expression 1, the area ratio of a peak corresponding to a hydroxyl group with respect to the peak area of the entire O1s waveform (hereinafter, referred to as an area ratio e) may be used. ).

  The area ratio a is calculated by dividing the sum of the peak area of the carboxyl group and the peak area of the hydroxyl group by the sum of all peak areas in the O1s waveform. The area ratio b is calculated by dividing the peak area of the ketone bond by the sum of all peak areas in the O1s waveform. Further, the area ratio c is calculated by dividing the peak area of the carboxyl group by the sum of all peak areas in the C1s waveform excluding the π bond. The area ratio d is calculated by dividing the peak area of the ketone bond by the sum of all peak areas in the C1s waveform excluding the π bond. The area ratio e is the ratio of the peak area of the hydroxyl group in the sum of all peak areas in the O1s waveform.

  “B × (c / d)” on the right side in Equation 1 corresponds to the area ratio of the peak corresponding to the carboxyl group in the O1s waveform. By obtaining this value, the peak component contained in peak A, that is, the peak of the carboxyl group and the peak of the hydroxyl group can be separated, and as a result, the area ratio e can be obtained.

  When the base material is PEEK, the peak of the ether bond is also included in the C1s waveform and the O1s waveform. Therefore, in order to separate the peak component of the peak A, the entire O1s waveform of the peak corresponding to the ether bond in the O1s waveform The ratio of area to the peak area of the C1s waveform (hereinafter referred to as area ratio f) and the ratio of the peak corresponding to the ether bond in the C1s waveform to the peak area of the entire C1s waveform (hereinafter referred to as area ratio g). The area ratios f and g can be substituted into the area ratios b and d.

  When the hydrophilic functional group is a phosphate group, the central atom is a phosphorus atom, and the ratio of the peak area of the phosphate group to the P2p waveform may be calculated. Furthermore, when the hydrophilic functional group is a sulfo group, the central atom is a sulfur atom, and the ratio of the peak area of the sulfo group to the S2p waveform may be calculated.

  In the biological implant according to the present invention, the ratio of at least one hydrophilic functional group on the hydrophilic surface is 30% or more, preferably 30 to 85% in terms of the peak area ratio. When the ratio of at least one of the hydrophilic functional groups on the hydrophilic surface is less than 30% in terms of the peak area ratio, the adhesion of the cells involved in bone formation to the hydrophilic surface is not sufficient, so that the binding to the bone It is difficult to increase the strength, and it may take a long time to bond with the bone. If the ratio of at least one hydrophilic functional group on the hydrophilic surface is 30 to 85% in terms of the peak area ratio, it is preferable because a long time is not required for the hydrophilic treatment on the substrate surface.

  In the biological implant according to the present invention, the higher the proportion of the carboxyl group among the hydrophilic functional groups on the hydrophilic surface, the better. The carboxyl group has the ability to form apatite nuclei, and when the amount of carboxyl group introduced onto the surface is large, it can be expected that bone formation in vivo is particularly promoted.

  When the XPS measurement is performed on the central atom in the hydrophilic functional group, for example, the C1s waveform has a desired peak waveform in the range of 280-294 eV, the P2p waveform has 127-142 eV, the S2p waveform has 160-174 eV, and the O1s waveform has a range of 526-536 eV. Can be detected.

  Here, the manufacturing method of the biological implant which concerns on this invention, and the effect | action of the biological implant which concerns on this invention are demonstrated.

  First, PEEK is formed by, for example, injection molding. Furthermore, a lump shape, a rod shape, a granular shape, or the like is selected as the shape of the biological implant. In the case of a granular biological implant, the molded PEEK may be processed into a particle having a diameter of 0.35 to 10 mm, for example. Further, in the case of a massive or rod-shaped biological implant, the molded PEEK may be processed to have a desired size.

  A hydrophilic functional group is then imparted to PEEK. As a method for imparting a hydrophilic functional group, low-pressure oxygen plasma treatment, UV ozone treatment and atmospheric pressure plasma treatment are preferable, and atmospheric pressure plasma treatment capable of obtaining a particularly excellent hydrophilic surface is particularly preferable. When the XPS measurement is performed on the hydrophilic functional group, the atmospheric pressure plasma treatment is preferably performed so that the peak area ratio of at least one hydrophilic functional group is 30% or more. The processing conditions of the atmospheric pressure plasma processing will be described after explanation of the action of the biological implant according to the present invention. A hydrophilic surface can be formed by applying a hydrophilic functional group to the surface of PEEK at a specific ratio by the atmospheric pressure plasma. Thereby, the biological implant which concerns on this invention can be obtained.

  The biological implant according to the present invention has a mechanical property close to that of a bone, and can form a strong bond with the bone in a short time. The fact that the bond between the living body implant and the bone according to the present invention is strong will be described with reference to the drawings.

FIG. 1 shows a living implant 1 which is one embodiment of the present invention. The biological implant 1 has a hydrophilic surface 4 (hereinafter, simply referred to as “surface 4”) in which a hydroxyl group and a carboxyl group, which are examples of the hydrophilic functional group 3, are provided on the surface of the PEEK 2. Since the biological implant 1 shown in FIG. 1 is placed in a body fluid (not shown), the carboxyl group 3 is ionized to release a proton, thereby forming a carboxylate, which is indicated as “—COO ⁻ ”. The hydroxyl group is shown as “—OH”.

  As shown in FIG. 2, since the hydrophilic surface 4 has a high affinity between the surface 4 and the body fluid in the living body, cells 5 and proteins that can contribute to bone formation contained in the body fluid (see FIG. 2). (Not shown) is adhered. The surface 4 having hydrophilicity adheres the cells, proteins, and the like earlier than the surface of the substrate having no hydrophilicity. Regardless of whether or not the cells 5 and proteins are adhered, calcium ions dissolved in the body fluid are attracted to the hydrophilic functional group 3 as shown in FIG.

  Furthermore, as shown in FIG. 3, when the calcium ion concentration in the vicinity of the hydrophilic surface 4 in the biological implant 1 is increased, phosphate ions dissolved in the body fluid are attracted. The phosphate ions in the body fluid are attracted to the calcium ions near the carboxyl group and remain in the vicinity of the carboxyl group and the calcium ion.

  When calcium ions and phosphate ions remain in the vicinity of the hydrophilic functional group 3, the concentrations of calcium ions and phosphate ions in the vicinity of the biological implant 1 increase. Furthermore, when the concentration of the apatite is higher than the formable concentration in the vicinity of the surface 4, that is, the supersaturation level of calcium ions and phosphate ions is reached, the apatite nuclei 6 are generated on the surface 4 as shown in FIG. 4. By further attracting calcium ions, phosphate ions, and other compounds to the apatite nucleus 6, hydroxyapatite is formed using the apatite nucleus 6 as a nucleus. On the other hand, the cells 5 adhered on the surface 4 gradually grow.

  The hydrophilic functional group 3 and the calcium ion and phosphate ion contained in the apatite nucleus 6 are bonded by chemical bonding. Thereby, the biological implant 1 and hydroxyapatite will be firmly bonded. That is, when the surface 4 of PEEK2 is formed, the adhesiveness of cells contributing to bone formation is increased, and further, apatite nucleus 6 is chemically generated. Therefore, the biological implant according to the present invention is firmly attached to bone. A simple bond can be formed in a short time.

  Furthermore, the biological implant according to the present invention has a high hydrophilicity because the ratio of at least one hydrophilic functional group on the hydrophilic surface is 30% or higher in terms of the peak area ratio. Adhesion of cells 5 and proteins to the surface 4 can be accelerated. In addition, since a large amount of calcium ions and phosphate ions in the body fluid can be kept in the vicinity of the hydrophilic surface 4 by chemical bonding, it takes a short time until the apatite nucleus 6 is formed and grows into hydroxyapatite. be able to.

  Hereinafter, the atmospheric pressure plasma treatment will be described.

  When PEEK is subjected to an atmospheric pressure plasma treatment, a hydrophilic functional group is imparted to PEEK to form a hydrophilic surface. The atmospheric pressure plasma treatment is a treatment capable of imparting various functional groups to the surface of the material and activating the surface of the material by directly colliding the high density plasma with the surface of the material under atmospheric pressure. . In the atmospheric pressure plasma processing, the plasma generation unit may be scanned on the surface of the material, or the plasma generation unit may be fixed and the material stage may be moved for processing. The time for irradiating the surface of the material with the plasma may be appropriately set according to the relationship between the density of the plasma to be irradiated, the concentration of radicals to be generated, the irradiation width of the plasma, and the surface area of the material to be processed. Note that activation of the material surface proceeds by irradiating the material surface with plasma for a long time, so that the amount of hydrophilic functional groups introduced to the material surface can be adjusted by the plasma irradiation time.

As processing conditions of atmospheric pressure plasma processing in which the ratio of at least one hydrophilic functional group on the hydrophilic surface is a high density of 30% or more in the peak area ratio, for example, the plasma electron density is 10 ¹¹ to 10 ¹⁶ / cm ³ , the gas type is a mixed gas of argon and oxygen, the oxygen concentration is 0.5 to 5%, the gas flow rate is 1 to 20 L / min, and the irradiation distance is 0.5 to 30 mm. And the condition that the plasma irradiation time on the material surface is 30 seconds / cm ² to 30 minutes / cm ² .

As a further preferable aspect of the biological implant according to the present invention, an aspect in which a bioactive substance is supported on a surface having a hydrophilic functional group can be exemplified. The bioactive substance is not particularly limited as long as it is a substance having a chemical binding ability to bone in a living body. For example, calcium phosphate compound, bioglass, crystallized glass (also referred to as glass ceramic), calcium carbonate, and the like. 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. 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 Clinical "(edited by Hideki Aoki et al., Published on April 10, 1987, Quintessence Publishing Co., Ltd.). Of the above-mentioned bioactive substances, calcium phosphate compounds are preferred, and hydroxyapatite is particularly preferred.

  As a method for supporting a bioactive substance such as hydroxyapatite on a hydrophilic surface, for example, a method in which the bioimplant according to the present invention is alternately immersed in a solution containing calcium ions and a solution containing phosphate ions for a certain period of time alternately. Can be mentioned. The order in which the biological implant is immersed in the solution containing calcium ions and the solution containing phosphate ions is not particularly limited. The immersion time is preferably 1 minute to 5 hours, and particularly preferably 3 minutes to 3 hours. If it is in the range of 1 minute-5 hours and it is this immersion time, sufficient amount of calcium ion and phosphate ion will be carry | supported by the hydrophilic surface.

  Examples of the solution containing calcium ions include a solution containing 10 mM calcium ions. The solution containing calcium ions only needs to contain at least calcium ions, and includes sodium ions, potassium ions, magnesium ions, carbonate ions, silicate ions, sulfate ions, nitrate ions, chloride ions, hydrogen ions, and the like. However, it is preferable that the phosphate ion is not substantially contained. Specifically, the solution containing calcium ions usually includes an aqueous solution of a compound that has high water solubility and does not adversely affect the human body. For example, calcium chloride, calcium hydroxide, calcium nitrate, calcium formate, acetic acid Examples include calcium, calcium propionate, calcium butyrate or calcium lactate aqueous solutions, and mixed solutions thereof. An aqueous solution of calcium chloride is preferred.

  Examples of the solution containing phosphate ions include a solution containing 10 mM phosphate ions. The solution containing phosphate ions may contain at least phosphate ions, and includes sodium ions, potassium ions, magnesium ions, carbonate ions, silicate ions, sulfate ions, nitrate ions, chloride ions, hydrogen ions, and the like. However, it is preferable that calcium ions are not substantially contained. Specifically, the solution containing phosphate ions usually includes an aqueous solution of a compound that has high water solubility and does not adversely affect the human body. For example, phosphoric acid, disodium hydrogen phosphate, dihydrogen phosphate Examples of the aqueous solution include sodium, dipotassium hydrogen phosphate or potassium dihydrogen phosphate, and mixed solutions thereof. An aqueous solution of dipotassium hydrogen phosphate is preferable.

  In addition, after immersing a base material in the solution containing a calcium ion and the solution containing a phosphate ion, it is preferable to introduce | transduce a hydrophilic functional group to the base-material surface, for example by atmospheric pressure plasma processing etc. When the treatment in this order is performed, it is possible to make it difficult to cause a state in which the hydrophilicity of the substrate surface is lowered due to the adsorption of a large amount of hydroxyapatite to the terminal end portion of the hydrophilic functional group to be introduced. A hydrophilic functional group can be secured.

  The support of the bioactive substance is not limited to the above method. For example, the substrate is dipped in a solution containing a large amount of the bioactive substance in advance and dried, and then the substrate surface is hydrophilicized by, for example, atmospheric pressure plasma treatment. A functional group may be introduced.

  As described above, when the hydrophilic functional group and the bioactive substance coexist on the surface of the biological implant according to the present invention, in addition to the contribution of the apatite nucleation ability of the hydrophilic functional group itself, This contributes to an increase in calcium ions in the vicinity of the surface of the implant, and as a result, the ability to form apatite nuclei in the hydrophilic functional group and the bioactive substance is increased, so that the strong bond with the bone proceeds faster.

(Sample preparation)
A plurality of molded products having a size of φ10 × 2 mm were cut out from rod-like PEEK (φ10 × 1000 mm, manufactured by VICTREX), and the surface was polished with # 1000 sandpaper to prepare a sample. As an example, the plasma electron density is 10 ¹¹ to 10 ¹⁶ / cm ³ , the gas type is a mixed gas of argon and oxygen, the oxygen concentration is 1%, and the gas flow rate is 5 L / min. The atmospheric pressure plasma treatment was performed on the PEEK surface under the conditions that the irradiation distance was 1 mm and the plasma irradiation time on the material surface was 1 minute / cm ² .

(XPS measurement)
As an XPS measurement device, a scanning X-ray photoelectron spectroscopic analyzer (device name: Quantera SXM) manufactured by ULVAC-PHI was used. Measurement was performed under the measurement conditions. For example, when the waveform is separated as shown in FIG. 5 for the C1s peak obtained by XPS measurement, the ratio of carboxyl groups on the hydrophilic surface formed in PEEK is 7 as the peak area ratio of C1s as shown in Table 1. 9%. For example, when the waveform is separated as shown in FIG. 5 for the O1s peak, the proportion of hydroxyl groups on the hydrophilic surface formed in PEEK was 45.3% as the peak area ratio of O1s as shown in Table 1. . Further, as shown in Table 1, the water contact angle of the material surface immediately after the atmospheric pressure plasma treatment was 12.3 °. For Example 2 and Comparative Examples 1 to 4 shown below, the measurement results of the samples are shown in Table 1 as in Example 1.

In Example 2, the treatment was performed in the same manner as in Example 1 except that the plasma irradiation time on the material surface was set to 30 seconds / cm ² under the treatment conditions of the atmospheric pressure plasma treatment. As a result of performing XPS measurement on Example 2 in the same manner as in Example 1, the ratio of carboxyl groups on the hydrophilic surface formed in PEEK was 3.9% in terms of the peak area ratio of C1s. Moreover, the ratio of the hydroxyl group in the hydrophilic surface formed in PEEK was 31.4% in the peak area ratio of O1s. The water contact angle of the material surface immediately after the atmospheric pressure plasma treatment was 35.4 °.

Comparative Example 1

In Comparative Example 1, the treatment was performed in the same manner as in Example 1 except that the plasma irradiation time on the material surface was set to 10 seconds / cm ² under the treatment conditions of the atmospheric pressure plasma treatment. As a result of performing XPS measurement for Comparative Example 1 in the same manner as in Example 1, the ratio of carboxyl groups on the hydrophilic surface formed in PEEK was 1.9% in terms of the peak area ratio of C1s. Moreover, the ratio of the hydroxyl group in the hydrophilic surface formed in PEEK was 29.4% in the peak area ratio of O1s. The water contact angle of the material surface immediately after the atmospheric pressure plasma treatment was 41.0 °.

Comparative Example 2

  In Comparative Example 2, the same material as in Example 1 was used as the base material, and a low-pressure oxygen plasma processing apparatus (plasma dry cleaner, model: PX-1000, manufactured by SAMCO) was used instead of atmospheric pressure plasma processing. Low-pressure oxygen plasma treatment was performed at an output of 500 W and a treatment time of 10 minutes. The hydrophilic functional group imparted by this low-pressure oxygen plasma treatment was a hydroxyl group and a carboxyl group as in the sample subjected to the atmospheric pressure plasma treatment. As a result of performing XPS measurement for Comparative Example 2 in the same manner as in Example 1, the ratio of carboxyl groups on the hydrophilic surface formed in PEEK was 14.9% as the peak area ratio of C1s. Moreover, the ratio of the hydroxyl group in the hydrophilic surface formed in PEEK was 19.9% in the peak area ratio of O1s. The water contact angle of the material surface immediately after the low-pressure oxygen plasma treatment was 14.1 °.

Comparative Example 3

In Comparative Example 3, the same material as in Example 1 was used as the base material, and instead of atmospheric pressure plasma treatment, a UV ozone treatment device (desktop optical surface treatment device, model: PL16-110, Sen Special Light Source Co., Ltd.) UV ozone treatment was performed by setting the condition of a treatment time of 10 minutes while maintaining the distance between the light source and the sample adjusted so that the illuminance at 254 nm was 30 mW / cm ² . The hydrophilic functional group imparted by this UV ozone treatment was a hydroxyl group and a carboxyl group, as in the sample treated with atmospheric pressure plasma and the sample treated with low pressure oxygen plasma. As a result of performing XPS measurement for Comparative Example 3 in the same manner as in Example 1, the ratio of carboxyl groups on the hydrophilic surface formed in PEEK was 18.9% in terms of the peak area ratio of C1s. Moreover, the ratio of the hydroxyl group in the hydrophilic surface formed in PEEK was 3.1% in the peak area ratio of O1s. The water contact angle on the material surface immediately after UV ozone treatment was 18.3 °.

Comparative Example 4

  In Comparative Example 4, a sample was prepared in the same manner as in Example 1 except that atmospheric pressure plasma treatment was not performed. As a result of performing XPS measurement for Comparative Example 4 in the same manner as in Example 1, the ratio of carboxyl groups on the surface of PEEK was 0% in terms of the peak area ratio of C1s. Moreover, the ratio of the hydroxyl group on the surface of PEEK was 0% in terms of the peak area ratio of O1s. This measurement result was a result as the theoretical value of PEEK which does not contain a hydrophilic functional group in a base material. The water contact angle on the material surface was 90.6 °.

(Evaluation of cell adhesion)

It was decided to evaluate the adhesiveness of cells involved in bone formation on the surface of the samples of Examples and Comparative Examples using mouse osteoblast-like cells (MC3T3-E1). Specifically, MC3T3-E1 was cultured in an α-MEM medium containing 10% fetal bovine serum and antibiotics so as to be 90% confluent, and this was cultured on a 24-well cell culture plate. Each placed sample was seeded at a cell number of 4 × 10 ⁴ cells / well. After culturing this in a 5% CO ₂ incubator at 37 ° C. for 4 hours, the sample was transferred to a new 24-well cell culture plate, added with the same amount of medium as in the culture, and further cultured for 24 hours. The number of cells adhered to the sample surface was counted using Cell Counting Kit-8 (manufactured by Dojindo Laboratories). The results are shown in Table 2.

  As a result of counting the number of cells, when the number of cells adhering to the sample surface of Comparative Example 4 using untreated PEEK as a sample was taken as 100%, the number of cells adhering to the sample surface of Example 1 Is 118%, the number of cells adhering to the sample surface of Example 2 is 111%, the number of cells adhering to the sample surface of Comparative Example 1 is 104%, and the number of cells adhering to the sample surface of Comparative Example 2 is The number was 105%, and the number of cells adhering to the sample surface of Comparative Example 3 was 104%.

  From the above results, when the ratio of at least one hydrophilic functional group on the hydrophilic surface separated from the peak obtained by X-ray photoelectron spectroscopy measurement for the central atom, the peak corresponding to the hydrophilic functional group The example of the biological implant according to the present invention having an area ratio of 30% or more is superior to the comparative example in terms of initial cell adhesion. Furthermore, when it is embedded in a living body as a living body implant, the cells rapidly adhere to the sample surface, so that bone formation proceeds faster than in the comparative example, and a strong bond with the bone can be formed in a short time. It was suggested.

  The biological implant according to the present invention can be used for, for example, a bone filling material, an artificial joint member, an osteosynthesis material, an artificial vertebral body, an intervertebral body spacer, a vertebral body cage, and an artificial tooth root.

DESCRIPTION OF SYMBOLS 1 Bioimplant 2 Polyetheretherketone 3 Hydrophilic functional group 4 Hydrophilic surface 5 Cell 6 Apatite nucleus

Claims (6)

A bio-implant formed of engineering plastic,
Having a hydrophilic surface provided with at least one hydrophilic functional group;
The ratio of at least one of the hydrophilic functional groups on the hydrophilic surface corresponds to the hydrophilic functional group when the peak obtained by X-ray photoelectron spectroscopy measurement for the central atom in the hydrophilic functional group is separated by waveform. The living body implant characterized by being 30% or more as a peak area ratio.   The biological implant according to claim 1, wherein the engineering plastic is polyetheretherketone.   The biological implant according to claim 1 or 2, wherein the hydrophilic surface is formed by atmospheric pressure plasma treatment.   The bioimplant according to any one of claims 1 to 3, wherein a bioactive substance is supported on the hydrophilic surface.   The biological implant according to claim 4, wherein the bioactive substance is a calcium phosphate compound.   The biological implant according to claim 5, wherein the calcium phosphate compound is hydroxyapatite.

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