KR950008173B1 - Bioactive vitreous composition for bone implants, filaments mdde therefrom and method - Google Patents

Abstract

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Description

Bioactive glassy composition for bone graft, filaments made therefrom and method thereof

The present invention relates to a so-called bioactive glassy composition or glass for bone graft according to claim 1.

This type of glass has been the subject of research since the 1970s, and under the title “Ceramic Implants for Humans” by Larry L. Hench, ADVANCED CERA MIC MATERIALS, Vol. 1, No. 4 1986. pp. 306-310 and 324.

Examples of such known glass are disclosed in the following patent data: FR-A-2 243 915; US-A-4 159 358; US-A-4 171 544; US-A-4 234 972; GB-A-2 080 281; DE-A-3 248 649; EP-A-0 145 210; EP-A-0 154 513.

Such known glasses are not only biologically compatible but can also be biodegranation by the interaction mechanism described below.

Contacting the type of glass in question with human or animal interstitial liquid results in the formation of a gel with an ionic composition similar to the ossification front that is encountered during natural bone-remodeling. The gel thus formed is recognized as a substrate for precipitation of the bone formation matrix by osteoblasts. Collagen fibers, matrix mucopolysaccharides, and gels have the property of precipitating hydroxylapatite, which allows the formation of a recognized bond between the glass and the newly added bone matrix.

In many cases, the glass implants need to be degraded until the bone graft disappears as the bone is gradually formed and / or reformed to leave room for later.

In the experiments conducted, it was found that this could not be achieved completely when using the above known bioactive glass. This glass cannot be reduced to filament by drawing in a bath of fused glass and drawing through a die. In other words, when drawn out, it becomes a ceramic at the exit of the mold, forming a brittle product with properties that are very different from those required for biologically sensible glass filaments or fibers.

For this reason, the only way to use such known glass for prosthetic implants is to grind the glass into powder for use. In most uses, the powder is prepared in paste form to pack defects of the bond with the binder. The powder particles are not uniform in size but irregular in size in the range of several micrometers to several hundred micrometers. Due to the non-uniform size of the particles, most of the smallest particles are completely reabsorbed during the bone reconstruction process while the largest particles are not reabsorbed or sensitized, resulting in undesirable glassy inclusions discontinuously formed in the reconstructed bone Is caused. If the particles of different sizes are arranged randomly, the bone fibers likewise grow arbitrarily even when the fibers are required to be reconstituted in a regular arrangement for the purpose of strengthening the mechanical strength of the bone.

In some uses, when the powder is used for supplemental transplantation, on one side the blood forms a mixture with the powder to form a shield that prevents bone growth, while the powder particles are loaded into the bloodstream to form a blood clot. It becomes possible.

The biggest problem in the background of the present invention is to provide a glass that can be used to form a bone graft without the disadvantages described above.

According to the invention, this problem can be substantially solved using the glassy composition described in the characterizing part of claim 1 hereinafter.

The invention also relates to a filament or fiber obtained by drawing the glassy composition, a product obtained from the filament, and a method of producing the filament.

Experiments show that both K ₂ O and Al ₂ O ₃ maintain the amorphous state when the glassy composition is drawn into the filament to prevent the glassy composition from ceramicizing. This amorphous state persists until the end of the filament's life.

The presence of K ₂ O in the bioactive glassy composition is also beneficial in terms of bioactivity. In this regard, K ₂ O may also be an advantageous substitute for Na ₂ O intended for hypertension patients or patients who may be hypertension.

However, when the amount of K ₂ O is increased, the glassy composition is characterized in that it is more soluble in water. This means that glassy compositions with too high content percentages of K ₂ O can interact with moisture in the atmosphere, causing hydrolysis of K ₂ O to occur and soften or even turn into gel under normal ambient conditions. Therefore, filaments of glassy compositions with too high percentages of K ₂ O can be stored only in completely dry air or can be treated, for example, by weaving, but this is very impractical from an industrial point of view.

Unwanted effects of K ₂ O can be successfully mitigated by adding Al ₂ O ₃ to the glassy composition. However, an increase in the amount of Al ₂ O ₃ has the drawback of reducing the reactivity of the composition, that is, the affinity for bone tissue.

It has been found that the glassy composition having a content of K ₂ O and Al ₂ O ₃ within the scope of the present invention not only prevents ceramicization of the drawn filament but also maintains affinity for bone tissue.

FR-A-2 243 915, GB-A-2 080 281, DE-A-3 248 649 and EP-A-0 145 210 all have K ₂ O from 0% to (FR-A-2 243 915 discloses a bioactive glassy composition containing indeterminately up to 20% of 0.4%). The use of K ₂ O as an anticeramic agent has not been taught in these documents. GB-A-2 080 281 and US-A-4 708 652 disclose both bioactive glassy compositions containing Al ₂ O ₃ + ZrO ₂ + Nb ₂ O ₅ in indeterminate amounts of 0 to 8%. have. The percentage of Al ₂ O ₃ has not been specified. In one aspect, these data disclose Al ₂ O ₃ , ZrO ₂ and Nb ₂ O ₅ as reaction modifiers in terms of bioactivity. On the other hand, Al ₂ O ₃ , ZrO ₂ and Nb ₂ O ₅ are disclosed as inhibitors in terms of bioactivity. In addition, the compositions disclosed in GB-A-2 080 281 and US-A-4 708 652 and containing indeterminate amounts of Al ₂ O ₃ are mainly ceramic type. In other words, this document does not teach the use of Al ₂ O ₃ as an anti-ceramic agent.

According to the invention, it is possible to produce filaments or fibers having a diameter of 10-50 μm. From such filaments or fibers, for example, bundles of fabrics, fabrics, in particular products such as gauze and nets, and felts, and special products made of powders obtained by grinding the filaments of fragments and filaments Can be obtained.

The bundle of filaments or fibers of the glassy composition of the present invention inserts the filaments into the bone injury so as to be oriented in the direction in which the bone fibers grow, allowing regular growth to favor the mechanical strength of the remodeled bone into the implant. Can be used.

Filaments or fibers of small diameter can be fully sensitized, ie they can be completely replaced with progressively remodeled and regenerated bone tissue.

The fabrics made from the glass filaments of the present invention, in particular nets and gauze, and felt and cotlon-wools, act in the same way as the bundles of fibers in terms of degradation, but with several valleys. Allows growth in the desired direction. Therefore, the net or gauze allows bone tissue to form reticular tissue similar to the original bone tissue.

Nets or gauze can be used in the form of bonds to join broken areas of the bone.

The filaments of the glassy composition according to the invention can be broken into pieces or small cylindrical shapes whose length is the same size as the diameter. For example, the cylinder can be manufactured to have a diameter and a length of 20 μm.

The preparations thus formed to form pastes with binders can be implanted with the same technique as implanting glass according to the prior art, but the sensitivity of the implants is due to the difference in filling the defects of bone with uniformly sized particles. And complete replacement with bone tissue over time. Naturally, such use is judged solely by the fact that there is no risk of blood clots with the blood and / or that the powder particles are not likely to be captured by the blood.

However, the particulates of the glassy composition according to the invention can be applied, for example, by a plasma spraying technique as at least a partial coating to a permanent prosthesis made of titanium, for example, gradually and finally completely into the bone tissue. By improving the fixation on the surrounding bone. In such use, a uniform and homogeneous coating can be formed because the dimensions of the glass particles are uniform.

In the case of using known glass particles that can be used in combination with living organisms, since the size of the particles is not uniform in part, in particular, when the glass is sprayed and applied by the plasma spray method at a high temperature, the known glass is ceramic This is not possible because it has become so.

Glass filaments or fibers, and fabrics made from such fibers, are known from FR-A-2 548 658, which contains, as a main component, calcium phosphate and up to 80% by weight of CaO + P ₂ O ₅ , including alumina, silica , Sodium oxide, iron oxide, magnesium oxide kaolin and mixtures thereof.

Although it is entirely compatible with living organisms and is recognized by osteoblasts as hydroxylapatite, the fabric made from this fiber is permanently bound to the remodeled bone tissue because the fiberglass has no biodegradation. Will remain.

Hereinafter, two novel preferred glass compositions according to the present invention are disclosed.

[Composition I]

The composition basically consists of the following component weight percentages. :

SiO ₂ 50%; P ₂ O ₅ 6%; CaO 16%; Na ₂ O 20%; K ₂ O 5%; MgO 1%; Al ₂ O ₃ 2%.

[Composition II]

The composition basically consists of the following component weight percentages. :

SiO ₂ 50%; P ₂ O ₅ 6%; CaO 16%; Na ₂ O 15%; K ₂ O 5%; MgO 1%; Al ₂ O ₃ 2%; B ₂ O ₃ 5%.

In both compositions, an error of ± 7% of the weight percent of each component is acceptable.

From a biological point of view, the actions of the two compositions are identical. The composition of the present invention is formed into a filament by melting in a crucible provided with a mold at the bottom to draw the molten composition through the mold. In particular, it is preferable that the bath and the filament avoid containing impurities and that the crucible consists of substantially pure platinum.

Composition I can be drawn into filaments very easily, but the temperature range over which the glassy material can become very fluid is extremely narrow, between about 800 ° C and 1050 ° C. Therefore, one problem is that the temperature of the melting bath must be tightly controlled.

In composition II, the presence of B ₂ O ₃ extends the temperature range at which the composition can be drawn into filaments without ceramicization to about 900 ° C. to 1050 ° C. However, within this temperature range the glassy material is no more fluid than Composition I and therefore the drawing speed must be tightly controlled.

To the compositions of the present invention, at least trace amounts of calcium fluoride and / or calcium fluorophosphate can be added in small proportions to catalyze any biological process. Compositions comprising such fluorides are particularly suitable for making dental implants.

Tests were carried out in vivo in rats and rabbits using a fibrous and powdered composition of I and II according to the protocol for filling fibers and powders in the tibial bone marrow cavity of each animal.

By varying the time period from 10 days to 7 months, the animal was sacrificed and bones taken from the test subjects were taken and prepared for light microscopy, electron scanning microscopy, and X-ray microanalyzer testing.

Ten days later, optical microscopy of the obtained specimens revealed that cells with basophilic cytoplasm were attached to the surface of the fibers and particles and began to form a bone matrix. That is, it was confirmed that there was no rejection reaction.

Examination on the 20th and 30th days showed that the fibrous material and the particulate matter were completely enclosed in the bone matrix without interposing a membrane or capsule between the glassy composition and the biological substrate. Moreover, some cells that are similar in appearance to basic bone cells have been shown to coalesce with a matrix near the glassy composition. This confirms that there is no septum that inhibits the growth of bone between the glassy composition and the living substrate.

On day 30, defects in the cortical layer were completely filled with newly formed bone. The fibers of the glassy composition incorporated in the bony matrix were individual, the histological cross section taken on the plane perpendicular to the major axis of the fiber was circular, and the histological cross section taken on the plane parallel to the major axis of the fiber was rectangular.

Also on day 30, the particles of the glassy composition were incorporated into the bone matrix without intervening linking membranes, despite the appearance of aggregates of irregular appearance.

In the cross section of the tibia examined thereafter after a certain time interval (2 to 7 months), no change was observed in the glassy composition as long as the glassy composition remained incorporated in the bone matrix. As a result of bone remodeling, examinations at 4, 5, 6 and 7 months revealed resorption Iacunae that extended to the bone surrounding the implant and exposed its surface. The bovine consists of a similar number of areas, as desired, in which the vasculature is likely to form.

Investigations at the same time intervals revealed that the aggregates of the particles of the glassy composition and the fibers released from the bony matrix were irregular and disrupted and gradually absorbed by the large multinuclear cells. That is, they are gradually removed from the matrix.

Glassy materials that do not come into contact with osteogenic cells, such as those that have migrated out of the periosteum, have been shown to be surrounded by inflammatory infiltrate predominantly composed of polymorphonuclear cells and giant multinuclear cells. The presence of inflammatory infiltrates is evidence of desirable potentiation of blood circulation.

In the tests carried out, not only the surface properties of the glassy compositions according to the invention were confirmed, but if there were sufficient numbers of cells differentiated to have osteogenic activity at the site of the implant, the glassy composition was boned without intervening connective tissue. The fact that it can be incorporated into the matrix has been shown to have osteoconductive properties that are histologically proven. The fibers and particles of the glassy composition filled into the tibial injuries all exhibited this property. In the case of fibers, immersion in blood forms a three-dimensional network, or "felt", the void space defined between the fibers, providing a broad surface that can soon adhere to the forming cells as a whole. However, the particles of the glassy composition of the present invention form a dense aggregate upon contact with blood and only the outer surface thereof is used for bonding. Thus, the chemical surface properties of the two forms of the composition, i.e., the fiber and the particle form, are different, and the biological response may vary depending on physical properties such as shape or size, for example. In general, experimental fibers can be manipulated more easily than particles and are more evenly distributed over defects in the bone. In the experiments performed, once incorporated into the bone matrix, the fiber or particle aggregates of the glassy compositions of the present invention were irradiated up to 7 months with no further changes and no cellular reactions. This is due to the substance incorporated no longer in contact with the interstitial liquid at a rate at which the interstitial circulation in the bone is not sufficient to begin a significant emotional process.

Since the siliceous residues remaining in the bone matrix do not appear to interfere with the bone remodeling process, the absorbance lacunae has already been observed in the damaged area of the tibia that has been fully recovered up to that time. Osteoclasts appear to cause uptake of the matrix but do not appear to attack the fibers of the particles incorporated therein, so that when the entirety of the matrix surrounding it is absorbed, the glassy composition in the bovine becomes a component of blood vessels and cells. Contact with At this stage the histological appearance of the fibers appears in broken form, which means that the dissolution process of the glassy composition is in progress and the fragments are being absorbed into large multinuclear cells.

Bone remodeling consists of continuous resorption and addition, and the dissolution or reincorporation of the glassy composition in the newly added matrix appears to be influenced by two factors: 1) Bone formation in the bovine Number of cells; 2) Shape and Size of Glassy Material: In fact, the fiber exhibits a generalized dissolution, and the aggregate of several particles also has a surface of newly added material.

From the above results, the properties of the biological reply are not only influenced by the chemical properties of the material, but also by the shape and size of the fibers and particles, and it is particularly advantageous to have uniform dimensions.

Claims (17)

Bioactive glassy composition for bone graft consisting of 40 to 55 wt% SiO ₂ , 4 to 8 wt% P ₂ O ₅ , 20 to 40 wt% CaO (MgO), and / or 30% or less K ₂ O The composition may be drawn from the dissolution tank into filaments or fibers by containing between 2% and 9% K ₂ O and Al ₂ O ₃ and between 0.5% and 2.5% Al ₂ O ₃ as a stabilizing oxide. Bioactive glassy composition for bone transplant, characterized in that there is. The method of claim 1, wherein the weight percentages of the respective components are substantially 50% SiO ₂ , P ₂ O ₂ 6%, CaO 16%, Na ₂ O 20%, K ₂ O 5%, MgO 1%, Al ₂ O ₃ A glassy composition, consisting of 2% and allowing a variation of ± 7% in the percentage of content of each component. The method of claim 1, wherein the weight percentages of the respective components are substantially 50% SiO ₂ , P ₂ O ₂ 6%, CaO 16%, Na ₂ O 15%, K ₂ O 5%, MgO 1%, Al ₂ O ₃ 2%, B ₂ O ₃ 5%, the glass composition, characterized in that a variation of ± 7% in the content percentage of each component is allowed. The glassy composition according to any one of claims 1 to 3, which contains at least trace amounts of calcium fluoride and / or calcium fluorophosphate. Use of the glassy composition according to any one of claims 1 to 4 for forming a bone implant or part thereof. Filament prepared by drawing the glassy composition according to claim 1. The filament according to claim 6, wherein the diameter is 10 to 50 µm. A filament bundle consisting of a plurality of filaments according to claims 6 and 7 for implantation into a defect in a bone. Mesh or gauze fabric formed from the filaments according to claims 6 and 7 for repairing defects in the bone. Felt or chock-faced shaping filaments according to claims 6 and 7 for repairing bone defects. A particulate formation made from a filament according to claim 6 or 7 for repairing a defect in a bone or for use in the manufacture of a product for bone graft. The particulate product according to claim 11, wherein the filament is formed by crushing the filament or a small columnar product. 12. The particulate product of claim 11, wherein the particulate product is in the form of a powder prepared by grinding the filaments. 14. A permanent bone prosthesis consisting of a solid object made of a material compatible with a living body, wherein at least a portion of the surface of the object is formed by applying the particulate product according to any one of claims 11 to 13. Permanent bone prosthesis, characterized in that the coating. 15. The prosthesis of claim 14 wherein the coating layer is formed by applying a particulate preparation made by the Plasma Spraying technique. A method for producing a filament of a bioactive glassy composition for bone graft by drawing a molten composition from a fusion tank via a mold, wherein the glassy composition according to any one of claims 1 to 3 is used. . 17. The method of claim 16, wherein a crucible of substantially pure platinum is used to contain the melt.