Biological implant and method for manufacturing same

Abstract

One aspect of the present invention relates to a biological implant including a base material having a porous layer on at least a part of the surface thereof, and silver particles supported on the porous layer. The arithmetic average roughness Ra of a surface part and / or a bottom part of the porous layer is 0.20 μm or more, and in the porous layer, surface part arithmetic average roughness Ra / bottom part arithmetic average roughness Ra is from 0.5 to 1.5.

Description

Biological implant and method for producing the same

[0001] The present disclosure relates to a biological implant and a method for producing the same.

[0002] Orthopedic biological implants and dental implants are generally made of metal such as titanium alloy. When such a metal implant is embedded in bone, it is desirable that friction exists between the implant surface and the bone to improve fixation to the bone. It has heretofore been known to provide a porous layer on the surface of a metal base material constituting an implant.

[0003] For example, Patent Document 1 discloses an implant having a porous surface with micro-roughness formed by a 3D printing process. It is also described that the implant described in Patent Document 1 is treated by laser ablation or acid etching so that the porous surface has nano-roughness.

[0004] On the other hand, antibacterial properties are also required for biological implants. As one method for imparting antibacterial properties to biological implants, supporting silver particles on the surface is conceivable. However, it has been found that in a biological implant having a porous layer as described in Patent Document 1, when an attempt is made to support silver particles after nano-roughening treatment such as etching, regions with a small amount of supported silver particles occur depending on the location, particularly in the outermost layer portion.

[0005] Japanese National Publication of International Patent Application No. 2024-522901

[0006] A biological implant according to one aspect of the present disclosure includes a base material having a porous layer on at least a part of a surface thereof, and silver particles supported on the porous layer, wherein an arithmetic average roughness Ra of at least one of a surface portion and a bottom portion of the porous layer is 0.20 µm or more, and in the porous layer, a ratio of the arithmetic average roughness Ra of the surface portion to the arithmetic average roughness Ra of the bottom portion is 0.5 to 1.5.

[0007] Furthermore, a method for manufacturing a bio-implant relating to another aspect of this disclosure includes preparing a substrate having a porous layer on at least a portion of its surface, performing a process to form irregularities on the porous layer, then performing an etching process on the porous layer after the process, and subsequently supporting silver particles on the porous layer.

[0008] Figure 1 is a flowchart showing an example of a method for measuring the arithmetic mean roughness Ra. Figure 2 is a diagram showing an example of an image of the cross-section of the implant body used for the measurement in Figure 1. Figure 3 is a diagram showing an example of an image of the cross-section of the implant body used for the measurement in Figure 1. Figure 4 is a diagram showing an example of an image of the surface of the implant body used for the measurement in Figure 1. Figure 5 is a diagram showing an example of a binarized image of the cross-section of the implant body used for the measurement in Figure 1. Figure 6 is a cross-sectional SEM image showing the surface roughness of the example sample and the comparative example sample. Figure 7 is a surface SEM image showing the silver-supported state of the example sample and the comparative example sample. The white grains represent silver particles.

[0009] The embodiments relating to this disclosure will be described below in detail, but this disclosure is not limited to these.

[0010] [Bio-implant] The bio-implant according to this embodiment includes a substrate having a porous layer on at least a part of its surface, and silver particles supported on the porous layer. The arithmetic mean roughness Ra of at least one of the surface and bottom portions of the porous layer is 0.20 μm or more. Furthermore, in the porous layer, the ratio of the surface arithmetic mean roughness Ra to the bottom arithmetic mean roughness Ra is 0.5 to 1.5.

[0011] The bio-implant of this embodiment exhibits excellent osseointegration due to having a porous layer with the above-described structure. Furthermore, since the silver particles are relatively uniformly supported in the porous layer, it is believed that it can exhibit excellent antibacterial properties. Therefore, the bio-implant of this embodiment combines both osseointegration and antibacterial properties.

[0012] The bio-implants of this embodiment may be, for example, dental implants, artificial joints such as femoral stems or acetabular shells, and spinal surgical implants such as spinal fixation instrumentations.

[0013] Examples of base material materials include metals, ceramics, and plastics. Examples of metals include titanium, titanium alloys, stainless steel, cobalt-chromium alloys, and zirconium alloys. Examples of titanium alloys include alloys to which at least one of the following is added to titanium: aluminum, tin, zirconium, molybdenum, nickel, palladium, tantalum, niobium, vanadium, or platinum. Specific examples of titanium alloys include Ti-6Al-4V alloy. Examples of ceramics include alumina, zirconia, alumina-zirconia composite ceramics, and calcium phosphate. Examples of plastics include polyethylene, fluororesins, epoxy resins, and PEEK resins.

[0014] In preferred embodiments, the substrate is preferably composed of at least one selected from titanium, titanium alloys, stainless steel, cobalt-chromium alloys, zirconium alloys, tantalum, or calcium phosphate.

[0015] The porous layer of the bio-implant in this embodiment is not particularly limited as long as it has a three-dimensional structure with spaces or voids. The spaces or voids may be formed as appropriate according to the shape of the site where the implant surgery is desired, but it is preferable to form a porous structure that can reproduce the morphology of cancellous bone. This enhances the initial fixation when the implant is embedded in the bone and promotes the intrusion of new bone into the porous layer after embedding, thereby improving the osseointegration of the implant.

[0016] Examples of porous layers include structures consisting of an inner wall and a cellular grid providing multiple cavities, stochastic lattice structures such as cancellous bone-like porous structures, and periodic lattice structures such as diamond structures.

[0017] One specific example is the structure comprising an inner wall and a cell grid providing multiple cavities, wherein at least a portion of the grid is formed without interruption of continuity by one or more types of geometric meshes (e.g., polygons) repeated in the space of the entire substrate or a portion thereof.

[0018] In the implant of this embodiment, it is sufficient that a porous layer is provided on at least a portion of the surface of the substrate, and the proportion is not particularly limited. It may be on only one side of the substrate, on both sides, or the entire surface of the substrate may be covered with the porous layer. The proportion and location of the porous layer on the substrate may be appropriately set depending on the shape of the implant and the site where the implant will be used.

[0019] In this embodiment, the arithmetic mean roughness Ra of at least one of the surface and bottom portions of the porous layer is 0.20 μm or more. In a preferred embodiment, the arithmetic mean roughness Ra of the surface and bottom portions of the porous layer is 0.20 μm or more. In another preferred embodiment, the arithmetic mean roughness Ra of at least one of the surface and bottom portions of the porous layer may be 0.21 μm or more. Alternatively, the arithmetic mean roughness Ra of the surface and bottom portions of the porous layer may be 0.21 μm or more. Alternatively, the arithmetic mean roughness Ra of at least one of the surface and bottom portions of the porous layer may be 0.29 μm or more. More preferably, the arithmetic mean roughness Ra of the surface and bottom portions of the porous layer is 0.29 μm or more. The upper limit of the arithmetic mean roughness Ra is not particularly limited, but from the viewpoint of reducing fatigue strength, it is preferably 0.6 μm or less.

[0020] Furthermore, in the porous layer of this embodiment, the ratio of the arithmetic mean roughness Ra of the surface to the arithmetic mean roughness Ra of the bottom is 0.5 to 1.5.

[0021] In this specification, the "surface" of a porous layer refers to the outermost surface of the porous layer. The "bottom" of a porous layer refers to the surface of the porous layer that is in contact with the substrate (i.e., the interface between the porous layer and the substrate). Furthermore, if the porous layer is composed of a cell grid as described above, the front end of the grid (the grid furthest forward (outer) when the porous layer is viewed from above) is called the "surface," and the inside of the grid (the grid furthest inward (inner) when the porous layer is viewed from above) is called the "bottom." The porous layer may be, for example, a structure consisting of a cell grid providing an inner wall and multiple cavities, a stochastic lattice structure, or a periodic lattice structure.

[0022] A more preferable range for the ratio of surface arithmetic mean roughness Ra to bottom arithmetic mean roughness Ra is 0.7 to 1.3.

[0023] The arithmetic mean roughness Ra of at least one of the surface and bottom of the porous layer is 0.20 μm or more, and the ratio of the surface arithmetic mean roughness Ra to the bottom arithmetic mean roughness Ra is 0.5 to 1.5, thereby providing the bio-implant having the porous layer with excellent osseointegration properties. Furthermore, since the porous layer can relatively uniformly support the silver particles described later, the antibacterial properties of the bio-implant of this embodiment are improved.

[0024] (Method for measuring arithmetic mean roughness Ra) In this embodiment, the arithmetic mean roughness Ra is the value obtained after performing a macro-roughening treatment on a porous layer, followed by a micro-roughening treatment. When evaluating a surface subjected to such treatment using general roughness measurement methods (for example, JIS B 0633:2001 and JIS B 0601:2013), the obtained surface roughness largely depends on the irregularities that existed before the roughening treatment such as acid etching, and it is not possible to properly evaluate the submicron-order irregularities formed by acid etching, etc. Therefore, in this embodiment, the arithmetic mean roughness Ra was calculated by preparing a cross-section of the treated surface after the micro-roughening treatment, acquiring irregularity information with a scanning electron microscope (SEM; sometimes simply referred to as "SEM" in this specification), and using a method to remove the irregularities that existed before the micro-roughening treatment by filtering, thereby evaluating the submicrometer-order irregularities formed by the roughening treatment such as acid etching.

[0025] Figure 1 is a flowchart showing the method for measuring surface roughness. The arithmetic mean roughness Ra mentioned above is measured by this method. First, in step S11, each implant is cut with a cutting plane perpendicular to the surface of the implant body after the macro-roughening and micro-roughening treatments have been completed, for example, a cutting plane that includes the central axis of each implant body.

[0026] Next, in step S12, the cross-section of each implant body was imaged using a SEM at a magnification of, for example, 5000x. Here, a Hitachi® SEM "S-3400N" was used to image a portion of the implant body surface.

[0027] Figures 2 and 3 schematically show examples of captured images. Figure 2 shows an image obtained by imaging the cross-section of an implant at a magnification of 100x. Figure 3 shows an image obtained by imaging the same cross-section of an implant at a magnification of 5000x. Figure 3 shows the imaging region R1 in Figure 2. In the example in Figure 2, the imaging region R1 corresponds to the valley of the implant. The lateral length of the imaging region R1 is 25.4 μm, and the vertical length is 19.1 μm.

[0028] In each captured image, the pixel values ​​of the pixel group representing the implant have different pixel values ​​from the pixel values ​​representing the background. In the examples in Figures 2 and 3, the pixel values ​​of the implant are higher than the pixel values ​​of the background.

[0029] Figure 4 shows an image obtained by imaging the surface of the implant. This image was obtained by scanning electron microscope (SEM) at a magnification of 5000x. As can be seen from Figures 3 and 4, the surface of the implant has fine irregularities.

[0030] The image captured in Figure 3, acquired by the SEM, is input to a predetermined image processing device. The image processing device is an electronic circuit and includes at least one processor to provide image processing capabilities. The processor includes, for example, one or more circuits or units configured to execute one or more data calculation procedures or processes by executing instructions stored in associated memory. In other embodiments, the processor may be firmware (e.g., discrete logic components) configured to execute one or more data calculation procedures or processes. Note that all or some of the functions of the image processing device may be implemented by hardware circuits that do not require software to implement their functions.

[0031] Referring again to Figure 1, in step S13, the image processing device performs image processing on the captured image to obtain a first curve that shows the contour of the implant body's surface. As a specific example, the image processing device first performs binarization on the captured image to obtain a binarized image. Figure 5 is a schematic diagram showing an example of a binarized image. The image processing device obtains a first curve based on this binarized image. The image processing device obtains an edge image by performing edge extraction processing on the binarized image, such as the Canny method, and then performs thinning processing such as Hilditch on this edge image to obtain the first curve. This first curve is the contour curve of the implant body's surface at a measurement length of 25.4 μm. Note that the method for obtaining the first curve is not limited to this, and the first curve may be obtained by other algorithms or manual tracing.

[0032] Here, image processing was performed using the image processing software "WinROOF (trademark)" manufactured by Mitani Corporation. The image processing device performs the above-mentioned image processing and obtains the first curve by executing various procedures defined by the software. The image processing device running the software has the functionality to perform the operations described below.

[0033] Now, the first curve includes a wavy component showing a surface roughness of about 1 μm to 3 μm formed by macro-roughening treatments such as blasting, and a roughness component showing a surface roughness of several hundred nm formed by micro-roughening treatments such as etching. Here, we remove this wavy component and extract the roughness component.

[0034] Referring again to Figure 1, in step S14, the image processing device removes the undulation component, i.e., the long-wavelength component, from the first curve. Specifically, the image processing device applies a Gaussian filter to the first curve with a cutoff value of 5 μm to obtain the second curve. In other words, by adopting a cutoff value of 5 μm, which is shorter than the period of the surface roughness (undulation component) generated by the blasting process, and performing a high-pass filter on the first curve, the undulation component caused by macro-roughening processes such as blasting is removed from the first curve to obtain the second curve. Therefore, this second curve mainly represents the surface roughness (irregularity component) formed by micro-roughening processes such as etching.

[0035] Next, in step S15, the image processing device calculates the arithmetic mean roughness Ra using the second curve. This arithmetic mean roughness Ra is obtained by averaging the absolute values ​​of the differences between the average value in the height direction of the second curve and each point on the second curve.

[0036] The method for forming the porous layer in this embodiment is not particularly limited. After forming a porous layer having a desired porous structure, a process is performed to create irregularities in the porous layer (macro-roughening treatment), and then an etching treatment (micro-roughening treatment) is performed on the porous layer after the above treatment to obtain a porous layer that satisfies the above-mentioned arithmetic mean roughness Ra specification. These processes will be described in detail in the manufacturing method described later.

[0037] The silver particles used in the present embodiment are not particularly limited as long as they can be supported on the porous layer, but preferably contain silver particles having a particle diameter of 5 μm or less. For example, the silver particles may be metallic silver particles or silver compound particles having an antibacterial effect. For example, two or more types of silver particles may be mixed and used. For example, two or more types of silver particles having different particle diameters may be mixed and used.

[0038] The shape of the silver particles may be spherical or irregular. In the present specification, the "particle diameter" means the diameter of a spherical particle, and means the maximum length of an irregularly shaped particle. In the present embodiment, the more preferred particle diameter of the silver particles is 3 μm or less, more preferably 1 μm or less. The smaller the particle diameter of silver particles, the larger the specific surface area, so that the force acting per unit volume becomes stronger, which has the advantage that silver particles are more difficult to detach. On the other hand, the lower limit of the particle diameter is not particularly limited, but is, for example, 5 nm or more. In the present embodiment, the particle diameter of silver particles is a value measured by observing the surface of the silver particles at a magnification of 50,000 times with a field emission scanning electron microscope (FE-SEM).

[0039] In the biological implant according to the present embodiment, the silver particles only need to be supported on the porous layer, but silver particles may also be supported on the base material in addition to the porous layer.

[0040] The amount of silver particles supported on the porous layer (and the base material) is not particularly limited, but the amount of silver particles per unit area of the porous layer (and the base material) is 1 μg / cm ２ or more, and 150 μg / cm ２ or less. It is considered that this allows the biological implant of the present embodiment to further improve antibacterial properties. A more preferred upper limit is 100 μg / cm ２ or less. A more preferred range of the amount of silver particles is 1 μg / cm ２ or more and 30 μg / cm ２ or less.

[0041] In this embodiment, the supported amount of silver particles can be measured by immersing the porous layer (and the base material) supporting silver particles in a nitric acid solution to dissolve silver, and measuring the total amount of silver in the nitric acid solution. Alternatively, as an alternative method, the amount of silver particles can be measured by observing and analyzing the silver particles on the surface of the porous layer (and the base material) with a field emission scanning electron microscope (FE-SEM). Instead of observing and analyzing silver particles on the entire surface of the porous layer, the supported amount of silver particles may be calculated by observing and analyzing silver particles present in a partial region of the surface of the porous layer and measuring the amount of silver particles per unit area.

[0042] Furthermore, in the biological implant of this embodiment, it is preferable that in a part of all the silver particles supported on the porous layer (and the base material), the contact length between the silver particles and the porous layer (and the base material) is 70% or more of the particle diameter of the silver particles. When the contact length between the silver particles and the porous layer (and the base material) falls within this range, detachment of the silver particles from the porous layer (and the base material) can be reduced. Said contact length means the contact length observed in cross-sectional observation including the porous layer (and the base material) and the silver particles.

[0043] Said "cross-sectional observation" means cutting the porous layer (and the base material) supporting silver particles in the vertical direction with an ion beam, and observing the obtained cross-section with a transmission electron microscope (TEM).

[0044] In the biological implant of this embodiment, it is not necessary for the contact length of all silver particles supported on the porous layer (and the base material) to be 70% or more of the particle diameter of the silver particles, and it is sufficient that a part of all supported silver particles satisfies the above specification. From the viewpoint of safety, among all silver particles supported on the porous layer (and the base material), it is preferable that the proportion of silver particles satisfying the above specification is 50% or more, more preferably 70% or more, and still more preferably 80% or more.

[0045] The aspect ratio of the silver particles supported in the porous layer is preferably 1.1 or higher. This increases the contact area between the silver particles and the porous layer (and substrate) relative to the volume of the silver particles, thus improving adhesion. In this specification, "aspect ratio" means the value obtained by dividing the particle diameter (R) of the silver particles by the height (H) of the silver particles. The aspect ratio of the silver particles can be determined, as with the contact length described above, by cutting the porous layer (and substrate) supporting the silver particles vertically with an ion beam and observing the resulting cross-section with a transmission electron microscope (TEM).

[0046] In the bio-implant of this embodiment, the silver particles may be directly supported on the porous layer (and substrate). Alternatively, in the bio-implant of this embodiment, the silver particles may be supported on an oxide film on the surface of the porous layer (and substrate) formed by the oxidation of the porous layer (and substrate). Alternatively, in the bio-implant of this embodiment, the silver particles may be embedded in the oxide film on the surface of the porous layer (and substrate).

[0047] The silver particles may be supported on a portion of the porous layer, or they may be supported on the entire surface of the porous layer. Furthermore, in addition to the porous layer, they may also be supported on the substrate as described above. In that case, they may be supported on a portion of the substrate or on the entire surface. From the viewpoint of obtaining antibacterial properties for the bio-implant, it is preferable that the silver particles are supported on the porous layer and the entire surface of the substrate.

[0048] Examples of oxide film compositions include niobium oxide, titanium oxide, tantalum oxide, or zirconia oxide.

[0049] In this embodiment, if the substrate is composed of at least one selected from titanium, titanium alloy, stainless steel alloy, or cobalt-chromium alloy, the oxide film may contain oxides of the components constituting the substrate. For example, there may be a layer of oxide made of a different component from the components constituting the substrate between the substrate and the silver particles.

[0050] The thickness of the oxide film is not particularly limited, but the thickness of the oxide film may be smaller than the particle size of the silver particles supported on the substrate. Since the particle size of the silver particles in this embodiment is 5 μm or less, the thickness of the oxide film may be 1 μm or less, 0.75 μm or less, or 200 nm or less.

[0051] [Method for Manufacturing a Biomedical Implant] Next, a method for manufacturing a biomedical implant as described above will be explained. The method for manufacturing a biomedical implant according to this embodiment includes preparing a substrate having a porous layer on at least a part of its surface; performing a process to form irregularities on the porous layer; then performing an etching process on the porous layer after the process; and subsequently supporting silver particles on the porous layer.

[0052] - Steps to prepare a substrate having a porous layer on at least a portion of its surface The method for forming the porous layer on at least a portion of the substrate surface is not particularly limited and can be formed using known methods. Specifically, for example, it can be formed by additive manufacturing (additive manufacturing) using a 3D modeling program for electronic processors. Examples of additive manufacturing processes include EBM (electron beam melting), DMLS (direct metal laser sintering), DED (directed energy deposition), or BJT (binder jetting), and the layer can be formed by one of these processes alone or in combination.

[0053] Alternatively, it can be formed by titanium thermal spraying, fiber mesh sintering, bead sintering, or direct sintering of porous metals. Preferred embodiments include EBM and DMLS, which can integrally fabricate the substrate and the porous layer and fabricate porous layers of various forms.

[0054] - Process to form irregularities in the porous layer Next, irregularities are formed in the porous layer obtained above. The irregularities referred to here are irregularities obtained by so-called macro roughening treatment, and are not particularly limited as long as they can form macro-order irregularities in the porous layer. This treatment can increase the surface roughness of the porous layer. Furthermore, by going through this treatment, silver particles can be uniformly supported in the porous layer of the bio-implant of this embodiment. If necessary, the same process to form irregularities may be performed not only on the porous layer but also on the substrate.

[0055] Examples of processes for forming the aforementioned irregularities include blasting, sputtering, ion beam processing, barrel polishing, laser processing, and grinding. Among these, blasting is preferred because it is applicable to a wide range of product forms and is the least expensive manufacturing process.

[0056] Blasting is a process in which fine abrasive material is sprayed onto the surface to be processed. Examples of abrasive materials include glass beads, alumina, calcium phosphate, borax, or silicon carbide. When creating irregularities through blasting, the blasting time can be set appropriately depending on the type of abrasive used, but it is preferable to blast for about 10 to 60 seconds.

[0057] The surface roughness of the porous layer (and substrate) can be increased compared to the surface roughness of the implant body before treatment by a process that creates irregularities (also called an irregularity formation process). More specifically, this process creates a surface roughness of 1 μm or more and 3 μm or less on the porous layer (and substrate). In other words, various conditions in the irregularity formation process (for example, in the case of blasting, the size of the abrasive, the speed of the abrasive, the amount of abrasive, and the processing time) are set so that a surface roughness of about 1 μm to 3 μm is formed. The surface roughness of the porous layer (and substrate) after the irregularity formation process can be measured according to the general ISO 25178. Roughness measurement may also be performed according to JIS B 0601:2013 and JIS B 0633:2001.

[0058] ・Etching Treatment Next, the porous layer after the surface roughening treatment is subjected to etching. The etching treatment in this embodiment is a so-called micro-roughening treatment, in which the surface is roughened by bringing the etching solution into contact with the surface to be processed, utilizing the chemical reaction (corrosive action) between the etching solution and the surface to be processed. Through this treatment, fine irregularities of micro size (on the order of several hundred nm) are formed on the porous layer that is to be processed. Furthermore, even if the porous layer has a complex porous structure, the etching solution can also come into contact with the inner surface of the porous structure, so micro-sized irregularities can be uniformly formed on the inner surface of the porous structure. This etching treatment is expected to improve the micro-anchoring effect in bone formation and increase the amount of silver supported. In addition to the effect of surface roughening, the etching treatment is also expected to have effects such as dissolving the glass beads used in the blast treatment in the previous step and surface cleaning by removing organic matter. If necessary, the same etching treatment may be performed not only on the porous layer but also on the substrate.

[0059] The etching process can be carried out, for example, by immersing a bio-implant having a porous layer in an etching solution. Preferably, an acidic solution is used as the etching solution. More specifically, examples include one or more acidic solutions selected from hydrochloric acid, sulfuric acid, nitric acid, hydrogen fluoride, hydrogen peroxide, and ammonium fluoride. More preferably, a mixed acid containing ammonium fluoride, sulfuric acid, and hydrogen peroxide can be used as the acidic solution containing ammonium fluoride. The etching time is not particularly limited and can be set appropriately depending on the etching solution used. For example, when using an acidic solution containing ammonium fluoride as the etching solution, a time of 30 to 90 seconds is preferred.

[0060] - Step of supporting silver particles Next, silver particles are supported on the porous layer that has undergone each roughening treatment. The means of supporting the silver particles are not particularly limited, but for example, they can be obtained by applying a dispersion liquid containing silver particles to the porous layer (and, if necessary, also to the substrate), and then heating (heat treating) the substrate having the porous layer in an atmospheric environment.

[0061] The dispersion containing silver particles is not particularly limited as long as it is a solution in which silver particles are dispersed in liquid. For example, the solvent for the dispersion in this embodiment may be water, ethanol, 2-propanol, decane, tetradecane, etc. Furthermore, the dispersion may contain additives, and specific additives may include, for example, various surfactants such as polyethylene glycol.

[0062] Average particle size (D) of silver particles contained in the dispersion ５０ The particle size is preferably 100 nm or less. This average particle size is a value measured by dynamic light scattering.

[0063] The concentration of silver particles in the dispersion is preferably between 100 mg / L and 10,000 mg / L. This silver particle concentration range offers advantages such as ensuring the safety of the bio-implant and improving its antibacterial properties.

[0064] There are no particular limitations on the method of applying the dispersion to the substrate, but for example, the substrate having a porous layer may be immersed in the dispersion containing silver particles, or the dispersion may be sprayed onto the surface of the porous layer (and substrate) using a dispenser or spray. After applying the dispersion, the dispersion is dried so that the silver particles contained in the dispersion adhere to and are supported on the surface of the porous layer (and substrate) of the substrate. The dispersion may be dried naturally, or it may be dried by spin coating, blowing dry air, or the like.

[0065] Alternatively, methods for depositing silver without applying a silver dispersion, such as liquid-phase synthesis, sol-gel deposition, electrodeposition, mist CVD, sputtering, or vapor deposition, may be used.

[0066] Next, the substrate having a porous layer supporting silver particles is heated to a temperature of 300°C or higher in an atmospheric environment. In this embodiment, "in an atmospheric environment" means that the operation is carried out under atmospheric conditions without replacing the heating container with an inert gas or the like. The atmospheric environment may be, for example, an atmosphere consisting of approximately 78% nitrogen, 20% oxygen, and 2% other components, which is the composition of air. The heating means is not particularly limited and may be a method of heating the entire substrate using an electric furnace, or localized heating using a laser or microwave (for example, if the area where the silver particles are supported is only the porous layer, the porous layer may be heated). This heat treatment deforms the silver particles and can increase the contact area with the porous layer (and substrate). When the contact area between the silver particles and the porous layer (and substrate) increases, the silver particles adhere firmly to the porous layer (and substrate), thus reducing the possibility of the silver particles detaching. The heating temperature should be 300°C or higher, but 350°C or higher is more preferable. There is no particular upper limit to the heating temperature, but it is preferable to keep it below 700°C because silver may sublimate if it exceeds 700°C. There is no particular limit to the heating time, but it is preferable to keep it between 5 and 120 minutes, for example.

[0067] As described above, this specification discloses various aspects of technology, the main technologies among them are summarized below.

[0068] A bio-implant according to a first aspect of the present disclosure comprises a substrate having a porous layer on at least a portion of its surface, and silver particles supported on the porous layer, wherein the arithmetic mean roughness Ra of at least one of the surface and bottom portions of the porous layer is 0.20 μm or more, and the ratio of the surface arithmetic mean roughness Ra to the bottom portion of the porous layer is 0.5 to 1.5.

[0069] A bio-implant according to a second aspect of this disclosure is a bio-implant according to the first aspect, wherein the arithmetic mean roughness Ra of the surface and bottom of the porous layer is 0.20 μm or more.

[0070] A third aspect of the present disclosure is a bio-implant in which, in the first and second aspects of the bio-implant, the amount of silver particles supported on the porous layer is 1 μg / cm³ per unit area. ２ Above, 150μg / cm ２ It is as follows:

[0071] A bio-implant according to a fourth aspect of this disclosure is a bio-implant according to any of the first to third aspects, wherein in a portion of the whole silver particles supported on the porous layer, the contact length between the silver particles and the porous layer is 70% or more of the particle diameter of the silver particles.

[0072] A bio-implant according to a fifth aspect of this disclosure is a bio-implant according to a fourth aspect, wherein the proportion of silver particles in which the contact length between the silver particles and the porous layer is 70% or more of the particle diameter of the silver particles is 50% or more of the total silver particles supported in the porous layer.

[0073] A bio-implant according to the sixth aspect of this disclosure is a bio-implant according to any of the first to fifth aspects, wherein the silver particles include silver particles with a particle diameter of 5 μm or less.

[0074] A method for manufacturing a bio-implant according to the seventh aspect of this disclosure is a bio-implant according to any of the first to sixth aspects, wherein the substrate is composed of at least one selected from titanium, titanium alloy, stainless steel, cobalt-chromium alloy, zirconium alloy, tantalum, or calcium phosphate.

[0075] A bio-implant according to the eighth aspect of this disclosure is a bio-implant according to any of the first to seventh aspects, wherein the silver particles include silver particles having an aspect ratio of 1.1 or more.

[0076] A bio-implant according to the ninth aspect of this disclosure is a bio-implant according to any of the first to eighth aspects, wherein the substrate has an oxide film on its surface.

[0077] A method for manufacturing a bio-implant according to the tenth aspect of this disclosure is a method for manufacturing a bio-implant according to any of the first to ninth aspects, comprising: preparing a substrate having a porous layer on at least a portion of its surface; performing a process to form irregularities on the porous layer; then performing an etching process on the porous layer after the process; and subsequently supporting silver particles on the porous layer.

[0078] A method for manufacturing a bio-implant according to an eleventh aspect of the present disclosure is a manufacturing method according to the tenth aspect, wherein the process for forming the irregularities is at least one selected from the group consisting of blasting, sputtering, ion beam processing, barrel polishing, laser processing, and grinding.

[0079] A method for manufacturing a bio-implant according to a twelfth aspect of the present disclosure is a manufacturing method according to the tenth or eleventh aspect, which includes performing the etching process using an acidic solution.

[0080] A method for manufacturing a bio-implant according to a thirteenth aspect of the present disclosure is a manufacturing method according to any tenth to twelfth aspect, which includes applying a dispersion containing silver particles to the porous layer, and then heating the substrate having the porous layer at a temperature of 300°C or higher in an atmospheric environment to support the silver particles on the porous layer.

[0081] A method for manufacturing a bio-implant according to a fourteenth aspect of this disclosure is a manufacturing method according to any of the tenth to thirteenth aspects, which includes preparing a substrate having a porous layer on at least a portion of its surface by additive manufacturing.

[0082] The present disclosure will be further described below with reference to examples, but the present disclosure is not limited in any way by these examples.

[0083] <Test Example 1> [Sample Preparation] (Example 1) First, a disc made of Ti-6Al-4V alloy with a diameter of 14 mm (thickness: porous layer 1.2 mm, base material portion: approximately 4-5 mm) was prepared as a base material having a porous layer. Using glass beads (Potters Barotini "M-13") as an abrasive, the disc was blasted for 30 seconds in a "Blast Cabinet BS-1" manufactured by Atsuchi Iron Works. Next, the disc made of Ti-6Al-4V alloy was placed in an acid solution containing ammonium fluoride (a mixed acid containing ammonium fluoride, sulfuric acid, and hydrogen peroxide) and etched by shaking for 60 seconds. Then, a silver particle dispersion was prepared by dispersing silver particles with a particle size of 30 nm at a concentration of 1200 mg / L, and 100 μL of the prepared silver particle dispersion was dropped onto the disc made of Ti-6Al-4V alloy. Subsequently, deliquidation was performed using a Mikasa MS-A200 spin coater. Next, the titanium plate supported with silver particles was heated in an electric furnace at 350°C for 10 minutes under atmospheric conditions to obtain the example sample.

[0084] (Comparative Example) A disc made of Ti-6Al-4V alloy was prepared in the same manner as in the example, and the same etching treatment as in the example was performed (blasting was not performed). A silver particle dispersion was prepared by dispersing silver particles with a particle size of 30 nm at a concentration of 2500 mg / L, and 100 μL of the prepared silver particle dispersion was dropped onto the disc made of Ti-6Al-4V alloy. Then, the dispersion was removed using a Mikasa spin coater "MS-A200". Next, the disc made of Ti-6Al-4V alloy with the silver particles supported was heated in an electric furnace at 350°C for 10 minutes in an atmospheric atmosphere to obtain a comparative example sample.

[0085] [Cross-sectional observation of samples] The following four samples were prepared for cross-sectional observation. None of the following four samples for cross-sectional observation were subjected to any treatment to support silver particles. ・Sample 1: A sample prepared in the same manner as Comparative Example 1, except that etching was not performed (no blasting or etching) ・Sample 2: A sample prepared in the same manner as Example 1, except that etching was not performed (blasting performed, no etching) ・Sample 3: A sample prepared in the same manner as Comparative Example 1, except that the etching time was set to 90 seconds (no blasting, etching performed) ・Sample 4: A sample prepared in the same manner as Example 1, except that the etching time was set to 90 seconds (blasting and etching performed)

[0086] Each of the above samples was cut perpendicular to the surface of the porous material to prepare samples for cross-sectional observation. Cross-sectional photographs of each sample are shown in Figure 6. Figure 6 shows images obtained by imaging the cross-section of the sample at a magnification of 5000x using a scanning electron microscope (SEM).

[0087] Then, using these images, the arithmetic mean roughness Ra of each sample was calculated based on the "Method for Measuring Arithmetic Mean Roughness Ra" described above. These values ​​are summarized in Table 1.

[0088]

[0089] From the results in Figure 6 and Table 1, it was confirmed that in the porous layer obtained by performing both blasting and etching, the arithmetic mean roughness Ra of at least one of the surface and bottom portions was 0.20 μm or greater, and that the ratio of surface arithmetic mean roughness Ra to bottom arithmetic mean roughness Ra in the porous layer was between 0.5 and 1.5.

[0090] [Supporting Silver Particles] The surface (tip) and bottom (interior) of the samples obtained in the above example (with blast treatment) and comparative example (without blast treatment) were observed at 100x, 1000x, and 5000x magnification using a scanning electron microscope (SEM) (Hitachi High-Tech "S-3400N"). The respective SEM images are shown in Figure 7.

[0091] In the photographs in Figure 7, the image of the surface (left) was taken at 100x magnification, and the image on the right is a further magnified 50x (i.e., 5000x magnification). Similarly, the image of the bottom (left) was taken at 1000x magnification, and the image on the right is a further magnified 5x (i.e., 5000x magnification). In each image, the white particles represent silver particles.

[0092] As can be seen from the image in Figure 7, in both the example and the comparative example, silver particles are supported in almost the same way at the bottom (inside) of the porous layer, but at the surface (tip), the comparative example has almost no silver particles supported compared to the example.

[0093] From the above, it was confirmed that with the substrate (bio-implant) having a porous layer according to this embodiment, there is little variation in the amount of silver particles supported on the surface and bottom of the porous layer, and the silver particles are supported relatively uniformly.

Claims

1. A bio-implant comprising a substrate having a porous layer on at least a portion of its surface, and silver particles supported on the porous layer, wherein the arithmetic mean roughness Ra of at least one of the surface and bottom portions of the porous layer is 0.20 μm or more, and the ratio of the surface arithmetic mean roughness Ra to the bottom portion of the porous layer is 0.5 to 1.

5.

2. The bio-implant according to claim 1, wherein the arithmetic mean roughness Ra of the surface and bottom of the porous layer is 0.20 μm or more.

3. The amount of silver particles supported on the porous layer per unit area is 1 μg / cm³. ２ Above, 150μg / cm ２ The bio-implant according to claim 1 or 2, which is as follows:

4. The bio-implant according to claim 3, wherein in a portion of the whole silver particles supported on the porous layer, the contact length between the silver particles and the porous layer is 70% or more of the particle diameter of the silver particles.

5. The bio-implant according to claim 4, wherein the proportion of silver particles in which the contact length between the silver particles and the porous layer is 70% or more of the particle diameter of the silver particles is 50% or more of the total silver particles supported in the porous layer.

6. The bio-implant according to any one of claims 1 to 5, wherein the silver particles include silver particles with a particle diameter of 5 μm or less.

7. The bio-implant according to any one of claims 1 to 6, wherein the substrate is composed of at least one selected from titanium, titanium alloy, stainless steel, cobalt-chromium alloy, zirconium alloy, tantalum, or calcium phosphate.

8. The bio-implant according to any one of claims 1 to 7, wherein the silver particles include silver particles having an aspect ratio of 1.1 or more.

9. The bio-implant according to any one of claims 1 to 8, wherein the substrate has an oxide film on its surface.

10. A method for manufacturing a bio-implant according to any one of claims 1 to 9, comprising: preparing a substrate having a porous layer on at least a portion of its surface; performing a process to form irregularities on the porous layer; then performing an etching process on the porous layer after the process; and subsequently supporting silver particles on the porous layer.

11. The method for manufacturing a bio-implant according to claim 10, wherein the process for forming the irregularities is at least one selected from the group consisting of blasting, sputtering, ion beam processing, barrel polishing, laser processing, and grinding.

12. A method for manufacturing a bio-implant according to claim 10 or 11, wherein the etching process is performed using an acidic solution.

13. A method for manufacturing a bio-implant according to any one of claims 10 to 12, comprising applying a dispersion containing silver particles to the porous layer, and then heating the substrate having the porous layer at a temperature of 300°C or higher in an atmospheric environment to support the silver particles on the porous layer.

14. A method for manufacturing a bio-implant according to any one of claims 10 to 13, comprising preparing a substrate having a porous layer on at least a portion of its surface by additive manufacturing.

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