JPS61238245A - Ceramic-fibrin composite for prosthesis of living body and its production - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Field of Application] The present invention relates to an apatite ceramic-fibrin composite suitable for biological replacement and a method for producing the same.

[Conventional technology]

As a material for prosthetic defects in the hard tissue of living organisms, granules of hydroxyapatite ceramic (hereinafter simply referred to as apatite), which is most similar to the blue component, or a material obtained by molding apatite powder into a predetermined shape and sintering it are used. I've been exposed to it.

In addition, sintered alumina sintered bodies (alumina ceramic bodies) and the like have been widely used as prosthetic materials in a shape that matches the shape of the bone defect.

[Problem that the invention seeks to solve]

However, the above-mentioned prosthetic materials made of apatite are used in granular or solid form by being implanted into a part of the hard tissue of a living body, but since apatite itself is inorganic, it has no osteoinductive ability in the living body. In addition, in the case of filling the defect with granular material, it is not only difficult to fix the body to the defect, but also has the disadvantage that it does not have a biological support function.
In addition, solid materials are not difficult to process to match the shape of the bone defect, but they allow bone intrusion and bond with the bone during bone growth. It is difficult to obtain a sintered body having such porosity (voids), and the apatite sintered body has the drawback of low mechanical strength.

On the other hand, prosthetic materials made of granular or solid materials made of alumina ceramic are similar to those using apatite mentioned above.
Granular materials lack fixation properties, and solid materials have disadvantages of poor moldability.

[Means for solving problems]

Therefore, in the present invention, a bioprosthetic member is produced by mixing a fibrinogen solution with a granular material made of ceramics such as alumina, zirconia, and hydroxyapatite, which have excellent biocompatibility, and then adding thrombin to this mixed solution. The aim is to produce a composite consisting of ceramic particles and fibrin that can be tossed.

[Example 1] l m MCaO1z-containing (7) 10111 M T
ris-Hcl buffer (2 with PE(7,0)
．． Prepare a 0% fibrinogen solution. This 2.0
% fibrinogen solution with an average particle size of 300
Add 60 mg of μ-sized hydroxyapatite (hereinafter referred to as HAP) particles and stir with a mixer to suspend the mixture, and add 100 μ of thrombin at a concentration of 100 μ/machine.
1 is added instantaneously to cause the enzymatic reaction between fibrinogen and thrombin, and the suspension of hydroxyapatite instantly becomes gel-like. This is poured into a mold having a desired shape, a pressure of 47.3 kg/ej is applied, excess water is removed, and E (operation to increase the filling rate of AP particles is performed).

Thereafter, it was removed from the mold and dried at room temperature for 24 hours or more to obtain an agar-like RAP ceramic-fibrin composite.

In this case, the E of the composite (the filling rate of AP particles is about 40%,
The average pore diameter was 200μ.

[Example 2] 0.5 #f M CeLQlz containing (7) IQ m
MTris-HOI buffer (pH 7,0)
Prepare a 1.0% fibrinogen solution. This one
．． After adding 100 µl of alumina particles with an average particle diameter of 3 µm to 500 µl of 0% fibrinogen solution, 100 µl of thrombin was added instantaneously while stirring vigorously with a mixer to suspend it. Due to the enzymatic reaction, the suspension containing alumina particles becomes gel-like. This was poured into a mold with the desired shape, and a pressure of 18.5 kg/cd was applied to remove excess moisture and increase the filling rate of alumina particles, and then it was taken out of the mold and left at room temperature. It was dried for 24 hours or more to completely remove water, and an agar-like alumina ceramic-fibrin composite was obtained.

In this composite, the filling rate of alumina particles was 20% and the average pore diameter was 20 μm.

[Example 3] l m ld CaQlz-containing (7) 10 m M
Tris-Tlcl buffer (PH7,0')
Prepare a 2.0% fibrinogen solution. This 2
．． 0% fibrinogen solution at 250°ad with an average particle size of 3am, 100μm, 30011m%
Add 60 mg of four types of apatite particles of 1500 μm and suspend them, and add 100 μl of thrombin at a concentration of 100 u/ml to form a gel.

Next, this gel-like liquid was filled into a predetermined mold, and 10 k
Four types of samples A to D shown in Table 1 were prepared by pressure molding at a pressure of g/14 g/14, removing excess moisture, and drying.

The agar-like ceramic-fibrin composite obtained in the above example has a certain degree of elasticity and can be cut with a knife or scissors or shaped into a desired shape, and can be reused. When it absorbs moisture, it returns to the gel-like molded product before deairing and drying.

Therefore, such a ceramic-fibrin composite can be used as an artificial bone or a bone filling material.

In this case, the spaces between the ceramic particles are filled with fibrin or air, and the ceramic particles are collectively supported by the fibrin. Furthermore, V-purin itself is gradually absorbed by the living body, but as new bone gradually grows and invades the gap after absorption, early fusion with the bone is achieved.

By the way, in order to obtain a bioprosthetic material having an optimal range for bone growth and penetration in order to fuse with the bone as described above, in the above example, the average particle diameter of the RAPAP particles, lumina particles, and apatite particles used is 0.3. Ceramic particle-fibrin composites were prototyped with varying particle filling rates ranging from 2 to 70%, and the average pore diameter of the composites was measured. This measurement result is the first
It is shown in the graphs of FIG. 2, FIG. 3, and FIG. According to this, there is no difference in the average pore diameter depending on the type of ceramic particles used, and with a ceramic particle diameter of 0.5 to 3000μ,
Those with a particle filling rate in the range of 2 to 65% have a pore diameter of 30 to 65%.
It had a diameter of 2000 μm. However, when the average particle diameter of the ceramic is 1 μm or less, it is difficult to uniformly disperse the ceramic particles. In addition, it was difficult to uniformly disperse the particles when the particle filling rate was less than 5%. On the other hand, when the ceramic particle size is 2000 μm or more or the particle filling rate is 55% or more, it is difficult to perform arbitrary cutting using scissors, a knife, etc.

In addition, the relationship between the average pore diameter of the ceramic particle-fibrin composite and the pressure when molded into a predetermined shape was calculated by using apatite particles with four types of average particle diameters and changing the molding pressure. It was measured. The results are shown in Figure 4, which shows that the molding pressure was 20 kg/cJ.
Even if the particle filling rate is above 50%, it is in a saturated state, so the molding pressure is 5 to 20 kg/
It is sufficient to form the molding with c11 or so, and it is unrelated to the type of particles such as E (AP particles, alumina particles, etc.).

Next, 15 pieces each of the four types of test pieces A, B, C, and D prepared in Example 3 were implanted into the tibia neck of a domestic rabbit. At the same time, a bone defect with the same dimensions as the test piece (5 mm in diameter, 3 mm in thickness) was created and filled with apatite particles having an average particle diameter of 300 μm (this is used as a comparison group). The animals in which the test piece of Sample A was embedded in this way were called Group A, and those in which the test piece of Sample B was embedded were called Group B, and Groups 0 and D were similarly named and subjected to animal experiments. In this case, the rabbits were sacrificed 3 weeks, 6 weeks, and 12 weeks after incubation, and 5 specimens from each of the A-D and comparison groups were collected together with fresh bones and fixed in formalin. When the non-decalcified specimen was examined histologically using an optical microscope, the following findings were found.

1) Three weeks after implantation, slight inflammation was observed in the tissue in contact with the test piece in Group A. However, B, C,
The outer periphery of the specimen in Group D was covered with new bone, and no inflammation was observed. On the other hand, in the comparison group, bone growth from around the bone defect was observed, but it was not remarkable in Groups B, C, and D. In addition, elution of fibrin was observed in all samples in the A=D group.

1:) Six weeks after treatment, the slight inflammatory findings observed in the tissue in contact with the test piece in Group A during the 4th week had disappeared. In addition, in all of the test pieces of Groups A to D, the edges of the test pieces were completely covered with new bone, and furthermore, bone intrusion into the gaps between the RAP particles was observed. These effects were particularly remarkable in Group B, Group 0, and Group D.

On the other hand, in the comparison group, bone intrusion between the apatite particles was observed, but the amount of intrusion was smaller than in Groups B, 0, and D, and was similar to Group A.

111) After 12 weeks, bone invaded the inside of the test specimen in both groups A to D, and the fibrin in the gaps between apatite particles completely disappeared, and in its place, bone grew and invaded. Ta. On the other hand, in the comparison group, bone had invaded approximately 70% of the gaps between the apatite particles, but 30% of the remaining gaps remained void.

〔Effect of the invention〕

As shown above, according to the present invention, the average particle diameter of ceramic particles having excellent affinity with living organisms is 0.5 to 3000μ.
Since the particles are integrally bonded with fibrin, the pore diameter is 30 to 30, which is suitable for bone growth penetration.
To provide an excellent ceramic-fibrin composite for a bioprosthesis, which has a diameter of 2000βm, can be immediately cut into a desired shape according to the shape of a prosthetic site with scissors, etc., and can achieve early fusion with the bone. be able to.

[Brief explanation of drawings]

Figures 1, 2, and 3 are graphs showing the relationship between average particle diameters of hydroxyapatite particles, alumina particles, and apatite particles, respectively, and uniform pore diameter, and Figure 4 is a graph showing the relationship between molding pressure in the manufacturing process and apatite particle size. FIG. 3 is a graph showing the relationship between the particle filling ratio of the particles.

Claims (3)

[Claims] (1) A ceramic-fibrin composite for bioprosthesis, characterized by being composed of ceramic particles such as alumina, zirconia, and hydroxyapatite and fibrin. (2) The average diameter of the ceramic particles is 1.0 to 2000.
The ceramic-fibrin composite for bioprosthesis according to claim 1, wherein the ceramic particles have a filling rate of 5 to 55%. (3) A method for producing a ceramic-fibrin composite for bioprosthesis, which involves the step of mixing ceramic particles such as alumina, zirconia, hydroxyapatite, etc. with a fibrinogen solution and then adding thrombin to the mixed solution.