WO2012036286A1 - Artificial bone, artificial bone manufacturing device, and artificial bone manufacturing method - Google Patents

Artificial bone, artificial bone manufacturing device, and artificial bone manufacturing method Download PDF

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Publication number
WO2012036286A1
WO2012036286A1 PCT/JP2011/071262 JP2011071262W WO2012036286A1 WO 2012036286 A1 WO2012036286 A1 WO 2012036286A1 JP 2011071262 W JP2011071262 W JP 2011071262W WO 2012036286 A1 WO2012036286 A1 WO 2012036286A1
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Prior art keywords
artificial bone
bone
bioceramics
plasma
artificial
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PCT/JP2011/071262
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French (fr)
Japanese (ja)
Inventor
智志 浜口
悠 森口
一仁 増田
潔 岡田
陽 名井
秀樹 吉川
大成 李
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国立大学法人大阪大学
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Priority to JP2012534072A priority Critical patent/JPWO2012036286A1/en
Publication of WO2012036286A1 publication Critical patent/WO2012036286A1/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
    • A61L27/3641—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix characterised by the site of application in the body
    • A61L27/3645—Connective tissue
    • A61L27/365—Bones
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/02—Inorganic materials
    • A61L27/10—Ceramics or glasses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/56—Porous materials, e.g. foams or sponges

Definitions

  • the present invention relates to an artificial bone containing bioceramics, an artificial bone manufacturing apparatus, and an artificial bone manufacturing method.
  • Patent Document 1 proposes a calcium phosphate-based sintered material that has a porous body having open pores and facilitates entry of bone tissue into the open pores.
  • the conventional artificial bone is an artificial bone containing hydroxyapatite, and the structure has been improved so as to activate bone regeneration by closely communicating the pores of hydroxyapatite.
  • bone tissue cells osteoblasts
  • blood vessels enter the pores, and bone tissue formation is performed at an early stage.
  • the present invention has been made in order to solve the above technical problem, and has improved (modified) properties without improving (remodeling) the structure, so that the artificial bone and artificial bone activated by bone regeneration can be obtained. It aims at providing a manufacturing apparatus and an artificial bone manufacturing method.
  • the characteristic configuration of the artificial bone of the present invention is an artificial bone containing bioceramics, and the bioceramics have a modified structure activated by bone regeneration. Therefore, by improving (modifying) the properties without improving (remodeling) the structure, an artificial bone activated by bone regeneration can be obtained.
  • the modified structure is a plasma modified structure.
  • atmospheric pressure plasma can be irradiated in the atmosphere. Therefore, a vacuum device is not required and the reforming process is easy. As a result, it can be used intraoperatively.
  • the bioceramics are porous. Therefore, compared with non-porous bioceramics, the modified area activated by bone regeneration is wide, and the osteoconductivity is improved. As a result, early healing in the bone defect portion is possible.
  • the bioceramics have continuous spherical open pores.
  • the continuous spherical open pores are spherical and communicate in a three-dimensional manner. Therefore, when bone regeneration is activated by plasma irradiation, it is easy to introduce combustion gas into the pores, and a wide range of plasma modification is possible.
  • the continuous spherical open pores have larger pore diameters than the intergranular void-like open pores and closed pores, so that biological fluid and bone tissue cells (osteoblasts) can penetrate into the pores, thereby improving the bone conduction ability. It can improve.
  • the bioceramics contain calcium phosphate-containing ceramics or glass ceramics. Since calcium phosphate-containing ceramics or glass ceramics are generally used as artificial bone materials, they are easily available. In addition, calcium phosphate-containing ceramics (for example, hydroxyapatite) is also a component of living bone, and is easily adapted to regenerated bone.
  • the angle formed between the tangent of the droplet and the surface of the bioceramic can be 0 to 15 degrees.
  • the composition ratio (O / P) of oxygen (O) and phosphorus (P) is 6.0 to 7.0 on the surface of the bioceramic.
  • the composition ratio (O / Ca) of oxygen (O) to calcium (Ca) may be 4.0 to 5.0.
  • an artificial bone manufacturing apparatus including bioceramics, and the bioceramics are subjected to a modification process for activating bone regeneration.
  • a processing device According to the artificial bone manufacturing apparatus according to the present invention, the above-described artificial bone of the present invention can be manufactured. Therefore, it is possible to manufacture an artificial bone activated by bone regeneration by modifying without improving the structure.
  • the processing apparatus irradiates the bioceramics with plasma.
  • plasma can be irradiated in the atmosphere. Therefore, a vacuum device is not required and the reforming process is easy. As a result, it can be used intraoperatively.
  • the artificial bone manufacturing apparatus further includes a region control device that controls the region of the modification process.
  • a region control device that controls the region of the modification process.
  • the region control apparatus controls the plasma irradiation time to the bioceramics.
  • the plasma When extending the plasma irradiation time to bioceramics, the plasma reaches the non-modified layer inside the artificial bone, and the non-modified layer inside the artificial bone has a modified structure that activates bone regeneration. obtain.
  • the plasma irradiation time is shortened, a modified structure in which the non-modified layer near the surface of the artificial bone is activated by bone regeneration can be used. As a result, the modified portion can be selectively formed, and an artificial bone according to the purpose can be manufactured.
  • the region control device controls the pressure in the surrounding space including the artificial bone.
  • plasma can be introduced into the porous ceramic ceramic.
  • the inside of the porous bioceramics is activated by bone regeneration.
  • plasma can be introduced to every corner of the pore.
  • the modified porous structure of the bioceramics can be more reliably formed.
  • a characteristic configuration of the artificial bone manufacturing method according to the present invention is a method for manufacturing an artificial bone containing bioceramics, and the bioceramics are subjected to a modification process for activating bone regeneration. Process steps to include.
  • the artificial bone manufacturing method of the present invention the above-described artificial bone of the present invention can be manufactured. Therefore, it is possible to manufacture an artificial bone activated by bone regeneration by modifying without improving the structure.
  • the treatment step is performed by irradiating the bioceramics with plasma.
  • the method further includes a region control step of controlling the region of the modification process.
  • the bioceramics are oxidized to increase the oxygen composition ratio of the bioceramics.
  • XPS X-ray photoelectron analysis
  • FIG. 1 is a photograph showing an artificial bone 100 and a conventional artificial bone 200 according to Embodiment 1 of the present invention.
  • FIG. 1A1 is a photograph showing the artificial bone 100
  • FIG. 1A2 is a photograph in which a part of the cross section of the artificial bone 100 is enlarged.
  • the artificial bone 100 is an artificial material that compensates for a defect in a living bone.
  • the artificial bone 100 includes an unmodified layer 110 and a modified layer 120.
  • the modified layer 120 has a modified structure activated by bone regeneration.
  • the modified layer 120 includes bioceramics.
  • An example of a modified structure activated by bone regeneration is a plasma modified structure.
  • Plasma modification can occur by irradiating the bioceramics with plasma. Plasma modification can improve the hydrophilicity, cell adhesion, and cell growth of the modified layer 120.
  • the bioceramics contained in the modified layer 120 are porous.
  • the modified layer 120 has a plurality of pores. It is the wall that separates the pores from the pores. There are several types of pores. For example, they are continuous spherical open pores, intergranular void-like open pores, and closed pores. Details of the pores will be described later with reference to FIG.
  • FIG. 1 (a2) also represents the penetration depth of water when a water drop is dropped on the artificial bone 100.
  • the modified layer 120 is a portion where water easily enters (easy to enter layer), and the non-modified layer 110 represents a portion where water is difficult to enter (an intrusion non-easy layer).
  • FIG. 1 (b1) is a photograph showing a conventional artificial bone 200
  • FIG. 1 (b2) is a photograph in which a part of the conventional artificial bone 200 is enlarged.
  • the artificial bone 200 contains bioceramics and is porous.
  • the artificial bone 200 does not have a modified structure activated by bone regeneration. Therefore, the surface of the artificial bone 200 is poorly hydrophilic and repels liquid.
  • FIG. 2 is a photograph or schematic diagram showing the porosity of the artificial bone 100. Various pores will be described with reference to FIG.
  • FIG. 2 (a1) is a photograph showing the artificial bone 100a
  • FIG. 2 (a2) is a photograph in which a part of the cross section of the artificial bone 100a is enlarged.
  • the artificial bone 100a has continuous spherical open pores.
  • the pore is a minute cavity included in a group of objects
  • the open pore is a pore connected to the outside air.
  • the continuous spherical open pores are a plurality of open pores, each of which is spherical and is a plurality of open pores communicating three-dimensionally.
  • FIG. 2 (b1) shows an artificial bone 100b
  • FIG. 2 (b2) is a schematic view of an enlarged part of the artificial bone 100b
  • FIG. 2 (b3) further enlarges a part of the artificial bone 100b.
  • FIG. The artificial bone 100b has an internal structure different from that of the artificial bone 100a. That is, the artificial bone 100b is an aggregate of microparticles (individuals), and there are gaps between adjacent microparticles, which form pores. That is, the artificial bone 100b has intergranular void-like open pores.
  • the intergranular void-like open pores are open pores in which voids formed between particles are continuous.
  • FIG. 2 (c1) is a photograph showing the artificial bone 100c
  • FIG. 2 (c2) is a photograph showing an enlarged part of the cross section of the artificial bone 100c.
  • the artificial bone 100c has closed pores. Closed pores are pores that are isolated inside an object. Therefore, it is not connected to the outside air. Each of the plurality of pores included in the artificial bone 100c is divided by a wall portion.
  • FIG. 3 is a table showing an example of a conventional artificial bone 200.
  • the artificial bone 200 contains bioceramics like the artificial bone 100, the artificial bone 200 does not have a modified structure activated by bone regeneration.
  • the artificial bone 100 can be manufactured by subjecting the bioceramics contained in the artificial bone 200 to a modification treatment for activating bone regeneration.
  • the artificial bone 200 is a modified unprocessed artificial bone that has not been modified, and the artificial bone 100 is a modified artificial bone that has been modified.
  • a specific example of the modification process for activating bone regeneration is a plasma modification process, which can be performed by irradiating the bioceramics with plasma.
  • the artificial bone 200a is an artificial bone sold by PENTAX HOYA under the trade name Bonfil.
  • the composition of the artificial bone 200a is hydroxyapatite.
  • the artificial bone 200a has closed pores and does not communicate. Depending on the product, the pore diameter is 90, 200, 300 ⁇ m, and the porosity is 60, 70%.
  • the artificial bone 200b is an artificial bone sold by Covalent Materials under the trade name Neoborn.
  • the composition of the artificial bone 200b is hydroxyapatite.
  • the artificial bone 200b has continuous spherical open pores and is communicated.
  • the pore diameter is about 150 ⁇ m and has a porosity of 75%.
  • the communication diameter is 50 ⁇ m.
  • the average pore diameter of the artificial bone 200b is preferably 90 ⁇ m or more and 600 ⁇ m or less from the viewpoint of facilitating introduction of cells and nutrients for bone regeneration into the artificial bone. Further, the porosity is 50% or more and 90% or less, and particularly preferably 65% or more and 85% or less. Further, the average pore diameter of the communicating portion of the continuous spherical open pores of the artificial bone 200b is preferably 20 ⁇ m or more, and more preferably 40 ⁇ m or more.
  • the artificial bone 200b can be manufactured by stirring foaming. Specifically, the artificial bone 200b can be manufactured by executing steps 1 to 4 described below.
  • Polyethyleneimine or the like is added to the hydroxyapatite powder as a cross-linkable resin, and mixed and crushed using water as a dispersion medium to prepare a slurry (step 1).
  • polyoxyethylene lauryl ether or the like is added as a foaming agent, and stirred to foam (Step 2).
  • sorbitol glycidyl ether or the like is added as a crosslinking agent, and the resulting foamy slurry is cast and dried with the foam structure fixed (step 3).
  • the foamy slurry is sintered at about 800 to 1300 ° C. (step 4).
  • the artificial bone 200c is an artificial bone sold under the name Seratite from Nippon Special Ceramics.
  • the composition of the artificial bone 200c is 70% hydroxyapatite and 30% ⁇ -TCP ( ⁇ -tricalcium phosphate).
  • the artificial bone 200c is porous and has a pore diameter of 150 to 200 ⁇ m, but the connectivity is not so good.
  • the communication diameter is 40 to 80 ⁇ m.
  • the artificial bone 200d is an artificial bone sold under the name Bone Serum P by Olympus Terumo Biomaterial.
  • the composition of the artificial bone 200d is hydroxyapatite.
  • the artificial bone 200d is porous and has a pore diameter of 30 to 400 ⁇ m, but has no connectivity.
  • the artificial bone 100 can be manufactured by subjecting the bioceramics contained in the artificial bone 200 to a modification treatment for activating bone regeneration.
  • various artificial bones can be adopted.
  • the artificial bone 200 preferably includes bioceramics made of a material that does not have biological harm and has sufficient mechanical strength. Specifically, it contains at least one of alumina, zirconia, silica, mullite, diopside, wollastonite, alite, belite, arkelmanite, montcerite, biological glass, and calcium phosphate ceramics. Calcium phosphate ceramics are most suitable because of their excellent biocompatibility.
  • the artificial bone 200 preferably contains hydroxyapatite, which is a main component of bone.
  • FIG. 4 is a schematic view showing a site where an artificial bone is transplanted into an experimental animal. Rabbits were used as experimental animals. A cylindrical artificial bone 100 and an artificial bone 200 (both having a diameter of 6 mm and a length of 15 mm) were implanted into the femoral medial condyle of a rabbit, and the bone regeneration functions of the artificial bone 100 and the artificial bone 200 were compared. The artificial bone 100 was produced by irradiating the artificial bone 200b described with reference to FIG. 3 with plasma for 1 hour and 30 minutes.
  • FIG. 5 is a photograph showing the degree of bone regeneration in the artificial bone 100 and the artificial bone 200.
  • FIG. 5A shows the degree of bone regeneration in the artificial bone 100
  • FIG. 5B shows the degree of bone regeneration in the artificial bone 200.
  • the result is 3 weeks after the artificial bone 100 and the artificial bone 200 are transplanted into the rabbit.
  • the circular cross section of the cylinder was divided into three regions (Zone 1, Zone 2, and Zone 3 in order from the outer periphery to the inside), and the degree of bone regeneration in each region was compared. In all three regions of each of the artificial bone 100 and the artificial bone 200, biological fluid and undifferentiated cells have invaded. However, the degree of invasion of bone tissue cells (osteoblasts) was more suitable for the artificial bone 100 than for the artificial bone 200.
  • osteoblasts bone tissue cells
  • FIG. 6 is a photograph showing the degree of bone regeneration in Zone 3 of the artificial bone 100 and Zone 3 of the artificial bone 200.
  • 6A shows the degree of bone regeneration in the artificial bone 100
  • FIG. 6B shows the degree of bone regeneration in the artificial bone 200.
  • a white part shows the wall part (part which is not a continuous spherical open pore) of an artificial bone.
  • the artificial bone 100 according to the first embodiment of the present invention has been described above with reference to FIGS.
  • the artificial bone of the present invention is an artificial bone containing bioceramics, and the bioceramics have a modified structure activated by bone regeneration. Therefore, by improving (modifying) the properties without improving (remodeling) the structure, an artificial bone activated by bone regeneration can be obtained.
  • the modified structure is a plasma modified structure.
  • atmospheric pressure plasma can be irradiated in the atmosphere. Therefore, a vacuum device is not required and the reforming process is easy. As a result, it can be used intraoperatively.
  • the bioceramics are porous. Therefore, compared with non-porous bioceramics, the modified area activated by bone regeneration is wide, and the osteoconductivity is improved. As a result, early healing in the bone defect portion is possible.
  • the bioceramics have continuous spherical open pores.
  • the continuous spherical open pores are spherical and communicate in a three-dimensional manner. Therefore, when bone regeneration is activated by plasma irradiation, it is easy to introduce combustion gas into the pores, and a wide range of plasma modification is possible.
  • the continuous spherical open pores have larger pore diameters than the intergranular void-like open pores and closed pores, so that biological fluid and bone tissue cells (osteoblasts) can penetrate into the pores, thereby improving the bone conduction ability. It can improve.
  • the bioceramics contain calcium phosphate-containing ceramics or glass ceramics. Since calcium phosphate-containing ceramics or glass ceramics are generally used as artificial bone materials, they are easily available. Furthermore, calcium phosphate-containing ceramics are also components of living bones and are easily adapted to regenerated bone.
  • all the artificial bone 100 is not necessarily made of bioceramics. Some can be bioceramics. Moreover, not all bioceramics have a modified structure in which bone regeneration is activated. A part of bioceramics may have a modified structure in which bone regeneration is activated. Therefore, the modified portion can be selected, and the artificial bone can be properly used according to the purpose. In particular, when a modified structure can be provided up to the deep part of the artificial bone, bone regeneration extends to the deep part of the artificial bone, and early healing at the bone defect part is possible.
  • the artificial bone 100 having the non-modified layer 110 and the modified layer 120 has been described.
  • the artificial bone 100 only needs to have the modified layer 120 as long as it has the modified layer 120.
  • the presence or absence of 110 is not limited.
  • the manufactured artificial bone 100 has only the modified layer 120 among the non-modified layer 110 and the modified layer 120.
  • the modified structure activated by bone regeneration is not limited to the plasma modified structure.
  • the modified structure is activated by bone regeneration, it can be a modified structure by dilute hydrochloric acid treatment.
  • the artificial bone 200b is selected as the target of the plasma processing.
  • the target of is not limited to the artificial bone 200b.
  • the artificial bone 200a, the artificial bone 200c, the artificial bone 200d, and other various artificial bones described with reference to FIG. 3 can be used.
  • FIG. 7 is a schematic view showing an artificial bone manufacturing apparatus 300 according to Embodiment 2 of the present invention.
  • the artificial bone 100 is manufactured by the artificial bone manufacturing apparatus 300.
  • the artificial bone manufacturing apparatus 300 functions as a processing apparatus that irradiates the bioceramics included in the artificial bone 200 with plasma A and performs a modification process for activating bone regeneration.
  • the manufacturing method using the artificial bone manufacturing apparatus 300 includes a processing step of performing a modification process for activating bone regeneration on bioceramics.
  • the treatment process is performed by irradiating the bioceramics with plasma.
  • the artificial bone manufacturing apparatus 300 includes a gas supply pipe 312, a first electrode 314 a, a second electrode 314 b, and a voltage application device 316.
  • the gas supply pipe 312 is a gas supply pipe made of an insulator having an inner diameter of about 2 to 5 mm (for example, quartz, glass, plastic, etc.).
  • the gas supply pipe 312 has a jet port 312a.
  • the helium gas B that has passed through the inner cavity of the gas supply pipe 312 is ejected from the ejection port 312a.
  • the first electrode 314a and the second electrode 314b are a pair of coaxial plasma generating electrodes.
  • the 1st electrode 314a and the 2nd electrode 314b are each installed in the upstream and downstream on the outer periphery of the edge part by the side of the jet nozzle 312a of the gas supply pipe 312.
  • a pulse voltage is applied to the first electrode 314a, and the second electrode 314b is set to the ground potential.
  • the voltage application device 316 applies a low-frequency pulse voltage of about 10 to 100 kHz (for example, 6 to 12 kV, 13 kHz) between the first electrode 314a and the second electrode 314b to cause pulse discharge, thereby generating a jet outlet.
  • a plasma jet hereinafter also referred to as an LF (Low Frequency) plasma jet
  • LF Low Frequency plasma jet
  • LF plasma jet has rare features in two respects.
  • a plasma jet having a shape with a large ratio of length to diameter, that is, an aspect ratio can be obtained.
  • the columnar discharge is not maintained, but a small plasma lump (plasma bullet) is synchronized with the power supply frequency, and has a very high velocity compared to the medium gas flow (for example, It is moving at about 10,000 times the gas flow rate: about 10 km / s). Therefore, the plasma bullet is not moved by the medium gas flow, but is driven by the electric field and moved.
  • a plasma lump (plasma bullet) is ejected in a pulse shape, and therefore, a thermal non-equilibrium state is created by non-equilibrium in time. Since it is a thermal non-equilibrium plasma, it is possible to irradiate a high energy component without increasing the temperature of the object.
  • FIG. 8 is a schematic diagram showing another artificial bone manufacturing apparatus 320 according to Embodiment 2 of the present invention.
  • the artificial bone manufacturing apparatus 320 includes an artificial bone manufacturing apparatus 300 and a first region control apparatus 330.
  • the first area control device 330 controls the area of the reforming process. Details of the function of the first area control device 330 will be described with reference to FIG.
  • the components included in the artificial bone manufacturing apparatus 300 have been described with reference to FIG.
  • the manufacturing method by the artificial bone manufacturing apparatus 320 includes a processing step of performing a modification process for activating bone regeneration on the bioceramics and a region control step of controlling the region of the modification process.
  • the region control process is executed by controlling the plasma irradiation time to the bioceramics.
  • FIG. 9 is a photograph showing the artificial bone 100 having the modified layer 120 with various thicknesses.
  • the first region control device 330 can control the thickness of the modified layer 120 by controlling the plasma irradiation time to the bioceramics.
  • FIG. 9A shows an artificial bone that is not irradiated with plasma (ie, an artificial bone 200).
  • FIG. 9B shows an artificial bone 100 that has been plasma-irradiated for 10 seconds.
  • FIG. 9C shows the artificial bone 100 that has been plasma-irradiated for 1 minute.
  • FIG. 9D shows an artificial bone 100 that has been plasma-irradiated for 5 minutes.
  • FIG. 9E shows an artificial bone 100 that has been plasma-irradiated for 10 minutes.
  • FIG. 9F shows the artificial bone 100 that has been plasma-irradiated for 30 minutes.
  • FIG. 9G shows the artificial bone 100 that has been plasma-irradiated for 60 minutes. As the irradiation time increases, the thickness of the artificial bone modified layer 120 increases.
  • FIG. 10 is a graph showing the relationship between the plasma irradiation time to the artificial bone 200 and the thickness of the modified layer 120.
  • the vertical axis represents the thickness of the modified layer 120 of the artificial bone 100
  • the horizontal axis represents the plasma irradiation time on the surface of the artificial bone 100.
  • the thickness of the modified layer 120 was about 120 ⁇ m when the irradiation time was 10 seconds, about 300 ⁇ m when the irradiation time was 1 minute, and about 350 ⁇ m when the irradiation time was 5 minutes.
  • the thickness of the artificial bone modified layer 120 is about 460 ⁇ m, when the irradiation time is 30 minutes, it is about 820 ⁇ m, and when the irradiation time is 60 minutes, it is about 890 ⁇ m. It was. As the irradiation time increases, the thickness of the artificial bone modified layer 120 increases.
  • FIG. 11 is a schematic diagram showing still another artificial bone manufacturing apparatus 400 according to Embodiment 2 of the present invention.
  • the artificial bone manufacturing apparatus 400 includes an artificial bone manufacturing apparatus 300 and a second area processing apparatus 420 that controls the area of the modification process.
  • the components included in the artificial bone manufacturing apparatus 300 have been described with reference to FIG.
  • the manufacturing method using the artificial bone manufacturing apparatus 400 includes a processing step of performing a modification process for activating bone regeneration on the bioceramics and a region control step of controlling the region of the modification process.
  • the region processing step is executed by controlling the pressure in the surrounding space including the artificial bone.
  • the second region processing device 420 controls the region of the reforming process by controlling the pressure in the surrounding space including the artificial bone.
  • the second region processing apparatus 420 includes a chamber 402 and a pressure increasing / decreasing apparatus 404.
  • An artificial bone 200 is disposed inside the chamber 402 and defines a peripheral space including the artificial bone 200.
  • the pressurizing / depressurizing device 404 can adjust the number of repetitions of pressure increase and pressure reduction according to the degree of communication of the artificial bone 200. By repeating the pressure increase and the pressure reduction, the plasma A penetrates into the artificial bone 200 and the inside of the artificial bone 200 is subjected to plasma processing. As a result, the thickness of the modified layer 120 of the artificial bone increases with an increase in the number of repetitions of pressure increase and pressure reduction.
  • the configuration of the artificial bone manufacturing apparatus capable of controlling the pressure in the surrounding space including the artificial bone is not limited to the configuration of the artificial bone manufacturing apparatus 400.
  • the artificial bone manufacturing apparatus 600 described below with reference to FIG. 12 can also control the pressure in the surrounding space including the artificial bone.
  • FIG. 12 is a schematic diagram showing still another artificial bone manufacturing apparatus 600 according to Embodiment 2 of the present invention.
  • the artificial bone manufacturing apparatus 600 includes a plasma generator 610, a plasma chamber 620, and a third region processing apparatus 630.
  • the plasma generator 610 generates plasma A by forming a dielectric barrier discharge.
  • the plasma generator 610 includes an upper electrode and a dielectric (for example, a glass plate).
  • the voltage applied to the plasma generator 610 is a voltage (including a sine wave voltage and a pulse voltage) that varies periodically with time in the range of 10 to 100 kHz.
  • the plasma chamber 620 includes a first gate 622 for introducing the plasma generation gas B (air, helium gas, etc.), a second gate 624 for leading the exhaust gas from the plasma chamber 620 to the decompression chamber 630, and the artificial bone manufacturing apparatus 600.
  • exhaust means 626 for exhausting the exhaust gas C to the outside.
  • a sample stage 628 on which the artificial bone 200 is disposed and a plasma generator 610 are provided, and a peripheral space including the artificial bone is defined.
  • the plasma generator 610 and the plasma chamber 620 function as a processing apparatus that performs a modification process for activating bone regeneration on bioceramics.
  • the third region processing device 630 controls the region of the reforming process by controlling the pressure in the surrounding space including the artificial bone.
  • the third region processing apparatus 630 includes a chamber 632 and a pressure increasing / decreasing apparatus 634.
  • the pressure increasing / decreasing device 634 is an exhaust pump, a piston, a diaphragm or the like that adjusts the pressure in the pressure reducing chamber 632.
  • the pressure increase / decrease device 634 can adjust the discharge speed of the exhaust gas D in the pressure reduction chamber 632 to control the pressure increase / decrease in the surrounding space including the artificial bone.
  • Dielectric barrier discharge can be easily formed using various power sources from commercial to high frequency specifications, and plasma can be generated.
  • the artificial bone 200 is placed in the plasma chamber to reduce the pressure in the plasma chamber. be able to. Therefore, the plasma can be penetrated into the pores of the artificial bone 200 (inside the artificial bone 200), and the inside of the artificial bone 200 can be modified.
  • FIG. 13 is a diagram for explaining changes in wettability due to artificial bone surface treatment.
  • FIG. 13A is a photograph showing the wettability of the artificial bone 200 (conventional artificial bone).
  • FIG. 13B is a photograph showing the wettability of the artificial bone 100 (the artificial bone of the present invention).
  • FIG. 13C is a graph showing the contact angle of the artificial bone.
  • the artificial bone 100 was manufactured by irradiating the artificial bone 200 with plasma for 5 minutes.
  • a droplet is dropped on the surface of the artificial bone 100 and the artificial bone 200, and the contact angle between the droplet and the artificial bone (the tangent of the droplet and the solid surface (the artificial bone surface ) was measured.
  • the contact angle of the artificial bone 200 was about 70 degrees.
  • the contact angle of the artificial bone 100 was about 12 degrees. Due to the surface modification of the artificial bone by plasma irradiation, the contact angle between the droplet and the artificial bone became 10 to 15 degrees, and the wettability increased. It can be judged that the surface of the artificial bone is modified by the plasma irradiation and the hydrophilicity is increased.
  • the degree of modification of the surface and inside of the artificial bone progressed, and the wettability of the artificial bone could be increased.
  • the plasma irradiation time exceeded 30 minutes, the contact angle became 0 degrees.
  • the artificial bone surface modification by plasma irradiation increased wettability (hydrophilicity), the contact angle between the droplet and the artificial bone became narrow, and the contact angle between the droplet and the artificial bone became 0-15 degrees. .
  • the artificial bone 200 having the grain boundary void open pores or the artificial bone 200 having the closed pores is irradiated with plasma.
  • plasma easily enters the artificial bone. This is because the continuous spherical open pores have higher pore connectivity than the grain boundary void-like open pores and closed pores. Therefore, according to the artificial bone 100 produced by irradiating plasma on the artificial bone 200 having continuous open pores, the degree of modification inside the artificial bone proceeds and the wettability of the artificial bone can be increased.
  • FIG. 14 is a graph showing the results of X-ray photoelectron analysis (XPS: X-ray Photoelectron Spectroscopy) on the artificial bone surface.
  • the horizontal axis of the graph indicates the binding energy, and the vertical axis of the graph indicates the absorption intensity (relative intensity).
  • (A) is the result of X-ray photoelectron analysis on the surface of the artificial bone 200
  • (b) is the result of X-ray photoelectron analysis on the upper surface of the artificial bone 100
  • (c) is the result of the lower surface of the artificial bone 100. It is a result of an X-ray photoelectron analysis.
  • the upper surface of the artificial bone 100 is positioned on the high plasma density side in the plasma processing chamber, and the lower surface of the artificial bone 100 is positioned on the low plasma density side in the plasma processing chamber. It was.
  • Plasma was generated using a mixed gas of He and O 2 (He 80%, O 2 20%), and the surface of the artificial bone 200 was irradiated with plasma to produce the artificial bone 100.
  • He He 80%, O 2 20%
  • plasma irradiated with plasma to produce the artificial bone 100.
  • an X-ray photoelectron analyzer (product number: ESCA-850M / manufactured by Shimadzu Corporation) was used.
  • Table 1 is a table showing the results of X-ray photoelectron analysis on the artificial bone surface (composition ratio of the artificial bone surface).
  • the artificial bone to be analyzed contains hydroxyapatite as a bioceramic.
  • the ratio (Ca / P) of calcium (Ca) to phosphorus (P) was 1.29.
  • the ratio (O / P) of oxygen (O) to phosphorus (P) is 4.49, and the ratio of oxygen (O) to calcium (Ca) (O / Ca). ) was 3.47.
  • Ca / P was 1.33
  • O / P was 6.45
  • O / Ca was 4.85.
  • Ca / P was 1.28
  • O / P was 6.09
  • O / Ca was 4.75.
  • the types of elements and the composition ratios of the elements may be different.
  • ⁇ -TCP ⁇ -tricalcium phosphate
  • the constituent ratio of the elements is different from that when hydroxyapatite is included.
  • the glass ceramics are included as the bioceramics, the types and the composition ratios of the elements are different from those in the case where the hydroxyapatite is included.
  • plasma is generated using a mixed gas of He and O 2 (He 80%, O 2 20%), and the surface of the artificial bone 200 is irradiated with plasma to form the artificial bone 100.
  • a mixed gas of He and O 2 may be a mixed gas containing oxygen, such as a mixed gas of argon (Ar) and oxygen or a mixed gas of nitrogen and oxygen.
  • the plasma irradiation time to bioceramics when the plasma irradiation time to bioceramics is increased, the plasma reaches the unmodified layer inside the artificial bone,
  • the non-modified layer inside the bone can be made into a modified structure in which bone regeneration is activated.
  • a modified structure in which the non-modified layer near the surface of the artificial bone is activated by bone regeneration can be used.
  • the modified portion can be selectively formed, and an artificial bone according to the purpose can be manufactured.
  • plasma can be introduced into the porous ceramic ceramic by decompressing the surrounding space.
  • plasma can be introduced to every corner of the pore.
  • the modified porous structure of the bioceramics can be more reliably formed.
  • the control target by the region control device is limited to the plasma irradiation time to the bioceramics and the pressure in the surrounding space including the artificial bone.
  • the region control device may include a moving device that moves the position of the plasma processing device to change the irradiation position on the bioceramics.
  • the pressure and type of plasma to be irradiated are not limited.
  • the plasma temperature is equal to or lower than the sintering temperature of bioceramics, the bone regeneration can be activated without changing the structure of the bioceramics.
  • an artificial bone manufacturing apparatus including each of a first region control device that controls the plasma irradiation time, a second region control device that controls the pressure in the surrounding space, and a third region control device.
  • the number of area control devices provided in the artificial bone manufacturing apparatus of the present invention is not limited to one.
  • the artificial bone manufacturing apparatus 400 may further include a first region control device that controls the plasma irradiation time in the artificial bone manufacturing apparatus 300.
  • the artificial bone manufacturing apparatus 600 may further include a first region control device in the plasma generation device 610.
  • the artificial bone manufacturing apparatus 400 and the artificial bone manufacturing apparatus 600 can control the plasma irradiation time and the control of the pressure in the surrounding space, and can accurately determine the position, size, and range of the processing region in the bioceramics. It can be controlled.
  • the artificial bone, the artificial bone manufacturing apparatus, and the artificial bone manufacturing method of the present invention can be used to realize defect filling in bone defects and voids mainly in the medical field such as surgery and orthopedics.

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Abstract

The purpose of the present invention is to provide an artificial bone in which bone regeneration is activated by improving (modifying) the properties of the structure. The artificial bone (100) contains bioceramics, and the bioceramics have a modified structure in which bone regeneration is activated. The modified structure can be a plasma modified structure. The bioceramics can be porous. The bioceramics have connected spherical open pores. The bioceramics can contain calcium phosphate-containing ceramics or glass ceramics.

Description

人工骨、人工骨製造装置及び人工骨製造方法Artificial bone, artificial bone manufacturing apparatus and artificial bone manufacturing method
　本発明は、バイオセラミックスを含む人工骨、人工骨製造装置及び人工骨製造方法に関する。 The present invention relates to an artificial bone containing bioceramics, an artificial bone manufacturing apparatus, and an artificial bone manufacturing method.
　従来から外科、整形外科等の医療分野において、疾病、事故、手術等によって生じた骨の欠損部及び空隙に対して、自分の他の身体部分の骨を採取、充填することで骨組織の再建を図ることが広く行われてきた。しかし、骨採取のための手術は合併症が多く大きな苦痛を伴う上に、骨採取に要する費用や労力も多大である。また、欠損部が広範囲に及ぶ場合、欠損部を人骨だけで補綴するには十分な量が確保できないことも多い。このため、近年、補綴用人工骨材に関する研究が盛んに行われている。例えば、ハイドロキシアパタイトは、骨補填材として生体内に埋入した場合、これを足場として速やかに骨修復が行われ、新生骨と直接結合するという優れた骨伝導能を発揮する。また、β－リン酸三カルシウム（β－ＴＣＰ）も、生体内で分解され易く、徐々に新生骨に置換するという特徴を有している。 Traditionally, in the medical field such as surgery and orthopedics, bone tissue is reconstructed by collecting and filling bones of other body parts for bone defects and voids caused by diseases, accidents, surgery, etc. Has been widely practiced. However, the operation for bone collection has many complications and great pains, and the cost and labor required for bone collection are also great. Moreover, when a defect part covers a wide range, it is often impossible to secure a sufficient amount for prosthesis with a human bone alone. For this reason, research on artificial bones for prosthesis has been actively conducted in recent years. For example, when hydroxyapatite is embedded in a living body as a bone grafting material, bone repair is quickly performed using this as a scaffold, and excellent bone conduction ability of directly bonding to new bone is exhibited. Further, β-tricalcium phosphate (β-TCP) is also easily degraded in vivo and has a feature of gradually replacing new bone.
　しかし、無気孔で緻密なリン酸カルシウム系焼結材を埋入した場合には、生体内での骨組織形成が遅く、治癒までに長期間を要する。そのため、開気孔を有する多孔質体とし、開気孔内に骨組織が入り込み易くしたリン酸カルシウム系焼結材が提案されている（特許文献１）。 However, when a non-porous and dense calcium phosphate sintered material is embedded, bone tissue formation in the living body is slow and it takes a long time to heal. For this reason, a calcium phosphate-based sintered material that has a porous body having open pores and facilitates entry of bone tissue into the open pores has been proposed (Patent Document 1).
　このように、従来の人工骨はハイドロキシアパタイトを含む人工骨であって、ハイドロキシアパタイトの多孔を緻密連通させることで骨再生活性化するよう構造改善されていた。バイオセラミックスの特殊多孔質構造においては、骨組織細胞（骨芽細胞）や血管が孔内に入り込み、骨組織形成が早期になされる。 Thus, the conventional artificial bone is an artificial bone containing hydroxyapatite, and the structure has been improved so as to activate bone regeneration by closely communicating the pores of hydroxyapatite. In the special porous structure of bioceramics, bone tissue cells (osteoblasts) and blood vessels enter the pores, and bone tissue formation is performed at an early stage.
特開２００２－１７８４６号公報JP 2002-17846 A
　しかし、人工骨の構造を特殊多孔質構造に改善するには、人工骨を形成する段階で特殊な工程が必要であった。また、人工骨の構造を改善させるのみならず、さらに容易な改良をすることで、骨伝導能を向上させる技術が求められている。 However, in order to improve the structure of the artificial bone to a special porous structure, a special process was required at the stage of forming the artificial bone. In addition to improving the structure of artificial bones, there is a need for a technique for improving osteoconductivity by making further easy improvements.
　本発明は、上記技術的課題を解決するためになされたものであり、構造を改善（改造）することなく性質を改善（改質）することで、骨再生活性化された人工骨、人工骨製造装置及び人工骨製造方法を提供することを目的とする。 The present invention has been made in order to solve the above technical problem, and has improved (modified) properties without improving (remodeling) the structure, so that the artificial bone and artificial bone activated by bone regeneration can be obtained. It aims at providing a manufacturing apparatus and an artificial bone manufacturing method.
　上記課題を解決するために、本発明の人工骨の特徴的な構成は、バイオセラミックスを含む人工骨であって、バイオセラミックスは、骨再生活性化された改質構造を有する。従って、構造を改善（改造）させることなく性質を改善（改質）させることで、骨再生活性化された人工骨を得ることができる。 In order to solve the above-mentioned problem, the characteristic configuration of the artificial bone of the present invention is an artificial bone containing bioceramics, and the bioceramics have a modified structure activated by bone regeneration. Therefore, by improving (modifying) the properties without improving (remodeling) the structure, an artificial bone activated by bone regeneration can be obtained.
　本発明に係る人工骨の好適な実施形態によれば、改質構造は、プラズマ改質構造である。例えば大気圧プラズマは、大気中で照射し得る。従って、真空装置が不要となり、改質プロセスが安易である。その結果、術中での使用も可能となる。 According to a preferred embodiment of the artificial bone according to the present invention, the modified structure is a plasma modified structure. For example, atmospheric pressure plasma can be irradiated in the atmosphere. Therefore, a vacuum device is not required and the reforming process is easy. As a result, it can be used intraoperatively.
　本発明に係る人工骨の好適な実施形態によれば、バイオセラミックスは多孔質である。従って、多孔質でないバイオセラミックスと比較して、骨再生活性化された改質面積が広く、骨伝導能が向上する。その結果、骨欠損部における早期治癒が可能となる。 According to a preferred embodiment of the artificial bone according to the present invention, the bioceramics are porous. Therefore, compared with non-porous bioceramics, the modified area activated by bone regeneration is wide, and the osteoconductivity is improved. As a result, early healing in the bone defect portion is possible.
　本発明に係る人工骨の好適な実施形態によれば、バイオセラミックスは連球状開気孔を有する。連球状開気孔は、球状であり、３次元的に連通している。従って、プラズマ照射によって骨再生活性化する場合は、燃焼ガスを気孔内に導入し易く、広範囲なプラズマ改質が可能となる。さらに、連球状開気孔は、粒界空隙状開気孔や閉気孔と比べ、気孔径が大きいため、気孔内にまで生体液や骨組織細胞（骨芽細胞）が侵入し得、骨伝導能を向上し得る。 According to a preferred embodiment of the artificial bone according to the present invention, the bioceramics have continuous spherical open pores. The continuous spherical open pores are spherical and communicate in a three-dimensional manner. Therefore, when bone regeneration is activated by plasma irradiation, it is easy to introduce combustion gas into the pores, and a wide range of plasma modification is possible. Furthermore, the continuous spherical open pores have larger pore diameters than the intergranular void-like open pores and closed pores, so that biological fluid and bone tissue cells (osteoblasts) can penetrate into the pores, thereby improving the bone conduction ability. It can improve.
　本発明に係る人工骨の好適な実施形態によれば、バイオセラミックスは、リン酸カルシウム含有セラミックス又はガラスセラミックスを含有する。リン酸カルシウム含有セラミックス又はガラスセラミックスは、人工骨の材料として一般に使用されているので、入手が容易である。さらに、リン酸カルシウム含有セラミックス（例えば、ハイドロキシアパタイト）は生体骨の成分でもあり、再生骨に馴染みやすい。 According to a preferred embodiment of the artificial bone according to the present invention, the bioceramics contain calcium phosphate-containing ceramics or glass ceramics. Since calcium phosphate-containing ceramics or glass ceramics are generally used as artificial bone materials, they are easily available. In addition, calcium phosphate-containing ceramics (for example, hydroxyapatite) is also a component of living bone, and is easily adapted to regenerated bone.
　本発明に係る人工骨の好適な実施形態によれば、改質構造は、液滴の接線とバイオセラミックの表面とのなす角度が０度～１５度であり得る。 According to a preferred embodiment of the artificial bone according to the present invention, in the modified structure, the angle formed between the tangent of the droplet and the surface of the bioceramic can be 0 to 15 degrees.
　本発明に係る人工骨の好適な実施形態によれば、バイオセラミックの表面において、酸素（Ｏ）とリン（Ｐ）との組成比（Ｏ／Ｐ）は６．０～７．０であり、酸素（Ｏ）とカルシウム（Ｃａ）との組成比（Ｏ／Ｃａ）は４．０～５．０であり得る。 According to a preferred embodiment of the artificial bone according to the present invention, the composition ratio (O / P) of oxygen (O) and phosphorus (P) is 6.0 to 7.0 on the surface of the bioceramic. The composition ratio (O / Ca) of oxygen (O) to calcium (Ca) may be 4.0 to 5.0.
　上記課題を解決するために、本発明に係る人工骨製造装置の特徴的な構成は、バイオセラミックスを含む人工骨の製造装置であって、バイオセラミックスに骨再生活性化のための改質処理をする処理装置を備える。本発明に係る人工骨製造装置によれば、上記説明した本発明の人工骨を製造することができる。従って、構造を改善させることなく改質させることで骨再生活性化された人工骨を製造し得る。 In order to solve the above-described problems, a characteristic configuration of an artificial bone manufacturing apparatus according to the present invention is an artificial bone manufacturing apparatus including bioceramics, and the bioceramics are subjected to a modification process for activating bone regeneration. A processing device. According to the artificial bone manufacturing apparatus according to the present invention, the above-described artificial bone of the present invention can be manufactured. Therefore, it is possible to manufacture an artificial bone activated by bone regeneration by modifying without improving the structure.
　本発明に係る人工骨製造装置の好適な実施形態によれば、処理装置は、バイオセラミックスにプラズマを照射する。例えば大気圧プラズマは、大気中で照射し得る。従って、真空装置が不要となり、改質プロセスが安易である。その結果、術中での使用も可能となる。 According to a preferred embodiment of the artificial bone manufacturing apparatus according to the present invention, the processing apparatus irradiates the bioceramics with plasma. For example, atmospheric pressure plasma can be irradiated in the atmosphere. Therefore, a vacuum device is not required and the reforming process is easy. As a result, it can be used intraoperatively.
　本発明に係る人工骨製造装置の好適な実施形態によれば、改質処理の領域を制御する領域制御装置を更に備える。その結果、処理領域の位置、大きさ、範囲を精度よく制御し得る。 According to a preferred embodiment of the artificial bone manufacturing apparatus according to the present invention, the artificial bone manufacturing apparatus further includes a region control device that controls the region of the modification process. As a result, the position, size, and range of the processing area can be controlled with high accuracy.
　本発明に係る人工骨製造装置の好適な実施形態によれば、領域制御装置は、バイオセラミックスへのプラズマ照射時間を制御する。バイオセラミックスへのプラズマ照射時間を長くする場合には、人工骨の内部の非改質層に至るまでプラズマが到達し、人工骨の内部の非改質層を骨再生活性化した改質構造にし得る。また、プラズマ照射時間を短くする場合には、人工骨の表面付近の非改質層を骨再生活性化した改質構造にし得る。その結果、改質部分を選択的に形成し得、目的に応じた人工骨を製造し得る。 According to a preferred embodiment of the artificial bone manufacturing apparatus according to the present invention, the region control apparatus controls the plasma irradiation time to the bioceramics. When extending the plasma irradiation time to bioceramics, the plasma reaches the non-modified layer inside the artificial bone, and the non-modified layer inside the artificial bone has a modified structure that activates bone regeneration. obtain. When the plasma irradiation time is shortened, a modified structure in which the non-modified layer near the surface of the artificial bone is activated by bone regeneration can be used. As a result, the modified portion can be selectively formed, and an artificial bone according to the purpose can be manufactured.
　本発明に係る人工骨製造装置の好適な実施形態によれば、領域制御装置は、人工骨を含む周辺空間の圧力の加減を制御する。周辺空間を減圧することで、バイオセラミックスの多孔内部にプラズマを導入し得る。その結果、バイオセラミックスの多孔内部を骨再生活性化した改質構造にし得る。また、周辺空間の圧力の加減を繰り返すことで、多孔内の隅々までプラズマを導入し得る。その結果、バイオセラミックスの多孔内部をより確実に改質構造にし得る。 According to a preferred embodiment of the artificial bone manufacturing apparatus according to the present invention, the region control device controls the pressure in the surrounding space including the artificial bone. By depressurizing the surrounding space, plasma can be introduced into the porous ceramic ceramic. As a result, it is possible to obtain a modified structure in which the inside of the porous bioceramics is activated by bone regeneration. In addition, by repeatedly increasing and decreasing the pressure in the peripheral space, plasma can be introduced to every corner of the pore. As a result, the modified porous structure of the bioceramics can be more reliably formed.
　上記課題を解決するために、本発明に係る人工骨製造方法の特徴的な構成は、バイオセラミックスを含む人工骨の製造方法であって、バイオセラミックスに骨再生活性化のための改質処理をする処理工程を包含する。本発明に係る人工骨製造方法によれば、上記説明した本発明の人工骨を製造することができる。従って、構造を改善させることなく改質させることで骨再生活性化された人工骨を製造し得る。 In order to solve the above-described problems, a characteristic configuration of the artificial bone manufacturing method according to the present invention is a method for manufacturing an artificial bone containing bioceramics, and the bioceramics are subjected to a modification process for activating bone regeneration. Process steps to include. According to the artificial bone manufacturing method of the present invention, the above-described artificial bone of the present invention can be manufactured. Therefore, it is possible to manufacture an artificial bone activated by bone regeneration by modifying without improving the structure.
　本発明に係る人工骨製造方法の好適な実施形態によれば、処理工程は、バイオセラミックスにプラズマを照射することにより実行される。 According to a preferred embodiment of the method for producing an artificial bone according to the present invention, the treatment step is performed by irradiating the bioceramics with plasma.
　本発明に係る人工骨製造方法の好適な実施形態によれば、改質処理の領域を制御する領域制御工程を更に包含する。 According to a preferred embodiment of the artificial bone manufacturing method according to the present invention, the method further includes a region control step of controlling the region of the modification process.
　本発明に係る人工骨製造方法の好適な実施形態によれば、処理工程において、バイオセラミックスを酸化し、バイオセラミックスの酸素組成比を増加させる。 According to a preferred embodiment of the artificial bone manufacturing method according to the present invention, in the treatment step, the bioceramics are oxidized to increase the oxygen composition ratio of the bioceramics.
本発明の実施形態１に係る人工骨及び従来の人工骨を示す写真である。It is a photograph which shows the artificial bone which concerns on Embodiment 1 of this invention, and the conventional artificial bone. 本発明の実施形態１に係る人工骨の多孔質を示す写真又は模式図である。It is the photograph or schematic diagram which shows the porosity of the artificial bone which concerns on Embodiment 1 of this invention. 従来の人工骨の例を示す表である。It is a table | surface which shows the example of the conventional artificial bone. 実験動物への人工骨の移植部位を示す模式図である。It is a schematic diagram which shows the transplant site | part of the artificial bone to an experimental animal. 本発明の実施形態１に係る人工骨と従来の人工骨とにおける骨再生の程度を示す写真である。It is a photograph which shows the grade of the bone regeneration in the artificial bone which concerns on Embodiment 1 of this invention, and the conventional artificial bone. 本発明の実施形態１に係る人工骨のＺｏｎｅ３と従来の人工骨のＺｏｎｅ３とにおける骨再生の程度を示す写真である。It is a photograph which shows the grade of the bone regeneration in Zone3 of the artificial bone which concerns on Embodiment 1 of this invention, and Zone3 of the conventional artificial bone. 本発明の実施形態２に係る人工骨製造装置を示す模式図である。It is a schematic diagram which shows the artificial bone manufacturing apparatus which concerns on Embodiment 2 of this invention. 本発明の実施形態２に係る他の人工骨製造装置を示す模式図である。It is a schematic diagram which shows the other artificial bone manufacturing apparatus which concerns on Embodiment 2 of this invention. 様々な厚みの改質層を有する人工骨を示す写真である。It is a photograph which shows the artificial bone which has a modified layer of various thickness. 従来の人工骨へのプラズマ照射時間と改質層の厚みとの関係を示すグラフである。It is a graph which shows the relationship between the plasma irradiation time to the conventional artificial bone, and the thickness of a modified layer. 本発明の実施形態２に係る更に他の人工骨製造装置を示す模式図である。It is a schematic diagram which shows the further another artificial bone manufacturing apparatus which concerns on Embodiment 2 of this invention. 本発明の実施形態２に係る更に他の人工骨製造装置を示す模式図である。It is a schematic diagram which shows the further another artificial bone manufacturing apparatus which concerns on Embodiment 2 of this invention. 人工骨表面処理による濡れ性の変化を説明する図である。It is a figure explaining change of wettability by artificial bone surface treatment. 人工骨表面におけるＸ線光電子分析（ＸＰＳ）の結果を示すグラフである。It is a graph which shows the result of the X-ray photoelectron analysis (XPS) in the artificial bone surface.
　図１～図１４を参照して、本発明の人工骨、人工骨製造装置及び人工骨製造方法に関する実施形態を説明する。本発明は、以下に説明する実施形態や図面に記載される構成に限定されることを意図せず、当該構成と均等な構成も含む。
[実施形態１]
[人工骨]
　図１は、本発明の実施形態１に係る人工骨１００及び従来の人工骨２００を示す写真である。図１（ａ１）は、人工骨１００を示す写真であり、図１（ａ２）は、人工骨１００の断面の一部を拡大した写真である。人工骨１００は、生体骨の欠損部分を補う人工的な素材である。人工骨１００は、非改質層１１０と改質層１２０とを含む。 With reference to FIGS. 1 to 14, embodiments of the artificial bone, the artificial bone manufacturing apparatus, and the artificial bone manufacturing method of the present invention will be described. The present invention is not intended to be limited to the configurations described in the embodiments and drawings described below, and includes configurations equivalent to those configurations.
[Embodiment 1]
[Artificial bone]
FIG. 1 is a photograph showing an artificial bone 100 and a conventional artificial bone 200 according to Embodiment 1 of the present invention. FIG. 1A1 is a photograph showing the artificial bone 100, and FIG. 1A2 is a photograph in which a part of the cross section of the artificial bone 100 is enlarged. The artificial bone 100 is an artificial material that compensates for a defect in a living bone. The artificial bone 100 includes an unmodified layer 110 and a modified layer 120.
　改質層１２０は、骨再生活性化された改質構造を有する。改質層１２０は、バイオセラミックスを含む。骨再生活性化された改質構造の一例は、プラズマ改質構造である。プラズマ改質は、バイオセラミックスにプラズマを照射することで起こし得る。プラズマ改質によって、改質層１２０の親水性、細胞接着性及び細胞増殖性が改善され得る。改質層１２０に含まれるバイオセラミックスは、多孔質である。改質層１２０は複数の気孔を有する。気孔と気孔とを区分するのは、壁部である。気孔には複数の種類がある。例えば、連球状開気孔、粒界空隙状開気孔及び閉気孔である。気孔の詳細は、図２を参照して後述する。プラズマ改質によって改質層１２０の親水性が改善されるため、改質層１２０の多孔質内に液体が吸収される。従って、図１（ａ２）は、人工骨１００ の上に水滴を垂らした時の、水の侵入深さをも表す。改質層１２０は水の侵入し易い個所（侵入容易層）であり、非改質層１１０は、水の侵入し難い個所（侵入非容易層）を表す。 The modified layer 120 has a modified structure activated by bone regeneration. The modified layer 120 includes bioceramics. An example of a modified structure activated by bone regeneration is a plasma modified structure. Plasma modification can occur by irradiating the bioceramics with plasma. Plasma modification can improve the hydrophilicity, cell adhesion, and cell growth of the modified layer 120. The bioceramics contained in the modified layer 120 are porous. The modified layer 120 has a plurality of pores. It is the wall that separates the pores from the pores. There are several types of pores. For example, they are continuous spherical open pores, intergranular void-like open pores, and closed pores. Details of the pores will be described later with reference to FIG. Since the hydrophilicity of the modified layer 120 is improved by the plasma modification, the liquid is absorbed into the porous layer of the modified layer 120. Therefore, FIG. 1 (a2) also represents the penetration depth of water when a water drop is dropped on the artificial bone 100. The modified layer 120 is a portion where water easily enters (easy to enter layer), and the non-modified layer 110 represents a portion where water is difficult to enter (an intrusion non-easy layer).
　図１（ｂ１）は、従来の人工骨２００を示す写真であり、図１（ｂ２）は、従来の人工骨２００の一部を拡大した写真である。人工骨１００と同様、人工骨２００もバイオセラミックスを含み、多孔質である。しかし、人工骨２００は骨再生活性化された改質構造を有しない。従って、人工骨２００の表面は親水性が悪く、液体を弾く。 FIG. 1 (b1) is a photograph showing a conventional artificial bone 200, and FIG. 1 (b2) is a photograph in which a part of the conventional artificial bone 200 is enlarged. Like the artificial bone 100, the artificial bone 200 contains bioceramics and is porous. However, the artificial bone 200 does not have a modified structure activated by bone regeneration. Therefore, the surface of the artificial bone 200 is poorly hydrophilic and repels liquid.
　図２は、人工骨１００の多孔質を示す写真又は模式図である。図２を参照して、種々の気孔を説明する。 FIG. 2 is a photograph or schematic diagram showing the porosity of the artificial bone 100. Various pores will be described with reference to FIG.
　図２（ａ１）は、人工骨１００ａを示す写真であり、図２（ａ２）は、人工骨１００ａの断面の一部を拡大した写真である。人工骨１００ａは、連球状開気孔を有する。ここで、気孔とは、ひとまとまりの物体に含まれる微小な空洞であり、開気孔は、外気と接続している気孔である。連球状開気孔は、複数の開気孔であって、それらの各々が球状であり、３次元的に連通している複数の開気孔である。 FIG. 2 (a1) is a photograph showing the artificial bone 100a, and FIG. 2 (a2) is a photograph in which a part of the cross section of the artificial bone 100a is enlarged. The artificial bone 100a has continuous spherical open pores. Here, the pore is a minute cavity included in a group of objects, and the open pore is a pore connected to the outside air. The continuous spherical open pores are a plurality of open pores, each of which is spherical and is a plurality of open pores communicating three-dimensionally.
　図２（ｂ１）は、人工骨１００ｂを示し、図２（ｂ２）は、人工骨１００ｂの一部を拡大した模式図であり、図２（ｂ３）は、人工骨１００ｂの一部を更に拡大した模式図である。人工骨１００ｂは、人工骨１００ａと異なる内部構造を有する。すなわち、人工骨１００ｂは、微小粒子（個体）の集合体であり、隣接する微小粒子の間に隙間を有し、これが細孔をなす。すなわち、人工骨１００ｂは、粒界空隙状開気孔を有する。ここで、粒界空隙状開気孔とは、粒子と粒子との間に生じる空隙が連なる開気孔である。 2 (b1) shows an artificial bone 100b, FIG. 2 (b2) is a schematic view of an enlarged part of the artificial bone 100b, and FIG. 2 (b3) further enlarges a part of the artificial bone 100b. FIG. The artificial bone 100b has an internal structure different from that of the artificial bone 100a. That is, the artificial bone 100b is an aggregate of microparticles (individuals), and there are gaps between adjacent microparticles, which form pores. That is, the artificial bone 100b has intergranular void-like open pores. Here, the intergranular void-like open pores are open pores in which voids formed between particles are continuous.
　図２（ｃ１）は、人工骨１００ｃを示す写真であり、図２（ｃ２）は、人工骨１００ｃの断面の一部を拡大した写真である。人工骨１００ｃは、閉気孔を有する。閉気孔は物体内部に孤立している気孔である。従って、外気と接続していない。人工骨１００ｃに含まれる複数の気孔の各々は、壁部によって区分されている。 FIG. 2 (c1) is a photograph showing the artificial bone 100c, and FIG. 2 (c2) is a photograph showing an enlarged part of the cross section of the artificial bone 100c. The artificial bone 100c has closed pores. Closed pores are pores that are isolated inside an object. Therefore, it is not connected to the outside air. Each of the plurality of pores included in the artificial bone 100c is divided by a wall portion.
　図３は、従来の人工骨２００の例を示す表である。人工骨２００は、人工骨１００と同様にバイオセラミックスを含むが、人工骨２００は骨再生活性化された改質構造を有しない。しかし、人工骨２００に含まれるバイオセラミックスに骨再生活性化のための改質処理を施すことによって、人工骨１００を製造し得る。人工骨２００は改質処理されていない改質未処理人工骨であり、人工骨１００は改質処理されている改質処理済人工骨である。骨再生活性化のための改質処理の具体例は、プラズマ改質処理であり、バイオセラミックスにプラズマを照射することで実行し得る。 FIG. 3 is a table showing an example of a conventional artificial bone 200. Although the artificial bone 200 contains bioceramics like the artificial bone 100, the artificial bone 200 does not have a modified structure activated by bone regeneration. However, the artificial bone 100 can be manufactured by subjecting the bioceramics contained in the artificial bone 200 to a modification treatment for activating bone regeneration. The artificial bone 200 is a modified unprocessed artificial bone that has not been modified, and the artificial bone 100 is a modified artificial bone that has been modified. A specific example of the modification process for activating bone regeneration is a plasma modification process, which can be performed by irradiating the bioceramics with plasma.
　人工骨２００ａは、ペンタックスＨＯＹＡから販売名ボンフィルで販売されている人工骨である。人工骨２００ａの組成は、ハイドロキシアパタイトである。人工骨２００ａは、閉気孔を有し、連通性はない。製品に応じて気孔径は９０、２００、３００μｍ、気孔率は６０、７０％である。 The artificial bone 200a is an artificial bone sold by PENTAX HOYA under the trade name Bonfil. The composition of the artificial bone 200a is hydroxyapatite. The artificial bone 200a has closed pores and does not communicate. Depending on the product, the pore diameter is 90, 200, 300 μm, and the porosity is 60, 70%.
　人工骨２００ｂは、コバレントマテリアルから販売名ネオボーンで販売されている人工骨である。人工骨２００ｂの組成は、ハイドロキシアパタイトである。人工骨２００ｂは、連球状開気孔を有し、連通性がある。気孔径は、約１５０μｍであり、気孔率７５％を有する。連通径は、５０μｍである。 The artificial bone 200b is an artificial bone sold by Covalent Materials under the trade name Neoborn. The composition of the artificial bone 200b is hydroxyapatite. The artificial bone 200b has continuous spherical open pores and is communicated. The pore diameter is about 150 μm and has a porosity of 75%. The communication diameter is 50 μm.
　なお、人工骨の内部にまで骨再生のための細胞や栄養を導入し易くする等の観点から、人工骨２００ｂの平均気孔径は９０μｍ以上６００μｍ以下であることが好ましい。また、気孔率は５０％以上９０％以下であり、特に、６５％以上８５％以下が好ましい。また、人工骨２００ｂの連球状開気孔の連通部分の平均孔径は２０μｍ以上であることが好ましく、４０μｍ以上であることがより好ましい。 Note that the average pore diameter of the artificial bone 200b is preferably 90 μm or more and 600 μm or less from the viewpoint of facilitating introduction of cells and nutrients for bone regeneration into the artificial bone. Further, the porosity is 50% or more and 90% or less, and particularly preferably 65% or more and 85% or less. Further, the average pore diameter of the communicating portion of the continuous spherical open pores of the artificial bone 200b is preferably 20 μm or more, and more preferably 40 μm or more.
　人工骨２００ｂは、撹拌起泡により製造し得る。具体的には、下記に示すステップ１～ステップ４を実行することで人工骨２００ｂを製造することができる。 The artificial bone 200b can be manufactured by stirring foaming. Specifically, the artificial bone 200b can be manufactured by executing steps 1 to 4 described below.
　ハイドロキシアパタイト粉末に、架橋重合性樹脂としてポリエチレンイミン等を添加し、分散媒として水を用いて、混合、解砕し、スラリーを調製する（ステップ１）。スラリーに、起泡剤としてポリオキシエチレンラウリルエーテル等を添加し、撹拌して起泡させる（ステップ２）。スラリーに、架橋剤としてソルビトールグリシジルエーテル等を添加し、得られた泡沫状スラリーを注型して、泡構造を固定した状態で乾燥させる（ステップ３）。泡沫状スラリーを８００～１３００℃程度で焼結する（ステップ４）。 Polyethyleneimine or the like is added to the hydroxyapatite powder as a cross-linkable resin, and mixed and crushed using water as a dispersion medium to prepare a slurry (step 1). To the slurry, polyoxyethylene lauryl ether or the like is added as a foaming agent, and stirred to foam (Step 2). To the slurry, sorbitol glycidyl ether or the like is added as a crosslinking agent, and the resulting foamy slurry is cast and dried with the foam structure fixed (step 3). The foamy slurry is sintered at about 800 to 1300 ° C. (step 4).
　人工骨２００ｃは、日本特殊陶業から販売名セラタイトで販売されている人工骨である。人工骨２００ｃの組成は、ハイドロキシアパタイト７０％、β－ＴＣＰ（β－リン酸三カルシウム）３０％である。人工骨２００ｃは多孔質であり、気孔径は１５０～２００μｍであるが、連通性はあまり良くない。連通径は、４０～８０μｍである。 The artificial bone 200c is an artificial bone sold under the name Seratite from Nippon Special Ceramics. The composition of the artificial bone 200c is 70% hydroxyapatite and 30% β-TCP (β-tricalcium phosphate). The artificial bone 200c is porous and has a pore diameter of 150 to 200 μm, but the connectivity is not so good. The communication diameter is 40 to 80 μm.
　人工骨２００ｄは、オリンパステルモバイオマテリアルから販売名ボーンセラムPで販売されている人工骨である。人工骨２００ｄの組成は、ハイドロキシアパタイトである。人工骨２００ｄは多孔質であり、気孔径は３０～４００μｍであるが、連通性はない。 The artificial bone 200d is an artificial bone sold under the name Bone Serum P by Olympus Terumo Biomaterial. The composition of the artificial bone 200d is hydroxyapatite. The artificial bone 200d is porous and has a pore diameter of 30 to 400 μm, but has no connectivity.
　上述のように人工骨２００に含まれるバイオセラミックスに骨再生活性化のための改質処理を施すことによって、人工骨１００を製造し得る。人工骨２００ａ、人工骨２００ｂ、人工骨２００ｃ、人工骨２００ｄ以外に、種々の人工骨を採用し得る。人工骨２００は、好適には、生体為害性を有さず、かつ、十分な機械的強度を有する材質のバイオセラミックスを含む。具体的には、アルミナ、ジルコニア、シリカ、ムライト、ディオプサイド、ウォラストナイト、エーライト、べライト、アーケルマナイト、モンティセライト、生体用ガラスおよびリン酸カルシウム系セラミックスのうち、少なくとも１種を含む。リン酸カルシウム系セラミックスは生体適合性に優れ、最も好適である。リン酸カルシウム系セラミックスとしては、ハイドロキシアパタイト、リン酸三カルシウム、フッ化アパタイトが挙げられる。特に、骨との同化性、癒着性、強度等の観点から、人工骨２００は骨の主組成成分であるハイドロキシアパタイトを含むことが好ましい。 As described above, the artificial bone 100 can be manufactured by subjecting the bioceramics contained in the artificial bone 200 to a modification treatment for activating bone regeneration. In addition to the artificial bone 200a, the artificial bone 200b, the artificial bone 200c, and the artificial bone 200d, various artificial bones can be adopted. The artificial bone 200 preferably includes bioceramics made of a material that does not have biological harm and has sufficient mechanical strength. Specifically, it contains at least one of alumina, zirconia, silica, mullite, diopside, wollastonite, alite, belite, arkelmanite, montcerite, biological glass, and calcium phosphate ceramics. Calcium phosphate ceramics are most suitable because of their excellent biocompatibility. Examples of calcium phosphate ceramics include hydroxyapatite, tricalcium phosphate, and fluoride apatite. In particular, from the viewpoint of assimilation with bone, adhesion, strength, and the like, the artificial bone 200 preferably contains hydroxyapatite, which is a main component of bone.
　以下、図４～図６を参照して本発明の人工骨１００の効果を説明する。 Hereinafter, the effects of the artificial bone 100 of the present invention will be described with reference to FIGS.
　図４は、実験動物への人工骨の移植部位を示す模式図である。実験動物としてウサギを用いた。円柱形の人工骨１００と人工骨２００（共に直径６ｍｍ、長さ１５ｍｍ）をウサギの大腿骨内側顆に移植して、人工骨１００と人工骨２００との骨再生機能を比較した。図３を参照して説明した人工骨２００ｂにプラズマを１時間３０分照射することによって、人工骨１００を作製した。 FIG. 4 is a schematic view showing a site where an artificial bone is transplanted into an experimental animal. Rabbits were used as experimental animals. A cylindrical artificial bone 100 and an artificial bone 200 (both having a diameter of 6 mm and a length of 15 mm) were implanted into the femoral medial condyle of a rabbit, and the bone regeneration functions of the artificial bone 100 and the artificial bone 200 were compared. The artificial bone 100 was produced by irradiating the artificial bone 200b described with reference to FIG. 3 with plasma for 1 hour and 30 minutes.
　図５は、人工骨１００と人工骨２００とにおける骨再生の程度を示す写真である。図５（ａ）は、人工骨１００における骨再生の程度を示し、図５（ｂ）は、人工骨２００における骨再生の程度を示す。ウサギに人工骨１００と人工骨２００とを移植してから３週間後の結果である。円柱の円形断面を３つの領域（外周から内部にかけて順番にＺｏｎｅ１、Ｚｏｎｅ２、Ｚｏｎｅ３）に区分して、各々の領域における骨再生の程度を比較した。人工骨１００と人工骨２００との各々の３つの全ての領域において、生体液や未分化細胞は侵入していた。しかし、骨組織細胞（骨芽細胞）の侵入の程度は、人工骨２００よりも人工骨１００の方が好適であった。 FIG. 5 is a photograph showing the degree of bone regeneration in the artificial bone 100 and the artificial bone 200. FIG. 5A shows the degree of bone regeneration in the artificial bone 100, and FIG. 5B shows the degree of bone regeneration in the artificial bone 200. The result is 3 weeks after the artificial bone 100 and the artificial bone 200 are transplanted into the rabbit. The circular cross section of the cylinder was divided into three regions (Zone 1, Zone 2, and Zone 3 in order from the outer periphery to the inside), and the degree of bone regeneration in each region was compared. In all three regions of each of the artificial bone 100 and the artificial bone 200, biological fluid and undifferentiated cells have invaded. However, the degree of invasion of bone tissue cells (osteoblasts) was more suitable for the artificial bone 100 than for the artificial bone 200.
　図６は、人工骨１００のＺｏｎｅ３と人工骨２００のＺｏｎｅ３とにおける骨再生の程度を示す写真である。図６（ａ）は、人工骨１００における骨再生の程度を示し、図６（ｂ）は、人工骨２００における骨再生の程度を示す。白色部分は、人工骨の壁部（連球状開気孔でない部分）を示す。複数の連球状開気孔の内部には生体液や未分化細胞は侵入しているが、生体液や未分化細胞の侵入の程度は、人工骨２００よりも人工骨１００の方が好適であった。骨組織細胞（骨芽細胞）への分化は、人工骨１００においてのみ確認し得た。 FIG. 6 is a photograph showing the degree of bone regeneration in Zone 3 of the artificial bone 100 and Zone 3 of the artificial bone 200. 6A shows the degree of bone regeneration in the artificial bone 100, and FIG. 6B shows the degree of bone regeneration in the artificial bone 200. A white part shows the wall part (part which is not a continuous spherical open pore) of an artificial bone. Although the biological fluid and undifferentiated cells have invaded the inside of the plurality of continuous spherical open pores, the degree of invasion of the biological fluid and undifferentiated cells is more suitable for the artificial bone 100 than for the artificial bone 200. . Differentiation into bone tissue cells (osteoblasts) could be confirmed only in the artificial bone 100.
　以上、図１～図６を参照して、本発明の実施形態１の人工骨１００を説明した。本発明の人工骨によれば、バイオセラミックスを含む人工骨であって、バイオセラミックスは、骨再生活性化された改質構造を有する。従って、構造を改善（改造）させることなく性質を改善（改質）させることで、骨再生活性化された人工骨を得ることができる。 The artificial bone 100 according to the first embodiment of the present invention has been described above with reference to FIGS. According to the artificial bone of the present invention, it is an artificial bone containing bioceramics, and the bioceramics have a modified structure activated by bone regeneration. Therefore, by improving (modifying) the properties without improving (remodeling) the structure, an artificial bone activated by bone regeneration can be obtained.
　また、本発明の好適な人工骨によれば、改質構造は、プラズマ改質構造である。例えば大気圧プラズマは、大気中で照射し得る。従って、真空装置が不要となり、改質プロセスが安易である。その結果、術中での使用も可能となる。更に、本発明の好適な人工骨によれば、バイオセラミックスは多孔質である。従って、多孔質でないバイオセラミックスと比較して、骨再生活性化された改質面積が広く、骨伝導能が向上する。その結果、骨欠損部における早期治癒が可能となる。 Also, according to the preferred artificial bone of the present invention, the modified structure is a plasma modified structure. For example, atmospheric pressure plasma can be irradiated in the atmosphere. Therefore, a vacuum device is not required and the reforming process is easy. As a result, it can be used intraoperatively. Furthermore, according to the preferred artificial bone of the present invention, the bioceramics are porous. Therefore, compared with non-porous bioceramics, the modified area activated by bone regeneration is wide, and the osteoconductivity is improved. As a result, early healing in the bone defect portion is possible.
　更に、本発明の好適な人工骨によれば、バイオセラミックスは連球状開気孔を有する。連球状開気孔は、球状であり、３次元的に連通している。従って、プラズマ照射によって骨再生活性化する場合は、燃焼ガスを気孔内に導入し易く、広範囲なプラズマ改質が可能となる。さらに、連球状開気孔は、粒界空隙状開気孔や閉気孔と比べ、気孔径が大きいため、気孔内にまで生体液や骨組織細胞（骨芽細胞）が侵入し得、骨伝導能を向上し得る。 Furthermore, according to the preferred artificial bone of the present invention, the bioceramics have continuous spherical open pores. The continuous spherical open pores are spherical and communicate in a three-dimensional manner. Therefore, when bone regeneration is activated by plasma irradiation, it is easy to introduce combustion gas into the pores, and a wide range of plasma modification is possible. Furthermore, the continuous spherical open pores have larger pore diameters than the intergranular void-like open pores and closed pores, so that biological fluid and bone tissue cells (osteoblasts) can penetrate into the pores, thereby improving the bone conduction ability. It can improve.
　更に、本発明の好適な人工骨によれば、バイオセラミックスは、リン酸カルシウム含有セラミックス又はガラスセラミックスを含有する。リン酸カルシウム含有セラミックス又はガラスセラミックスは、人工骨の材料として一般に使用されているので、入手が容易である。さらに、リン酸カルシウム含有セラミックスは生体骨の成分でもあり、再生骨に馴染みやすい。 Furthermore, according to the preferred artificial bone of the present invention, the bioceramics contain calcium phosphate-containing ceramics or glass ceramics. Since calcium phosphate-containing ceramics or glass ceramics are generally used as artificial bone materials, they are easily available. Furthermore, calcium phosphate-containing ceramics are also components of living bones and are easily adapted to regenerated bone.
　なお、本発明の実施形態１において、人工骨１００の全てがバイオセラミックスで作製されるに限らない。一部がバイオセラミックスであり得る。また、バイオセラミックスの全てが骨再生活性化された改質構造を有するに限定されない。バイオセラミックスの一部が骨再生活性化された改質構造であり得る。従って、改質部分を選択し得、目的に応じて人工骨を使い分け得る。特に、人工骨の深部に至るまで改質構造を有し得る場合には、骨の再生が人工骨の深部にまで及び、骨欠損部における早期治癒が可能となる。 In the first embodiment of the present invention, all the artificial bone 100 is not necessarily made of bioceramics. Some can be bioceramics. Moreover, not all bioceramics have a modified structure in which bone regeneration is activated. A part of bioceramics may have a modified structure in which bone regeneration is activated. Therefore, the modified portion can be selected, and the artificial bone can be properly used according to the purpose. In particular, when a modified structure can be provided up to the deep part of the artificial bone, bone regeneration extends to the deep part of the artificial bone, and early healing at the bone defect part is possible.
　更に、本発明の実施形態１において、非改質層１１０と改質層１２０とを有する人工骨１００について説明したが、人工骨１００は、改質層１２０を有しさえすれば非改質層１１０の有無は限定されない。人工骨２００へのプラズマ照射によって、人工骨２００の全てを改質した場合は、製造された人工骨１００は非改質層１１０と改質層１２０とのうち、改質層１２０のみを有する。 Furthermore, in Embodiment 1 of the present invention, the artificial bone 100 having the non-modified layer 110 and the modified layer 120 has been described. However, the artificial bone 100 only needs to have the modified layer 120 as long as it has the modified layer 120. The presence or absence of 110 is not limited. When all of the artificial bone 200 is modified by plasma irradiation to the artificial bone 200, the manufactured artificial bone 100 has only the modified layer 120 among the non-modified layer 110 and the modified layer 120.
　更に、本発明の実施形態１において、骨再生活性化された改質構造は、プラズマ改質構造に限定されない。骨再生活性化された改質構造である限りは、希塩酸処理による改質構造であり得る。 Furthermore, in Embodiment 1 of the present invention, the modified structure activated by bone regeneration is not limited to the plasma modified structure. As long as the modified structure is activated by bone regeneration, it can be a modified structure by dilute hydrochloric acid treatment.
　更に、本発明の実施形態１において、プラズマ処理の対象として、人工骨２００ｂを選択したが、骨再生活性化のための改質処理を実行して人工骨１００を製造し得る限りは、プラズマ処理の対象は人工骨２００ｂに限定されない。人工骨２００ｂ以外にも、図３を参照して説明した人工骨２００ａ、人工骨２００ｃ、人工骨２００ｄやその他種々の人工骨を活用し得る。
[実施形態２]
[人工骨製造装置及び人工骨製造方法]
　図７は、本発明の実施形態２に係る人工骨製造装置３００を示す模式図である。人工骨製造装置３００によって、人工骨１００が製造される。人工骨製造装置３００は、人工骨２００に含まれるバイオセラミックスに対してプラズマＡを照射し、骨再生活性化のための改質処理をする処理装置として機能する。人工骨製造装置３００による製造方法は、バイオセラミックスに骨再生活性化のための改質処理をする処理工程を包含する。処理工程は、バイオセラミックスにプラズマを照射することにより実行される。 Furthermore, in the first embodiment of the present invention, the artificial bone 200b is selected as the target of the plasma processing. The target of is not limited to the artificial bone 200b. In addition to the artificial bone 200b, the artificial bone 200a, the artificial bone 200c, the artificial bone 200d, and other various artificial bones described with reference to FIG. 3 can be used.
[Embodiment 2]
[Artificial bone manufacturing apparatus and artificial bone manufacturing method]
FIG. 7 is a schematic view showing an artificial bone manufacturing apparatus 300 according to Embodiment 2 of the present invention. The artificial bone 100 is manufactured by the artificial bone manufacturing apparatus 300. The artificial bone manufacturing apparatus 300 functions as a processing apparatus that irradiates the bioceramics included in the artificial bone 200 with plasma A and performs a modification process for activating bone regeneration. The manufacturing method using the artificial bone manufacturing apparatus 300 includes a processing step of performing a modification process for activating bone regeneration on bioceramics. The treatment process is performed by irradiating the bioceramics with plasma.
　人工骨製造装置３００は、ガス供給管３１２と第１電極３１４ａと第２電極３１４ｂと電圧印加装置３１６とを備える。ガス供給管３１２は内径が２～５ｍｍ程度の絶縁体（たとえば、石英、ガラス、プラスチックなど）からなるガス供給管である。ガス供給管３１２は、噴出口３１２ａを有する。噴出口３１２ａからは、ガス供給管３１２の内腔を通ったヘリウムガスＢが噴出される。第１電極３１４ａと第２電極３１４ｂとは、同軸状の一対のプラズマ発生用の電極である。第１電極３１４ａと第２電極３１４ｂとは、ガス供給管３１２の噴出口３１２ａ側の端部の外周上の上流側と下流側とに各々設置されている。第１電極３１４ａにパルス電圧を印加し、第２電極３１４ｂをグラウンド電位とする。電圧印加装置３１６は、１０～１００ｋＨｚ程度の低周波のパルス電圧（例えば、６～１２ｋＶ、１３ｋＨｚ）を第１電極３１４ａと第２電極３１４ｂとの間に印加してパルス放電させることにより、噴出口３１２ａから細く伸びるプラズマジェット（以下、ＬＦ（Ｌｏｗｅｒ　Ｆｒｅｑｕｅｎｃｙ）プラズマジェットとも称する）を生成する。なお、第１電極３１４ａをグラウンド電位にして、第２電極３１４ｂにパルス電圧を印加しても、プラズマジェットを生成し得る。 The artificial bone manufacturing apparatus 300 includes a gas supply pipe 312, a first electrode 314 a, a second electrode 314 b, and a voltage application device 316. The gas supply pipe 312 is a gas supply pipe made of an insulator having an inner diameter of about 2 to 5 mm (for example, quartz, glass, plastic, etc.). The gas supply pipe 312 has a jet port 312a. The helium gas B that has passed through the inner cavity of the gas supply pipe 312 is ejected from the ejection port 312a. The first electrode 314a and the second electrode 314b are a pair of coaxial plasma generating electrodes. The 1st electrode 314a and the 2nd electrode 314b are each installed in the upstream and downstream on the outer periphery of the edge part by the side of the jet nozzle 312a of the gas supply pipe 312. A pulse voltage is applied to the first electrode 314a, and the second electrode 314b is set to the ground potential. The voltage application device 316 applies a low-frequency pulse voltage of about 10 to 100 kHz (for example, 6 to 12 kV, 13 kHz) between the first electrode 314a and the second electrode 314b to cause pulse discharge, thereby generating a jet outlet. A plasma jet (hereinafter also referred to as an LF (Low Frequency) plasma jet) extending narrowly from 312a is generated. Note that the plasma jet can be generated even when the first electrode 314a is set to the ground potential and the pulse voltage is applied to the second electrode 314b.
　ＬＦプラズマジェットは、２つの点で希有な特徴を有している。まず、他の種類の大気圧プラズマ生成装置とは異なり、直径に対する長さの比すなわちアスペクト比が大きい形状のプラズマジェットが得られる。また、高時間分解能測定によると、柱状の放電が維持されているのではなく、小さなプラズマの塊（プラズマ・ブレット）が電源周波数と同期して、媒質ガス流に比べてきわめて大きな速度（たとえば、ガス流速の１万倍程度：１０ｋｍ／ｓ程度）で移動している。したがって、プラズマ・ブレットは媒質ガス流によって流されているわけではなく、電場により駆動されて移動している。 LF plasma jet has rare features in two respects. First, unlike other types of atmospheric pressure plasma generation apparatuses, a plasma jet having a shape with a large ratio of length to diameter, that is, an aspect ratio can be obtained. Also, according to the high time resolution measurement, the columnar discharge is not maintained, but a small plasma lump (plasma bullet) is synchronized with the power supply frequency, and has a very high velocity compared to the medium gas flow (for example, It is moving at about 10,000 times the gas flow rate: about 10 km / s). Therefore, the plasma bullet is not moved by the medium gas flow, but is driven by the electric field and moved.
　ＬＦプラズマジェットではパルス状にプラズマ塊（プラズマ・ブレット）が射出されるため、時間的に非平衡となることによって、熱的に非平衡の状態が作り出される。熱非平衡なプラズマであるので、対象物の温度上昇をもたらすことなく高エネルギー成分を照射することができる。 In the LF plasma jet, a plasma lump (plasma bullet) is ejected in a pulse shape, and therefore, a thermal non-equilibrium state is created by non-equilibrium in time. Since it is a thermal non-equilibrium plasma, it is possible to irradiate a high energy component without increasing the temperature of the object.
　図８は、本発明の実施形態２に係る他の人工骨製造装置３２０を示す模式図である。人工骨製造装置３２０は、人工骨製造装置３００と第１領域制御装置３３０とを備える。第１領域制御装置３３０は、改質処理の領域を制御する。第１領域制御装置３３０の機能の詳細は、図９を参照して説明する。人工骨製造装置３００が備える構成要素については、図７を参照して説明したので、その説明は省略する。人工骨製造装置３２０による製造方法は、バイオセラミックスに骨再生活性化のための改質処理をする処理工程と改質処理の領域を制御する領域制御工程を包含する。領域制御工程は、バイオセラミックスへのプラズマ照射時間を制御することにより実行される。 FIG. 8 is a schematic diagram showing another artificial bone manufacturing apparatus 320 according to Embodiment 2 of the present invention. The artificial bone manufacturing apparatus 320 includes an artificial bone manufacturing apparatus 300 and a first region control apparatus 330. The first area control device 330 controls the area of the reforming process. Details of the function of the first area control device 330 will be described with reference to FIG. The components included in the artificial bone manufacturing apparatus 300 have been described with reference to FIG. The manufacturing method by the artificial bone manufacturing apparatus 320 includes a processing step of performing a modification process for activating bone regeneration on the bioceramics and a region control step of controlling the region of the modification process. The region control process is executed by controlling the plasma irradiation time to the bioceramics.
　図９は、様々な厚みの改質層１２０を有する人工骨１００を示す写真である。第１領域制御装置３３０がバイオセラミックスへのプラズマ照射時間を制御することで、改質層１２０の厚さを制御し得る。図９（ａ）は、プラズマ照射されていない人工骨（即ち人工骨２００）を示す。図９（ｂ）は、１０秒間プラズマ照射された人工骨１００を示す。図９（ｃ）は、１分間プラズマ照射された人工骨１００を示す。図９（ｄ）は、５分間プラズマ照射された人工骨１００を示す。図９（ｅ）は、１０分間プラズマ照射された人工骨１００を示す。図９（ｆ）は、３０分間プラズマ照射された人工骨１００を示す。図９（ｇ）は、６０分間プラズマ照射された人工骨１００を示す。照射時間の増加に伴って人工骨の改質層１２０の厚みが増加する。 FIG. 9 is a photograph showing the artificial bone 100 having the modified layer 120 with various thicknesses. The first region control device 330 can control the thickness of the modified layer 120 by controlling the plasma irradiation time to the bioceramics. FIG. 9A shows an artificial bone that is not irradiated with plasma (ie, an artificial bone 200). FIG. 9B shows an artificial bone 100 that has been plasma-irradiated for 10 seconds. FIG. 9C shows the artificial bone 100 that has been plasma-irradiated for 1 minute. FIG. 9D shows an artificial bone 100 that has been plasma-irradiated for 5 minutes. FIG. 9E shows an artificial bone 100 that has been plasma-irradiated for 10 minutes. FIG. 9F shows the artificial bone 100 that has been plasma-irradiated for 30 minutes. FIG. 9G shows the artificial bone 100 that has been plasma-irradiated for 60 minutes. As the irradiation time increases, the thickness of the artificial bone modified layer 120 increases.
　図１０は、人工骨２００へのプラズマ照射時間と改質層１２０の厚みとの関係を示すグラフである。縦軸は人工骨１００の改質層１２０の厚みを示し、横軸は人工骨１００の表面へのプラズマ照射時間を示す。改質層１２０の厚みは照射時間が１０秒の場合は約１２０μｍであり、照射時間が１分の場合は約３００μｍであり、照射時間が５分の場合は約３５０μｍであった。さらに、照射時間が１０分の場合は人工骨の改質層１２０の厚みは約４６０μｍであり、照射時間が３０分の場合は約８２０μｍであり、照射時間が６０分の場合は約８９０μｍであった。照射時間の増加に伴って人工骨の改質層１２０の厚みが増加する。 FIG. 10 is a graph showing the relationship between the plasma irradiation time to the artificial bone 200 and the thickness of the modified layer 120. The vertical axis represents the thickness of the modified layer 120 of the artificial bone 100, and the horizontal axis represents the plasma irradiation time on the surface of the artificial bone 100. The thickness of the modified layer 120 was about 120 μm when the irradiation time was 10 seconds, about 300 μm when the irradiation time was 1 minute, and about 350 μm when the irradiation time was 5 minutes. Further, when the irradiation time is 10 minutes, the thickness of the artificial bone modified layer 120 is about 460 μm, when the irradiation time is 30 minutes, it is about 820 μm, and when the irradiation time is 60 minutes, it is about 890 μm. It was. As the irradiation time increases, the thickness of the artificial bone modified layer 120 increases.
　図１１は、本発明の実施形態２に係る更に他の人工骨製造装置４００を示す模式図である。人工骨製造装置４００は人工骨製造装置３００と改質処理の領域を制御する第２領域処理装置４２０とを備える。人工骨製造装置３００が備える構成要素については、図７を参照して説明したので、その説明は省略する。人工骨製造装置４００による製造方法は、バイオセラミックスに骨再生活性化のための改質処理をする処理工程と改質処理の領域を制御する領域制御工程を包含する。領域処理工程は、人工骨を含む周辺空間の圧力の加減を制御することにより実行される。 FIG. 11 is a schematic diagram showing still another artificial bone manufacturing apparatus 400 according to Embodiment 2 of the present invention. The artificial bone manufacturing apparatus 400 includes an artificial bone manufacturing apparatus 300 and a second area processing apparatus 420 that controls the area of the modification process. The components included in the artificial bone manufacturing apparatus 300 have been described with reference to FIG. The manufacturing method using the artificial bone manufacturing apparatus 400 includes a processing step of performing a modification process for activating bone regeneration on the bioceramics and a region control step of controlling the region of the modification process. The region processing step is executed by controlling the pressure in the surrounding space including the artificial bone.
　第２領域処理装置４２０は、人工骨を含む周辺空間の圧力の加減を制御することによって、改質処理の領域を制御する。第２領域処理装置４２０は、チャンバ４０２と加減圧装置４０４とを備える。チャンバ４０２の内部に人工骨２００が配置されており、人工骨２００を含む周辺空間を定義する。加減圧装置４０４は、人工骨２００の連通性の程度に応じて、増圧と減圧との繰り返し回数を調整し得る。増圧と減圧とを繰り返すことによって、人工骨２００の内部にまでプラズマＡが侵入し、人工骨２００の内部がプラズマ処理される。その結果、増圧と減圧との繰り返し回数の増加に伴って人工骨の改質層１２０の厚みが増加する。 The second region processing device 420 controls the region of the reforming process by controlling the pressure in the surrounding space including the artificial bone. The second region processing apparatus 420 includes a chamber 402 and a pressure increasing / decreasing apparatus 404. An artificial bone 200 is disposed inside the chamber 402 and defines a peripheral space including the artificial bone 200. The pressurizing / depressurizing device 404 can adjust the number of repetitions of pressure increase and pressure reduction according to the degree of communication of the artificial bone 200. By repeating the pressure increase and the pressure reduction, the plasma A penetrates into the artificial bone 200 and the inside of the artificial bone 200 is subjected to plasma processing. As a result, the thickness of the modified layer 120 of the artificial bone increases with an increase in the number of repetitions of pressure increase and pressure reduction.
　なお、人工骨を含む周辺空間の圧力の加減を制御し得る人工骨製造装置の構成は、人工骨製造装置４００の構成に限定されない。例えば、図１２を参照して下記に説明する人工骨製造装置６００も、人工骨を含む周辺空間の圧力の加減を制御し得る。 It should be noted that the configuration of the artificial bone manufacturing apparatus capable of controlling the pressure in the surrounding space including the artificial bone is not limited to the configuration of the artificial bone manufacturing apparatus 400. For example, the artificial bone manufacturing apparatus 600 described below with reference to FIG. 12 can also control the pressure in the surrounding space including the artificial bone.
　図１２は、本発明の実施形態２に係る更に他の人工骨製造装置６００を示す模式図である。人工骨製造装置６００は、プラズマ発生装置６１０とプラズマチャンバ６２０と第３領域処理装置６３０とを備える。 FIG. 12 is a schematic diagram showing still another artificial bone manufacturing apparatus 600 according to Embodiment 2 of the present invention. The artificial bone manufacturing apparatus 600 includes a plasma generator 610, a plasma chamber 620, and a third region processing apparatus 630.
　プラズマ発生装置６１０は、誘電体バリア放電を形成することでプラズマＡを発生する。プラズマ発生装置６１０は、上部電極と誘電体（たとえば、ガラス板）とを備える。プラズマ発生装置６１０への印加電圧は１０～１００ｋＨｚの周期的に時間変動する電圧（正弦波電圧、パルス電圧を含む）である。プラズマチャンバ６２０は、プラズマ発生ガスＢ（空気、ヘリウムガス等）を導入する第１ゲート６２２と、プラズマチャンバ６２０から減圧チャンバ６３０に排気ガスを導出する第２ゲート６２４と、人工骨製造装置６００の外部に排気ガスＣを排出する排出手段６２６とを含む。プラズマチャンバ６２０内には、人工骨２００が配置された試料ステージ６２８とプラズマ発生装置６１０とが設けられており、人工骨を含む周辺空間を定義する。プラズマ発生装置６１０とプラズマチャンバ６２０とは、バイオセラミックスに骨再生活性化のための改質処理をする処理装置として機能する。 The plasma generator 610 generates plasma A by forming a dielectric barrier discharge. The plasma generator 610 includes an upper electrode and a dielectric (for example, a glass plate). The voltage applied to the plasma generator 610 is a voltage (including a sine wave voltage and a pulse voltage) that varies periodically with time in the range of 10 to 100 kHz. The plasma chamber 620 includes a first gate 622 for introducing the plasma generation gas B (air, helium gas, etc.), a second gate 624 for leading the exhaust gas from the plasma chamber 620 to the decompression chamber 630, and the artificial bone manufacturing apparatus 600. And exhaust means 626 for exhausting the exhaust gas C to the outside. In the plasma chamber 620, a sample stage 628 on which the artificial bone 200 is disposed and a plasma generator 610 are provided, and a peripheral space including the artificial bone is defined. The plasma generator 610 and the plasma chamber 620 function as a processing apparatus that performs a modification process for activating bone regeneration on bioceramics.
　第３領域処理装置６３０は、人工骨を含む周辺空間の圧力の加減を制御することによって、改質処理の領域を制御する。第３領域処理装置６３０は、チャンバ６３２と加減圧装置６３４とを備える。例えば、加減圧装置６３４は、減圧チャンバ６３２内の圧力を調整する排気ポンプ、ピストン、ダイヤフラム等である。加減圧装置６３４によって減圧チャンバ６３２内の排気ガスＤの排出スピードを調整し、人工骨を含む周辺空間の圧力の加減を制御し得る。 The third region processing device 630 controls the region of the reforming process by controlling the pressure in the surrounding space including the artificial bone. The third region processing apparatus 630 includes a chamber 632 and a pressure increasing / decreasing apparatus 634. For example, the pressure increasing / decreasing device 634 is an exhaust pump, a piston, a diaphragm or the like that adjusts the pressure in the pressure reducing chamber 632. The pressure increase / decrease device 634 can adjust the discharge speed of the exhaust gas D in the pressure reduction chamber 632 to control the pressure increase / decrease in the surrounding space including the artificial bone.
　誘電体を含む電極系は一種のコンデンサとみなせるため、プラズマ発生装置６１０へは交流電圧を印加しなければならない。商用から高周波仕様まで様々な電源を使って簡単に誘電体バリア放電を形成し、プラズマを発生し得る。 Since an electrode system including a dielectric can be regarded as a kind of capacitor, an AC voltage must be applied to the plasma generator 610. Dielectric barrier discharge can be easily formed using various power sources from commercial to high frequency specifications, and plasma can be generated.
　なお、図１１及び図１２を参照して説明したように、人工骨製造装置４００や人工骨製造装置６００によれば、プラズマチャンバ内に人工骨２００を入れて、プラズマチャンバ内の圧力を低下することができる。従って、人工骨２００が有する気孔内（人工骨２００の内部）にまでプラズマを侵入させ、人工骨２００の内部を改質することができる。 As described with reference to FIGS. 11 and 12, according to the artificial bone manufacturing apparatus 400 and the artificial bone manufacturing apparatus 600, the artificial bone 200 is placed in the plasma chamber to reduce the pressure in the plasma chamber. be able to. Therefore, the plasma can be penetrated into the pores of the artificial bone 200 (inside the artificial bone 200), and the inside of the artificial bone 200 can be modified.
　図１３は、人工骨表面処理による濡れ性の変化を説明する図である。図１３（ａ）は、人工骨２００（従来の人工骨）の濡れ性を示す写真である。図１３（ｂ）は、人工骨１００（本発明の人工骨）の濡れ性を示す写真である。図１３（ｃ）は、人工骨の接触角を示すグラフである。 FIG. 13 is a diagram for explaining changes in wettability due to artificial bone surface treatment. FIG. 13A is a photograph showing the wettability of the artificial bone 200 (conventional artificial bone). FIG. 13B is a photograph showing the wettability of the artificial bone 100 (the artificial bone of the present invention). FIG. 13C is a graph showing the contact angle of the artificial bone.
　人工骨１００は、人工骨２００にプラズマを５分照射することにより製造された。人工骨表面処理による濡れ性の変化を調べるため、人工骨１００と人工骨２００との表面に液滴を垂らし、液滴と人工骨との接触角（液滴の接線と固体表面（人工骨表面）とのなす角度θ）を計測した。人工骨２００の接触角度は、約７０度であった。人工骨１００の接触角度は、約１２度であった。プラズマ照射による人工骨表面改質によって、液滴と人工骨との接触角が１０度～１５度になり、濡れ性が増した。プラズマ照射によって人工骨の表面が改質され、親水性が増したと判断し得る。 The artificial bone 100 was manufactured by irradiating the artificial bone 200 with plasma for 5 minutes. In order to investigate the change in wettability due to the artificial bone surface treatment, a droplet is dropped on the surface of the artificial bone 100 and the artificial bone 200, and the contact angle between the droplet and the artificial bone (the tangent of the droplet and the solid surface (the artificial bone surface ) Was measured. The contact angle of the artificial bone 200 was about 70 degrees. The contact angle of the artificial bone 100 was about 12 degrees. Due to the surface modification of the artificial bone by plasma irradiation, the contact angle between the droplet and the artificial bone became 10 to 15 degrees, and the wettability increased. It can be judged that the surface of the artificial bone is modified by the plasma irradiation and the hydrophilicity is increased.
　なお、プラズマ照射時間を更に増すことで、人工骨の表面や内部の改質程度が進み、人工骨の濡れ性を増すことができた。例えばプラズマ照射時間が３０分を越えた場合、接触角は０度になった。プラズマ照射による人工骨表面改質によって、濡れ性（親水性）が増し、液滴と人工骨との接触角が狭くなり、液滴と人工骨との接触角は０度～１５度になった。 In addition, by further increasing the plasma irradiation time, the degree of modification of the surface and inside of the artificial bone progressed, and the wettability of the artificial bone could be increased. For example, when the plasma irradiation time exceeded 30 minutes, the contact angle became 0 degrees. The artificial bone surface modification by plasma irradiation increased wettability (hydrophilicity), the contact angle between the droplet and the artificial bone became narrow, and the contact angle between the droplet and the artificial bone became 0-15 degrees. .
　また、連球状開気孔を有する人工骨２００にプラズマ照射して作製した人工骨１００を用いる場合は、粒界空隙状開気孔を有する人工骨２００や閉気孔を有する人工骨２００にプラズマ照射して作製した人工骨１００の場合と比較してプラズマが人工骨内部に侵入し易い。連球状開気孔は、粒界空隙状開気孔や閉気孔と比較して、気孔の連通性が高いからである。従って、連球状開気孔を有する人工骨２００にプラズマ照射して作製した人工骨１００によれば、人工骨の内部の改質程度が進み、人工骨の濡れ性を増すことができる。 In addition, when using the artificial bone 100 produced by irradiating plasma on the artificial bone 200 having the continuous spherical open pores, the artificial bone 200 having the grain boundary void open pores or the artificial bone 200 having the closed pores is irradiated with plasma. Compared to the case of the manufactured artificial bone 100, plasma easily enters the artificial bone. This is because the continuous spherical open pores have higher pore connectivity than the grain boundary void-like open pores and closed pores. Therefore, according to the artificial bone 100 produced by irradiating plasma on the artificial bone 200 having continuous open pores, the degree of modification inside the artificial bone proceeds and the wettability of the artificial bone can be increased.
　図１４は、人工骨表面におけるＸ線光電子分析（ＸＰＳ：Ｘ－ｒａｙ　Ｐｈｏｔｏｅｌｅｃｔｒｏｎ　Ｓｐｅｃｔｒｏｓｃｏｐｙ）の結果を示すグラフである。グラフの横軸は結合エネルギーを示し、グラフの縦軸は吸収強度（相対強度）を示す。（ａ）は人工骨２００の表面におけるＸ線光電子分析の結果であり、（ｂ）は人工骨１００の上表面におけるＸ線光電子分析の結果であり、（ｃ）は人工骨１００の下表面におけるＸ線光電子分析の結果である。人工骨１００の上表面は、プラズマ処理時のチャンバ中で、プラズマ密度が高い側に位置し、人工骨１００の下表面は、プラズマ処理時のチャンバ中で、プラズマ密度が低い側に位置していた。 FIG. 14 is a graph showing the results of X-ray photoelectron analysis (XPS: X-ray Photoelectron Spectroscopy) on the artificial bone surface. The horizontal axis of the graph indicates the binding energy, and the vertical axis of the graph indicates the absorption intensity (relative intensity). (A) is the result of X-ray photoelectron analysis on the surface of the artificial bone 200, (b) is the result of X-ray photoelectron analysis on the upper surface of the artificial bone 100, and (c) is the result of the lower surface of the artificial bone 100. It is a result of an X-ray photoelectron analysis. The upper surface of the artificial bone 100 is positioned on the high plasma density side in the plasma processing chamber, and the lower surface of the artificial bone 100 is positioned on the low plasma density side in the plasma processing chamber. It was.
　ＨｅとＯ2との混合ガス（Ｈｅ８０％程度、Ｏ2２０％程度）を用いてプラズマを発生させ、人工骨２００の表面をプラズマ照射することによって人工骨１００を作製した。Ｘ線光電子分析には、Ｘ線光電子分析装置（品番：ＥＳＣＡ－８５０Ｍ／島津製作所製）を用いた。 Plasma was generated using a mixed gas of He and O 2 (He 80%, O 2 20%), and the surface of the artificial bone 200 was irradiated with plasma to produce the artificial bone 100. For the X-ray photoelectron analysis, an X-ray photoelectron analyzer (product number: ESCA-850M / manufactured by Shimadzu Corporation) was used.
　表１は、人工骨表面におけるＸ線光電子分析の結果（人工骨表面の組成比）を示す表である。分析対象の人工骨は、バイオセラミックとしてハイドロキシアパタイトを含む。
Table 1 is a table showing the results of X-ray photoelectron analysis on the artificial bone surface (composition ratio of the artificial bone surface). The artificial bone to be analyzed contains hydroxyapatite as a bioceramic.
Figure JPOXMLDOC01-appb-T000001
 　人工骨２００の表面において、カルシウム（Ｃａ）とリン（Ｐ）との比率（Ｃａ／Ｐ）は、１．２９であった。同様に人工骨２００の表面において、酸素（Ｏ）とリン（Ｐ）との比率（Ｏ／Ｐ）は、４．４９であり、酸素（Ｏ）とカルシウム（Ｃａ）との比率（Ｏ／Ｃａ）は、３．４７であった。人工骨１００の上表面において、Ｃａ／Ｐは、１．３３であり、Ｏ／Ｐは、６．４５であり、Ｏ／Ｃａは、４．８５であった。人工骨１００の下表面において、Ｃａ／Ｐは、１．２８であり、Ｏ／Ｐは、６．０９であり、Ｏ／Ｃａは、４．７５であった。
Figure JPOXMLDOC01-appb-T000001
 On the surface of the artificial bone 200, the ratio (Ca / P) of calcium (Ca) to phosphorus (P) was 1.29. Similarly, on the surface of the artificial bone 200, the ratio (O / P) of oxygen (O) to phosphorus (P) is 4.49, and the ratio of oxygen (O) to calcium (Ca) (O / Ca). ) Was 3.47. On the upper surface of the artificial bone 100, Ca / P was 1.33, O / P was 6.45, and O / Ca was 4.85. On the lower surface of the artificial bone 100, Ca / P was 1.28, O / P was 6.09, and O / Ca was 4.75.
　ＨｅとＯ2との混合ガスを用いて発生させたプラズマを照射することで、Ｃａ／Ｐに大きな変化はなかったが、Ｏ／ＰとＯ／Ｃａとはプラズマを照射することによって増加し、人工骨表面の組成比に変化が見られた。ＨｅとＯ2との混合ガスを用いて発生させたプラズマを人工骨２００の表面に照射することによって人工骨表面（バイオセラミックス）が酸化し、人工骨表面（バイオセラミックス）の酸素組成比が増えた。人工骨２００の表面において、酸素（Ｏ）とリン（Ｐ）との組成比（Ｏ／Ｐ）が約４．５であり、酸素（Ｏ）とカルシウム（Ｃａ）との組成比（Ｏ／Ｃａ）が約３．５の場合、人工骨１００の表面において、Ｏ／Ｐは６．０～７．０であり、Ｏ／Ｃａは４．０～５．０であった。 By irradiating plasma generated using a mixed gas of He and O 2 , there was no significant change in Ca / P, but O / P and O / Ca increased by irradiating plasma, There was a change in the composition ratio of the artificial bone surface. By irradiating the surface of the artificial bone 200 with plasma generated using a mixed gas of He and O 2 , the artificial bone surface (bioceramics) is oxidized, and the oxygen composition ratio of the artificial bone surface (bioceramics) increases. It was. On the surface of the artificial bone 200, the composition ratio (O / P) between oxygen (O) and phosphorus (P) is about 4.5, and the composition ratio (O / Ca) between oxygen (O) and calcium (Ca). ) Is about 3.5, O / P was 6.0 to 7.0 and O / Ca was 4.0 to 5.0 on the surface of the artificial bone 100.
　なお、分析対象の人工骨にハイドロキシアパタイトではなく他のバイオセラミックスが含まれる場合は、元素の種類や元素の構成比が異なることもあり得る。例えば、バイオセラミックスとしてβ－ＴＣＰ（β―リン酸三カルシウム）が含まれる場合は、ハイドロキシアパタイトが含まれる場合と比較して、元素の構成比が異なる。さらに、バイオセラミックスとしてガラスセラミックスが含まれる場合も、ハイドロキシアパタイトが含まれる場合と比較して、元素の種類、構成比は異なる。 In addition, when the artificial bone to be analyzed contains other bioceramics instead of hydroxyapatite, the types of elements and the composition ratios of the elements may be different. For example, when β-TCP (β-tricalcium phosphate) is included as bioceramics, the constituent ratio of the elements is different from that when hydroxyapatite is included. Furthermore, when the glass ceramics are included as the bioceramics, the types and the composition ratios of the elements are different from those in the case where the hydroxyapatite is included.
　Ｘ線光電子分析のために、ＨｅとＯ2との混合ガス（Ｈｅ８０％程度、Ｏ2２０％程度）を用いてプラズマを発生させ、人工骨２００の表面をプラズマ照射することによって人工骨１００を作製したが、プラズマ照射によって人工骨表面が酸化し、人工骨表面の酸素組成比が増える限りは、ＨｅとＯ2との混合ガスによるプラズマ発生に限定されない。混合ガスは、アルゴン（Ａｒ）と酸素との混合ガスや窒素と酸素との混合ガス等、酸素を含んだ混合ガスであり得る。 For X-ray photoelectron analysis, plasma is generated using a mixed gas of He and O 2 (He 80%, O 2 20%), and the surface of the artificial bone 200 is irradiated with plasma to form the artificial bone 100. However, as long as the artificial bone surface is oxidized by plasma irradiation and the oxygen composition ratio of the artificial bone surface is increased, plasma generation by a mixed gas of He and O 2 is not limited. The mixed gas may be a mixed gas containing oxygen, such as a mixed gas of argon (Ar) and oxygen or a mixed gas of nitrogen and oxygen.
　本発明の好適な人工骨製造装置及び人工骨製造方法によれば、バイオセラミックスへのプラズマ照射時間を長くする場合には、人工骨の内部の非改質層に至るまでプラズマが到達し、人工骨の内部の非改質層を骨再生活性化した改質構造にし得る。また、プラズマ照射時間を短くする場合には、人工骨の表面付近の非改質層を骨再生活性化した改質構造にし得る。その結果、改質部分を選択的に形成し得、目的に応じた人工骨を製造し得る。 According to the preferred artificial bone production apparatus and artificial bone production method of the present invention, when the plasma irradiation time to bioceramics is increased, the plasma reaches the unmodified layer inside the artificial bone, The non-modified layer inside the bone can be made into a modified structure in which bone regeneration is activated. When the plasma irradiation time is shortened, a modified structure in which the non-modified layer near the surface of the artificial bone is activated by bone regeneration can be used. As a result, the modified portion can be selectively formed, and an artificial bone according to the purpose can be manufactured.
　本発明の好適な人工骨製造装置及び人工骨製造方法によれば、周辺空間を減圧することで、バイオセラミックスの多孔内部にプラズマを導入し得る。その結果、バイオセラミックスの多孔内部を骨再生活性化した改質構造にし得る。また、周辺空間の圧力の加減を繰り返すことで、多孔内の隅々までプラズマを導入し得る。その結果、バイオセラミックスの多孔内部をより確実に改質構造にし得る。 According to the preferred artificial bone production apparatus and artificial bone production method of the present invention, plasma can be introduced into the porous ceramic ceramic by decompressing the surrounding space. As a result, it is possible to obtain a modified structure in which the inside of the porous bioceramics is activated by bone regeneration. In addition, by repeatedly increasing and decreasing the pressure in the peripheral space, plasma can be introduced to every corner of the pore. As a result, the modified porous structure of the bioceramics can be more reliably formed.
　なお、本発明の実施形態２において、改質処理の領域を制御し得る限りは、領域制御装置による制御対象は、バイオセラミックスへのプラズマ照射時間や人工骨を含む周辺空間の圧力の加減に限らない。例えば、領域制御装置は、プラズマ処理装置の位置を移動してバイオセラミックスへの照射位置を変更する移動装置を備え得る。 In the second embodiment of the present invention, as long as the region of the modification process can be controlled, the control target by the region control device is limited to the plasma irradiation time to the bioceramics and the pressure in the surrounding space including the artificial bone. Absent. For example, the region control device may include a moving device that moves the position of the plasma processing device to change the irradiation position on the bioceramics.
　更に、本発明の実施形態２において、照射するプラズマの圧力および種類は限定されない。例えば、プラズマ温度が、バイオセラミックスの焼結温度以下であれば、バイオセラミックスの構造を変更することなく、骨再生活性化された改質が可能となる。 Furthermore, in Embodiment 2 of the present invention, the pressure and type of plasma to be irradiated are not limited. For example, if the plasma temperature is equal to or lower than the sintering temperature of bioceramics, the bone regeneration can be activated without changing the structure of the bioceramics.
　更に、本発明の実施形態２において、プラズマ照射時間を制御する第１領域制御装置、周辺空間の圧力の加減を制御する第２領域制御装置及び第３領域制御装置の各々を備える人工骨製造装置を説明したが、本発明の人工骨製造装置が備える領域制御装置の数は、１つに限定されない。例えば、人工骨製造装置４００は、人工骨製造装置３００にプラズマ照射時間を制御する第１領域制御装置を更に備え得る。また、人工骨製造装置６００は、プラズマ発生装置６１０に第１領域制御装置を更に備え得る。この場合、人工骨製造装置４００及び人工骨製造装置６００は、プラズマ照射時間の制御及び周辺空間の圧力の加減の制御が可能となり、バイオセラミックスに占める処理領域の位置、大きさ、範囲を精度よく制御し得る。 Furthermore, in Embodiment 2 of the present invention, an artificial bone manufacturing apparatus including each of a first region control device that controls the plasma irradiation time, a second region control device that controls the pressure in the surrounding space, and a third region control device. However, the number of area control devices provided in the artificial bone manufacturing apparatus of the present invention is not limited to one. For example, the artificial bone manufacturing apparatus 400 may further include a first region control device that controls the plasma irradiation time in the artificial bone manufacturing apparatus 300. The artificial bone manufacturing apparatus 600 may further include a first region control device in the plasma generation device 610. In this case, the artificial bone manufacturing apparatus 400 and the artificial bone manufacturing apparatus 600 can control the plasma irradiation time and the control of the pressure in the surrounding space, and can accurately determine the position, size, and range of the processing region in the bioceramics. It can be controlled.
　本発明の人工骨、人工骨製造装置及び人工骨製造方法によれば、主に、外科、整形外科等の医療分野において、骨の欠損部及び空隙への欠損補填の実現に利用可能である。 The artificial bone, the artificial bone manufacturing apparatus, and the artificial bone manufacturing method of the present invention can be used to realize defect filling in bone defects and voids mainly in the medical field such as surgery and orthopedics.
１００　　人工骨
１１０　　非改質層
１２０　　改質層
２００　　従来の人工骨
３００　　人工骨製造装置
３２０　　人工骨製造装置
３３０　　第１領域制御装置
４００　　人工骨製造装置
４２０　　第２領域処理装置
６００　　人工骨製造装置
６１０　　プラズマ発生装置
６２０　　プラズマチャンバ
６３０　　第３領域処理装置 100 Artificial bone 110 Non-modified layer 120 Modified layer 200 Conventional artificial bone 300 Artificial bone manufacturing device 320 Artificial bone manufacturing device 330 First region control device 400 Artificial bone manufacturing device 420 Second region processing device 600 Artificial bone manufacturing device 610 Plasma generator 620 Plasma chamber 630 Third region processing apparatus

Claims (15)

  1. 　バイオセラミックスを含む人工骨であって、
    　前記バイオセラミックスは、骨再生活性化された改質構造を有する、人工骨。     An artificial bone containing bioceramics,
    The bioceramic is an artificial bone having a modified structure activated by bone regeneration.
  2. 　前記改質構造は、プラズマ改質構造である、請求項１に記載の人工骨。 The artificial bone according to claim 1, wherein the modified structure is a plasma modified structure.
  3. 　前記バイオセラミックスは多孔質である、請求項１又は請求項２に記載の人工骨。 The artificial bone according to claim 1 or 2, wherein the bioceramics are porous.
  4. 　前記バイオセラミックスは連球状開気孔を有する、請求項１から請求項３のうちの一項に記載の人工骨。 The artificial bone according to any one of claims 1 to 3, wherein the bioceramics have continuous spherical open pores.
  5. 　前記バイオセラミックスは、リン酸カルシウム含有セラミックス又はガラスセラミックスを含有する、請求項１から請求項４のうちの一項に記載の人工骨。 The artificial bone according to one of claims 1 to 4, wherein the bioceramics contain calcium phosphate-containing ceramics or glass ceramics.
  6. 　前記改質構造は、液滴の接線と前記バイオセラミックの表面とのなす角度が０度～１５度である、請求項１から請求項５のうちの一項に記載の人工骨。 The artificial bone according to any one of claims 1 to 5, wherein the modified structure has an angle formed between a tangent of a droplet and a surface of the bioceramic in a range of 0 degrees to 15 degrees.
  7. 　前記バイオセラミックの表面において、酸素（Ｏ）とリン（Ｐ）との組成比（Ｏ／Ｐ）は６．０～７．０であり、酸素（Ｏ）とカルシウム（Ｃａ）との組成比（Ｏ／Ｃａ）は４．０～５．０である、請求項１から請求項６のうちの一項に記載の人工骨。 On the surface of the bioceramic, the composition ratio (O / P) of oxygen (O) to phosphorus (P) is 6.0 to 7.0, and the composition ratio of oxygen (O) to calcium (Ca) ( The artificial bone according to one of claims 1 to 6, wherein O / Ca) is 4.0 to 5.0.
  8. 　バイオセラミックスを含む人工骨の製造装置であって、
    　前記バイオセラミックスに骨再生活性化のための改質処理をする処理装置を備えた、人工骨製造装置。     An apparatus for producing an artificial bone containing bioceramics,
    An artificial bone manufacturing apparatus comprising a processing apparatus for performing a modification process for activating bone regeneration on the bioceramics.
  9. 　前記処理装置は、前記バイオセラミックスにプラズマを照射する、請求項８に記載の人工骨製造装置。 The artificial bone manufacturing apparatus according to claim 8, wherein the processing apparatus irradiates the bioceramics with plasma.
  10. 　前記改質処理の領域を制御する領域制御装置を更に備えた、請求項８又は請求項９に記載の人工骨製造装置。 The artificial bone manufacturing apparatus according to claim 8 or 9, further comprising a region control device that controls the region of the modification treatment.
  11. 　前記領域制御装置は、前記バイオセラミックスへのプラズマ照射時間を制御する、請求項１０に記載の人工骨製造装置。 The artificial bone manufacturing apparatus according to claim 10, wherein the region control device controls a plasma irradiation time to the bioceramics.
  12. 　前記領域制御装置は、前記人工骨を含む周辺空間の圧力の加減を制御する、請求項１０又は請求項１１に記載の人工骨製造装置。 The artificial region manufacturing device according to claim 10 or 11, wherein the region control device controls the pressure increase / decrease in a surrounding space including the artificial bone.
  13. 　バイオセラミックスを含む人工骨の製造方法であって、
    　前記バイオセラミックスに骨再生活性化のための改質処理をする処理工程を包含する、人工骨製造方法。     A method for producing an artificial bone containing bioceramics,
    A method for producing an artificial bone, comprising a treatment step of modifying the bioceramics to activate bone regeneration.
  14. 　前記処理工程は、前記バイオセラミックスにプラズマを照射することにより実行される、請求項１３に記載の人工骨製造方法。 The artificial bone manufacturing method according to claim 13, wherein the treatment step is performed by irradiating the bioceramics with plasma.
  15. 　前記処理工程において、前記バイオセラミックスを酸化し、前記バイオセラミックスの酸素組成比を増加させる、請求項１３又は請求項１４に記載の人工骨製造方法。 The method for manufacturing an artificial bone according to claim 13 or 14, wherein, in the treatment step, the bioceramics are oxidized to increase an oxygen composition ratio of the bioceramics.
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