JP2005185433A - Bioceramic composite structure - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a high-toughness and high-strength bioceramic composite structure without impairing biocompatibility in the composite structure combining a core material of dense ceramics with sufficient strength or a metal and a porous skin material of a calcium phosphate-based sintered compact. <P>SOLUTION: The composite structure 1 in which a plurality of single-core structural bodies 4 formed by covering an outer periphery of an elongated core material 2 with the porosity of 5% or less with the skin material 3 with the porosity of 25% or more and having pores communicating in three dimensions are gathered and bundled side by side is biologically used such as for a bone filling material. <P>COPYRIGHT: (C)2005,JPO&NCIPI

Description

  The present invention is a biological ceramic member comprising a substantially cylindrical composite structure in which a plurality of single core structures formed by coating the outer periphery of a long core material with a skin material having a different composition, The present invention relates to 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 have excellent biocompatibility, but have extremely low toughness values and easily break, making it difficult to use them 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 that the addition of a small amount of sodium pyrophosphate to calcium phosphate improves the fluidity when cemented by adding a curable aqueous solution, resulting in a dense hardened body and increased strength. Has been.
JP-A-2-52664 JP-A-14-253664

  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. .

  Further, in the method for strengthening calcium phosphate cement for living bone treatment described in Patent Document 2, although the strength is improved, the obtained sintered body has a low porosity and does not form a continuous pore. Due to the slow growth of cells, the problem remains that it is difficult for the living body to absorb.

  The present invention has been made in order to solve the above-mentioned problems, and the object thereof is a composite structure in which a dense ceramic or metal core material having sufficient strength and a skin material of a porous calcium phosphate sintered body are combined. An object of the present invention is to provide a ceramic composite structure for living body having high toughness and high strength without impairing biocompatibility in the body.

  As a result of studying the above problems, the present inventors have determined that a single core having a structure in which a dense oxide ceramic having sufficient strength or an alloy such as titanium is used as a core and the surface thereof is covered with porous biocompatible ceramics. By converging multiple structures, toughness and strength can be increased, and a composite suitable as a bone grafting material that has three-dimensionally continuous pores and allows osteoblasts to grow sufficiently It was found that it became a structure.

  That is, the composite structure of the present invention comprises a composite structure obtained by converging a plurality of single-core structures formed by coating the outer periphery of a long core material with a skin material having a different composition. The skin material is made of biocompatible ceramics having three-dimensionally continuous pores.

  Here, when the area ratio c / s between the core material c and the skin material s in the cross section of the composite structure is between 1 and 10, the strength and biocompatibility balance as a bone filling material is good, and the bone The effect as a filling material is exhibited effectively.

  As described above in detail, according to the composite structure of the present invention, a simple oxide ceramic or metal having sufficient strength is used as a core, and the surface is covered with porous biocompatible ceramics. By converging a plurality of core structures, a composite structure suitable as a bone filling material capable of sufficiently growing osteoblasts in three-dimensionally continuous pores is obtained.

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

  Referring to FIG. 1A, a composite structure 1 includes a single-core structure 4 in which a densely sintered ceramic or alloy is used as a core 2 and the outer periphery thereof is covered with biocompatible ceramics 3 having different compositions. Basic structure. The single-core structure 4 has a cylindrical structure having a concentric cross section as shown in the perspective view of FIG.

  Further, as shown in FIG. 2A, the composite structure 1 according to the present invention has a structure in which a plurality of single-core structures 4 are converged, and the skin material 3 of the biocompatible ceramic is densely sintered. The ceramic or metal core 2 is continuously surrounded. At this time, the core material 2 has a hexagonal cross-sectional shape as shown in the figure when converged with a dense structure, but may be intentionally other shapes such as a round shape or a star shape. The number can be controlled by the part or shape of the living bone used as the filling material. The area ratio c / s between the skin material 3 and the core material 2 in the cross section of the composite structure is preferably 1 to 10. As shown in the perspective view of FIG. 2 (b), the composite structure 1 is a cylindrical multi-core structure having a multi-core structure in which a plurality of single-core structures 4 are converged. It is processed and used according to the shape of the bone.

  Here, in the composite structure 1 for living body ceramics according to the present invention, for example, a skin material 3 made of porous ceramics having a porosity of 25% or more, particularly 40 to 90%, more preferably 45 to 70%, having biocompatibility. The core material 2 is made of a dense ceramic or metal having a porosity of 5% or less, particularly 2% or less, and the toughness and strength are increased. Excellent compressive strength and bending strength by arranging in dimension. In addition, the biocompatible porous ceramic skin material 3 arranged three-dimensionally so as to cover the core material 2 works to promote the growth of osteoblasts from the living bone to the bone prosthetic material, thereby increasing the strength and the living body. It becomes a composite structure with excellent affinity.

  The composite structure 1 of the present invention can freely select a combination of materials of the core material 2 and the skin material 3, and the ratio between the skin material 3 and the core material 2 can be arbitrarily controlled. Here, when the area ratio c / s between the area c of the core material 2 and the area s of the skin material 3 in the cross section of the composite structure 1 is between 1 and 10, strength and biocompatibility suitable as a bone grafting material. And is preferably 1 to 5, more preferably 1 to 3. When the area ratio c / s is less than 1, the ratio of dense ceramics is reduced, and the strength of the composite structure itself is lowered. For example, it may be less than 30 MPa required as a artificial bone substitute material. On the other hand, when the area ratio c / s exceeds 10, the strength is sufficient, but since the density of pores in the composite structure is low, the growth of osteoblasts is suppressed and a long time is required for healing. It comes to be.

  In the present invention, in order to calculate the area ratio c / s between the skin material 3 and the core material 2 in the cross section of the composite structure 1, for example, a scanning electron microscope (SEM) photograph in an arbitrary cross section of the structure 1 The sum of the cross-sectional areas of the core materials observed in step c can be calculated as c, and the total cross-sectional area of the arbitrary cross section of the composite structure 1 minus the area c of the core material 2 can be calculated as s. It can be easily obtained by an image analysis method or the like.

  Furthermore, the Young's modulus of the composite structure can be adjusted by controlling the area ratio between the core material c and the skin material s of the present invention and the porosity of each, and for example, the Young's modulus of living bone is controlled to about 30 GPa. As a result, it becomes more suitable as a bone filling material.

As the skin material 3 of the composite structure 1 used in the present invention, a calcium phosphate compound generally known as a biocompatible porous ceramic is suitable, 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), dihydrogen phosphate Calcium (Ca (H ₂ PO ₄ ) · H ₂ O), hydroxyapatite HAP (Ca ₁₀ (PO ₄ ) ₆ (OH) ₂ ) and the like.

On the other hand, the material of the core material 2 is a material that is not harmful to the living body and is preferably a dense ceramic or metal having biocompatibility. For example, alumina (Al ₂ O ₃ ), zirconia (ZrO ₂ ), silica ( SiO ₂ ), titania (TiO ₂ ), titanium and titanium alloys, cobalt chromium alloys, stainless steel alloys and the like. The ceramics listed here may contain auxiliary agents such as Ti, Mg, Zr, Hf, and Y as appropriate.

  The average secondary particle size of the ceramic crystal particles forming the skin material 3 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 2 is preferably 0.1 to 10 μm, particularly 0.5 to 3 μm in terms of improving toughness and strength.

  Moreover, although the size of the composite structure 1 is changed according to the part and shape of the living bone to be compensated, the pore size of the porous ceramics of the skin material 3 is 50 to 200 μm, so that the single core structure 4 is 0. About 5-5mm is good.

  In addition to the structure shown in FIGS. 1 and 2, the structure of the composite structure 1 is shown in FIG. 3 (a) 10A in which the composite structures 1 are arranged in a sheet shape, (b) Either 10B in which a plurality of sheets (a) are stacked in the same direction or 10C in which a plurality of sheets (c) and (a) are stacked in different directions may be used. These composite structures can be used for skulls, pelvises and the like.

(Production method)
Next, the method for producing the composite structure of the present invention will be described based on the schematic diagram of FIG. 4 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 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 skin material moldings 12 having a half-cylindrical shape are produced by a molding method such as the above.

  According to the present invention, when the raw material for the skin material molded body 12 is mixed in order to control the porosity of the skin material 6 to 25% or more, the amount of the organic binder added is 100 to 200 parts by volume, particularly It is desirable to set it as 120-150 volume parts. The hydroxyapatite raw material powder is preferably granulated to have a secondary particle size of 20 to 400 μm, particularly 50 to 200 μm, in terms of producing a uniform pore size and structure.

  Next, a composite molded body 13 in which two skin material molded bodies 12 are arranged on the outer periphery of the core material molded body 11 is manufactured, and the composite molded body 13 is coextruded (core body molded body 11, And the core material molded body 12 are simultaneously extrusion-molded) to produce the single core molded body 14 in which the skin material molded body 12 is coated on the outer periphery of the core material molded body 11 and extended to a thin diameter (step (step ( b)). Further, in order to produce a multi-fiber (filament) type multi-core molded body 15, a plurality of the co-extruded long single-core molded bodies 14 may be converged and co-extruded again. According to this, it is possible to obtain stronger adhesion between the single-core molded bodies 14 in the molded body. (See FIG. 4 (c)).

  In the coextrusion molding, the elongated single-core molded body 14 or the multi-core molded body 15 has a cross-sectional shape such as a circle, a triangle, a rectangle, or a hexagon by changing the die. It is also possible to mold into a desired shape.

  Further, according to the present invention, as shown in FIG. 3, when the composite structure 1 or the composite structure 10 in which the single-core structure 4 is converged in a sheet shape is formed as described above. The sheet-like molded body 10 is formed by arranging the composite structures 1 or the single-core structures 4. And if desired, a laminated body in which a composite molded body 1 or single core structures 4 in a sheet-like molded body (not shown) are laminated so as to form a predetermined angle such as parallel, orthogonal or 45 °. It can also be. In that case, an adhesive such as the binder is interposed between the composite molded body 1 or the single-core structure 4 as desired, and pressure is applied to the sheet-shaped molded body by cold isostatic pressing (CIP) or the like. Although it may be a thing, it is also possible to roll-roll a sheet-like molded object using a roll etc. as needed. Furthermore, when producing a sheet-like molded body, when a single-core molded body 14 or a multi-core molded body 15 is aligned, it is molded into a desired complex shape in advance using a molding method such as a known rapid prototyping method. It is also possible to do.

  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, by processing into a shape that matches the defect 17 of the living bone measured using X-rays, MRI, CT, etc., it can be used as, for example, a bone filling material as shown in FIG. In this case, as described above, it is desirable to perform a sintering process after previously forming the desired shape using the rapid prototyping technique.

  After the binder shown in Table 1 and the lubricant shown in Table 1 were added to the composition shown in Table 1 and kneaded, the composite structure after sintering was pressed so as to have the area ratio c / s shown in Table 1. Two molded bodies for a core material having a diameter and two molded bodies for a skin material having a half-cylindrical shape were produced.

  Then, as shown in FIG. 4, the core material molded body was coated around the core material molded body to produce single-core molded bodies (Examples 1 to 5). For comparison, a molded article having no core / skin structure was also produced (Example 6).

  Then, the single-core composite molded body was coextruded to produce a stretched multi-core molded body, and then the 100 stretched molded bodies were converged and molded again to produce a composite molded body. Thereafter, after removing the binder by heating the obtained molded body to 300 to 700 ° C. in 72 hours, the temperature was further raised at a heating rate of 2.5 ° C./min, and in vacuum at 1200 ° C. The composite structure of multi-core structure was obtained by baking for 2 hours, and also temperature-falling at 3 degree-C / min. 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. At that time, the Young's modulus based on JIS R1602 was also measured using a strain gauge method.

Furthermore, 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 by the image analysis method, and included in the core material The area ratio of the pores to be measured was measured, and the porosity in the core material was calculated. Furthermore, the porosity was calculated by the mercury intrusion method. The results are shown in Table 1.

  As is apparent from the results in Table 1, the sample No. 1 has no core / skin structure and is composed of a single hydroxyapatite material. No. 6 had a strength as low as 8.4 MPa.

  On the other hand, all of the example samples arranged according to the present invention had excellent bending strength with respect to the comparative example samples. Also, because it has a Young's modulus close to that of living bones, it is highly consistent, and since the pores are arranged three-dimensionally, it is estimated to be a bone filling material that promotes osteoblast growth. is there.

It is the perspective view and sectional drawing which show an example of the single core structure which is a basic unit of the composite structure of this invention. 2 is a perspective view and a cross-sectional view showing a multi-core structure in which a plurality of single-core structures in FIG. 1 as an example of the composite structure of the present invention are converged. It is a perspective view which shows the other embodiment of the composite structure of this invention. It is process drawing for demonstrating the manufacturing method of the composite structure of this invention. It is a schematic diagram which shows an example which uses the composite structure of this invention as a bone grafting material.

Explanation of symbols

1 Composite structure (multi-core structure)
2 Core material 3 Skin material 4 Single core structure 10 Sheet-shaped composite structure 11 Core material molded body 12 Skin material molded body 13 Composite molded body 14 Single core molded body 15 Multicore molded body 17 Damaged living bone

Claims (2)

A plurality of single-core structures formed by covering the outer periphery of a long core material having a porosity of 5% or less with a skin material having pores communicating in three dimensions with a porosity of 25% or more were converged in parallel. A ceramic composite structure for living body, characterized by comprising a composite structure. The composite structure according to claim 1, wherein an area ratio c / s between the core material c and the skin material s in a cross section of the composite structure is 1 to 10.

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