JPH11276510A - Surface modified bone prosthesis member and method of manufacturing the same - Google Patents

Abstract

(57) [Summary] [Problem] To provide a three-dimensional surface structure in which the ingrowth of new bone is early and the occupancy density of the bone is large, and thereby it can be safely applied to a site where a large shear strength is applied. A surface modified bone prosthesis member is provided. A three-dimensional porous body (bead block 1) made of a non-absorbable material for a living body such as a wire mesh or a bead combination.
Is filled with a mixture (CM chitin sponge 3) of CM chitin and calcium phosphate granules such as HAP, TCP, and AWGC. In addition, after immersing the three-dimensional porous body or the bone prosthesis member provided with the porous body at a desired portion of the surface in a CM chitin aqueous solution, the bone prosthesis member is pulled out and rapidly cooled, whereby such a bone prosthesis member is obtained. obtain.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a bone prosthesis used for reconstructing bone and joint functions lost due to aging, illness, accident, and the like, and more particularly, to a solid connection with bone by bone ingrowth. The present invention relates to a surface-modified bone prosthesis member having a three-dimensional porous body on its surface and a method for producing the same.

[0002]

2. Description of the Related Art Conventionally, as the above-mentioned surface-modified bone prosthesis member, one having beads in contact with bone has been put into practical use. In such a bone prosthesis member, ceramic beads are directly applied to the prosthesis member. It is known that it is sintered and fixed or fused by using slurry or glass of the material, and bones grow and penetrate (ingrowth) into the pores formed between the beads, so that good fixation with the bone can be obtained. Have been. As a bone prosthesis member of the same type, Japanese Patent Application Laid-Open No. 1-300947 discloses a method of separately manufacturing a bead carrier in which ceramic slurry and beads of the same material are poured into a cavity of a ceramic dish and sintered and fixed to the bone prosthesis member body. The attached one is shown.

[0003] Japanese Patent Application Laid-Open No. 1-223970 discloses a bone substitute for a bone defect prosthesis in which a base member is fitted into a through hole or a concave portion formed in the bone substitute, and the base member remains. It is described that a porous layer coated with a bioactive inorganic material such as apatite is provided on the surface on the side of contact with autologous bone.

[0004]

However, the above prior art has the following problems. That is, in the case of a bioprosthetic member having a porous structure provided on the surface thereof, and in which the inside of the porous body is not subjected to a treatment such as coating, it takes time for the ingrowth of the new bone to reach a deeper part, and Even if the bone ingrowth reaches a deep part, it often becomes a fragile state in which many voids remain, so that it has been difficult to apply it to a site where a large shear strength is applied. Further, in the conventional technique of performing treatment such as apatite coating on the inside of the porous material, although the rate of ingrowth of new bone is increased, the amount of bone is not improved as expected,
It was insufficient for application to a site where high shear strength was applied.

Therefore, the present invention is provided with a three-dimensional porous body in which the ingrowth of the new bone is early and the occupation density of the void is large, so that it can be safely applied to a site where a large shear strength is applied. It is an object of the present invention to provide a surface-modified bone prosthesis member that can be used.

[0006]

Means for Solving the Problems In order to solve the above-mentioned problems, the present inventors have studied in detail the mechanism of new bone formation and its ingrowth. It is effective to have a scaffold containing a biocompatible material that allows osteogenic powdered mesenchymal cells to enter and accumulate in the entire space and accumulate bone and chemically adhere to bone. Was found. And as a constituent material of such a scaffold, bioabsorbable carboxymethyl chitin (hereinafter abbreviated as CM chitin)
It was confirmed that the above problem was solved by using a mixture of granules of CM chitin and a calcium phosphate material, and the present invention was reached.

That is, according to the present invention, a three-dimensional porous body made of a non-absorbable material for a living body such as a wire mesh or a beaded combination is provided on the surface of a bone prosthesis member for replacing a living bone. An object of the present invention is to provide a surface-modified bone prosthesis member characterized in that a mixture of CM chitin and granules of a calcium phosphate-based material is filled in the body cavity.

The present invention also relates to a method of manufacturing the above-mentioned surface-modified bone prosthetic member, wherein a three-dimensional porous body made of a non-absorbable material for a living body such as a wire mesh or a bead combination is provided at a desired portion on the surface. Is immersed in an aqueous solution of carboxylmethyl chitin having viscosity mixed with granules of calcium phosphate material, and then quenched, and a method for producing a surface-modified bone prosthesis member, and the three-dimensional porous body is made of a calcium phosphate material. The present invention provides a method for producing a surface-modified bone prosthesis member, comprising immersing in a viscous aqueous solution of carboxylmethyl chitin mixed with the granules of the above, followed by rapid cooling, and fixing the porous body to a desired portion of the bone prosthesis member. It is something you want to do.

[0009] More specifically, the bone repair material of the present invention can be produced by the following method. First, CM chitin powder having a carboxymethylation degree of 50 to 80% is dissolved in distilled water to prepare a viscous aqueous solution, and HAP granules or TCP granules are mixed with the weight of the aqueous solution. Alternatively, the mixture is sufficiently stirred using a stirrer so that the TCP granules are uniformly dispersed.

Next, a three-dimensional porous body made of a non-absorbable material for a living body such as a wire mesh or a beaded composite or a bone prosthesis member provided with the porous body at a desired site on the surface is immersed in a CM chitin aqueous solution. Thereafter, it is pulled up and further quenched by dropping it into liquid nitrogen. Thereafter, the three-dimensional porous body or the bone prosthesis member provided with the same at a desired site on the surface is freeze-dried for 12 hours to 24 hours, and further, for 12 hours to 14 hours at 140 ° C. to 160 ° C. Apply vacuum thermal crosslinking. In addition, about what processed the three-dimensional porous body independently, finally, the porous body is fixed to a bone prosthesis member by an arbitrary method. Incidentally, the various conditions in the above-mentioned production method are preferably in the following ranges.

CM chitin: CM degree: 40 to 100%, weight average molecular weight: 100,000 to 500,000 Deacetylation degree: 40% or less HAP granules: particle size range 50 μm to 300 μm・ CM chitin aqueous solution concentration: 3% by weight to 10% by weight ・ Pore diameter: 10 to 100 μm ・ Average distance between calcium phosphate diameter compounds: 50 to 400 μm

[0012]

The surface-modified bone prosthesis member of the present invention (hereinafter, abbreviated as a bone prosthesis member) is provided with a three-dimensional porous body made of a non-absorbable material for a living body such as a wire mesh or a bead combination on the surface. Further, CM chitin and HA are contained in the pores of the porous body.
It is filled with a mixture with calcium phosphate granules such as P, TCP, and AWGC. This mixed material has a large number of micropores, and in a prosthetic site in a living body, the CM chitin holds granules of a calcium phosphate-based material in a prosthetic site, so that CM chitin can be permeated and absorbed, and various cells are stored. Provide an environment that is Then, under this environment, granules of the calcium phosphate-based material cause new bone formation, and new bone is formed with time in the CM chitin decomposition and absorption fossa.
As described above, the space and the occupancy rate of the new bone growth are large, and efficient bone formation with a large percentage of natural bone and early ingrowth to the deep part are guaranteed.

[0013]

DESCRIPTION OF THE PREFERRED EMBODIMENTS Embodiments of the present invention will be described below with reference to the drawings. FIG. 1 shows a bone prosthesis member F according to an embodiment of the present invention. The bone prosthesis member F is a plate 2 having a recess 2a.
A bead block 1 as a three-dimensional porous body in which a plurality of beads 1a are gathered in the hollow 2a.
The bead block 1 is placed at the prosthetic site with the side of the bead B facing the bone B. In addition, a CM chitin sponge 3 is filled in the cavity 2a of the bone prosthetic member F together with the bead block 1 together with the bead block 1, and the CM chitin sponge 3 is further filled with HA.
It has a structure supporting granules of calcium phosphate such as P, TCP, and AWGC.

The CM chitin sponge has an average pore size of 10
A sponge having a pore diameter range of 100 μm, and a mixture of CM chitin and granules of calcium phosphate having an average particle diameter of 50 to 300 μm, wherein the granules are present at an average interval of 50 to 400 μm. It is. In addition, since the calcium phosphate granules contained in the CM chitin sponge 3 have different sizes in the range of 50 to 300 μm, the pore size of the bead block 1 needs to be at least 300 μm or more.

Further, as shown in FIG. 2, the height h of the CM chitin sponge 3 when the bone prosthesis member F is to be prosthetic in a region where a shear load (rubbing) is received is 77 to 91 times the depth d of the recess 2a. % Is desirable. This is because the CM chitin sponge 3 is 1.1 mm in the height direction due to water absorption.
Since it has a coefficient of linear expansion of about 1.3 times, the modified height of the CM sponge in a dry state is adjusted so that swelling due to water absorption in the living body environment is suppressed to below the upper end of the depression 2a. It is important that the depth is 77% to 91% of the depth d of the depression 2a. This is because the CM chitin sponge 3 absorbs and swells in the area where the shear load (rubbing) is received.
If the height exceeds “a”, there is a risk of causing mechanical breakage. The above-described device is intended to avoid such a danger.

The bone prosthesis member F constructed as described above is
A mixture of CM chitin and granules of calcium phosphate such as HAP, TCP, and AWGC (CM chitin sponge 3) is filled in the space of the bead block 1 provided on the surface on the side of contact with the bone. Since the material is a porous material having a large number of micropores, it can transmit and absorb body fluid and provide an environment in which various cells are stored. Then, under this environment, granules of the calcium phosphate-based material cause new bone formation, and new bone is formed with time in the CM chitin decomposition and absorption fossa. As described above, the space and the occupancy rate of the new bone growth are large, and efficient bone formation with a large percentage of natural bone and early ingrowth to the deep part are guaranteed.

Next, a method of manufacturing the bone prosthetic member F will be described. Alumina particles having an average particle diameter of about 1 μm are granulated using an organic binder to produce alumina green beads (unfired beads) having an average diameter of about 2000 μm, and 800 ° C.
Calcination was performed to obtain beads 1. Next, after performing CIP molding of alumina powder having an average particle size of about 1 μm under a molding pressure of 3 t / cm ² , a plate 2 having a recess 2 a is formed by cutting,
This was calcined at 1100 ° C. After preparing the dish 2 and the alumina green beads, the bead block 1 is fixed in the recess 2a in the following procedure. The beads are put into the depression 2a of the dish 2 so as to form three layers. An alumina slurry having an average particle size of 1 μm was poured into the mixture, dried, and dried.
Bake at 90 ° C. As described above, the bead block 1 is formed in the recess 2a. In this case, the average particle size of the alumina beads 1a is 1600 μm, and the porosity is 30 to 4 μm.
0% and the average pore size was 400 to 500 μm.

Subsequently, the CM chitin sponge was prepared and filled into the bead block 1 in the following order: 1) CM chitin powder having a carboxymethylation degree of 50 to 80% was dissolved in distilled water. Then, the aqueous solution was adjusted to a concentration of 3% by weight. 2) Granules such as 1/5 of HAP based on the weight of the aqueous solution were mixed in, and sufficiently stirred using a stirrer so that the granules were uniformly dispersed in the solution. Stirred. The particle size range is 60 to 150 μm, and the CM chitin molecular weight distribution range is 10 to 150 μm.
3) Immerse the dish 2 provided with the bead block 1 in the mixed solution of the above 2) 4) Immediately put the dish 2 immersed in the solution in the above 3) into liquid nitrogen, and rapidly freeze it 5) The dish 2 frozen in the above 4) was freeze-dried. 6) The dried product of the above 5) was subjected to a vacuum heat treatment at a temperature of 140 ° C. to 160 ° C. for 24 hours to harden CM chitin in water (heat fixation). The bone prosthetic member F obtained by filling the CM chitin sponge 3 carrying calcium phosphate-based granules into the gaps of the bead blocks 3 provided in the depressions 2a of the dish 2 by such a crosslinked manufacturing method. Was completed.

Although the embodiment of the present invention has been described above, the present invention is not limited to the above-described embodiment, and it goes without saying that the present invention can take any form without departing from the object of the invention. For example, the porous body that modifies the surface of the bone prosthesis member is not limited to a bead block, but may be another form such as a fiber mesh. In addition, the bone prosthesis member is not limited to the one in which the porous body is provided on the base made of the dense body, and may be one in which the whole is formed of the porous body. The material is not limited to ceramic, but may be metal or polymer material. In short, any material can be selected as long as it is safe in a living body. Further, the production method is not limited to the method of performing the step of filling the CM chitin sponge after fixing the porous body to the base, and the method of filling the CM chitin sponge in the voids of the porous body and then fixing the base to the base. It may be.

[0020]

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS A plurality of bone prosthesis members in which through holes having a diameter of 1 mm are regularly formed in an alumina thin plate having a thickness of 150 μm at intervals of 500 μm and the thin plates are alternately shifted to allow the through holes to communicate in a three-dimensional direction. Test pieces were prepared.

These test pieces were divided into two groups, and only one group was filled with the CM chitin block by the method described above. That is, CM chitin powder having a carboxymethylation degree of 50 to 80% was dissolved in distilled water to prepare an aqueous solution having a concentration of 3% by weight. Thereafter, 1 to the weight of the aqueous solution
/ 5 volume of granules such as HAP was mixed and sufficiently stirred using a stirrer so that the granules were uniformly dispersed in the solution. The particle size range was 60 to 150 μm, and the CM chitin molecular weight distribution range was 100 to 2,000,000. Furthermore, immediately after the test piece was immersed in the mixed solution, it was put into liquid nitrogen and rapidly frozen. Then, the freeze-dried dried product is heated at a temperature of 140 ° C. to 160 ° C. for 24 hours,
A vacuum heat treatment was performed to crosslink CM chitin with water insolubilization (thermal fixation) and heat crosslinking.

The product which has been subjected to such processing is the product of the example, and the product which has not been processed is the product of the comparative example.

On the other hand, a recess of 10 mm × 15 mm × 2 mm in thickness was formed in the rabbit tibia, and the test piece was embedded in the recess, and the fixation to the bone was evaluated by histological analysis and peeling test. Testing was also performed. For histological analysis, two weeks, four weeks, and eight weeks were allowed to elapse in the state of being implanted in the tibia. At each time point, the rabbit was sacrificed, and a test piece and surrounding tissue were simultaneously collected from the tibia. . Then, these were fixed with ethanol, dehydrated, embedded in a resin, and sliced sections were stained with Drazin blue to prepare tissue specimens. Next, a micrograph of this tissue specimen was taken, and the fixation and the bone repair ability of the bone repair material were observed from the obtained photograph. As a result, the example product had a large amount of bone formed to a deep portion, whereas the comparative example product was clearly inferior in both bone mass and depth as compared with the example product.

[0024]

[Table 1]

Table 1 shows the results of a peeling test performed according to a conventional method. As is clear from Table 1, the peeling load value of the example product was remarkably superior to that of the comparative example.

[0026]

As described above, the bone prosthesis member of the present invention has a three-dimensional porous body made of a non-absorbable material for a living body such as a wire mesh or a beaded body fixed to the surface thereof. CM chitin and HAP, TCP, AWG in body space
Filling the mixture with calcium phosphate granules, such as C, provides an environment in which various cells are stored in CM chitin at the prosthetic site in a living body. Under this environment, granules of calcium phosphate-based material are provided. Causes new bone formation, and new bone is formed over time in the CM chitin decomposition and absorption fossa. From the above, the space and occupation rate of new bone growth is large, efficient and natural bone formation with a large proportion of natural bone, and early and deep ingrowth are guaranteed, so the bonding strength with bone is large, so large It has an excellent effect that it can be safely applied to a portion where shear stress is applied.

Further, according to the manufacturing method of the present invention, the above-described bone prosthesis member can be manufactured stably.

[Brief description of the drawings]

FIG. 1 is a sectional view of a bone prosthesis member according to an embodiment of the present invention.

FIG. 2 is an explanatory diagram showing a filling depth of a CM chitin sponge.

[Explanation of symbols]

 F Bone prosthesis member d Depth 1 Bead block (three-dimensional porous body) 1a Bead 2 Dish 2a Indent 3 CM chitin sponge

Claims (2)

[Claims] 1. A three-dimensional porous body made of a non-absorbable material for a living body such as a wire mesh or a bead-bonded body is fixed to the surface of a bone prosthetic member for replacing a living bone. A surface-modified bone prosthesis member, characterized in that a mixture of carboxymethyl chitin and granules of a calcium phosphate-based material is filled therein. 2. A three-dimensional porous body made of a non-absorbable material for a living body, such as a wire mesh or a beaded composite, or a bone bioprosthesis member having the porous body fixed to a desired portion of its surface, mixed with granules of a calcium phosphate material. A method for producing a surface-modified bone prosthesis member, which comprises immersing in a viscous aqueous solution of carboxylmethyl chitin, followed by quenching.