RU2609870C2 - Composite part to endosseous implantation and method of said part making - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention refers to medicine and represents implant for intraosseous implantation, made of material, containing: thermoplastic organic binder, representing polyetheretherketone; fibre filler, which fibres are made from poly(amide-imide); calcium-based filler representing tricalcium phosphate Ca₃(PO₄)₂ with hexagonal β-structure. Fibres, localised on implant surface layer, mainly delaminated from binder along entire length or on part of their length. Invention also relates to method of implant making.

EFFECT: technical result consists in uniform distribution of fibres, reinforced implant with increased depth of interpenetration between implant and bone tissue.

7 cl, 4 dwg

Description

The invention relates to a part intended for implantation in bone tissue, such as a dental implant, prosthesis or bone cavity filler, for medical or veterinary purposes, wherein said part is made of material which, in combination with a special manufacturing method, accelerates its osseointegration into the receiving (receptor) tissue.

Various implants made of a biocompatible polymer are known, the manufacturing method of which provides the creation of a surface structure containing micropores that promote cell colonization on the part of the receptor tissue and accelerate the osseointegration of the implant.

These known implants show very satisfactory results, however, the thickness of the osseointegration layer obtained by this mechanism, which corresponds to the depth of the surface micropores, is approximately 1000 nanometers (1 μm). However, it is well known that the thickness of the interpenetration of the tissue and the implant is at least 1 μm to 10 μm, especially when the elasticity characteristics of the implant and receptor tissue are different. Such improved interpenetration is especially desirable if the implant is reinforced, in particular, with fibers, especially at the beginning of the osseointegration process, when the forming cortical substance does not yet have an elastic modulus comparable to the elastic modulus of the implant.

In addition, such microporous surface structures are difficult and even impossible to obtain using cost-effective implant manufacturing methods, such as injection molding.

The invention is intended to fill in the shortcomings of the known technical solutions and to offer an implant and an economical method for its preparation, allowing to increase the depth of interpenetration between the implant and the receiving bone tissue.

In this regard, the object of the invention is a part intended for intraosseous implantation in vivo, made of a material containing:

- thermoplastic organic binder; and

- fiber filler,

while the fibers are mainly peeled from the binder on a part of their length in the surface layer of the specified part.

Fibers should be understood as microfibers, nanofibers or nanotubes, the ratio of the length of which to thickness is greater than 10. Microfibres are fibers whose thickness is of the order of a micrometer or micron, that is, the thickness of which is essentially from ^10-6 to ^10-5 meters. Nanofibers and nanotubes are fibers whose thickness is of the order of a nanometer, that is, essentially between 10 ^-9 and 10 ^-8 meters.

The stratification of the fibers in the surface layer allows you to create gaps that act like channels and due to the capillarity property in the thickness of this layer transfer organic liquids into it, thus accelerating the cell colonization of this layer. The nature of the fibers also promotes and accelerates, due to absorption, the movement of these organic liquids.

The invention can be applied in accordance with the preferred embodiments described below, which can be considered individually or in any technically feasible combination.

Preferably, the thermoplastic binder is made of polyetheretherketone (PEEK), known for its biocompatibility properties.

Preferably, the fiber filler comprises fibers made from a polymer of the aromatic polyamide family, which also have excellent biocompatibility properties in combination with improved mechanical characteristics. In particular, poly (amide-imide) fibers, whose glass transition temperature is close to the casting temperature "under PEEK pressure, provide, due to the easy deformation property during casting, uniform distribution of fibers in the implant, even if they are relatively long.

The effect of the conductivity of layered fibers in the surface layer allows to obtain a thickness of the specified layer of at least 2 μm, that is, significantly higher than that which can be obtained with implants made by plastic injection molding containing micropores on the surface without the effect of delamination.

Preferably, the material of the implant in addition to the fibers contains a filler of compounds based on calcium and phosphorus. These resorbable compounds promote osseointegration and healing.

Preferably, the filler of the calcium-based compound is made of tricalcium phosphate Ca ₃ (PO ₄ ) ₂ with a hexagonal β-structure. During the injection molding operation, these tricalcium phosphate compounds are transformed into crystals of non-stoichiometric resorbable calcium apatite.

Preferably, the material of the implantable part may also contain zeolite filler. Zeolites promote electrostatic bonds with the implantation medium and ionic adhesion to this medium. In addition, this filler helps to make the material radiopaque.

Preferably, the fiber filler comprises fibers made from calcium silicates (Ca ₂ SiO ₄ ). The presence of these fibers on the surface of the part accelerates the absorption of interstitial fluids in the implantation medium and, therefore, cell colonization of the surface of the part.

The object of the invention is also a method of manufacturing such an implant, wherein said method comprises the following steps, in which:

a) thermoplastic polymer and fiber filler are mixed by extrusion and granulation;

b) the part is molded by injection molding in a mold containing a cavity of the corresponding shape from the granulate obtained in step a);

c) the preform obtained in step b) is subjected to ultrasonic treatment in the pickling baths for the time necessary to separate the fibers in the surface layer.

The method of plastic injection molding allows you to economically obtain a finished implant of this type immediately after the molding operation and in large quantities. In addition, it allows you to orient the fibers using the flow of material entering the mold, and thus obtain the optimal reinforcing effect even for implants of complex shape. Physico-chemical treatment, combining the chemical effects of bathtubs and the mechanical effects of ultrasounds, allows you to simultaneously etch / clean the surface of the implant in order to remove any contaminants associated with the injection molding method and produce fiber separation in the surface layer that can create desired conductivity effect.

In order to obtain a part containing, in addition to fibers, calcium and phosphate-based compounds, the invention also provides a method for producing granulate or compound, comprising the steps of:

- make the first granulate or compound, mixing the polymer binder with the compounds introduced in the form of powders by extrusion and granulation; and

- this first granulate is mixed with fibers during the second extrusion and granulation operation so as to obtain a granulate used for the injection molding operation.

Preferably, filler from zeolites can also be added during the manufacture of the first granulate.

Preferably, the fiber filler comprises from 5 wt.% To 15 wt.% Of the mixture. This fraction simultaneously provides a significant effect of reinforcing the final part, allows it to be obtained using the injection molding method, and to mix the fibers with the polymer binder by extrusion and granulation or “compounding”, regardless of whether or not a filler of calcium-containing compounds was previously introduced and / or zeolites.

The object of the invention is also a granulate or compound for the manufacture by plastic injection molding of an implant reinforced with fibers, wherein said granulate contains:

- polymer binder made of polyetheretherketone (PEEK);

- 10-20 wt.% Filler from compounds containing calcium and zeolites;

- 5-15 wt.% Fiber filler.

This type of granulate can be used directly for plastic injection molding in step b) of the inventive method.

According to a first embodiment for producing the claimed granulate, the fiber filler comprises poly (amide-imide) fibers, the glass transition temperature of which is equal to or lower than the PEEK injection molding temperature.

According to a second embodiment of the claimed granulate, the fiber filler comprises calcium silicate (Ca ₂ SiO ₄ ) fibers.

After molding, the part is etched in a successive row of baths under the action of ultrasound to give it the ability to implant in vivo and to form a surface layer in it that promotes osseointegration in the receiving medium.

Preferably, the etching is carried out in a series of baths in the following order:

- immersion in a bath when exposed to ultrasound to reduce the number of particles containing iron;

- immersion in a solvent binder when exposed to ultrasound, which is inert with respect to the fibers.

The first bath allows you to remove surface contamination with metal particles of the foundry press and mold. The second bath, in which only the binder dissolves, allows, with the simultaneous action of ultrasounds, to obtain decoupling or separation between particles and the matrix in the surface layer. The order of passage through the baths is important because the acid can also have a reducing effect on the fibers and / or the filler of compounds containing calcium and zeolites and present on the surface. With the primary implementation of acid etching, the subsequent action of the solvent allows again to obtain these compounds on the surface.

According to a preferred embodiment, in particular the corresponding embodiment, in which the implant material contains fibers and a filler of zeolites and compounds containing calcium in the PEEK matrix, the etching operation includes immersion in the following baths containing:

- hydrochloric acid

- acetone

- hydrogen peroxide,

between which they rinse in a water bath also under the influence of ultrasound. In particular, if the claimed implantable part contains fibers of calcium silicate, the last bath of hydrogen peroxide allows you to create on the surface of these fibers located on the surface of the part, a layer of silicon dioxide (SiO ₂ ). This layer of silicon dioxide absorbs moisture and facilitates the passage of organic fluids in the surface layer of the implant.

The following is a description of preferred, but not restrictive embodiments of the invention, with reference to figures 1-4, in which:

Figure 1 is a front view of an intraosseous dental implant according to an example embodiment of the invention.

Figure 2 - detail Y of figure 1 in section along the line AA of figure 1.

FIG. 3 is a sectional view of the detail Z of FIG. 2 along the line AA in the surface of the implant according to an example embodiment of the invention during the implementation and intraosseous implant phases of the implant shown in FIGS. 3A-3E.

Figure 4 is a block diagram of the various phases of implementation and application of the claimed implant.

Figure 1 shows an example of an implant (100) having a complex shape, which can be economically obtained using the method of molding by plastic injection molding. This embodiment, which is not restrictive, illustrates the use of the invention for the manufacture of a dental implant. The specified dental implant contains the upper part (101), designed to accommodate add-ons, such as an abutment, and the so-called lower part (110), intended for implantation in the bone part. The lower part (110) may, if desired, contain embossed elements, such as grooves, contributing to its primary mechanical fixation in the nest, such as an opening made in the receiving bone tissue. These fastening grooves or embossed elements may have a size of the order of one millimeter. The specified implant is mainly made of a thermoplastic polymer having good biocompatibility properties, which can be used for injection molding technologies. For example, but not limited to, said polymer may be polyetheretherketone or PEEK marketed by VICTREX® under the name VICTREX® PEEK 150G®. Preferably, the binder may be a material containing calcium and zeolites, such as the material described in French patent FR 2722694 or in US patent US 5872159.

Figure 2 shows in detail a sectional view of an implant material containing a matrix (210) or a PEEK binder, particles (230) of calcium-containing compounds with a diameter of about 1 μm (10 ^-6 meters), and reinforcing fibers (220). According to this exemplary embodiment, the reinforcing fibers (220) are made of poly (amide-imide), for example, are fibers sold under the name KERMEL® TESN by KERMEL®, 20 Ryu Ampère, F-68027 Colmar, France. According to an exemplary embodiment using microfibers, the latter have a diameter of about 7 microns with a length of about 700 microns (0.7 mm). Since the implant is obtained using a plastic injection molding method, the PEEK molding temperature is equal to or higher than the glass transition temperature of this polymer so that the fibers can easily deform at the injection molding temperature and so that they can essentially follow the material flow.

According to a preferred embodiment, the fiber filler may also or exclusively comprise calcium silicate (Ca ₂ SiO ₄ ) fibers (not shown in FIG. 2). This material is tough at injection molding temperature and therefore does not deform at this temperature. Therefore, calcium silicate fibers preferably have a smaller size, of the order of 1 μm in diameter, with a length of 10 to 50 μm. In order to avoid any accumulation phenomenon during injection molding, the total amount of mixed fibers of any type should not exceed 15 wt.%.

Preferably, the filler (230) of the calcium containing compounds is made of tricalcium phosphate Ca ₃ (PO ₄ ) ₂ in phase β. The β phase of tricalcium phosphate is a crystalline phase with a hexagonal structure, stable at low temperature.

When exposed to the total moisture contained in powders of tricalcium phosphate, PEEK and possibly zeolites, this compound undergoes transformation during injection molding in accordance with the following reaction:

4 Ca ₃ (PO ₄ ) ₂ +4 (H ₂ O) => 3 ((Ca ₃ (PO ₄ ) ₂ ) (OH) ₂ Ca + 2HPO ₄ + ½O ₂

3 ((Ca ₃ (PO ₄ ) ₂ ) (OH) ₂ Ca corresponds to hydroxyapatite. This apatite is completely non-stoichiometric and, therefore, resorbable, which gives the material of the implantable part in accordance with the invention properties of integration into bone tissue, as with transplantation.

For this, the powders used during injection molding do not dehydrate. Preferably, they can be rehydrated, or phosphoric acid (H ₃ PO ₄ ) can be added to facilitate this reaction.

Shown in figure 3, the observation of the surface in an even larger view allows you to analyze the morphology of this surface depending on the stages of the method and the application of the claimed implantable parts, while the steps of the method are presented in figure 4.

According to an exemplary embodiment, an implant is obtained by performing the first step, the purpose of which is to obtain a granulate in which:

- 80 wt.% PEEK

- 10 wt.% Tricalcium phosphate (Ca ₃ PO ₄ )

- 10 wt.% Titanium dioxide (TiO ₂ )

The mixture is obtained by extrusion at temperatures ranging from 340 ° C to 400 ° C.

By granulating this extrudate, a first granulate is obtained which is mixed with 10% by weight of KERMEL® TECN type poly (amide-imide) fibers and calcium silicate fibers according to the same extrusion-granulation principle.

The obtained second granulate is used for molding (410) the implant by injection molding. The molding takes place at a temperature from 340 ° C to 400 ° C under a pressure of from 70 to 140 MPa, while the mold is heated to a temperature higher than the glass transition temperature of PEEK, that is, to a temperature of pre-heating the mold about 160 ° C.

Since the glass transition temperature of KERMEL® fibers is 340 ° C, they can deform at the injection molding temperature, which allows them to follow the material flow and are evenly distributed in the granulate during the extrusion-granulation operation and in the part during the molding operation injection molding.

After the molding operation (410), as shown in FIG. 3A, the implant surface is substantially smooth and contains several calcium and zeolite compounds (212) slightly protruding above the surface of the particles (211). Fibers (330), in this case, calcium silicate fibers, are also present near the surface and may protrude slightly from this surface. The implant surface also contains metal inclusions (340) resulting from contact with the mold and with the screws of the foundry press.

After the molding operation, the implant is subjected to processing by passing through a series of baths of chemical etching under the influence of ultrasound. For example, the following protocol gives good practical results, while ultrasound is used at a frequency of 42 kHz:

- HCl 30%: 35 minutes

- H ₂ O: 10 minutes (flushing)

- C ₃ H ₆ O (acetone): 35 minutes at the boiling point of acetone

- Drying the implant with evaporation of acetone

- H ₂ O ₂ 30%: 35 minutes

- H ₂ O: 10 minutes (washing).

After that, the implant is immersed, also under the action of ultrasound, in sterilizing substances:

- GIGASEPT® 12%: 35 minutes

- H ₂ O ppi: 35 minutes

In this case, a bath in a GIGASEPT® solution is optional.

In a first step (420), the implant is acid etched in hydrochloric acid. The purpose of this etching is mainly to remove metallic inclusions. Upon completion of this etching, the implant surface shown in FIG. 3B does not contain inclusions or particles containing calcium that protruded from the surface and the corresponding depressions remained in their place (311).

After washing in the next step (430), the implant is immersed in an acetone bath, also under the influence of ultrasound. As shown in FIG. 3C, after this step (430), a certain PEEK thickness was dissolved, as a result of which particles (211, 212) of compounds containing calcium and zeolites that were previously located below the surface appeared. The action of ultrasound also contributes to the separation between the fibers (330) appearing on the surface and their implantation in the matrix.

After washing in the next step (440), the implant is subjected to treatment in a hydrogen peroxide bath, also under the influence of ultrasound. As shown in FIG. 3D, this bath does not substantially alter the surface morphology. On the other hand, it affects the surface of calcium silicate fibers, promoting oxidation and the formation of silicon dioxide (SiO ₂ ) on their surface.

Preferably, the implant is then placed in a sterilization casing for passage through an autoclave. At the same time, it goes through a sterilization cycle at a temperature of about 135 ° C for 10 minutes at a pressure of about 2150 hPa. This autoclave sterilization operation contributes to the surface etching function; it can be combined with ethylene oxide treatment or gamma rays. In addition, it promotes the crystallization of particles of calcium compounds on the surface. After this sterilization, the implant is packaged in a sterile package and is ready for implantation in bone tissue.

During implantation (450) of the indicated implant into the tissue, organic fluids such as blood, due to capillarity, follow the delamination between the fibers and the matrix, both in the case of KERMEL fibers and in the case of calcium silicate fibers, see FIG. 3E. In the case of calcium silicate fibers, the silicon dioxide present on the surface of these fibers absorbs these liquids and facilitates their movement below the surface. On the surface and, due to conductivity through the fibers, below this surface, calcium-based compounds (211) come into contact with these organic liquids. The resorptive capacity of these compounds promotes cell colonization, which leads to the implantation of the implant surface in bone tissue.

The application of this surface treatment to a known implant containing only calcium phosphate compounds and titanium dioxide in a PEEK matrix allows an active surface layer thickness of about 1 μm to be obtained. The same treatment with respect to an implant of identical shape, but made of a material containing an additional 10 wt.% Poly (amide-imide) fibers or calcium silicate fibers, allows to obtain a thickness of the active surface layer of 3.6 μm.

The presented description clearly shows that, thanks to its various distinguishing features and their advantages, the present invention allows to obtain the desired technical result. In particular, it makes it possible to obtain a reinforced implant made by injection molding, containing a surface layer of osseointegration with a thickness of at least three times the thickness obtained without reinforcement.

Claims (18)

1. The implant intended for intraosseous implantation in vivo, characterized in that it is made of a material containing: - thermoplastic organic binder, which is a polyether etherketone, and - fiber filler, the fibers of which are made of poly (amide-imide), - filler from a compound based on calcium, which is tricalcium phosphate Ca ₃ (PO ₄ ) ₂ with a hexagonal β-structure, the fibers localized on the surface layer of the implant are mainly peeled from the binder along the entire length or part of their length. 2. The implant according to claim 1, characterized in that it contains fibers made of calcium silicate (Ca ₂ SiO ₄ ). 3. The implant according to claim 1, characterized in that the thickness of the surface layer is greater than or equal to 2000 nanometers. 4. The implant according to claim 1, characterized in that it further comprises a filler of zeolites. 5. A method of manufacturing an implant according to any one of paragraphs. 1-4, characterized in that it contains stages in which: a) polyetheretherketone and a poly (amide-imide) filler are mixed by extrusion and granulation; and b) form the implant by injection molding in a mold containing a cavity of the corresponding form, from the granulate obtained in step a); and c) the preform obtained in step b) is subjected to processing in the pickling baths under the influence of ultrasound for the time necessary for the separation of the fibers in the surface layer. 6. The method according to p. 5, characterized in that the fiber filler is from 5 wt.% To 15 wt.% The mixture. 7. The method according to p. 5, characterized in that step c) of the method includes the following operations: - passing through a bath of hydrochloric acid when exposed to ultrasound to reduce the number of particles containing iron; and - passing acetone through a bath when exposed to ultrasound; - passing hydrogen peroxide through the bath, between which they rinse in a water bath also under the influence of ultrasound.

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