JP2006006756A - Biological ceramic composite structure - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a biological ceramic composite structure with optimum mechanical strength and bio-compatibility as a biological bone prosthesis material. <P>SOLUTION: The biological ceramic composite structure consists of a single-core structure or a multi-core structure with a plurality of bundled single-core structures. The single-core structure comprises a long core material made of metal or high-strength ceramics, an intermediate layer made of calcium phosphate whose porosity is not more than 10%, or a mixture of calcium phosphate and at least one of the materials constituting the core material, and a facing material made of calcium phosphate whose porosity is at least 20%. The core material is covered with the intermediate layer, and the intermediate layer is covered with the facing material. <P>COPYRIGHT: (C)2006,JPO&NCIPI

Description

  The present invention relates to a living body ceramic structure suitable as a bone filling material to be embedded in a living body.

  2. Description of the Related Art Conventionally, bone has been repaired using a bone prosthetic material in a bone defect caused by trauma or the like. As this bone prosthetic material, those that provide a scaffold for bone formation and those that promote the growth of new osteoblasts while being absorbed by bone are known. The properties required for these materials are non-toxic, safe and excellent in mechanical strength, and must be compatible with living tissue and easily bind to bone tissue cells and vascular tissue. Is done.

  As such a material, a calcium phosphate-based sintered body made of a sintered body such as tricalcium phosphate (TCP) or hydroxyapatite (HAP) has been proposed so far. However, these calcium phosphate-based sintered bodies are excellent in biocompatibility, but have extremely low toughness values and easily break, making them difficult to use as reliable practical materials.

In order to cover the defects of the calcium phosphate sintered body having this fracture toughness value, attempts have been made to combine it with other materials or to make the calcium phosphate itself dense. For example, in Patent Document 1, a large number of voids having an average diameter of 0.1 to 2 mm are provided in the entire or surface portion of a substrate made of ZrO ₂ , Al ₂ O ₃ , TiO ₂ , SiC, and Si ₃ N _4. It is disclosed that filling with a porous calcium phosphate compound enables good bone formation while maintaining high strength.

Patent Document 2 discloses a composition in which titanium powder is packed in a thin tube, and this thin tube is placed in the center of a thick tube filled with hydroxyapatite powder, which is a kind of calcium phosphate, and the tube is pulled out while rotating. An inclined rod-shaped molded body can be produced, and this is subjected to cold isostatic pressing (CIP), followed by discharge plasma (SPS) firing, so that the central portion (core material portion) is made of titanium metal and has an outer periphery. It is described that a sintered body having an inclined structure of apatite ceramics was obtained.
JP-A-2-52664 JP 2001-259017 A

  However, the method of forming a large number of voids in the substrate described in Patent Document 1 tends to lower the strength of the substrate, and the above-described conventional ceramics have insufficient strength and may cause damage to the biological member. . In addition, since the calcium phosphate compound having excellent biocompatibility exists in a state where it is locally divided, there is a problem that blood flow is delayed and osteoblasts are not easily formed.

  In addition, a thin tube packed with titanium powder described in Patent Document 2 is placed in the center of a thick tube packed with hydroxyapatite powder, and the tube is pulled out while rotating to form a rod-shaped body with an inclined composition and fired. In the sintered body, the density at each part of the sintered body cannot be controlled, and the mechanical strength and biocompatibility as a biomaterial have not been optimized.

  The present invention has been made to solve the above-described problems, and an object of the present invention is to provide a ceramic composite structure for a living body that has both optimum mechanical strength and biocompatibility as a living bone substitute material.

  As a result of examining the above problems, the present inventors have used a dense metal or high-strength ceramic having a sufficient strength as a core material, and the surface of the calcium phosphate or calcium phosphate having a porosity of 10% or less and a material constituting the core material. A single-core structure formed by coating with an intermediate layer made of a mixture of at least one of them, and covering the outer periphery of the intermediate layer with a skin material made of calcium phosphate having a porosity of 20% or more, or this single-core It has been found that a multi-core structure obtained by concentrating a plurality of structures has a high mechanical strength and sufficient osteoblasts grow, so that it becomes a ceramic composite structure suitable as a bone filling material.

  That is, the biomedical ceramic composite structure according to the present invention has an outer periphery of a long core material made of metal or high-strength ceramic, and includes calcium phosphate having a porosity of 10% or less, or calcium phosphate and a material constituting the core material. The intermediate layer is coated with an intermediate layer made of a mixture of at least one kind, and the outer periphery of the intermediate layer is covered with a skin material made of calcium phosphate having a porosity of 20% or more.

  Here, the area ratio c of the core material in the cross section of the composite structure is 0.2 to 0.9, the area ratio m of the intermediate layer is 0.05 to 0.5, and the area ratio s of the skin material. Is 0.05 to 0.2, the balance between strength and biocompatibility as a bone filling material is particularly good, and the effect as a bone filling material is effectively exhibited.

  The biological ceramic composite structure of the present invention has a high mechanical strength and sufficient growth of osteoblasts because the composition and density in each part of the structure are controlled to the optimum conditions. Therefore, a ceramic composite structure suitable as a bone filling material is obtained.

  The composite structure of the present invention will be described with reference to the drawings which are one example thereof.

  According to FIG. 1 (a), the composite structure 1 is a long, preferably calcium phosphate having a porosity of 10% or less around the outer periphery of a core material 2 made of a dense metal or high-strength ceramic with a porosity of 3% or less. Or it coats with the intermediate | middle layer 3 which consists of a mixture of calcium phosphate and at least 1 sort (s) of the material which comprises the said core material 2, and the outer periphery of the intermediate | middle layer 3 is covered with the skin material 4 which consists of calcium phosphate with a porosity of 20% or more. It consists of the single core structure 5 formed by coating. As shown in the perspective view of FIG. 1B, the single-core structure 5 has a cylindrical structure having a concentric cross section.

  Here, the living body ceramic composite structure 1 of the present invention having the above-described structure has a high mechanical strength and sufficiently grows osteoblasts, and thus is a structure suitable as a bone filling material.

  That is, when the porosity of the core material 2 exceeds 3%, it is difficult to obtain mechanical strength as a biomaterial. A desirable range of the porosity of the core material 2 is 2% or less, and a more desirable range is 1% or less. Moreover, when the porosity of the skin material 4 is less than 20%, the growth of osteoblasts is suppressed, biocompatibility is impaired, and healing takes a long time. A desirable range of the porosity of the skin material 4 is 25%, and a more desirable range is 30% or more. Furthermore, if the intermediate layer 3 having a porosity of 10% or less does not exist, peeling may occur at the interface between the core material 2 and the skin material 4, and the reliability as a structure is impaired. A desirable range of the porosity of the intermediate layer 3 is 7% or less, and a more desirable range is 5% or less.

  Further, the area ratio c of the core material 2 in the cross section of the composite structure 1 is 0.2 to 0.9, preferably 0.5 to 0.9, and the area ratio m of the intermediate layer 3 is 0.05. -0.5, preferably 0.1-0.2, and especially when the area ratio s of the skin material 4 is 0.05-0.2, preferably 0.1-0.2. The balance between strength and biocompatibility as a material is good, and the effect as a bone grafting material is effectively exhibited.

  Furthermore, according to the present invention, the bio-ceramic composite structure is not limited to the single-core structure 5 of FIG. 1, and a plurality of single-core structures 5 are provided as shown in FIG. The converged multi-core structure 6 may be used. In this case, the skin material 4 of the biocompatible ceramics is a densely sintered ceramic or metal core 2 and an island shape of the intermediate layer 3 surrounding the periphery. It becomes the structure which continuously surrounds the part which is scattered in.

  In addition, it is also possible to adjust the Young's modulus of the composite structure 1 because the composite structure 1 is composed of the multi-core structure 6. It becomes a more suitable material.

  In the case of this multi-core structure 6, the porosity of the core material 2 may be slightly larger than the porosity of the core material 2 in the single-core structure because of the multi-core structure. That is, the porosity in this case is preferably 5% or less, and more preferably 4% or less.

(Skin material and core material)
The material of the core material 2 of the composite structure 1 used in the present invention is a material that is not harmful to the living body and is preferably a dense ceramic or metal having a porosity of 3% or less that has biocompatibility, such as stainless steel ( For example, a metal having excellent corrosion resistance such as SUS316, SUS316L), cobalt-chromium alloy, cobalt-chromium-nickel alloy, titanium, titanium alloy (eg, Ti-6% Al-4% V, Ti-49-51% Ni). Can be used. Among them, it is particularly preferable to use a shape memory alloy (Ti-49 to 51% Ni). Since this shape memory alloy has excellent followability to repeated loads, resilience, and fatigue characteristics, stability and durability are improved during long-term embedding.

Alternatively, as the core material 2, for example, alumina (Al ₂ O ₃ ), zirconia (ZrO ₂ ), silica (SiO ₂ ), titania (TiO ₂ ), silicon nitride (Si ₃ N ₄ ), silicon carbide (SiC), etc. A material having excellent strength and hardness, such as ceramics, can be used. The ceramics mentioned here may contain auxiliary agents such as Ti, Mg, Zr, Hf, and Y as appropriate.

On the other hand, the skin material is suitable calcium phosphate compounds which are commonly known as biocompatible porous ceramic, for example tricalcium phosphate _{TCP (Ca 3 (PO 4)} 2), tetracalcium phosphate (Ca _{4 (PO 4)} 2 _O), octacalcium phosphate _{(Ca 8 H 2 (PO 4} ) 6 · 5H 2 O), calcium hydrogen phosphate (CaHPO _4), calcium dihydrogen phosphate _(Ca (H 2 PO ₄ ) · H ₂ O), hydroxyapatite HAP (Ca ₁₀ (PO ₄ ) ₆ (OH) ₂ ), zirconia (ZrO ₂ ), or other inorganic materials, or polyether ketone, polyether ether ketone, polyallyl ether ketone Examples of such ketone resins and thermoplastic resins such as polyphenylene sulfide and polysulfone. In the present invention, one or more of these can be used in any combination. Various additives such as stabilizers and reinforcing materials may be added to the biomedical resin material 8.

  In addition, the average secondary particle size of the crystal particles of the sintered body forming the skin material is 10 to 300 μm, preferably 50 to 200 μm, in order to maintain pores necessary for growing osteoblasts. On the other hand, the dense ceramic or metal forming the core material is preferably 0.1 to 10 μm, particularly 0.5 to 3 μm in terms of improving toughness and strength.

  Furthermore, the size of the composite structure 1 can be changed as appropriate according to the site and shape of the damaged living bone 20 to be compensated as shown in FIG. 3, but the pore size of the porous calcium phosphate ceramics of the skin material 4 Is 50 to 200 μm, the single core structure 5 is preferably about 0.5 to 5 mm.

  In addition to the form of the structure shown in FIGS. 1 and 2, the structure of the composite structure is (A) a composite structure 1 as shown in FIG. Either 9B in which a plurality of sheets of a) are stacked in the same direction, or 9C in which a plurality of sheets of (c) and (a) are stacked in different directions may be used. These sheet-like composite structures can be used for skulls and pelvises.

(Production method)
Next, a method for producing the composite structure of the present invention will be described based on the schematic diagram of FIG. 5 in the case where the core material is alumina and the skin material is hydroxyapatite.

  First, an auxiliary agent is appropriately added to and mixed with alumina powder having an average particle diameter of 0.01 to 3.5 μm, and paraffin wax, polystyrene, polyethylene, ethylene-ethyl acrylate, ethylene-vinyl acetate, polybutyl methacrylate, polyethylene are added thereto. An organic binder such as glycol or dibutyl phthalate is added and kneaded, and the core material molded body 11 is formed into a cylindrical shape by a molding method such as press molding, extrusion molding, or cast molding.

  On the other hand, a hydroxyapatite raw material powder having an average particle size of 0.1 to 10 μm is appropriately added with a dispersant, a foaming agent, and an antifoaming agent in addition to the above-mentioned binder and kneaded, and then press molding, extrusion molding or cast molding. Two intermediate layer shaped bodies 12 having a half-cylindrical shape are produced by a molding method such as the above.

  On the other hand, a hydroxyapatite raw material powder having an average particle size of 0.1 to 100 μm is appropriately added with a dispersant, a foaming agent, and an antifoaming agent in addition to the above-mentioned binder and kneaded, and press molding, extrusion molding, or cast molding. The two half-cylindrical shaped moldings 13 for the skin material are produced by a molding method such as the above.

  According to the present invention, when mixing the raw material for the intermediate layer molded body 12 in order to control the porosity of the intermediate layer 6 to 10% or less, the amount of the organic binder added is 40 to 95 parts by volume, particularly 50 to 90 parts by volume are desirable. In addition, it is desirable that the hydroxyapatite raw material powder for the intermediate layer molded body is granulated to have a secondary particle diameter of 1 to 50 μm, particularly 2 to 10 μm, in order to produce a sintered body having a dense structure.

  Furthermore, when mixing the raw material for the skin material molded body 13 in order to control the porosity of the skin material 4 to 20% or more, the amount of the organic binder added is 100 to 200 parts by volume, particularly 120 to 150 volumes. It is desirable to be a part. Furthermore, it is desirable that the hydroxyapatite raw material powder for the skin material molded body is granulated to have a secondary particle size of 20 to 400 μm, particularly 50 to 200 μm, in order to produce a uniform pore size and structure.

  Next, a composite molded body 14 in which two intermediate layer molded bodies 12 are arranged on the outer periphery of the core material molded body 11 and a skin material molded body 13 is arranged on the outer periphery of the intermediate layer molded body 12 is provided. The composite molded body 14 is manufactured and coextruded (the core molded body 11, the intermediate layer molded body 12 and the skin material molded body 13 are simultaneously extruded) to form the outer periphery of the core molded body 11. The intermediate layer molded body 12 and the skin material molded body 13 are sequentially coated to produce a single core molded body 15 extended to a thin diameter (see step (b)). Further, in order to produce a multi-fiber (filament) type multi-core molded body 16, a plurality of the co-extruded long single-core molded bodies 15 may be collected and co-extruded again. According to this, it is possible to obtain stronger adhesion between the composite structures in the molded body. (See FIG. 6).

  In the coextrusion molding, the cross-sectional shape of the elongated elongated shaped body can be formed into a desired shape such as a circle, a triangle, a quadrangle, or a hexagon by changing the die. It is.

  Further, according to the present invention, as shown in FIG. 4, when forming a sheet-like composite molded body in which the single-core molded body 5 and the multi-core molded body 6 are converged into a sheet shape, as described above. The produced single-core molded body 5 and multi-core molded body 6 are arranged to form a sheet-like molded body. Further, if desired, the arranged sheet-like molded bodies are laminated so that the single-core molded bodies 5 and the multi-core molded bodies 6 in the sheet-like molded bodies are parallel, orthogonal, or at a predetermined angle such as 45 °. It can also be set as a laminated molded body. In that case, an adhesive such as the binder is interposed between the single-core molded body 5 and the multi-core molded body 6 as desired, and pressure is applied to the sheet-shaped molded body by a cold isostatic pressing (CIP) or the like. It is also possible to roll-roll the sheet-like molded body using a roll or the like. Furthermore, when producing a sheet-like molded body, it is also possible to use a molding method such as a known rapid prototyping method when aligning the single-core molded body 5 or the multi-core molded body 6.

  Thereafter, the molded body is subjected to a binder removal treatment and then fired to produce the composite structure of the present invention. As the firing method, vacuum or atmosphere firing, gas pressure firing, hot press, discharge plasma sintering, or the like is used depending on the core material and the skin material. The firing temperature is desirably 750 ° C to 1300 ° C.

  After sintering, it can be used as a bone prosthetic material by processing it into a shape that matches the defect of the living bone measured using X-rays, MRI, CT, or the like. Moreover, after forming into a desired shape in advance using the rapid prototyping technique, a sintering process may be performed.

  After adding and kneading a binder and a lubricant in a total proportion of 85 parts by mass to titanium powder having an average particle size of 0.3 μm, a cylindrical shaped core material was produced by press molding. Next, after adding and kneading a binder and a lubricant in a proportion of 50 parts by mass to the hydroxyapatite powder having an average particle size of 0.2 μm, the molded product for a half-cylindrical intermediate layer is formed by press molding. 2 were prepared, and the intermediate layer molded body was disposed around the core body molded body. Further, after adding and kneading a binder and a lubricant in a ratio of 120 parts by mass in total to a hydroxyapatite powder having an average particle size of 0.2 μm, a half-cylindrical molded body for skin material is formed by press molding. Two composites were produced, and a composite molded body in which the molded body for the skin material was covered around the molded body for the intermediate layer.

  And the single core molded object which consists of a triple structure of a core material-intermediate layer-skin material was produced by coextrusion molding of this composite molded object. Furthermore, this single-core molded body was subjected to binder removal treatment by raising the temperature to 300 to 700 ° C. in 72 hours, and then fired at 1200 ° C. for 10 minutes in a vacuum by a discharge plasma sintering method.

  The obtained composite structure was processed into a size of φ10 × 30 mm, and subjected to a three-point bending test based on JIS R1601, and the bending strength was measured. Moreover, when the cross section which grind | polished the obtained composite structure was observed with the metal microscope or the scanning electron microscope, and the area ratio of each site | part was computed by the image-analysis method, the area ratio c of a core material is 0. 75, the area ratio m of the intermediate layer was 0.17, and the area ratio s of the skin material was 0.08.

  Moreover, when the area ratio of the pores contained in the core material was measured from the structure observation photograph and the porosity in the core material was calculated, it was 0.2%. Similarly, the porosity of the intermediate layer was 5%, and the porosity of the outer skin material was 32%.

(Comparative Example 1)
While loading 0.2 g of titanium hydride powder into a cylindrical cylindrical tube made of glass, this was placed on the central part of a cylindrical rubber tube filled with 0.2 g of hydroxyapatite powder while rotating the thin glass tube. After extracting, pressurization of 1000 MPa was performed with a cold isostatic press. And after performing binder removal processing by heating up this composite molded object to 300-700 degreeC in 72 hours, it baked at 1200 degreeC for 10 minutes by the discharge plasma sintering method in vacuum, and a composite structure is obtained. Produced.

  As a result of evaluating the obtained composite structure in the same manner as in the example, the bending strength was 110 MPa. Further, the polished cross section of the obtained composite structure was observed with a metal microscope or a scanning electron microscope, and the area ratio c / s between the core material and the skin material was calculated by an image analysis method. c / s was 5. Furthermore, from this structure observation photograph, the area ratio of pores included in the area of the central circle portion of the structure having a radius of 1/5 from the radius R of the entire structure from the center of the structure is measured. Then, the porosity of the central part was calculated to be 1%. Similarly, when the porosity of the outer peripheral ring portion having a length of 1/5 with respect to the radius R of the entire structure was measured from the outer periphery, it was confirmed that the porosity was 2% and the biocompatibility was poor. It was done.

(Comparative Example 2)
A composite structure was manufactured in the same manner as in the example except that the amount of the organic binder added in the intermediate layer was changed to 90 parts by weight with respect to the composite structure of the example.

  As a result of evaluation in the same manner as in Examples, the polished cross section of the obtained composite structure was observed with a metal microscope or a scanning electron microscope, and the area ratio c / s between the core material and the skin material was determined by image analysis. As a result, the area ratio c / s was 5. Furthermore, from this structure observation photograph, the porosity of the core material was 0.2%, the porosity of the intermediate layer was 15%, and the porosity of the skin material was 27%.

  Although the bending strength was 100 MPa, as a result of observing the fracture surface, peeling was observed at the interface between the core material and the intermediate layer.

FIG. 2 is a perspective view (b) and a cross-sectional view (a) showing an example of a single core structure which is an embodiment of the biomedical ceramic composite structure of the present invention. It is the perspective view (b) and sectional drawing (a) which show an example of the multi-core structure which is the other embodiment of the ceramic composite structure for biological bodies of this invention. It is a schematic diagram at the time of practical use of the ceramic composite structure for living body of the present invention. (A)-(c) is a perspective view which shows the other example of the ceramic composite structure for biological bodies of this invention. (A) (b) is process drawing for demonstrating the manufacturing method of the ceramic composite structure for biological bodies of this invention. It is process drawing for demonstrating the modification of the manufacturing method of the ceramic structure for biological bodies of this invention.

Explanation of symbols

DESCRIPTION OF SYMBOLS 1 Composite structure 2 Core material 3 Intermediate | middle layer 4 Skin material 5 Single core structure 6 Multi-core structure 9 Sheet-like composite structure 11 Molded body 12 Core material molded body 13 Skin material molded body 14 Composite molded body 15 Single-core molded body 16 Multi-core molded body 17 Sheet-shaped molded body 18 Laminated molded body 20 Damaged living bone

Claims (2)

The outer periphery of a long core material made of metal or high-strength ceramic is coated with an intermediate layer made of calcium phosphate having a porosity of 10% or less or a mixture of calcium phosphate and at least one of the materials constituting the core material. In addition, a bio-ceramic composite structure in which the outer periphery of the intermediate layer is covered with a skin material made of calcium phosphate having a porosity of 20% or more. The area ratio c of the core material in the cross section of the ceramic composite structure is 0.2 to 0.9, the area ratio m of the intermediate layer is 0.05 to 0.5, and the area ratio s of the skin material is 0. The biocomposite ceramic composite structure according to claim 1, which is 0.05 to 0.2.

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