FR3118576A1 - Joint implant receiving osteochondrogenic cells for the reconstruction of articular cartilage - Google Patents

Abstract

The present invention relates to an implant for the repair of articular cartilage, the implant comprising:a biocompatible support (3) configured to be placed above a first surface of bone, comprising a receiving surface (4) configured to delimit a bottom of a cell development space (60), the cell development space (60) thus formed extending between the receiving surface (4) and a second surface of bone facing the first bone surface,and a repair matrix superimposed on the receiving surface (4), the repair matrix comprising a volume of osteochondrogenic cells intended to grow in the cell development space (60).The repair matrix may including including a periosteal graft. Figure for abstract: Figure 3

Description

Joint implant receiving osteochondrogenic cells for the reconstruction of articular cartilage

FIELD OF THE INVENTION

The present invention relates to a prosthetic device to be implanted in a joint for the repair of damaged or deteriorated articular cartilage. One goal is to restore the mobility and cushioning functionality provided by the cartilage.

More specifically, the invention relates to an implant for the repair of articular cartilage, comprising a biocompatible support and a cellular matrix for repairing the cartilage. Illustrative examples of such a joint implant are described below and illustrated in the appended figures. The implant comprising the biocompatible support is configured to allow the development of a population of osteochondrogenic cells in the joint cavity and to promote the directed differentiation of these cells.

STATE OF THE ART

A chondropathy is manifested by a disintegration of one or more cartilaginous surfaces, which lose their mechanical properties of protection of the bone surfaces and damping of the mechanical stresses of a joint. Untreated, chondropathy can degenerate into advanced osteoarthritis, causing significant chronic pain and can be very debilitating, especially for the elderly patient.

If we take the example of the knee, during natural walking or squatting movements, the pressure exerted on the knee joint between the femur and the tibia is very important. If the function of mobility and cushioning of the articular cartilage is not maintained, these natural movements are painful.

These lesions of the articular cartilage can be located on only one of the two articular surfaces which face each other, but most often, the two articular cartilage surfaces opposite are affected. Joint lesions generally find their source either in age-related cartilage wear (osteoarthritis), or in joint trauma, especially in young subjects.

It should be noted that arthropathy lesions can also affect the bone underlying the cartilaginous layer called “subchondral bone”. Indeed, it is known that one of the first radiological signs of osteoarthritis in the cartilage is the presence of "micro-geodes" in the subchondral bone.

In current medical practice, the degree of severity of arthropathy is assessed clinically by the ICRS functional score, and radiologically (MRI) by the ICRS grade or according to the Outerbridge classification.

In the beginning forms of osteoarthritis, various treatments are offered based on general anti-inflammatories or by local injection. We can also perform intra-articular injections, for example injections of hyaluronic acid (we speak of “visco-supplementation”) or plasma enriched with platelets.

Relatively minimally invasive therapeutic approaches under arthroscopy can also be proposed, such as joint lavage with debridement, Pridie's microperforation technique, the micro-fracture technique, osteochondral allografts, osteochondral autografts ("mosaicplasty"), or use of three-dimensional matrices composed of collagen and hydroxyapatite.

The techniques mentioned above, however, give fairly transient results, and histologically, the reformed cartilage is generally of poor quality with fibrocartilage-type tissue. This is why, in practice, it is mainly resorted to "arthroplasties" (installation of a joint prosthesis) in the event of advanced osteoarthritis. The joints most frequently affected by arthroplasty are the hip and the knee.

For example, for an advanced chondropathy of the knee, a permanent unicompartmental or total knee prosthesis will be placed permanently fixed during a surgical procedure under anesthesia.

Mention may be made, for example, of the international patent application published under the number WO 2005/016175 A2 . In this document, the prosthesis is designed in a rigid biocompatible material to restore the expected mechanical properties of the joint.

However, in the case of such a joint prosthesis, the patient must then be rehabilitated for quite a long time. Significant medical care in a specialized center is necessary, with physiotherapy and other supportive care.

With such a joint prosthesis, there are also risks of loss of mechanical functionality over time (by mechanical wear of the components of the prosthesis), and/or infection of the prosthetic material.

Incidentally, temporary intra-articular implants have also been proposed. For example, an implant is placed in the joint cavity comprising a pocket of silicone-enriched gel, which swells to conform to the volume of the joint cavity. Such an implant is illustrated and described in the international patent application published under the number WO 2008/120215 A2 . However, this last type of treatment has not given very convincing results, in particular because the natural repair of the cartilage is not sufficiently stimulated.

It follows from the foregoing that the cartilage repair techniques and the various articular implants known to the state of the art do not allow a sufficiently qualitative and durable repair of the articular cartilage.

The known techniques therefore do not respond appropriately to the public health challenges of treating joint pain and joint mobility disorders, which affect young people as well as the elderly.

GENERAL DESCRIPTION OF THE INVENTION

In view of the foregoing, there is a need for an improved joint implant capable of locally promoting the repair of one or more areas of deteriorated cartilage of a diarthrodial joint.

In order to permanently repair the articular cartilage, the desired implant must promote the formation of new articular cartilage of good quality. This newly formed tissue must be made up of different layers of chondrocytes (superficial, transitional, radial layers, calcified cartilage) which are specific to articular cartilage (these different layers being a reflection of the functional complexity of articular cartilage) and give it its remarkable mechanical qualities. sustainable over time. The different functional layers of articular cartilage are for example described in terms of structure and composition, in particular cellular, in the following scientific publication: Composition and Structure of Articular Cartilage: A Template for Tissue Repair , Poole, Kojima, Yasuda, Mwale, Kobayashi , Laverty, October 2001, Clinical Orthopedics and Related Research 391(391):S26-S33.

Advantageously, the desired implant must also make it possible to obtain a layer of subchondral bone, underlying the layers of cartilage. The set formed by the aforementioned chondrocyte layers and the subchondral bone layer corresponds to an “osteochondral unit”.

For example, we are looking for a joint implant suitable for use in the knee (femorotibial or patellofemoral joint) or the hip joint, particularly in humans. However, the implant variants described below are adaptable for any joint in the human or animal body.

In particular, there is a need for a joint implant whose placement, and possible subsequent removal in certain cases, are easy and minimally invasive for the patient. In the case of an implant intended to be integrated into the joint, it is important that the implant be well tolerated by the body.

Preferably, the desired implant is configured to adapt well to various morphologies of the joint to be treated.

An additional objective is that the surface of the repaired cartilage presents a geometry very close to the geometry of the native cartilage. The aim is thus to restore satisfactory mobility of the joint and to achieve optimal geometrical operating criteria aimed at avoiding further wear of the cartilage after treatment.

A secondary objective is to provide an implant which allows the simultaneous treatment of two areas of deteriorated cartilage, located on the two opposite sides of the natural mobility plane of the articular cavity.

It is proposed to meet these needs, according to one aspect of the invention, an implant for the repair of articular cartilage, the implant comprising:
a biocompatible support configured to be placed over a first bone surface,
the support comprising a reception surface configured to delimit a bottom of a cellular development space, the cellular development space thus formed extending between the reception surface and a second surface of bone located opposite the first surface back,
a repair matrix superimposed on the receiving surface, the repair matrix comprising a volume of osteochondrogenic cells intended to grow in the cell growth space.

It is thus proposed to implant in the joint a device comprising a support of biocompatible material. The support is positioned on a first bone surface. In non-limiting examples, the support can take the form of a perforated plate through or of a three-dimensional network comprising empty spaces, the empty spaces then being able to be obtained by 3D printing.

The perforated plate can then be embedded in the articular cartilage at the level of a deteriorated sector of the cartilage.

The implantation of this plate preferably follows a gesture of trimming the deteriorated articular surface, this gesture aiming to "flatten" the sector of deteriorated cartilage generally comprising a central part made up of thinned, cracked or even totally eburnated cartilage (areas of complete disappearance of the cartilage). The trimming can also make it possible to flatten lateral sectors of deteriorated cartilage of poor quality (“bulges”) in relief.

Preferably, the biocompatible support extends over the entire exposed bone surface resulting from the trimming, this latter bone surface itself covering the entire extent of the deteriorated sector of cartilage.

More generally, the receiving surface of the support delimits an empty volume forming a cell development space. The cell development space is formed between the receiving surface of the support and a second facing bone surface. Non-limitingly, the void volume may for example be formed between, on the one hand, the surface for receiving the biocompatible support, and on the other hand, a second surface for receiving a second support placed on the second bone surface. .

When the patient receives the implant, the cell development space, defined by one or more biocompatible supports, is provided with a repair matrix made up of immature osteochondrogenic cells.

Thanks to the configuration of the implant of the invention, the osteochondrogenic cells have a cell development space within which they proliferate until they completely colonize this space.

By leaving the implant in place in a context of immobility of the joint for a sufficient period of time, osteochondrogenic cells are allowed to multiply within the cell development space, directly in the joint cavity. As will be described in detail hereinafter, following mobilization of the joint which occurs after the immobilization phase of the joint, the differentiation of osteochondrogenic cells is directed to specifically form new articular cartilage on the surface. and, if necessary, to also form deep subchondral bone.

In a non-limiting manner, the receiving surface can accurately reproduce the geometry of the surface of the native articular cartilage (that is to say before deterioration of the cartilage). This latter geometry can be determined on a case-by-case basis for each patient, in particular using medical imaging tools.

Optional and non-limiting characteristics of the implant for the repair of articular cartilage as defined above are the following, taken alone or in any of the technically possible combinations:

- the support has a contact edge intended to be embedded in an edge of a bone cavity of the first bone surface.

- said edge is an edge of a bone cavity formed by trimming.

- the contact edge comprises a closed contour.

- the contact edge forms a periphery of the receiving surface.

- the support comprises an underlying surface opposite the receiving surface, the support defining a plurality of through microcavities.

- Each said microcavity passes through the receiving surface and the underlying surface.

- the through microcavities comprise at least one punching, and/or comprise at least one void region, the void region then being preferably obtained by 3D printing.

- the implant comprises a network formed of a plurality of stiffening elements placed against the receiving surface, a stiffness against shearing at the level of the stiffening elements being strictly greater than a stiffness against shearing at a zone central cell development space.

- the repair matrix is placed against the stiffening elements.

- the repair matrix is placed against the stiffening elements over more than 50% of a total surface of the repair matrix, preferably more than 80% of said surface, even more preferably more than 90%.

- the first bone surface and the second bone surface belong to a joint of an individual.

- a concavity of the receiving surface is configured to correspond to a concavity of a natural mobility plane of said articulation.

- the repair matrix comprises a periosteum graft, preferably a tibial periosteum graft.

- the periosteal graft is a "free" non-vascularized graft.

- the periosteal graft is a vascularized pedunculated graft.

- the periosteal graft is taken from the anterior surface of the tibia.

- the implant comprises at least one fixation element, configured to mechanically stabilize the support with respect to the first bone surface.

- the fastening element comprises a screw, preferably a screw positioned obliquely, and/or comprises a clip and/or comprises a hook.

- the screw, and/or the staple, and/or the hook is configured to be implanted in a part of the subchondral bone lateral or underlying the implant.

- the screw, staple and/or hook is configured to be implanted in a non-carrying area of the first articular surface.

- the implant comprises a prosthetic net configured to be inserted between the support and the second articular surface, and configured to delimit with the receiving surface of the implant a cell development space.

- the prosthetic net is removable.

- the support is configured to be placed in the articular cavity and to be superimposed on the first articular surface, in a removable manner.

- the cell development space is defined inside a recess made in this removable support, the receiving surface being positioned at the level of the bottom of said recess.

- the bottom of the removable support has no perforations.

- a majority material of the support is a resorbable material configured to gradually integrate on the first bone surface, the support being preferably formed entirely of resorbable material.

- a majority material of the support is a polymer material, or is a bioceramic material.

- the polymer material is polyethylene, and/or polytetrafluoroethylene called PTFE.

- the support is made by 3D printing.

- the support is intended for placement on a surface of the femoro-tibial joint, or on a surface of the femoro-patellar joint, or on a surface of the talocrural joint, or on a surface of the glenohumeral joint, or on a surface of the acromioclavicular joint, or on a surface of the coxo-femoral joint.

GENERAL DESCRIPTION OF FIGURES

Other characteristics, aims and advantages of the implant will emerge from the description which follows, which is purely illustrative and not limiting, and which must be read in conjunction with the appended drawings, among which:

There schematically illustrates three cases of differentiation of mesenchymal stem cells into bone, fibrous or articular cartilage tissue depending on the mechanical stresses exerted on the mesenchymal stem cells.

Figures 2a to 2d schematically illustrate successive stages of an experimental operation comprising resection of a distal part of the femur, followed by implantation of a flap of periosteum in the joint cavity thus enlarged, then followed by mobilization mechanics of the femoro-tibial joint.

There represents several histological views at different magnifications of a rabbit knee joint, these views corresponding to the state of the joint as illustrated in the after an experimental surgical operation for bone and cartilage regeneration as schematized in FIGS. 2a to 2d.

There is a schematic view of two joint implants in a first application example. In this view, the damaged articular cartilage is being repaired.

Figures 4a to 4f illustrate successive stages of the repair of two deteriorated sectors of articular cartilage of the same femoro-tibial joint using implants according to the , from a deteriorated state of the cartilage sectors before trimming ( ) up to a repaired state of the cartilage sectors after placement of the implants and solicitation of the joint ( ).

There is a schematic view of a joint implant in a second application example, where the articular cartilage is being repaired.

There is a schematic view of a joint implant in a third application example, the biocompatible intra-articular support being associated with a removable prosthetic net. In this view, the damaged articular cartilage is being repaired.

Figures 7a to 7d illustrate successive stages of the repair of a damaged sector of articular cartilage using an implant according to the .

Figures 8a to 8c schematically illustrate a joint implant in a fourth example of application, where the articular cartilage located opposite the removable biocompatible intra-articular support is being repaired, and illustrate the stress on the joint during the repair articular cartilage.

There is a schematic view of two joint implants in a fifth application example, where an area of articular cartilage is being repaired.

DETAILED DESCRIPTION OF SEVERAL EMBODIMENTS OF THE INVENTION

The description below, supplemented by the appended figures, relates to a plurality of examples of articular implants in accordance with the invention making it possible to promote the repair of a deteriorated sector of cartilage of a femoro-tibial joint of a patient. human. It will however be understood that the invention finds an application, with the same advantages for the repair of a sector or several sectors of cartilage located in another joint in a human or animal patient. The placement of an implant according to the invention is in particular envisaged for the femoro-patellar joint, the talocrural joint, the gleno-humeral joint, the acromio-clavicular joint, the coxo-femoral joint.

The following examples provide for the use of a periosteal flap as a repair matrix capable of generating osteochondrogenic cells in the joint cavity; however, it should be noted that other types of cellular repair matrices known in tissue engineering may be used. In addition, the repair matrix may or may not be associated with substances promoting cell growth and differentiation directed towards cartilage cells, such as proteins, growth factors, etc.

It will also be noted that an implant according to the invention can be used to treat a joint which has previously been the subject of a decaptation maneuver, or for a joint which has not been the subject of this maneuver.

In all of the appended figures and throughout the description below, similar elements bear identical reference numerals.

General principles of articular cartilage repair using an implant

Articular cartilage is a flexible connective tissue present at the level of the joints, allowing the protection of the bone extremities, the damping of the pressure of the loads exerted on the bone extremities and the harmonious sliding of the articular surfaces vis-à-vis.

Articular cartilage is mainly made up of cells called chondrocytes, and an extracellular matrix (collagens, glycosaminoglycans). Chondrocytes have a function of synthesis and maintenance of cartilage tissue. They are located in cells that each contain one or more chondrocytes, called chondroplasts. Sectors of cartilage can be damaged by various pathologies affecting the cartilage. Natural joint cartilage repair is very ineffective. The evolution of cartilage lesions associates cracks in the cartilage, a decrease in its thickness, and lesions of the subchondral bone. This development can lead to complete obliteration of the cartilage with exposure of the subchondral bone (eburnation).

The articular cartilage is particularly present at the level of the epiphyseal surfaces of the long bones. Chondrocytes are derived from cell differentiation of stem cells located in adults in the most superficial layer of articular cartilage. However, their renewal is very slow, this tissue repairing itself with great difficulty.

The long bones, with the exception of the cartilages, are covered on their surface with a membrane called "periosteum" which provides the essential bone repair in the event of a fracture. The periosteum is rich in repair stem cells, such as osteochondrogenic cells. For a detailed description of the composition and role of the periosteum, reference may be made to the following publication: Periosteum contains skeletal stem cells with haigh bone regenerative potential controlled by Periostin , Duchamp de Lageneste et al., Nature Communications, February 2018 22; 9(1):773.

Faced with the difficulty for the body to spontaneously reproduce the articular cartilage, the implant proposed here aims to allow the regeneration of the cartilage in the damaged sectors, from osteochondrogenic cells (typically from an autologous periosteal graft).

The differentiation pathway of mesenchymal stem cells into specifically articular type chondrocytes depends in particular on the mechanical factors of the stem cell environment. This aspect falls within the more general framework of “mechanobiology” which studies the influence of local mechanical factors on cell differentiation pathways.

By way of illustration, on the attached, three pathways A, B and C of mesenchymal stem cell differentiation have been schematized.

From a volume of still immature osteochondrogenic cells 10, it is possible to influence the differentiation pathway and therefore the future functionality of the newly formed tissue, depending on the mechanical stresses exerted in the cell volume.

On "path A", the cells are "free" and no mechanical stress (or minimal stress) is exerted. Osteochondrogenic cells then preferentially give rise to 11A bone cells (osteocytes). The clinical illustration of this approach A is quite simply the future of the bone fracture site correctly stabilized by a cast or by an orthopedic assembly. The fracture site (fracture callus), in which osteochondrogenic cells from the periosteum or bone marrow are present early, will differentiate into bone after passing through the state of endochondral cartilage (not shown) 11a.

On “path B”, stretching forces FB are exerted in a preferred direction. The formation of a fibrous tissue 11b (constituent tissue of the ligaments) is then observed. A clinical illustration of this approach B is for example the surgical reconstruction of the external lateral ligament of the ankle by flap of periosteum taken from the fibula.

Finally, on “path C”, shear forces FC are exerted: the upper part of the volume of the osteochondrogenic cells is moved to the left and the lower part of said volume is moved to the right. To the Applicant's knowledge, this C pathway of differentiation has not to date been isolated naturally or during clinical practice. The proposed joint implant is thus based on voluntary shearing movements promoting a directed differentiation of osteochondrogenic cells towards the formation of chondrocytes, thus ultimately forming articular cartilage. After directed differentiation of the osteochondrogenic cells according to pathway C, new cartilaginous surfaces are obtained here extending along the cleavage plane 11c.

The various articular implant variants described below therefore aim to bring about a differentiation directed essentially towards a pathway similar to the C pathway, by creating a cell development space in the vicinity of at least one damaged sector of cartilage, space in which still immature osteochondrogenic cells multiply, then locally produce mechanical stresses inducing shearing phenomena of the cellular repair matrix in a plane close to the joint's natural mobility plane.

To provide sufficient space for cell development, it is proposed to use a biocompatible support which comprises a receiving surface, the latter being set back from the damaged sector of cartilage (for example placed at a depth greater than the depth of the superficial layer of cartilage). A repair matrix, such as for example an autologous periosteal graft, is placed in the cell development space. From this matrix, osteochondrogenic cells multiply in vivo . The joint can advantageously be made immobile for a certain period of time, allowing the multiplication of the osteochondrogenic cells without any mechanical constraint.

Once these osteochondrogenic cells (typically still in a relatively immature state) occupy the cell development space, the joint is mobilized to produce mechanical shear stresses within the formed cell volume. The shear plane thus produced will be located as close as possible to the mobility plane of the native joint.

This shearing movement is therefore generated in the space of cellular development, according to a cleavage plane of geometry identical to the natural mobility plane of the articular surfaces vis-à-vis the other.

Figures 2a to 2d schematically represent a rabbit femoro-tibial joint during successive stages of resection of the distal femur, then implantation of a periosteal graft and mobilization of the joint.

On the , before resection, the distal femur (right side of the ) comprises an articular cartilage surface 22, an epiphyseal subchondral bone 23 not shown in the figure, and a growth cartilage 24. A resection of the distal end of the femur is carried out at the level of the according to a PC resection plane, above the growth cartilage 24. A femoral defect is thus created between the tibia (left side of the ) and the rest of the femur. This femoral defect constitutes a volume in which a repair matrix 6 consisting of an autologous periosteal graft is implanted.

In addition, hinged external fixator pin passages 25 are drilled in the tibia and femur (here, a passage at the level of the tibia and a passage at the level of the femur are shown below the growth plates 24) to install a fixator. external articulated allowing initially the mechanical stabilization of the bone segments. The articulator is then placed in the locked position. Secondly, the articulator allows the mechanical mobilization of the femoro-tibial joint according to a plane close to the natural plane of mobility (the articulator then being placed in the unlocked position).

There represents the same joint at an early post-surgical time (a few days). As shown in this diagram, a matrix of osteochondrogenic cells grows into a cell space formed in place of the distal femur which was removed. Osteochondrogenic cells from the periosteal graft 10 and undifferentiated fill the space available between the rest of the femur and the tibia. It is also observed that the femoral growth cartilage 24 (right side of the figure) is activated here by tending to approach the tibial articular surface (towards the left), the growth cartilage will form a bony mass below it.

There represents the same joint at an intermediate post-surgical time, after the moment of the . The pins of the external fixator are fixed at the level of the pin passages 25 and the joint is mechanically mobilized, according to the directions of mobilization represented by the arrows of the . A biomechanical context of shearing of the osteochondrogenic cells is thus generated favorable to a differentiation of said cells towards chondrocytes at the surface (pathway C described above), and towards deep bone cells (pathway A described above). After a first mobilization, we thus observe the formation of a pre-cartilage 22bis facing the surface of the tibial cartilage 22, as well as the formation of a precursor of subchondral bone 23bis between the pre-cartilage 22bis and the cartilage of growth 24. At the end of the articular mobilization by the articulated fixator, for example after a period of 20 days of mobilization, one observes the formation of a new surface of femoral cartilage 22 on the surface of the regenerate, as illustrated on there . The geometry of the surface of the newly formed femoral cartilage 22 is very close to the geometry of the native femoral cartilage before resection and implantation of the periosteal graft.

There represents a series of real histological views at different magnifications, on which a rabbit knee joint (femorotibial joint) is visible after bone and cartilage repair. The views were acquired 20 days after the experimental surgical operation aimed at regenerating the lower end of the femur in its bony and cartilaginous components, by the implantation of a periosteal graft exposed in figures 2A to 2D.

On the left side of the , a femoro-tibial joint tibia is visible on a low area and a femoro-tibial joint femur is visible on a high area. The tibia 31 comprises a tibial growth cartilage 32 above which extend the epiphysis and the tibial plateau. The femoral region of osteoarticular regeneration 33 opposite the tibial plateau comprises a newly formed articular cartilage 34 on the surface and, deeper down, an endochondral cartilage 35. This upper part of the an ossification front 36 and a femoral growth plate 37. This histological view also shows the passage zone for a femoral fixation pin 38 which corresponds to one of the attachment points of the articulated external fixator .

On the upper right part of the , a histological view at a higher magnification has been shown, centered on the newly formed articular cartilage 34. This view makes it possible to observe the final phase of the reconstruction of the articular cartilage.

On the left side of this view, under a layer of perichondrium, one can observe an articular cartilage comprising the transitional and radial layers 34A. On this left side, no tangential layer is present on the surface of the transitional and radial layers 34A.

In the central part of this view, we observe a zone of "finalization" of the reconstruction, in which two sectors of tangential layer 34B are inserted in the thickness of the perichondrium.

On the right side of this view, there is a mature 34C cartilage visible on the surface. At this mature 34C cartilage, the tangential layer has connected with the underlying layers.

On the lower right part of the , a histological view at an even higher magnification is shown, centered on the tangential layer sectors 34B of the newly formed articular cartilage 34. The tangential layer sectors 34B are located under a layer of immature cells of the perichondrium, and are separated from the transitional layer by immature cells 39.

The experiments described above having validated the principle of articular cartilage repair using the implantation of a periosteum graft in the inter-articular space, followed by mechanical mobilization of the joint, we describe below a plurality of examples of articular implants implementing this principle in an improved manner.

Example 1 – Implant comprising two support plates embedded in the joint

There illustrates a joint implant according to a first embodiment, implanted in a femoro-tibial joint of a human patient. In the present example, two deteriorated sectors of cartilage are present on either side of a mobility plane P of the native joint. Two zones of cartilage 22 face each other, on either side of the natural plane of mobility of the joint P.

Each area of cartilage 22 here includes a damaged sector of cartilage. Each area of cartilage 22 extends over a subchondral bone 23. In the example of the , the subchondral bone 22 visible in the upper part of the figure is also damaged (lesions of the subchondral bone often associated with osteoarthritis as indicated above). Two interfaces I have been shown between each zone of cartilage 22 and the corresponding subchondral bone 23 .

Preferably, each zone of cartilage 22 (as well as possibly a part of the underlying subchondral bone 23) has been trimmed before the implant is placed. By "trimming" is meant a maneuver consisting in eroding the cartilage zone 22, so that the subchondral bone 23 is exposed. The trimming makes it possible to clean the deteriorated sector DA to be repaired, and makes it possible to optionally eliminate a "bead" which may be present on the edge of the deteriorated sector DA (such as the bead F of the ). The trimming process can give rise to micro-bleeding in the bone. Another advantage of trimming is that it creates micro-fractures at the level of subchondral bone 23 (subchondral cortical lamina and trabecular bone). Micro-fractures lead to minimal bone repair phenomena under the implant, with influx of new blood vessels and local release of growth factors.

Here, to promote the repair of the two damaged sectors of cartilage, the implant comprises two biocompatible supports 3 placed respectively on a first surface of bone 2 and on a second surface of bone 2a. Preferably, the first bone surface 2 and the second bone surface 2a are opposite each other. The two respective reception surfaces 4 of the two supports are here separated by an average distance L perpendicular to the cleavage plane P. It is recalled that the average total thickness of each of the two articular cartilages of an adult human femoro-tibial joint is about 5 millimeters.

A statistical analysis of the cartilage thicknesses of the ankle, knee and hip joints in humans is proposed in the following scientific publication: Thickness of human articular cartilage in joints of the lower limb , Shepherd, Seedhom, Ann Rheum Dis 1999 Jan ; 58(1): pp.27–34.

As will be detailed below, each support 3 comprises a receiving surface 4 which forms the bottom of a cell development space 60. The cell development space 60 is formed between the receiving surface 4 and a surface facing .

A receiving surface 4 is here formed on an upper face of the support 3 located on the femoral condyle, and another receiving surface 4 is here formed on a lower face of the support 3 located on the tibial plateau.

In the example of the , the cell development space 60 is thus delimited (locally perpendicular to the cleavage plane P) by the two reception surfaces 4, and is further delimited by contact edges 21 formed after trimming. The cell development space could be delimited directly by edges of the damaged cartilage area.

In addition, the implant initially comprises, as will be seen below, a repair matrix 6 placed above the receiving surface 4, in order to give rise to the multiplication of osteochondrogenic cells in the development space cellular 60.

• Biocompatible support

The support 3, formed from a biocompatible material, has the function of delimiting the cell development space 60 and of being implanted in the joint (here femoro-tibial) to allow the solicitation of the cells of the matrix according to the plane of P cleavage and direct the differentiation of cells present in cell development space 60.

In the example of the , each support 3 is embedded directly in a damaged area of cartilage, to repair said damaged area in situ. Ultimately, the support 3 is integrated into the joint. To do this, the support 3 can advantageously be formed from a resorbable material, in its entirety or for certain specific sectors. The support 3 can thus be integrated gradually into the joint, integrally with the cartilage zone 22 and with the subchondral bone 23.

The scientific publication Bioactive scaffolds for osteochondral regeneration , Deng, Chang, Wu, Journal of Orthopedic Translation (2019) 17, pp.15-25, lists materials of advantageous use in a biocompatible scaffold for implantation in the joint cavity. It is possible to envisage a support 3 composed of one or more materials chosen from the materials described in this document (see pages 19 and 20), namely polymer materials, materials based on extracellular matrix (ECM), bioceramic materials, biological glasses, biocompatible metallic materials. In the case of a support 3 made of resorbable material, one or more bioresorbable bioceramic(s) mentioned in the of this document, for example tricalcium phosphate called TCP, and/or a bioceramic/polymer mixture.

In another example, a majority material of the support 3 is a polymer material such as polyethylene and/or polytetrafluoroethylene called PTFE.

A shape of the support 3 suitable for easy placement and simple attachment to the bone surface is chosen. In the example of the , the supports can take the form of a thin plate (whose thickness in a direction substantially perpendicular to the cleavage plane P is small compared to an area of the receiving surface 4). The thin plate is then directly embedded in the damaged sector.

When the support 3 assumes such a thin plate shape, the support 3 preferably has a contact edge 31 which fits directly against the edges 21 formed after trimming at the level of the subchondral bone. Thus, the support 3 is placed in the continuity of the cartilage zone 22. Preferably, the support 3 is configured so that the receiving surface 4 is placed in the extension of the interface I between the cartilage zone 22 and the subchondral bone 23. An associated advantage is that the repaired cartilage then has a geometry close to that of the native cartilage before deterioration.

The contact edge 31 is preferably a closed contour. Preferably, the contact edge 31 extends all around the receiving surface 4, forming a periphery of the receiving surface 4. Said receiving surface 4 of the support 3 is thus completely integrated into the joint . For example, the thin plate of the support 3 is formed of at least one or more discoid parts or in the form of disc portions (depending on the geometry of the damaged sector).

The support 3 is preferably formed so that the receiving surface 4 best conforms with the geometry of the native bone/cartilage interface, with for example a more or less significant concavity, a more or less significant convexity, or more complex shapes with convexities or concavities of different radii in different planes of space.

Thus, very advantageously, the receiving surface 4 and the contact edge 31 precisely reproduce the geometry of the surface of the native articular cartilage requiring repair.

To accurately reproduce the geometry of the surface of the native articular cartilage, it is possible to acquire precise cartographic images of the state of the joint concerned in the patient before design and placement of the implant. To do this, standard radiography, arthroscanner, magnetic resonance imaging (MRI) (MRI in T2 relaxation time or in T1RHO) can be used. MRI imaging with so-called “dGEMRIC” (delayed Gadolinium-Enhanced MRI of articular Cartilage) acquisition sequences is also a powerful technique for establishing a 3D map of the state of the cartilage and calculating the surfaces that need to be repaired.

Very advantageously, when the support 3 is of the type directly embedded in the damaged sector as on the , the support 3 defines a plurality of through microcavities 8 which pass through the receiving surface 4, and which also pass through an underlying surface 5 of the support 3. The underlying surface 5 is opposite the receiving surface 4; the underlying surface 5 is for example either placed directly on the subchondral bone 23, or oriented towards a deteriorated zone of said subchondral bone 23.

Such crossing microcavities 8 put the cell development space 60 in direct communication with the layers of bone located under the cartilage, and possibly in direct communication with the bone marrow, said marrow also containing osteochondrogenic stem cells.

A first advantage is that blood vessels present in said layers of bone can vascularize and oxygenate the base of the cell development space 60.

In addition, these spaces locally confer mechanical stability to the stem cells of the cellular repair matrix, allowing them to engage in the A pathway of differentiation as illustrated in the . It is thus possible to generate volumes of subchondral bone inside the crossing microcavities 8, which promotes the regeneration of a new bone/cartilage interface close to the bone/cartilage interface of the native osteochondral unit .

One can for example form the through microcavities 8 by punching the support 3. In the present example, the thin plate forming each support 3 has a plurality of perforations, preferably regularly distributed over the surface of the thin plate. Alternatively, one or more void regions can be provided natively in the shape of the support 3. For example, if the support 3 is manufactured by 3D printing, the design of the 3D model of the support 3 can incorporate empty spaces in order to form the through microcavities 8 in the structure of the support.

With regard to the manufacture of the support 3 by 3D printing, reference may be made to the 3D printing techniques using biocompatible materials described (in particular on page 22) in the publication Bioactive scaffolds for osteochondral regeneration , Deng, Chang, Wu, Journal of Orthopedic Translation (2019) 17, pp.15-25, already cited above. In particular, one or more of the following techniques may be used: extrusion printing, laser printing, stereolithography, fused wire deposition (FDM), selective laser sintering (SLS), electro-spinning, etc.

It will be noted that the geometry of the underlying surface 5 opposite the receiving surface 4 can advantageously be adapted to the geometry of the surface of the subchondral bone 23, in particular if the latter is damaged and that "micro -geodes” or other convex and/or concave shapes are present in the subchondral bone.

For example, the underlying surface 5 visible on the reproduces the possible reliefs and hollows of the subchondral bone 23, so as to adapt to the underlying bone context of the implant. This improves the mechanical stability of the implant vis-à-vis the subchondral bone 23, in particular at the time of mobilization of the joint by a shearing movement as described above. The empty spaces present at the level of the underlying surface 5 are intended to be recolonized by bone tissue.

Optionally and advantageously (in particular in the case of a biocompatible support embedded directly in a subchondral bone surface), the shape of the underlying surface 5 is adapted to the surface of the subchondral bone 23 , and in particular to its reliefs and hollows, after the step of trimming the cartilage. This adaptation of the shape of the underlying surface 5 can advantageously be carried out by grinding the support, for example by the practitioner when placing the joint implant. An advantage is to guarantee an optimal correspondence between the concavities of the underlying surface 5 of the support and the concavities of the bony basement on the subchondral bone 23.

A support 3 of the type shown in the embedded directly in a damaged sector of the cartilage, after a possible procedure for trimming the damaged sector, has a number of advantages.

To improve the positioning and stability of the implant, it is possible to provide at least one fixing element 12 between the support 3 and the bone surface. Here, at least two oblique screws are used as fixation elements for each bracket 3, the oblique screws driving into the subchondral bone 23.

On the other hand, two supports 3 conforming for example to the example above can easily be embedded in two opposite articular sectors (here on the first bone surface 2 and the second bone surface 2bis), on both sides on the other side of the P cleavage plane. An advantage of this configuration is to simultaneously promote the repair of two damaged areas of cartilage, on both sides of the joint. However, the procedure for fitting the two supports 3 remains relatively non-invasive compared to the procedure for fitting a standard articular prosthesis.

To illustrate the procedure for laying the two supports 3 and repairing the damaged cartilage sectors, FIGS. 4a to 4d show annexed successive stages of installation and repair according to an example. Note that in these Figures 4a to 4d, the inter-articular space has been artificially enlarged for greater readability.

On the , the upper bone (femur) shows a deteriorated area DA extending into the cartilage area 22 and into the underlying subchondral bone 23. The lower bone (tibia), for its part, presents a deteriorated sector DB extending only inside the zone of cartilage 22. The two zones of deteriorated cartilage 22 present lateral beads F.

On the , the articular cavity is shown after trimming the damaged sectors DA and DB. A first bone surface 2 and a second bone surface 2bis are thus formed, suitable for receiving the supports 3. The bone surfaces receiving the implant are delimited by contact edges 21. Trimming thus makes it possible to obtain smooth walls to receive the implant. The beads F of the damaged cartilage are also removed.

Then, with reference to the , the actual placement of the implant is carried out. Each bone surface receives a support 3 at the interface between the cartilage and the subchondral bone. The contact edges 31 of the supports 3 are placed against the edges 21. Insofar as the supports 3 are here intended to be well fixed to the subchondral bone at the time of mobilization, as fixation elements 12 are used here oblique screws screwed into the subchondral bone 23. The elements for adaptation to the underlying bone context are schematized in a simplified manner on the , by cross shapes at the level of the underlying surface 5.

A repair die 6 is positioned in the space between the two receiving surfaces 4 of the two supports 3. Here, a single repair die 6 is used for the two supports 3; alternatively, each support could be provided with its own repair matrix.

The placement of the implant can for example be carried out by arthroscopy. This procedure is minimally invasive and the joint implant is well tolerated by the body.

We represented on the the result obtained after allowing the osteochondrogenic cells to multiply while the joint is left immobile for a period of a few days, in the cell development space 60 formed between the supports 3. Preferably, the osteochondrogenic cells come to fill the cell development space 60 both in the vicinity of the cleavage plane P and within the crossing microcavities 8.

Then, with reference to the , the joint is stressed mechanically, along the cleavage plane P (mobilization phase) and in the axis of interest for the joints of multidirectional mobility. In this example, a relative movement of the tibia relative to the femur is induced. The mechanical stressing of the joint can be carried out according to any known modality: stressing in physiotherapy, and/or use of a mechanical tool, etc.

After a certain time of solicitation, the osteochondrogenic cells present in the cell development space 60 begin to differentiate selectively towards the formation of articular cartilage.

Finally, we have represented on the the repair result obtained after the mobilization phase of the femoro-tibial joint. A repair result considered to be optimal has been illustrated: zones of repaired cartilage 22 have reformed in the continuity of the interfaces between the cartilage and the subchondral bone, in particular in the vicinity of the cleavage plane P, and the crossing microcavities 8 of the implant were filled with 23 volumes of subchondral bone.

Several preferential characteristics of the repair matrix 6 and of the optional stiffening elements 7 associated with the support 3 are detailed below.

• Cartilage repair matrix

The repair matrix 6 of the joint implant is intended to give rise to a volume of osteochondrogenic cells, developing in the cell development space 60 delimited by the support 3.

Preferably, before the placement of the implant, the repair matrix 6 takes the form of a solid cohesive element, not necessarily integral with the support(s) 3. During the placement of the support(s) 3, or just after said placement , the repair matrix 6 is superimposed on the receiving surface 4 of a support 3, possibly being sutured to the support 3. The repair matrix 6 is thus placed in a cell development space 60.

The repair matrix 6 then generates a multitude of osteochondrogenic cells.

Very preferably, when placing the implant, the repair matrix 6 comprises a periosteal graft. It is recalled that the periosteum and its biological function have been defined above.

Very advantageously (but not necessarily), the periosteal graft is a non-vascularized free graft. The periosteal flap then preferably has a maximum dimension less than a maximum dimension of the support 3. The graft can alternatively be a vascularized pedicled graft, or a combination of a non-vascularized graft and a vascularized graft if two grafts are used.

Also very advantageously, the periosteal graft results from an autograft. In other words, the cells forming the periosteal graft are autologous cells, from the same individual in which the joint implant is placed. The use of autologous cells promotes a much better tolerance of the osteochondrogenic cells, and ultimately of the chondrocytes of the repaired cartilage, by the body of the individual. Thus, cartilage regeneration is more effectively promoted and the risk of rejection is greatly reduced.

Preferably, the periosteal graft from which the repair matrix originates is taken in vivo from a healthy periosteum. In the example of the , the periosteum is for example taken from an area of anterior tibial periosteum. The procedure for harvesting a periosteal graft is easy and minimally invasive.

• Stiffening elements

Advantageously and not necessarily, at least one support 3 of the joint implant can be associated with a plurality of stiffening elements 7. One function of these stiffening elements 7 is to improve the directed differentiation of the cells generated from repair matrix 6.

Preferably, the cellular repair matrix which develops in space 60 has a “gel” type consistency.

This is why stiffening elements 7 make it possible to control more finely the rigidity of the repair matrix with respect to the shearing movement according to the cleavage plane P. Inside a volume occupied by the elements of stiffening 7 within the cell development space 60, a zone is created in which the stiffness of the repair matrix against shear is strictly greater than the stiffness of the repair matrix against shear in the vicinity of the cleavage plane P .

Preferably, a network of stiffening elements 7 is placed against the receiving surface 4 of the support 3. This network is for example positioned above this receiving surface 4, that is to say between this surface of reception 4 and the cleavage plane P. Thus, the matrix located at the bottom of the cell development space 60 is made more rigid.

The stiffening elements 7 thus induce the formation of a stiffness gradient within the implant, with decreasing stiffness from the support(s) 3 towards the center of the cell development space 60.

Such a stiffness gradient increases the effect of directed differentiation of osteochondrogenic cells towards chondrocytes, in order to better regenerate articular cartilage. Indeed, the osteochondrogenic cells close to the cleavage plane are induced to move more than the osteochondrogenic cells farther from the cleavage plane, which contributes to encouraging differentiation towards chondrocytes.

Preferably, each stiffening element 7 is of partially hollow structure, so that osteochondrogenic cells can position themselves there. Each stiffening element 7 takes for example the form of a thin three-dimensional crosspiece. The network of stiffening elements 7 can be obtained by 3D printing.

Advantageously, at least one stiffening element 7 is mechanically integral with the support 3. Preferably, the entire network of stiffening elements 7 is integral with the support 3.

By way of example, a stiffening element 7 in the form of a hollow grid can extend from the reception surface 4 of the support, in a direction of extension substantially perpendicular to the reception surface 4. The hollow grid can be formed of several perpendicular walls forming hollow parallelepiped cells, in which the osteochondrogenic cells can be contained. The repair matrix 6 can be laid on the upper surface of the hollow grid, while the lower surface of the hollow grid can follow the concavities of the surface of the subchondral bone. This embodiment for the stiffening element 7 is particularly relevant in the case where the support 3 is a thin plate embedded in the articular sector to be repaired.

In another example, in particular still for a support 3 in the form of a thin plate embedded in the bone, it is possible to use a plurality of unitary stiffening elements, each stiffening element being placed on a through perforation 8. The stiffening elements are formed of hollow rigid structures, for example of pyramidal shape and base parallel to the receiving surface 4.

In any one of the embodiments described above, the stiffening elements 7 are advantageously distributed regularly over the entire reception surface 4. When the repair matrix 6 is superimposed on the reception surface 4, the repair matrix 6 is preferably placed above the stiffening elements 7.

Example 2 – Implant comprising a single support embedded in an area to be repaired

There illustrates a joint implant according to a second embodiment, implanted in a femoro-tibial joint. Here again, in this example, two damaged sectors of cartilage are to be repaired on either side of a cleavage plane P.

Here, the deteriorated area of cartilage shown on a lower part of the extends over a larger area than the extension area of the opposite damaged sector.

In this second example, on the damaged sector illustrated on the lower part, a support 3 similar to the supports described above in relation to Example 1 is affixed. A receiving surface 4 is thus formed and delimits the bottom of a cell development space 60, preferably in the continuity of the interface between a zone of cartilage 22 and the underlying subchondral bone 23.

In this second example, unlike Example 1, no additional support is placed in the opposite damaged area. In other words, the joint implant here comprises a single support 3. Here, the support 3 is of the type embedded in the bone.

Thus, the cell development space 60 is delimited here by the reception surface 4 and the bone surface 2bis located opposite. The cell development space 60 is directly formed between the support 3 and the bone surface located opposite.

On the , the two deteriorated sectors of cartilage (located at the top and bottom) were trimmed before placing the implant. Thus, the cell development space 60 is delimited, on its upper part, by the bone surface 2a produced by trimming. Alternatively, said space could be delimited by a bone surface without trimming.

An implant according to Example 2 is advantageous in particular in the case where a zone of cartilage that is heavily damaged, and/or damaged over a large surface, is located opposite a zone of cartilage that is slightly damaged, and/or damaged over a smaller surface. . By using a single biocompatible support instead of two supports, the implant placement procedure is simplified, while allowing the formation of repaired cartilage on both sides of the cleavage plane.

In this case, the stiffness gradient is achieved inside the cell development space on the side without the implant, thanks to the “porous” three-dimensional structure of the subchondral bone. The pores of the subchondral bone constitute a space of stability for the osteochondrogenic cells during the mobilization of the joint, while the implant is in place.

Example 3 – Implant comprising a single embedded support facing a prosthetic mesh

There illustrates a joint implant according to a third embodiment, implanted in a femoro-tibial joint. Here, a single sector of cartilage is considered as a damaged sector to be repaired (sector located on the upper part of the ). The opposite cartilage is considered to be intact cartilage.

Integral cartilage does not require repair, so no additional support is placed in this intact cartilage. In other words, the joint implant here comprises a single support 3, similar to the supports described above in relation to Examples 1 and 2. Again here, the support 3 is of the type embedded in the bone.

According to a first preferential variant, before the joint mobilization phase, a prosthetic mesh 9 is placed on all or part of the bone surface 2a of the intact cartilage located opposite the support 3. The prosthetic mesh 9 is for example affixed simultaneously with the installation of the support, or just after the installation of the support. Here again, the deteriorated sector of cartilage has preferably been trimmed before placement of the support.

The prosthetic net 9 is interposed between the support 3 and the facing cartilage surface 2a, so that the cell development space 60 is delimited by the receiving surface 4 of the support 3 and by the surface 2a, while the osteochondrogenic cells advantageously colonize the inside of the meshes of the prosthetic net 9.

The prosthetic mesh 9 is formed from a biocompatible material. In a preferred example, a material of the prosthetic net 9 is a material commonly used to manufacture nets for the treatment of hernias, for example polypropylene and/or polyester. It is preferably a very flexible material that can easily conform to the geometry of the surface 2bis. For example, the prosthetic net 9 has a general mesh structure.

Preferably, the prosthetic net 9 is removable and can be easily moved or removed from the surface 2bis. During the procedure, the prosthetic mesh 9 is preferably secured to the surface 2bis so as to move with the bone segment during the mobilization phase.

An advantage of such a prosthetic mesh is to stiffen the repair matrix in the area of the cell development space 60. If the prosthetic mesh 9 is used in combination with stiffening elements 7 placed on the support 3, one forms thus two zones of high stiffness against shearing, on either side of the cleavage plane. This contributes to favoring the formation of chondrocytes.

By way of illustration, FIGS. 7a to 7d schematically represent successive stages of placing an implant according to Example 3 and of repairing the cartilage.

On the , after having trimmed the deteriorated sector of cartilage (upper part), a support 3 is embedded on the bone surface, here along the interface I between the cartilage zone 22 and the subchondral bone 23. places a repair matrix 6 on the support 3, typically a free flap of periosteum. Simultaneously, a prosthetic net 9 of the type described above is placed on the opposite bone surface. The prosthetic net 9 is temporarily secured mechanically with the corresponding bone surface.

Figures 7b and respectively illustrate steps similar to the steps previously described in relation to Figures 4d and 4e. On the , osteochondrogenic cells develop in cell development space 60. On the , the femoro-tibial joint is stressed along the cleavage plane P, by exerting shear stresses. By directed differentiation of osteochondrogenic cells, a 22bis pre-cartilage is formed near the P cleavage plane.

Finally, on the , it is considered that the deteriorated area of cartilage has been repaired. A repaired cartilage has formed over the support 3. The repaired cartilage is thus permanently integrated into the joint. Very advantageously, the prosthetic mesh 9 is then removed by separating it from the bone surface 2a. Any osteo-cartilaginous cellular elements integrated into the meshes of the net are taken away by the withdrawal of the prosthetic net 9, leaving the underlying pre-cartilage 22a intact. Thus, it is not necessary for the constituent material of the prosthetic net 9 to be a resorbable material.

Example 4 – Implant comprising a removable support placed next to an area to be repaired

There illustrates a joint implant according to a fourth embodiment, implanted in a femoro-tibial joint. Here, a single sector of cartilage (on an upper part of the figure) is considered as a damaged sector to be repaired.

Unlike the preceding Examples 1, 2 and 3, the biocompatible support 3 is here placed not at the damaged sector DA of cartilage to be repaired, but facing said damaged sector DA. Thus, the reception surface 4 delimits a bottom of a cell development space 60 opposite the damaged sector DA.

Very preferably, the support 3 is placed on a bone surface 2 corresponding to healthy and intact cartilage. This Example 4 is therefore particularly suitable for repairing a damaged sector DA located in front of a surface of healthy cartilage. The support 3 is here superimposed on a tibial plateau.

To accommodate support 3, the femoro-tibial joint has here been advantageously unfitted. The “decoaptation” of the joint refers to the operation consisting in removing by external manipulation of the joint the opposite bone surfaces on both sides of the joint cavity. Here, the joint has preferably been decaptured before placing the removable implant.

At the end of the decaptation, the bone surfaces face each other. Anatomical integrity is preserved.

Unlike Examples 1, 2 and 3 above, the biocompatible support 3 here does not have the form of a perforated thin plate.

Here, the support 3 has the shape of a base, advantageously matching the profiles of the femoral articular surface, and extends over a larger surface than the surface of the deteriorated sector DA of cartilage. To form a cell development space 60 facing the damaged sector DA, the support 3 comprises a recess 13. The receiving surface 4 is positioned at the bottom of the recess 13.

Due to the presence of the recess 13, the receiving surface 4 is set back from the contact surfaces 14 of the support 3. Preferably, the contact surfaces 14 are, for their part, in contact with the 2bis surface of the healthy cartilage lateral to the deteriorated zone.

Thus, in this Example 4, the cell development space 60 is delimited by the receiving surface 4, by the bottom of the damaged sector DA of cartilage, and by a peripheral edge 15 of the recess 13.

Preferably, a network of stiffening elements 7 is arranged on the receiving surface 4, inside the recess 13, as illustrated in the . The stiffening elements 7 are for example in accordance with the description above. The repair matrix 6 is then positioned on the stiffening elements 7 before the mobilization of the joint. It is not necessary here that the bottom of the support 3 has crossing microcavities. Preferably, the receiving surface 4 is continuous.

Alternatively, the repair matrix 6 could be superimposed directly on the receiving surface 4 made at the bottom of the recess 13.

Very advantageously, the support 3 is secured to the first bone surface 2 in a removable manner. Fixing elements (staples and/or hooks and/or screws) can be used to secure the support 3, for example on a non-bearing zone of healthy cartilage. The support 3 is for example provided to be maintained in the joint for a period of between 5 days and 30 days, preferably between 10 days and 20 days. The implant can then be removed, by separating the support 3 from the bone surface 2.

It will be understood that the support 3 is not necessarily formed here in a resorbable material, since the implant according to the present Example 4 is intended to be removed.

Preferably, the support 3 adapts to the morphology of the joint: for example, the underlying surface 5 has a shape complementary to the shape of the bone surface 2 and/or the contact surfaces 14 have a shape complementary to the shape of the surface 2a. Such a complementarity of shape between the bone and the support ensures ease of placement of the implant and improves comfort for the patient during the procedure, while facilitating the mechanical mobilization of the joint.

It is illustrated in dotted lines on the part of the joint's natural mobility plan. Before multiplication of the osteochondrogenic cells, the repair matrix 6 is preferably positioned close to this cleavage plane. To illustrate the phase of mechanical mobilization of the joint, we have shown on the and on the a relative displacement of the surface 2 and of the surface 2bis. During this relative movement, the damaged sector DA of cartilage moves relative to the support 3 bearing the receiving surface 4.

On the , support 3 is moved to the right and damaged sector DA is moved to the left. Conversely, on the , support 3 is moved to the left and damaged sector DA is moved to the right.

By alternating between a position that conforms to the and a position consistent with during mobilization of the joint, rapid shearing movements are generated within the cell development space 60. The shearing movements are made along the cleavage plane. Osteochondrogenic cells are therefore encouraged to differentiate in a way directed towards the chondrogenic pathway (pathway C of the ), in order to form healthy repaired cartilage.

Thanks to the specific structure of this removable biocompatible support, the proposed implant is easy to place and is also easy to remove once a repaired cartilage has been obtained in the area previously occupied by the damaged sector DA of cartilage.

Advantageously, neither the placement nor the removal of the implant are very invasive procedures. For example, a period of between 10 and 20 days may elapse between the placement of such an implant and the removal of such an implant.

In the event of deterioration of the two articular cartilages facing each other, it is possible to proceed sequentially with the positioning of two implants in accordance with this Example 4 respectively on one and the other of the deteriorated sectors of cartilage. For example, a first support 3 is placed on surface 2, then a second support (for example of identical design to first support 3) is placed on surface 2bis.

Example 5 – Implant comprising a removable support associated with an embedded support

There illustrates a joint implant according to a fifth embodiment, implanted in a femoro-tibial joint. Here again, a single sector of cartilage (on an upper part of the figure) is considered as a sector to be repaired.

As in the previous Example 4, a removable support 3 is positioned opposite the damaged sector of cartilage. This removable support 3 is placed on a bone surface 2 corresponding to a healthy and intact cartilage surface. This removable support 3 has a receiving surface 4 which delimits a bottom of a cell development space 60 opposite the damaged sector DA. In Example 5, the removable support 3 is temporarily fixed on the cartilage surface 22 and in the underlying subchondral bone 23, using screws 12. The screws 12 are preferably oriented obliquely to an axis perpendicular to the joint's natural plane of motion.

However, the removable support 3 is not placed directly opposite the damaged sector DA here, but is placed opposite an additional biocompatible support of the type presented above in relation to Examples 1, 2 and 3. This latter support is possibly designed in a resorbable material and made to integrate under the repaired cartilage, within the joint.

The removable support 3 thus forms a first receiving surface 4 on one side of the cleavage plane of the joint, and the additional support embedded in the bone forms a second receiving surface on the opposite side of the cleavage plane. In this Example 5, the cell development space 60 therefore extends between the first receiving surface and the second receiving surface.

The removal of the removable part of the implant is a simple act. The joint action of the removable part of the implant (support in the form of a base having a recess) and the non-removable part of the implant (support in the form of a thin plate intended to be integrated into the joint) allows to achieve a stiffness gradient within the cell development space and thus promote the directed differentiation of osteochondrogenic cells towards the formation of new intact cartilage.

Claims (19)

An implant for the repair of articular cartilage, the implant comprising:
- a biocompatible support (3) configured to be placed above a first bone surface (2),
the support (3) comprising a reception surface (4) configured to delimit a bottom of a cell development space (60), the cell development space (60) thus formed extending between the reception surface (4 ) and a second bone surface (2a) located opposite the first bone surface (2),
- a repair matrix (6) superimposed on the receiving surface (4), the repair matrix (6) comprising a volume of osteochondrogenic cells intended to develop in the cell development space (60). Implant according to Claim 1, in which the support (3) has a contact edge (31) intended to be embedded in an edge of a bone cavity (21) of the first bone surface (2), preferably in a bone cavity (21) formed by trimming. Implant according to claim 2, wherein the contact edge (31) forms a periphery of the receiving surface (4). Implant according to any one of claims 1 to 3, in which the support (3) comprises an underlying surface (5) opposite the receiving surface (4), the support (3) defining a plurality of through micro-cavities ( 8), each said microcavity passing through the receiving surface (4) and the underlying surface (5). Implant according to Claim 4, in which the through microcavities (8) comprise at least one punching and/or comprise at least one void region, the void region then being preferably formed by 3D printing. Implant according to any one of claims 1 to 5, the implant further comprising a network formed by a plurality of stiffening elements (7) placed against the receiving surface (4), a stiffness against shear at stiffening elements (7) being strictly greater than a stiffness against shearing at the level of a central zone of the cell development space (60). Implant according to Claim 6, in which at least one stiffening element (7) is mechanically integral with the support (3). Implant according to any one of claims 6 or 7, in which the repair matrix (6) is placed against the stiffening elements (7) over more than 50% of a total surface of the repair matrix (6), preferably more than 80% of said surface. Implant according to any one of Claims 1 to 8, in which the first bone surface (2) and the second bone surface (2a) belong to a joint of an individual, a concavity of the receiving surface ( 4) being configured to correspond to a concavity of a natural plane of mobility (P) of said articulation. Implant according to any one of Claims 1 to 9, in which the repair matrix (6) comprises a periosteal graft, preferably a free non-vascularized periosteal graft, even more preferably a periosteal graft derived from a tibial periosteum. Implant according to any one of claims 1 to 8, the implant comprising at least one fixation element (12) configured to mechanically stabilize the support (3) with respect to the first bone surface (2). Implant according to claim 11, wherein the fixation element (12) comprises a screw, preferably an obliquely positioned screw, and/or comprises a staple and/or comprises a hook. Implant according to any one of claims 1 to 12, the implant comprising a prosthetic net (9) configured to be inserted between the support (3) and the second bone surface (2a), and configured to delimit with the surface receiving (4) the cell development space (60), the prosthetic mesh (9) preferably being removable. Implant according to any one of claims 1 to 13, in which the support (3) is configured to overlap the first bone surface (2) in a removable manner. Implant according to Claim 14, in which the cellular development space (60) is defined inside a recess (13) made in the support (3), the receiving surface (4) being positioned at the level of a bottom of said recess (13). Implant according to any one of claims 1 to 15, in which a majority material of the support (3) is a resorbable material configured to gradually integrate on the first bone surface (2). Implant according to any one of claims 1 to 16, in which a majority material of the support (3) is a polymer material, said polymer material preferably being polyethylene or polytetrafluoroethylene called PTFE, or is a bioceramic material. Implant according to any one of Claims 1 to 17, in which the support (3) is manufactured by 3D printing. Implant according to any one of Claims 1 to 18, in which the support (3) is intended for placement:
- on a surface of the femoro-tibial joint,
- or on a surface of the patellofemoral joint,
- or on a surface of the talocrural joint,
- or on a surface of the glenohumeral joint,
- or on a surface of the acromioclavicular joint,
- or on a surface of the coxo-femoral joint.