JPH0773601B2 - Bioprosthetic material - Google Patents

Description

Description: TECHNICAL FIELD The present invention relates to a material suitable for filling / restoring a defective portion of a living body, and in particular, it has little biological rejection reaction and is well compatible with living tissue, and We propose a prosthesis material with excellent durability that has the property of binding to a living body with strong hard tissue.

[Conventional technology]

It has been customary to use artificial materials for restoration and restoration of tooth and bone defects, but despite many years of efforts,
The fact remains that many problems remain with the known prosthetic restoration materials. That is, as substitute materials for living teeth and bones, metal materials such as SUS316 stainless steel, cobalt-chromium alloys, titanium and titanium alloys, tantalum, zirconium, gold, silver and platinum, high density polyethylene and poly have been used. Organic hard materials such as tetrafluoroethylene and polymethylmethacrylate, composite resins and other composite materials, inorganic materials such as ceramics, bioglass, and carbon have been developed, and some of them have already been put into practical use.

By the way, such a prosthetic material and a prosthetic material have various performances required depending on a site to be used in a living body, a shape, a size, and the like, and suitability for them also varies depending on the material.

The conventional artificial prosthesis material has a problem that loosening is unavoidable when it is used in a living body for a long period of time. For example, as a method for fixing a hard prosthetic restoration material to bone in repairing a fractured site or artificial joint, (1) a self-locking method for fixing the restoration material and bone tissue structurally or geometrically, (2) A method of mechanically fixing with screws or spikes, (3) a method of adhering a prosthetic material and bone with bone cement, and the like are known.

However, these methods always had to be loosened over the years and had to be replaced even if the prosthetic material itself was not defective.

In addition, as another example, in the field of dental treatment, an implant is embedded in the alveolar bone, and a crown is placed on and fixed to the implant.
There is a method to restore the masticatory function. As the material of the implant, the above-mentioned various hard materials were used, and these were used properly according to various shapes such as a screw shape, a cylindrical shape, a pin shape, a natural root shape, and a blade shape, and the properties of the material. Such a device is necessary to bear the masticatory pressure that exerts the strongest force in the living body, and for example, a device has been required to increase the contact area between the isoplant and the bone.

[Problems to be solved by the invention]

However, it is difficult to form a sufficient amount of bone tissue in the surroundings with the conventionally known artificial prosthesis materials as described above, and in both cases, the bone and the artificial prosthesis material are bonded early and with sufficient strength. Was difficult.

By the way, as a technique aiming at solving the problems of such conventional techniques, JP-A-60-253455 discloses that "collagen as a support or a derivative thereof contains an osteogenic factor. Biomaterials characterized by
And the invention concerning the manufacturing method thereof.

However, although such a conventional technique has a general description of a biocompatible material to which a biomaterial containing a bone morphogenetic factor can be attached, nothing is specifically described as to what is a suitable material. Not not. Moreover, the exemplified bone morphogenetic factor is a human bone morphogenetic factor isolated and purified from human osteosarcoma, which is unreliable in terms of practical use.

[Means for solving problems]

Therefore, the present inventors previously mentioned in Japanese Patent Application No. 61-171760 that "a living body made of a silicon carbide material having a porous structure layer having a thickness of 0.1 mm or more at least on its surface is described as a material having extremely excellent biocompatibility. Proposal of "filling prosthesis material" was proposed, and the suitability of this silicon carbide material as a material for adhering a biomaterial containing a bone morphogenetic factor was examined, and a normal calf was found. , Was found to have excellent compatibility with bone morphogenetic proteins extracted from rat, rabbit, or human bone, and also with biocompatibility, and succeeded in developing an extremely excellent prosthetic material. Completed the invention.

That is, the present invention is a biomedical prosthesis material in which an osteogenic composite is adhered to voids of a porous structure layer of a silicon carbide material having a porous structure layer having a thickness of 0.1 mm or more at least in the surface layer portion. The core of this silicon carbide material is
The density is a dense sintered body having a density of 2.75 g / cm ³ or more, while the porous structure layer has an average void diameter of 10 to 500 μm, and the average void diameter gradually increases from the surface layer to the inside. It is a living body prosthetic restoration material characterized by having a structure that becomes smaller.

The prosthesis material according to the present invention is characterized in that the bone-forming composite is attached to the portion (in the void) of the porous structure layer of the silicon carbide material because the silicon carbide material itself is extremely biocompatible. Further, by adhering the osteogenic composite in the voids of the porous structure layer of the silicon carbide material, the osteogenic composite promotes in-vivo bone hyperproliferation and repair, and is early and sufficient. Form bone tissue with strength. Moreover, it is possible to bond the silicon carbide material and the in-vivo autologous bone in an extremely good condition.

The osteogenic complex used in the present invention preferably comprises an osteogenic protein and collagen or a derivative thereof. The reason for this is that bone morphogenetic protein exerts an osteoinductive action in vivo, and when it is combined with collagen or its derivative, the concentration of bone morphogenetic protein is kept constant and localized. Because you can. The reason for using collagen or a derivative thereof in the complex is that the collagen or a derivative thereof has a small immune reaction in vivo, has good affinity with bone, and does not impair the properties of the bone morphogenetic protein. This is because it has characteristics that it is easily absorbed by the living body and can be easily attached to the silicon carbide material.

In the present invention, it is necessary that at least the surface layer portion of the silicon carbide material, and 0.1 mm or more of the surface layer portion be a porous structure layer.

The reason why the surface layer portion needs to be a porous structure layer is that the surface layer portion having a porous structure layer is extremely compatible with living tissue and can be firmly bonded. Further, the reason why the thickness of the surface layer portion (porous structure layer) is required to be 0.1 mm or more is that if the thickness of the surface layer portion is less than 0.1 mm, the bond with living tissue can be made sufficiently strong. This is because it cannot be used and cannot be used. The preferable thickness of the surface layer is in the range of 0.3 to 1.0 mm.

Next, the silicon carbide material constituting the substrate of the material of the present invention is preferably a dense silicon carbide sintered body having a core having a density of 2.75 g / cm ³ or more. The reason is 2.
This is because a silicon carbide sintered body having a density of 75 g / cm ³ or more has extremely high strength, can be used in a very suitable manner even in a small-sized and highly stressed portion, and is excellent in practicality. .

The porous structure layer, which is one of the features of the present invention, will be described in detail below. First, the average pore size of this porous structure layer is 10 to 50.
The size is preferably 0 μm. The reason is that if the average pore diameter is smaller than 10 μm, it is difficult for the biological tissue to invade the porous structure layer, and it is impossible to obtain a good bond with the biological hard tissue. On the other hand, if it is larger than 500 μm, the porous structure is not formed. This is because not only the strength of the layer is lowered, but also it is difficult to obtain a good bond with the biological tissue due to the decrease in the number of bonding points with the biological tissue.

Further, as the structure of the porous structure layer, it is more advantageous that the average void diameter is gradually reduced from the surface layer to the inside. The reason is that, considering that the invasion of blood vessels into the void varies depending on the size of the void diameter, it is possible to form a portion that is not easily affected by the surrounding environment inside the porous structure layer, that is, hard tissue that is difficult to absorb. Because.

Next, it is advantageous that the porous structure layer has a structure in which fibers, whiskers, plates, and / or silicon carbide in the form of at least one of them are intertwined with each other and bonded to each other. More advantageously, it is composed of silicon carbide.

As mentioned above, it is generally important that the prosthetic restoration material have sufficient strength to withstand considerable impacts and forces. In response to this requirement, the present invention having the porous structure layer to which the bone-forming complex is attached exhibits extremely effective performance. That is, the prosthetic restoration material of the present invention is extremely strong because it is made of silicon carbide. In addition, when this is embedded in a living body, first, the living tissue invades into the pores of the porous structure layer, and the connective tissue invading is affected by the three-dimensional structure of the pores and the osteoconductivity of silicon carbide. It is easily calcified and transformed into bone tissue. As a result, the porous structure layer made of silicon carbide and the living tissue form a double mesh structure in which they are entangled with each other, and are firmly united with the living body.

(Operation) The method for producing the prosthetic restoration material of the present invention will be described below.

In the production of the prosthesis material according to the present invention, first, a dense silicon carbide sintered body (core material) formed into a desired shape, for example, a granular shape, a rod shape, a plate shape or a blade shape is formed. Then, after forming a porous structure layer on a required portion of the surface of the sintered body, the bone-forming composite is attached to the voids of the porous structure layer.

As a method for producing the dense silicon carbide sintered body, various methods such as a conventionally known atmospheric pressure sintering method, pressure sintering method or reaction sintering method can be used.

As a method for forming a porous structure layer on the surface of the dense silicon carbide sintered body, for example, a silicon carbide woven or non-woven fabric, felt, paper or the like is used, and these are cut into an appropriate size, and necessary. According to the above, an adhesive is used to adhere to the surface of the dense silicon carbide sintered body, and if necessary, a thread made of silicon carbide fiber or a thread made of carbon fiber is wound and fixed, and then fired. When chopped fibers are used, an adhesive is applied to the surface of the dense sintered carbonized carbonaceous material, and the chopped fibers are sprinkled thereon to be adhered and then fired. When whiskers or fine powders are used, a method of applying a suspension of these whiskers or fine powders to the surface of the dense silicon carbide sintered body and then firing it can be used. As the adhesive, various substances can be used, but among them, by using a mixture of an organic silicon polymer compound or a metal silicon powder and an organic substance, the dense silicon carbide sintered body can be obtained. The bond of the porous structure layer can be further strengthened. By using such an adhesive, the reason why the bond between the dense silicon carbide sintered body and the porous structure layer can be strengthened is that the adhesive changes to silicon carbide during firing and the dense It is considered that this is because the bonding point between the silicon carbide sintered body and the porous structure layer can be integrated.

The silicon carbide material of the present invention can be preferably used even if it is a silicon carbide material which is entirely composed of a porous structure.

(Example) Example 1 A dense silicon carbide sintered body having a diameter of 2 mm, a length of 20 mm, and a density of 3.07 g / cm ³ was used as a core material, and a phenol resin and a metal silicon powder were mixed on the surface by weight ratio. After applying the mixture mixed at 5: 6, the diameter is about 0.4μm and the length is 100 ~ 200μ.
m silicon carbide whiskers were sprinkled to a thickness of about 0.8 mm to obtain a green body.

The core material used had an average bending strength of about 60 kgf / mm ² .

The green molded body was placed in a graphite crucible capable of blocking outside air, and was fired in an argon gas atmosphere of 1 atm using a Tammann type firing furnace. The graphite crucible used had an internal volume of 50 ml.

The firing temperature rises to 2100 ° C at 2.5 ° C / min. And the maximum temperature is 2100 ° C.
Held for 1 hour.

The obtained sintered body has a porosity of about 70% and an average pore diameter of about 20.
The thickness of the porous structure layer was 0 μm, and the thickness of the porous structure layer was about 0.8 mm. The bonding strength between the core material and the porous structure layer was 18 kgf / mm ² .

Next, the sintered body is immersed for 24 hours in a mixture of an atelocollagen liquid produced from "human" type 1 collagen and an osteoinductive protein prepared by the method of Reddi et al. After being adhered therein, it was freeze-dried to obtain a sterilized silicon carbide implant.

The silicon carbide implant was placed in the femur of a monkey, and the shear bond strength with the bone was measured 2 months and 7 months after the implantation. The average of 100 kg / cm ² was already obtained 2 months after the implantation.
As described above, 7 months after the implantation, the average shear adhesive strength was 250 kg / cm ² , and the adhesive strength was sufficient to withstand the chewing pressure when used as a tooth root material. Example 2 As a core material, The same dense silicon carbide sintered body as in Example 1 was used, and at the surface thereof, a silicon carbide powder having an average particle size of 10 μm or less, containing at least 60% by weight of β-type silicon carbide.
Apply a suspension of silicon carbide powder containing, thickness 0.9mm
A green compact with a powder layer of a certain degree was obtained. The green compact was charged into a graphite crucible capable of blocking the outside air, and was fired in an argon gas atmosphere at 1 atm using a Tammann type firing furnace.

The graphite crucible used had an internal volume of 50 ml.

Firing up to 2200 ° C at 2.5 ° C / min., Maximum temperature 2200 ° C
Held for 6 hours.

The obtained sintered body has a porosity of about 63% and an average pore diameter of about 15%.
It has a porous structure layer of 0 μm and a thickness of about 0.8 mm on the surface layer, and the bonding strength between the core material and the porous structure layer is 25 kgf / mm ²
Met. The porous structure layer has an average aspect ratio of about 12
And has a three-dimensional network structure in which plate crystals having an average length of about 500 μm in the major axis direction are intricately entwined in multiple directions, and plate crystals having an aspect ratio of 3 to 50 occupy the porous structure layer. The ratio was about 98%.

Then, the bone-forming complex was attached to the porous structure layer by the same method as in Example 1, and the shear adhesive strength with the femur of the monkey was measured. The average adhesive strength was 80 kg / cm ² or more 2 months after implantation, Seven months after embedding, an average shear adhesive strength of 230 kg / cm ² was obtained, and the adhesive strength was sufficient to withstand as a root material.

Example 3 The core material is the same as in Example 1, but the dimensions are 20 × 20 × 2 mm.
After using the dense silicon carbide sintered body as described above, an organosilicon polymer compound was applied, and then a non-woven fabric made of silicon carbide fiber having a fiber diameter of about 13 μm was attached to obtain a green body.

The green body was fired in the same manner as in Example 1 to obtain a sintered body.

The obtained sintered body has a porosity of about 70% and an average pore diameter of about 200.
A porous structure layer having a thickness of μm and a thickness of about 0.7 mm is formed on the surface layer, and the bonding strength between the core material and the porous structure layer is 24
It was kgf / mm ² .

Then, after the bone-forming complex was attached to the porous structure layer by the same method as in Example 1, the shear adhesive strength with the femur of the monkey was measured, and it was 100 kg / cm ² or more on average 2 months after the implantation. ,
Seven months after the implantation, an average shear adhesive strength of 250 kg / cm ² was achieved, and it was confirmed that the adhesive strength was sufficient to support the body weight.

Example 4 Gelatin obtained from a normal lime treatment method using beef bone as a raw material (viscosity: 44 mp, jelly liquidity: 253 Bloom, pH: 5.8, water content: 11.
0%) was dissolved in water to obtain a gelatin solution having a concentration of 50 mg / ml.

Next, the bone morphogenetic protein is dissolved in 0.01 N hydrochloric acid to a concentration of 1.
A 0 mg / ml osteogenic protein solution was obtained.

0.2 ml of bone morphogenetic protein solution to 1.0 ml of the gelatin solution
The silicon carbide material prepared in Example 1 was dipped in a well-mixed solution, and the mixture was allowed to stand at 4 ° C. for about 20 hours to form a gelled product of the mixed solution in the voids of the porous structure layer of the silicon carbide material. Was attached.

The silicon carbide material to which the gelled substance was attached was immersed in a 0.02M phosphate buffer solution (pH: 7.2) containing 0.1% glutaraldehyde at 5 ° C. for 16 hours for crosslinking treatment.

Then, the crosslinked silicon carbide material was thoroughly washed, freeze-dried, and then gas sterilized to obtain a prosthetic material for prosthetic use in a living body.

When the compatibility of the prosthetic restoration material with bone was examined in the same manner as in Example 1, an adhesive strength sufficient to withstand the prosthetic restoration material was obtained.

〔The invention's effect〕

As is clear from the above description and the results of the examples, the prosthetic restoration material of the present invention has the characteristics described below, and the practical effects are remarkable.

(1) Since a porous structure layer of silicon carbide was formed on the surface of a strong core material made of a dense silicon carbide sintered body, and the bone forming composite was adhered in the voids of the porous structure layer,
Biological tissue is easily generated inside the porous structure layer, and hard bone organization (ossification) due to calcification easily occurs inside.

(2) The tip of the collagen fiber tissue inside the porous structure layer is ossified and integrated, the middle layer of the porous structure layer is cartilized, and the surface of the porous structure layer is covered with the newly formed collagen fiber tissue and integrated with the living bone tissue. As a result, the prosthetic restoration material is firmly joined by the anchor effect, and the appearance is as if it were a living bone.

(3) Since it has the appearance of living bone as described above, it exhibits antithrombogenicity, has very little irritation to living tissue, and has excellent affinity with living bodies.

(4) Since the whole is made of a silicon carbide material, it does not corrode, and its mechanical properties do not deteriorate with time in the living environment.

(5) It is also possible to cover an implantable artificial organ, for example, a pacemaker of the heart with the prosthetic restoration material according to the present invention and implant it in the vicinity of the living bone so as to be integrated and fixed with the living bone.

Claims (1)

[Claims] 1. A prosthetic material for implanting a living body, comprising a bone formation complex adhered to void portions of a porous structure layer of a silicon carbide material having a porous structure layer having a thickness of 0.1 mm or more at least in a surface layer portion. The core of this silicon carbide material has a
It is a dense sintered body of 2.75 g / cm ³ or more, while the porous structure layer has an average void diameter of 10 to 500 μm, and the average void diameter gradually decreases from the surface layer to the inside. A prosthetic restoration material for a living body, which has a structure.