FR3048874A1 - METHOD FOR MANUFACTURING TUBULAR STENT FOR IMPLANTATION IN ANATOMIC CONDUIT - Google Patents

Abstract

The invention relates to a method for manufacturing a tubular stent for implantation in an anatomical conduit, which comprises steps of generating (11) a three-dimensional virtual model of said anatomical conduit from dimensional data acquired by medical imaging; reducing (12) the dimensions of this virtual model by removing a thick layer ε from the entire peripheral surface of said virtual model; producing (13) a preform according to said three-dimensional virtual model; forming (15), on the peripheral surface of the preform, a tubular outer envelope of a biocompatible elastomeric material, of thickness ε, by soaking the preform in a solution of a crosslinkable precursor of said elastomeric material, and crosslinking; and demolding (16) the tubular outer casing thus formed.

Description

The present invention is in the field of tubular stents, intended to be implanted in an anatomical conduit of the human or animal body, to maintain the passage of a fluid and / or to avoid obstruction and / or sagging . More particularly, the present invention relates to a method of manufacturing a tubular stent for implantation in an anatomical conduit of the human or animal body.

A particularly preferred field of application of the invention, although not in any way limiting thereto, which will be described in more detail in the present description, is the manufacture of tracheobronchial stents, that is, ie intended to be implanted in the proximal airways of an individual, especially in the trachea and / or bronchi.

The present invention, however, also extends, in a similar manner, to the manufacture of tubular stents intended to be implanted in any other natural conduit of the human or animal body, whether it is a conduit of the respiratory tract, defining what is commonly called a column of air, or a flow conduit of a biological fluid.

Tubular stents are routinely used to treat certain pathologies associated with anatomical pathway alterations, such as obstruction or stenosis, resulting in narrowing of the affected anatomical conduit. For this purpose, the stent is implanted inside the conduit, in the area having a tendency to clog or sag, to keep it open and allow or facilitate the circulation of the fluid in its interior. At present, the tubular stents used consist of a wire mesh, or formed of a material with elastic deformation capacity flexible enough to conform to the shape of the conduit and rigid enough to maintain an artificial passage in the conduit, such as a silicone elastomer.

Tubular stents in the form of a wire mesh may be irritating to biological tissues delimiting the anatomical conduit, particularly when implanted into the trachea and / or bronchi. In addition, it occurs after establishment in the body a phenomenon of epithelialization of the prosthesis, that is to say its integration into the epithelium, which makes it difficult to extract when necessary.

The tubular stents most commonly used for implantation in the proximal airways are formed of silicone elastomer. According to the prior art, these stents are manufactured in series, by molding in molds generally reproducing the shape of the area of the anatomical conduit altered, but slightly smaller dimensions. In order to ensure that they are held in position in their implantation location in the conduit, these stents are furthermore provided on their external surface with numerous protuberances / asperities, for example in the form of protruding nipples intended to come into contact with the wall of the conduit, to ensure the maintenance of the tubular stent. Such stents are for example described in WO-A-89/07916.

However, such stents have several disadvantages. On the one hand, the presence of many protuberances on their surface can be irritating for the biological tissues delimiting the anatomical conduit. On the other hand, this presence does not always prevent the migration of the stent in the conduit, which migration is likely to generate medical complications.

The present invention aims to remedy the disadvantages of tubular stents intended to be implanted in an anatomical conduit of the human or animal body proposed by the prior art, in particular to the disadvantages described above, by proposing a manufacturing process that makes it possible to obtain a tubular stent which is permanently maintained at its implantation location, even when it is implanted in a substantially rectilinear cylinder-shaped zone, for example in a region of the trachea, and which also generates no adverse effect. irritation on biological tissues surrounding said area.

Additional objects of the invention are that this manufacturing process is simple and quick to implement, and that it allows to obtain such a stent at a reduced cost. For this purpose, it is proposed by the present inventors to manufacture a tubular stent made of an elastomeric material, whose outer surface is substantially smooth, that is to say substantially free of protruding asperities, and whose shape and dimensions are adapted to perfectly fit the walls of the anatomical canal in the implantation area. It has been found by the present inventors that a stent which responds to such characteristics, and therefore which, when it is implanted in the anatomic duct, has a large and continuous contact surface with the walls of the latter, remains perfectly stable. place at its implantation area, and this even when the anatomical conduit has a substantially cylindrical and substantially rectilinear shape, and that the stent is subjected to numerous deformations during the various movements of the anatomical conduit. Such deformations do not advantageously cause the migration of the stent into the conduit.

Thus, it is proposed by the present invention a method of manufacturing a tubular stent intended to be implanted in an area of an anatomical conduit of the human or animal body, more particularly an altered zone of said anatomical conduit, whose dimensional data have previously acquired by a medical imaging technique, this, in particular, to maintain the passage in said conduit or to prevent sagging.

By the present description is meant by anatomical conduit, any tubular body structure, such as a bronchus, trachea, blood vessel, artery, esophagus, ureter, bile duct, etc., or a set formed by such structures, for example an assembly comprising the trachea and bronchi.

The method according to the invention comprises steps of: a / from dimensional data relating to the biological tissues surrounding the anatomical conduit acquired by a medical imaging technique, generation by graphic modeling of a three-dimensional virtual model, in particular a model vector, in particular a polygonal model, of said zone of the anatomical conduit in which the tubular stent is intended to be implanted, for example of a zone of the air column at the level of the trachea and / or bronchi; b / reducing the size of the three-dimensional virtual model thus obtained by removing a thick layer ε of a given value from the entire peripheral surface of said three-dimensional virtual model; c / making a solid part, called positive preform, according to the three-dimensional virtual model thus resized; d / forming, on the peripheral surface of the positive preform thus obtained, a tubular external envelope of a biocompatible elastomeric material, of thickness ε, by soaking the positive preform in a solution of a crosslinkable precursor of the elastomeric material, and crosslinking; e / and separation of the tubular outer casing thus formed of the positive preform, to obtain the tubular stent.

By conventional means means, by biocompatible material, a material which does not interfere with the biological medium in which it is used, and does not cause any degradation. The tubular stent obtained by the process according to the invention has a substantially uniform thickness over its entire surface, equal to the value ε, to manufacturing inaccuracies. Thus, in practice, this thickness is equal to ε ± 0.3 mm, depending on the zones of the stent.

This tubular stent is advantageously perfectly adapted to the morphology of the area of the anatomical conduit in which it is intended to be implanted.

In particular, when the targeted anatomical conduit is a proximal airway of the individual, the endoprosthesis perfectly marries the tracheobronchial mucosa. This advantageously has the effect of suppressing migration phenomena, as well as the side effects, particularly irritation, compared to tracheobronchial implants proposed by the prior art. The stent obtained according to the invention can be used for the internal reinforcement of the anatomical duct, when the latter tends to sag, and / or to keep the anatomical duct open, when it tends to clog. By way of example, this stent can be used for the management of pathologies such as malignant obstructions of the proximal airways, stenosis of anastomoses after lung transplantation, benign tracheal stenosis, post-intubation, posttracheotomy or idiopathic stenosis. tracheobronchomalacia, estracheal fistula, etc.

The dimensional data relating to the biological tissues surrounding the anatomical conduit, from which the method according to the invention can be implemented, are in particular two-dimensional data or three-dimensional data. In particular, these can be tomographic or magnetic resonance imaging (MRI) data acquired by CT or MRI, respectively.

In a first step, the method according to the invention can thus comprise the computer processing of initial raw data acquired by scanner or MRI, in the form of two-dimensional sections, to generate the three-dimensional virtual model of the anatomical conduit, by isolating the relative data. to this duct, for example to the tracheobronchial air column.

This step a /, as well as the reduction step b / of the dimensions of the three-dimensional virtual model obtained, fall within the field of computer-aided design, and can be carried out by any hardware and by means of any conventional data processing software. in itself, for example using McNeel's Rhinoceros® software, SolidWorks® software or CATIA, etc.

According to particular embodiments, the method according to the invention also fulfills the following characteristics, implemented separately or in each of their technically operating combinations.

In general, all the materials used are compatible with the biomedical standards in force, and are in particular free of latex, products of animal or biological origin, and, where appropriate, medicinal substances.

In particular embodiments of the invention, the thickness ε, corresponding to the thickness of the layer of material removed from the virtual three-dimensional model, and to the thickness of the outer envelope, that is to say say tubular stent, is between 1 and 2 mm. Such a dimension is advantageously quite adapted to the anatomy of the proximal airways of individuals, whether adults or children, and also provides the necessary characteristics of elasticity and rigidity. for the intended medical application, in connection with the characteristics of the elastomeric material itself.

In order to obtain a thickness in such a range of values, the method according to the invention preferably comprises, in step d / of forming the tubular outer casing on the peripheral surface of the positive preform, a plurality of successive steps of dipping the preform in said solution, before the crosslinking operation. Preferably, a drying step is interposed between two successive dipping steps. This drying step is for example carried out for a period of 20 to 30 minutes, in particular about 25 minutes, in the open air and at room temperature.

The exact number of dipping operations performed determines the thickness of the endoprosthesis and its ultimate stiffness. It is within the skills of a person skilled in the art to determine this number of soaks, depending in particular on the characteristics of the elastomeric material used and the medical application in question. In particular, depending on the pathologies / medical indications, it may be necessary to implement more or less thick and / or rigid stents. With each dipping operation, a surface layer of material is formed on the positive preform, the various successive layers acquiring a cohesion with each other, and the capacity for elastic deformation, after a treatment aimed at achieving the crosslinking of the elastomer material. .

The operating parameters of the dipping and crosslinking operations depend on the crosslinkable precursor used, and the desired thickness ε for the outer shell. It is within the skill of those skilled in the art to determine them according to the precursor chosen and the desired thickness.

The soaking step (s) of the positive preform in the precursor solution are, for example, carried out at room temperature, that is to say between approximately 20 and 28 ° C., for example between 21 and 23 ° C.

Preferentially, the soaking step (s) of the positive preform in the precursor solution are furthermore carried out at a hygrometry of greater than or equal to 25%. The crosslinking operation can be performed by baking at a temperature above 100 ° C, for example about 125 ° C, for a period of between 1 and 3 hours, for example about 2 hours.

As indicated above, the positive preform is formed in a material compatible with the biomedical standards in force. In particular embodiments of the invention, the positive preform is formed of a rigid plastic material, in particular based on polyacetal. An example of such a material that can be used in the context of the invention is a poly (oxymethylene) copolymer, also known as polyformaldehyde, such as the material marketed by Quadrant Engineering Plastic Products under the name Ertacetal. ® POM C.

According to the invention, this preform constitutes the mold for subsequent soaking operations.

In particularly preferred embodiments of the invention, particularly because of the ease, speed and low cost of implementation associated, the positive preform is formed by three-dimensional printing or by three-dimensional machining. The invention can use for this purpose any apparatus that is conventional in itself for implementing such techniques, for example a 3D printer that cuts the virtual three-dimensional model, and deposits or solidifies the layer material. per layer, to reproduce this model as a physical part. The tubular outer casing is formed of biocompatible material, in particular a medical grade material, implantable long-term in the body. In particular embodiments of the invention, it is formed of polysiloxane elastomer, commonly called silicone elastomer, biocompatible.

This elastomer preferably has a hardness of between 30 and 70 Shore A. Such a characteristic, combined with a thickness of the external envelope substantially between 1 and 2 mm, advantageously gives the stent formed mechanical properties perfectly suited to a use by implantation in an anatomical conduit, reinforcement of the walls of this conduit and / or to keep it open.

In particular embodiments of the invention, the method comprises integrating, in the thickness of the tubular outer casing, at least one, preferably at least two, ring (s) of peripheral stiffening. (s) biocompatible material, in particular silicone.

Such peripheral rings advantageously confer on the endoprosthesis formed, locally, a greater axial rigidity. The number and the positioning of such peripheral rings along the length of the tubular stent is determined according to the indications of the pathology to be treated. Such determination falls within the skill of the skilled person. The integration of such a peripheral stiffening ring into the tubular outer casing may include in particular the threading of the peripheral ring around the positive preform, before the step d / of forming the tubular outer casing on the peripheral surface of the positive preform. In this way, during the operation of soaking the positive preform in the crosslinkable elastomer solution, the ring is embedded in the surface layer formed around the preform, and is thus fixed in the thickness of the outer envelope that forms after the crosslinking operation. When the diameter of the ring is greater than the thickness ε of the outer envelope, this ring forms an extra thickness on the outer surface of the stent obtained.

In particular embodiments of the invention, the method comprises a final sterilization step of the tubular stent obtained at the end of step e /. Such a sterilization step can be carried out by any method known per se, for example by treatment with ethylene oxide, sterilization in an autoclave, etc.

The process according to the invention can be applied to the manufacture of tubular stents of any shape. For example, for the treatment of pathologies of the proximal airways, it can be implemented for the manufacture of tubular stents of said simple shape, that is to say generally cylindrical, substantially rectilinear or slightly curved, for implantation into the only trachea; or for the manufacture of tubular stents of more complex form, in particular of bifurcated form, for example Y-shaped, for implantation for example in the trachea and the intersection of the trachea with both bronchi.

The features and advantages of the method according to the invention will appear more clearly in the light of the following examples of implementation, provided for illustrative purposes only and in no way limiting the invention, with the support of FIGS. 1 to 7, in FIG. which: - Figure 1 shows a block diagram illustrating the various steps of a method according to the invention; FIG. 2 shows a virtual model of an anatomical duct generated by graphic modeling; - Figure 3 shows a preform obtained during the implementation of a method according to the invention, on which is formed an outer casing; - Figure 4 shows a sectional view along a longitudinal plane of the preform and the outer casing of Figure 3; FIG. 5 shows examples of stents of simple shape obtained by a method according to the invention, (a), of completely smooth contour, (b) integrating stiffening rings; FIG. 6 shows examples of stents of complex shape obtained by a method according to the invention, (a), of completely smooth contour, (b) integrating stiffening rings; - And Figure 7 shows a photograph of a tubular stent obtained by a process according to the invention, and the corresponding preform.

A method of manufacturing a tubular stent according to the invention may comprise the steps illustrated schematically in the block diagram of FIG. 1. For the description which will be made hereinafter, one places oneself in the example, in no way of the invention, the manufacture of a stent intended to be implanted in the trachea of an individual, where appropriate at the intersection of the trachea and bronchi.

This method may comprise a prior step of acquiring dimensional data, in particular two-dimensional data, relating to the tissues surrounding the air column in which the stent is to be implanted, by a conventional medical imaging technique in itself. same, for example by scanner or MRI.

It then comprises a first step 11 of generating a three-dimensional graphical model of the air column in which the stent is to be implanted, by computer processing, according to a conventional method in itself, of two-dimensional data relating to the surrounding tissues. this air column, acquired by CT or MRI, for example, but not limited to, in the prior step described above. At the end of this step, we obtain a three-dimensional virtual model 20 as shown in Figure 2. which perfectly reproduces the area of the air column in which the stent is to be implanted.

The method then comprises a step 12 of reducing the dimensions of this virtual three-dimensional model 20, by removing, still by computer processing, a layer of material 21, of thickness ε, from the entire peripheral surface 22 of the virtual model 20, as shown in Figure 3. The thickness ε of the removed layer 21 is uniform over the entire surface of the workpiece. It is preferably between 1 and 2 mm.

The virtual model thus obtained represents the future soaking mold, also called positive preform, which will be formed in the next step of the process.

This next step 13 consists in the production of a positive preform 23, in the form of a solid part reproducing the virtual model resized in the previous step.

This preform 23 is preferably formed of a rigid material. It may for example be formed of plastic compatible with current biomedical standards, for example polyacetal copolymer. It is preferably formed by a 3D printing technique or 3D machining, conventionally in itself.

The method according to the invention furthermore preferably provides for the formation, at a longitudinal end of the preform 23, of an extension 24 for the subsequent fixing of a soaking sleeve.

If necessary, the method may comprise an intermediate step 14 of threading one or more peripheral stiffening rings around the preform 23. These rings are for example 2, 3 or 4. They are formed of biocompatible material , in particular of medical grade silicone. They have a rigidity greater than the rigidity of the outer envelope which will be formed in the next step of the process.

The method according to the invention then comprises a step 15 of forming, on the outer peripheral surface of the preform 23, an outer casing 25 of elastomeric material, in particular of silicone elastomer. This outer envelope is formed so as to have substantially thickness ε, manufacturing inaccuracies, as shown very schematically in Figure 4.

It is obtained by several successive dipping of the preform 23 in a so-called soaking solution containing a crosslinkable precursor of said elastomeric material, and crosslinking.

For example, the dipping solution may consist of a dispersion in xylene of PN 40000 dimethyl silicone elastomer, as sold by the company Applied Silicone.

The process may then comprise a plurality of steps for soaking the preform 23 in this solution at a temperature of between 21 and 23 ° C., these steps being separated by drying steps of each layer just formed on the preform. , lasting about 25 minutes each. At the end of these operations, the assembly can be baked, for example at 125 ° C. for 2 hours, to prepare the curing of the elastomeric material.

The method then comprises a step 16 of demolding the outer casing 25, that is to say of separation of the outer casing 25 and the preform 23, then, if necessary, a final sterilization step 17 of the outer casing 25, which forms the tubular stent according to the invention.

The outer contour of this tubular stent perfectly reproduces the internal contour of the anatomical duct of the individual whose two-dimensional data were initially acquired by medical imaging.

Examples of tubular stents obtained according to the invention are shown in Figures 5 and 6.

More particularly, the stent 25 shown in (a) in FIG. 5 has a generally cylindrical tubular shape, defining an internal lumen along its entire length, an advantageously smooth outer contour, and an evenly smooth inner contour, with no visible joint plane. . This stent is particularly suitable for implantation in the trachea. The stent 25 shown in (b) in Fig. 5 has a similar shape, but incorporates two peripheral stiffening rings 26, which locally impart greater axial rigidity. These rings form protruding ribs protruding from the outer surface of the stent. The tubular stent 25 shown in (a) in Figure 6 has a complex shape, particularly suitable for implantation at the intersection of the trachea and bronchi. It has a first tubular portion 251, intended to be positioned in the trachea, extended at one end by two tubular portions 252, 253, intended to be positioned respectively respectively in a bronchus. The stent 25 shown in (b) in Figure 6 has a similar shape, but incorporates three peripheral stiffening rings 26, which locally impart greater axial rigidity. Again, these rings form protruding ribs protruding from the outer surface of the stent. By way of example, FIG. 7 shows a photograph of a silicone tubular stent obtained by a process according to the invention, accompanied by the positive preform 23 used in its manufacture.

Once properly installed in the target area of the anatomic conduit, these stents all remain perfectly in place. They also generate no irritation in the tracheobronchial mucosa.

Claims (10)

1. A method of manufacturing a tubular stent (25) intended to be implanted in an area of an anatomical conduit of the human or animal body, characterized in that it comprises steps of: a / from relative dimensional data biological tissues surrounding said anatomical duct acquired by a medical imaging technique, generating (11) by graphical modeling of a three-dimensional virtual model (20) of said zone of said anatomical duct; b / reducing (12) the dimensions of said three-dimensional virtual model (20) by removing a layer (21) of thickness ε from the entire peripheral surface (22) of said three-dimensional virtual model (20); c / realization (13) of a solid part (23), called positive preform, according to said three-dimensional virtual model (20) of reduced dimensions; d / formation (15), on the peripheral surface of said positive preform (23), a tubular outer casing (25) of a biocompatible elastomeric material, of thickness ε, by soaking said positive preform (23) in a solution of a crosslinkable precursor of said elastomeric material, and crosslinking; e / and separating (16) the tubular outer casing (25) thus formed of said positive preform (23), to obtain said tubular stent. 2. Method according to claim 1, wherein the thickness ε is between 1 and 2 mm. 3. Method according to any one of claims 1 to 2, comprising, in step d / of forming (15) said tubular outer casing (25) on the peripheral surface of said positive preform (23), a plurality of successive steps of soaking said positive preform (23) in said solution, before said crosslinking operation. 4. Method according to any one of claims 1 to 3, wherein said positive preform (23) is formed of rigid plastic, in particular based on polyacetal. The method of any one of claims 1 to 4, wherein said positive preform (23) is formed by three-dimensional printing or three-dimensional machining. 6. A method according to any one of claims 1 to 5, wherein said tubular outer casing (25) is formed of biocompatible polysiloxane elastomer, preferably hardness between 30 and 70 Shore A. 7. Method according to any one of claims 1 to 6, comprising the integration into the thickness of said tubular outer casing (25) of at least one peripheral stiffening ring (26) of biocompatible material, in particular silicone. The method of claim 7, wherein integrating said peripheral stiffening ring (26) into the tubular outer shell (25) comprises threading (14) said peripheral ring (26) around said positive preform (23). ) before step d / forming (15) of said tubular outer casing (25) on the peripheral surface of said positive preform (23). 9. Method according to any one of claims 1 to 8, comprising a final step of sterilization (17) of the tubular stent (25) obtained at the end of step e /. The method of any one of claims 1 to 9, wherein said tubular stent (25) has a simple shape or a bifurcated form.