IMPLANTABLE DEVICE COMPRISING EXTERNAL MOBILIZATION MEANS FOR FORMATION OF ARTICULAR CARTILAGE - Patent application

Abstract

The present invention relates to a removable implantable device for the generation of articular cartilage, comprising a first support part (2) made of a biocompatible material, a second support part (3) made of a biocompatible material and movably attached to the first support part (2), the first support part (2) and the second support part (3) defining between them a cavity forming a cell expression space (40), the cell expression space (40) being provided for receiving osteochondrogenic cells proliferating within the cell expression space, and operable external mobilization means (5A, 5B) configured to move the second support part (3) relative to the first support part (2) in order to generate shear inside the cell expression space.

Description

[Technical field]

[0001] The present invention relates to an implantable device intended to induce the formation of articular cartilage to replace said areas of deteriorated cartilage, preferably suited to the individual's deteriorated articular cartilage morphology.

[0002] The invention relates in particular to an implantable device suitable for carrying out the formation of a specific cell layer of articular cartilage, the implantable device being combined with a cellular repair matrix, the repair matrix preferably comprising a periosteal graft. [Background technology]

[0003] Articular cartilage damage (or "cartilage disease") manifests as the breakdown of one or more cartilage surfaces, thereby losing their mechanical properties for protection of bone surfaces and damping of mechanical stresses in the joint. Untreated cartilage disease in humans can deteriorate into advanced osteoarthritis, causing significant chronic pain, which can become very severe, especially in elderly patients.

[0004] In the knee example, during natural walking or crouching movements, the pressure on the knee joint between the femur and the tibia is very high, and if the mobility and damping function of the articular cartilage is not maintained, these natural movements become painful.

[0005] Such lesions of articular cartilage may be located only on one of the two opposing articular surfaces, but both opposing articular cartilage surfaces may be affected. The cause of joint lesions is either age-related wear of the cartilage (osteoarthritis) or, especially in young people, joint trauma related to impacts or accidents. In current medical practice, the severity of cartilage diseases is assessed clinically by ICRS functional score and radiologically (MRI) by ICRS grade or by the Outerbridge classification.

[0006] The known prior art includes numerous therapeutic approaches for patients suffering from cartilage diseases. In early forms of osteoarthritis, anti-inflammatory treatments are proposed, either by systemic administration or by local injection. Intra-articular injections are also known, for example injections of hyaluronic acid (called "viscosupplementation") or injections of platelet-enriched plasma. Less invasive treatments under arthroscopy may also be proposed, such as joint lavage with debridement, the Pridie microdrill technique, microfracture techniques, or the use of a three-dimensional matrix made of collagen and hydroxyapatite.

[0007] However, the above mentioned procedures often lead to temporary results at the clinical level and uncertainty in the formation of new cartilage. Histologically, the cartilage formed in this manner is of poor quality.

[0008] Another known approach consists in transplanting one or more healthy osteochondral segments directly from the joint of the individual to be treated into a segment of the joint to be treated in the same individual (by "osteochondral autotransplantation"), in which case an osteochondral core is harvested, for example, from a non-weight-bearing area of ​​the joint to be treated and transferred to the segment requiring repair.

[0009] FIG. 1a shows an osteochondral autograft in the femoral condyle for treating the knee joint of a human individual (Reprise du sport apres autogreffe osteochondral en graft femoral condyles: 25 cas a 9 ans de recul moyen, Cognault, Seurat, Chaussard, Ionescu, Saragaglia, Revue de chirurgie orthopedic et traumatologique 101(2015) pages 215-220).

[0010] Figure 1a illustrates the "mosaicplasty" technique. Multiple cores 13 (four cores in this case) previously taken from the same individual are implanted in a mosaic arrangement into the damaged joint surface. Each core 13 includes a cartilage surface and an underlying thickness of subchondral bone. The cores 13 preferably have a diameter of approximately 7 or 8 millimeters and a length of approximately 15 millimeters.

[0011] However, the number of "donor" sites, i.e. non-weight-bearing joint areas, suitable for core harvest is limited, and therefore such osteochondral autograft techniques address the treatment of limited articular surface lesions (typically less than 3 cm2).

[0012] Another approach, called "osteochondral allografting," involves healthy osteochondral sections from another individual different from the one being treated. This technique is suitable for treating larger surface joint lesions using large amounts of osteochondral grafts.

[0013] However, this technique is currently difficult to implement because osteochondral harvesting must be performed on human cadavers less than 12 hours after death.

[0014] Figure 1b shows an example of an osteochondral core 13bis, for example intended for articular osteochondral allografts. The core 13bis is shown in isolation after harvesting and before implantation into a patient. The length of the core 13bis is in this case approximately 4 centimeters.

[0015] Given the limitations of the techniques presented above in connection with Figures 1a and 1b, it has been proposed to perform arthroplasty (implantation of an artificial joint) in cases of advanced osteoarthritis in humans. Joints frequently treated in this manner include, in particular, the hip and knee joints. In cases of advanced cartilage disease of the knee, a definitive unicompartmental or total knee prosthesis is frequently implanted surgically under anesthesia and permanently fixed.

[0016] International patent application with publication number WO2005 / 016175A2 describes a definitive artificial joint designed with a rigid biocompatible material that is directly implanted into the affected joint cavity to restore the expected mechanical properties of the joint. However, for such permanent artificial joints, long-term re-education of the joint must be performed. Substantial treatment in specialized centers, including physiotherapy sessions and symptomatic treatment, is often necessary.

[0017] There is also a serious risk of loss of the mechanical functionality of the artificial joint over time due to mechanical wear of the components of the artificial joint and / or due to infection of the prosthetic material.

[0018] From the above, it can be stated that, in the current situation, current surgical practices and techniques do not allow a completely satisfactory restoration of sufficient quality and durability of the articular cartilage and / or present the risk of infection and / or mechanical wear of the implantable device. In addition, some of these treatments from the known prior art require extensive medical and surgical therapy.

[0019] Thus, known approaches do not adequately address the public health challenge of treating joint pain and impaired joint mobility associated with cartilage lesions. Summary of the Invention

[0020] Thus, there is a need for implantable devices that can promote the generation of new areas of articular cartilage to replace areas of deteriorated cartilage in joints, particularly in the knee (femoral-tibial or patellofemoral joint) or in the human hip joint.

[0021] A desirable device should allow the formation of new osteochondral tissue, advantageously including a section of articular cartilage and a layer of subchondral bone.

[0022] To obtain good quality osteochondral tissue, the newly formed cartilage must contain the different layers of chondrocytes characteristic of articular cartilage (superficial, intermediate, radial and calcified cartilage layers). These different functional layers of articular cartilage are described in terms of structure and cellular composition in the following publication: Composition and Structure of Articular Cartilage: A Template for Tissue Repair, Poole, Kojima, Yasuda, Mwale, Kobayashi, Laverty, October 2001, Clinical Orthopaedics and Related Research 391(391): S26-S33.

[0023] A desirable device should have good surgical maneuverability and not require excessive medical intervention for its implantation. Preferably, the device should be easy to implant while allowing for the repair of a larger surface articular area compared to osteochondral autograft techniques.

[0024] Preferably, the desired device should induce the formation of new areas of cartilage, the geometry of which is well suited to the particular morphology of the joint to be treated. The surface of the repaired cartilage should have a geometry very close to that of the native cartilage, making it possible to meet the geometric criteria for optimal movement and to avoid new wear of the patient's cartilage after treatment.

[0025] A secondary objective is to provide a device that allows for the generation and implantation of newly formed cartilage segments in two areas of damaged cartilage on two opposing sides of the same injured joint.

[0026] In order to address the above-mentioned needs, a first aspect of the present invention provides a removable implantable device for generating articular cartilage, comprising: A first support made of a biocompatible material; a second support made of a biocompatible material and movably attached to the first support, the first support and the second support defining a cavity therebetween that forms a cell expression space, the cell expression space being provided to receive osteochondroprogenitor cells that grow within the cell expression space; and an operable external mobilization means configured to move the second support relative to the first support to generate shear inside the cell expression space.

[0027] The implantable device as defined above is intended to allow the formation of autologous osteochondral tissue immediately after implantation in an anatomical region, preferably different from the joint to be treated.

[0028] The implantable device is removable and is temporarily implanted in a cell-receptor space, preferably an intramuscular or subcutaneous area, of an individual, which is preferably separate from the joint to be treated.

[0029] One advantage of such a device is that, at the end of the external mobilization phase of the device, it allows the formation of osteochondral tissue with a geometry that matches the surface of the cartilage that needs to be repaired. The formed tissue can then be removed from the biocompatible support that helped to generate it and implanted into the joint to be treated.

[0030] The osteochondral tissue that is formed is then transplanted into the joint to be treated, for example, in a manner similar to the autograft or allograft techniques described above.

[0031] Optionally, and in a non-limiting manner, the implantable device according to this first aspect may have the following features, taken alone or in any technically feasible combination: The device comprises a closed housing formed by a first support and a second support, and a cell expression space is defined inside the housing. the first support includes an inner surface facing the second support, the second support being configured to slide relative to the first support along the inner surface; the second support is mounted so as to be translationally movable relative to the first support in a direction parallel to the extension surface of the inner face; the second support is rotatably mounted relative to the first support about an axis of rotation; At least one of the first support and / or the second support comprises a cylindrical side extending around the axis of rotation. the support further comprises a substantially vertical base on its side, the external mobilisation means comprising a handle which is forced to rotate together with the base and is rotatable about an axis of rotation. the external mobilisation means comprises at least one mobilisation string attached to the second support and configured to tow the second support; The mobilization cord is attached to a first outer surface of the second support. the device includes an additional articulated link attached to a second outer surface of the second support, the second outer surface being opposite the first outer surface. The mobilization string comprises a semi-rigid strand, preferably a strand made of a polymeric material. The device includes a slide configured to guide movement of the second support relative to the first support. At least one of the first support and / or the second support comprises a lattice. The lattice defines a number of cell growth cavities that open to the interior of the device. At least one of the first support and / or the second support comprises a network of stiffening elements fixed to said support. The shear stiffness in the stiffening element is indeed greater than the shear stiffness in the central region of the cell expression space.

[0032] A second aspect of the present invention is an implant for the generation of chondrocytes, comprising: An implantable device as defined above; The present invention relates to an implant comprising: a cellular repair matrix interposed between a first support portion of an implantable device and a second support portion of the implantable device, the cellular repair matrix comprising a large number of osteochondrogenic cells intended to proliferate within a cell expression space of the implantable device.

[0033] Optionally, and in a non-limiting manner, the implant according to this second aspect may have the following features, taken alone or in any technically feasible combination: The cellular repair matrix comprises at least one periosteal graft. -The periosteal graft is vascularized. -The periosteal graft is derived from the periosteum of the tibia. The implant is configured to be removably implanted into an intramuscular region of an individual. The implant is configured to be removably implanted into a subcutaneous region of an individual.

[0034] Other features, objects and advantages of the implant shall become apparent from the following description, which is given entirely by way of illustration and not by way of limitation and should be read with reference to the accompanying drawings, in addition to the already described Figures 1a and 1b, in which: [Brief description of the drawings]

[0035] [Figure 1a] FIG. 1 shows osteochondral autografting on the femoral condyle for treating the knee joint of a human individual. [Figure 1b] FIG. 1 shows an example of an osteochondral core 13bis for the purpose of articular osteochondral allotransplantation. [Diagram 2] FIG. 1 is a diagram illustrating diagrammatically three pathways for differentiation of mesenchymal stem cells into bone or fibrous or cartilage articular tissue depending on the mechanical stress applied to the mesenchymal stem cells. [Diagram 3]FIG. 13 is a schematic illustrating multiple sequential implantation steps: implantation according to an example of the invention in the intramuscular region, followed by mobilization of said implant by external links to promote the formation of new cartilage, followed by explantation of the device and transfer of the generated osteochondral structure to a recipient joint. [Figure 4a] FIG. 1 is a schematic perspective view from above of an implantable device according to a first exemplary embodiment, the device having the form of a parallelepiped housing, a first part of the device and a second part of the device being represented separately from each other, in which case a periosteal stalk graft is attached to the first part. [Figure 4b] FIG. 2 illustrates the same implantable device in a closed position, with the first and second portions mated one on top of the other. [Diagram 5] FIG. 4b is a schematic cross-sectional view (along plane AA shown in FIG. 4b) of the device of FIG. 4b while a periosteal graft is placed within the cell expression space. [Figure 6] FIG. 4b is a longitudinal cross-sectional view (along plane BB shown in FIG. 4a) of the device of FIG. 4b illustrating the relative movement of the first and second support portions and the expression of osteochondroprogenitor cells. [Figure 7] FIG. 4b is a schematic cross-sectional view of the device of FIG. 4b after mechanical mobilization of said implantable device, with the creation of two portions of osteochondral tissue inside the device, one convex and the other concave. [Figure 8] FIG. 2 is a diagram illustrating, in schematic form, the separation of a first support from a second support and from two portions of newly formed osteochondral tissue extracted from the two supports, the implantable device corresponding to the example of FIGS. 4a and 4b. [Figure 9] FIG. 2 is a schematic cross-sectional view of an implantable device according to a second exemplary embodiment, the device having the form of a parallelepiped housing with a curve and intended to generate a single portion of osteochondral tissue having a concave surface in the upper element. [Figure 10]FIG. 13 is a schematic longitudinal cross-sectional view of an implantable device according to a third exemplary embodiment, which, when implanted, has the general shape of a cylindrical housing and is implanted into a muscle, said device intended to generate two portions of newly formed osteochondral tissue having a flat shape facing each other. [Figure 11] FIG. 11 is a schematic longitudinal cross-sectional view of the device of FIG. 10 during mechanical mobilization of the device while osteochondroprogenitor cells are growing. [Figure 12] FIG. 13 is a schematic longitudinal cross-sectional view of an implantable device according to a fourth exemplary embodiment, the device having the general shape of a quasi-cylindrical housing, one base of which is convex and the other base of which is concave, the device being intended to generate a single portion of newly formed osteochondral tissue having a convex surface on the lower element. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0036] The examples of implantable devices described below are preferably intended for the formation of new cartilage which will then be implanted in the knee (femoral-tibial or patellofemoral joint) or hip joint, particularly in humans.

[0037] However, the various examples of implantable devices described below are adaptable to promote the generation of new areas of cartilage for any articular surface in the human or animal body.

[0038] The following example provides the use of a periosteal graft as a suitable repair matrix for generating osteochondrogenic cells inside the space provided in the implantable device. As seen below, the periosteal graft used is preferably harvested from the same individual and may or may not be vascularized.

[0039] However, it should be noted that other types of cell repair matrices known in tissue engineering may be used, which may or may not be combined with substances or compositions, such as proteins, growth factors, etc., that aid in the growth and directed differentiation into chondrocytes.

[0040] In all of the accompanying figures and throughout the following description, like elements are given the same alphanumeric reference numerals.

[0041] General principles for the formation of de novo articular cartilage Articular cartilage is a flexible connective tissue present within joints, which performs the mechanical functions of protecting the ends of bones, attenuating the stresses of loads on the bone ends, and ensuring the harmonious sliding of opposing articular surfaces.

[0042] Articular cartilage consists mainly of cells called chondrocytes and of an extracellular matrix (collagen, glycosaminoglycans). The function of chondrocytes is the synthesis and maintenance of cartilage tissue. They are located in compartments, each of which contains one or more chondrocytes. These compartments are called chondroblasts. Areas of cartilage can be deteriorated by various pathologies that affect cartilage. The natural repair of articular cartilage is very inefficient. The development of chondral lesions is complicated by cartilage cracks, reduction in the thickness of the cartilage, and lesions of the subchondral bone. Such development can lead to the complete disappearance of the cartilage with exposure of the subchondral bone (dentinization).

[0043] Articular cartilage is present especially on the epiphyseal surface of long bones. Chondrocytes are derived from the differentiation of stem cells located in the uppermost layer of articular cartilage in adults. However, chondrocyte regeneration is very slow and this tissue is very difficult to repair.

[0044] Long bones, except for the cartilaginous regions, are covered by a membranous surface called the "periosteum", which ensures bone repair in the event of fracture.

[0045] The periosteum is especially rich in repair stem cells for skeletal tissues (chondrogenic mesenchymal stem cells). For a detailed description of the composition and role of the periosteum, the following publication can be referenced: Periosteum contains skeletal stem cells with high bone regenerative potential controlled by Periostin, Duchamp de Lageneste et al., Nature Communications, February 2018 22; 9(1): 773.

[0046] Faced with the difficulty that the body has in spontaneously repairing articular cartilage in damaged areas of the articular surface, the device proposed here aims to reconstruct in the deteriorated areas an osteochondral tissue that is qualitatively and geometrically equivalent to the original articular cartilage (initial state before deterioration). The reconstruction of the osteochondral tissue is achieved by osteochondrogenic cells (typically from an autologous periosteal graft, as will be seen below).

[0047] The differentiation of mesenchymal stem cells into different types of connective tissues depends in particular on the mechanical stresses in the mesenchymal stem cell's environment. The study of these stresses falls within the more general context of "mechanobiology", which studies the influence of local mechanical factors on cell differentiation pathways.

[0048] By way of illustration, accompanying FIG. 2 shows three pathways A, B and C of differentiation of mesenchymal stem cells.

[0049] Starting from a large amount of still immature osteochondrogenic cells10, it is possible to influence the differentiation pathway and thus the phenotype and native functionality of the newly formed tissue through mechanical stresses applied to the cell volume.

[0050] In "pathway A", the cells are "free" and are not subjected to mechanical stress (or minimal stress). The osteochondrogenic cells then preferentially generate bone cells / osteocytes 11A. A clinical illustration of this pathway A is the future of a fracture site that has been properly stabilized by a cast or by an orthopedic assembly. The fracture site (fracture callus) is early populated by osteochondrogenic cells derived from the periosteum or bone marrow, which differentiate into bone (generally after passing through an endochondral state).

[0051] In "pathway B", a stretching force FB is applied in a preferred direction. The formation of fibrous tissue 11B (tissue that constitutes the ligament) is then observed. A clinical illustration of this pathway B is, for example, the surgical reconstruction of the lateral ligament of the ankle with a periosteal flap taken from the fibula.

[0052] Finally, in "pathway C", a shear force FC is applied, displacing the upper part of the osteochondrogenic cell volume to the left and the lower part of said volume to the right. To the best of the applicant's knowledge, this differentiation pathway C promoting osteochondrogenesis has not been addressed to date in nature or in medical-surgical practice. Thus, the proposed device relies on a shear motion applied to a cell volume, promoting the directed differentiation of osteochondrogenic cells towards the formation of chondrocytes to ultimately obtain a section of articular cartilage.

[0053] After directed differentiation of osteochondroprogenitor cells via pathway C, a new cartilage surface 11C is obtained, which in this case extends from one side to the other along the cleavage plane.

[0054] Various examples of implantable devices described below aim to drive directed differentiation of immature osteochondroprogenitor cells along a cell differentiation pathway similar to pathway C described above.

[0055] As will be seen below, the implantable device of the invention defines a cell expression space in which immature osteochondroprogenitor cells are induced to proliferate. A repair matrix, typically comprising a (preferably autologous) periosteal graft, is placed in this space. Mechanical stress is generated inside this space by external mobilization, generating shearing of the cell repair matrix in precise cleavage planes that are ideally reproducible with each movement.

[0056] To ensure the expression of osteochondrogenic cells and their directed differentiation into chondrocytes (pathway C), it is proposed here to temporarily implant an implantable device directly within the body of the individual to be treated in a tissue space favorable for the expression of these cells.

[0057] The selected space (e.g., muscle or subcutaneous area) nourishes the cellular repair matrix disposed inside the implantable device to promote the expression of osteochondrogenic cells, particularly when the device is implanted in an environment that can nourish the cellular repair matrix when the cellular repair matrix comprises a non-vascularized periosteal graft.

[0058] Highly preferably, an implantable device conforming to any one of the examples described below is not initially implanted in or near the joint to be treated, but rather is proposed to be temporarily implanted in another area of ​​the individual's body.

[0059] During the growth and directed differentiation phase of the osteochondroprogenitor cells, it is highly advantageous to removably implant the implantable device into an intramuscular area of ​​the individual, or into a subcutaneous area of ​​the individual.

[0060] The intramuscular area has a particularly favorable biological environment for the growth of new osteochondrogenic cells. The following publications can be cited regarding the interaction between the environment of the intramuscular area and the growth of osteochondrogenic cells: The potential role of muscle in bone repair, Liu, Schindeler, Little, J Musculoskelet Neuronal Interact 2010; 10(1) pp.71-76, as well as the following publication: Role of muscle stem cells during skeletal regeneration, Rana Abou-Khalil, Frank Yang, Shirley Lieu, Anais Julien, Jaselle Perry, Catia Pereira, Frederic Relaix, Theodore Miclau, Ralph Marcucio, Celine Colnot, Stem Cells, May 2015, 33(5): 1501-11. These two scientific publications show that the intramuscular area can not only have a high vascularization that can supply the blood flow that nourishes the graft, but also contains progenitor cells that directly contribute to bone repair.

[0061] It is therefore advantageous to use a periosteal graft as a repair matrix inside the implantable device and to place the implantable device inside the intramuscular region. The combined action of periosteal cells and adjacent myoblasts creates a particularly favorable environment for the proliferation and directed differentiation of osteochondrogenic cells to form new areas of cartilage and osteochondral tissue, including subchondral bone.

[0062] Below, the main steps in implanting an implantable device and obtaining a new section of cartilage are described by way of example.

[0063] Placement of implants and mechanical mobilization to promote cartilage formation Accompanying Figure 3 shows the successive implantation steps for an implant comprising a removable implantable device 1 and comprising a cellular repair matrix 4, in this case in an intramuscular area 80 of a muscle 8 of a human individual, followed by an external mobilization of said implant. Finally, the newly formed cartilage 12 is extracted from the device 1 and the newly formed cartilage 12 is transplanted in the area of ​​the articular surface of an area of ​​damaged cartilage 90 of the same individual, in this case the cut-out cavity 92.

[0064] In this case, the implantable device 1 has the form of a parallelepiped housing, which corresponds, for example, to any one of the examples 1A and 1B described below. The same method steps can be performed using other implantable devices.

[0065] The articular surface to be treated is preferably separate from the muscle 8. In other words, there is not necessarily a link between the damaged articular surface to be treated and the muscle selected for implanting the implantable device 1, except that the muscle very advantageously belongs to the same individual as the articular surface, in order to avoid possible rejection phenomena of the newly formed cartilage after implantation.

[0066] In this example, the muscle 8 is the calf. The intramuscular region 80 corresponds, for example, to the central area of ​​the calf.

[0067] To begin implantation, the intramuscular area 80 is exposed. For example, an incision is made in the muscle 8. Sufficient space is provided inside the muscle by the practitioner to insert the device 1.

[0068] The device 1 is then inserted into the intramuscular region 80. The device 1 is combined with a repair matrix (not shown in FIG. 3) that is inserted into the cell expression space inside the device 1 to form an implant for the formation of cartilage. The device 1 is typically closed around the repair matrix.

[0069] One role of the repair matrix is ​​to supply osteochondrogenic cells that, after proliferation and directed differentiation, are intended to differentiate into chondrocytes and form newly formed cartilage 12. Highly preferably, the repair matrix comprises a periosteal graft.

[0070] Preferably, the autologous periosteal graft is harvested, for example, from the individual's bone surface. In this example, the periosteal graft is harvested from the anterior surface of the tibia. For example, the periosteal graft is a very thin rectangular flap, for example, having a width of 1-5 cm and a length of 5-10 cm. Alternatively, the periosteal graft can come from any other bone of the individual. It may or may not be combined with a pedicle 44 (then referred to as a periosteal "flap").

[0071] The device 1 is associated with an external mobilization means that allows movement of a first portion 2 of the device 1 to be forced relative to a second portion 3 of the device 1. Thus, shear occurs between the two portions to generate shear stresses within the cellular repair matrix.

[0072] In this example, the external mobilisation means comprise mobilisation links 5, where a first pair of mobilisation links 5 are fixed to each side of the second part 3 and a second pair of links are fixed to each side of the first part 2.

[0073] This second pair of links allows to stabilize the first part 2 in position relative to the intramuscular area, while the mobilization link of the first pair of links is used to move the second part 3. To stabilize the second pair of links relative to the intramuscular area (particularly during mobilization of the device 1), fasteners 53 preferably secure said links to the skin. These fasteners 53 are preferably created by, for example, sutures during closure of the incision in the muscle 8.

[0074] If desired, more than two pairs of stabilizing or stabilizing links can be used.

[0075] Returning to Figure 3, to allow for subsequent mobilization after suturing of the intramuscular region 80, the mobilization link 5 in this case has a subcutaneous inner portion 52 and an outer portion 50 that is intended to remain outside the individual's skin. A mobilization link 5 of sufficient length is selected to have an outer portion 50 of sufficient length to ensure easy manipulation.

[0076] Here, the moveable link 5 comprises a semi-rigid strand, preferably with plasticized threads and / or sutures.

[0077] The incision in muscle 8 is then closed leaving a lateral portion 50 on the outside. The lateral portion 50 passes through an incision point 51 made in the skin, preferably above muscle 8. Fasteners 53 are then made as necessary.

[0078] The device 1 is made of one or more biocompatible materials, and the repair matrix is ​​preferably autologous, so the risk of rejection of the device 1 by the body is limited.

[0079] At this stage, the implantable device 1 remains, preferably immobile, in the intramuscular region 80 in a situation of muscle immobility. The advantage of this is to give the osteochondrogenic cells time to proliferate within the cell expression space inside the device 1. The osteochondrogenic cells then proliferate without any mechanical shear stress until they "settle" in the cell expression space.

[0080] In a following step, the device 1 is immobilized (preferably mechanically) in order to move the second housing part 3 relative to the first housing part 2. Prior to mobilization, the osteochondroprogenitor cells are generally in a relatively immature state, allowing their directed differentiation.

[0081] In the example illustrated in FIG. 3, during the external mobilization phase: - the first housing part 2 remains fixed relative to the muscle 8. For example, a mobilisation link 5 attached to the first part 2 is retained to force the first part 2 to remain fixed relative to the muscle. The second housing part 3 is moved relative to the muscle 8 and relative to the part 2 via a mobilization link 5 attached to the second part 3. For example, the mobilization link 5 located on one side of the second part 3 is pulled, for example in the mobilization direction D illustrated in Fig. 3, and then, alternately, the mobilization link 5 located on the opposite side of the second part 3 is pulled.

[0082] It should be understood that the mechanical means for external mobilization of the device 1 may be supplemented or replaced by alternative mobilization means. For example, electromechanical and / or electromagnetic mobilization means may be used. The second housing part 3 may, for example, be motorized and remotely controllable.

[0083] For example, the advantage of the use of electromechanical and / or electromagnetic mobilization means in combination with a control device integrated into the implantable device 1 is that it allows control of the external mobilization of the device 1 with the help of control signals, thereby eliminating the need to pull the mobilization links during the mobilization phase.

[0084] The external mobilization of the device 1 is preferably controlled in real time by the practitioner using medical imaging techniques, for example by ultrasound examination, to monitor the actual state of the movement. Optionally, the device 1 may be equipped with one or more sensors for detecting the movement and / or the velocity and / or the acceleration of the second part 3 relative to the first part 2. The device 1 may, for example, include one or more accelerometers.

[0085] Preferably, the periosteal graft remains vascularized by the pedicle 44 (if a vascularized graft is used), especially when the inferior surface of portion 2 is immobilized during external mobilization of device 1.

[0086] For this purpose, preferably a through-hole 46 is provided through the lower face of the first housing part 2 to allow the passage of the tube of the stalk 44 of the periosteal graft. Here, the through-hole 46 passes through the outer wall 24 of the first part 2, as shown in FIG. 4a. Here, the through-hole 46 is located in the central region of the lattice 42 present in the first part 2.

[0087] The through-hole 46 is preferably small. In fact, the periosteal pedicle graft (preferably of low thickness and flexibility) can be temporarily rolled up to slip through the small through-hole 46. The vascularized periosteum can then be spread and inserted into the cell expression space.

[0088] Alternatively, or in combination, a through hole may be provided in the second part 3 to allow the passage of a periosteal graft pedicle. However, to avoid pinching or twisting of the vascular pedicle 44 due to movement of the second part 3 during mobilization, it is advantageous for the vascular pedicle 44 to pass through the first part 2, which remains immobile relative to the muscle support.

[0089] The external mobilization phase of the implantable device 1 can be repeated as often as necessary for a period of time sufficient to generate shear stress inside the device, for example, a few minutes of mobilization can be performed daily, for example, for a period of 1-10 minutes.

[0090] In a subsequent step, once newly formed cartilage or cartilage 12 has been obtained in the cell expression space inside the device 1, the device 1 is removed from the body and degraded to retrieve one or more newly formed cartilages 12.

[0091] The intramuscular region 80 is reopened to remove the device 1 from the muscle, and then the first portion 2 is separated from the second portion 3 (an example of disassembly of the device 1 is described below in connection with accompanying FIG. 8).

[0092] As illustrated in the lower part of Figure 3, the resulting newly formed cartilage 12 preferably includes a cartilage surface 120 (in this case convex) on the surface, and a region of newly formed subchondral bone 122 below the cartilage surface 120.

[0093] The joint area 9 to be repaired, including an area of ​​damaged cartilage 90, is also depicted in FIG.

[0094] The newly formed cartilage 12 is then transplanted into the cut-out cavity 92 in place of the diseased area after excision of said cavity. In this example, the articular area 9 is the femoral condyle. The joint to be treated is the femoro-tibial joint.

[0095] However, it should be understood that the newly formed cartilage may also be transplanted to repair damaged areas of cartilage located in other joints. Implantation of the newly formed cartilage is particularly directed to the patellofemoral, talocrural, glenohumeral, acromioclavicular, and iliofemoral joints.

[0096] The resulting newly formed cartilage 12 is highly advantageously conformed to the geometry of the area of ​​damaged cartilage 90 that is to be repaired. Thus, the newly formed cartilage 12 is conformed to the area of ​​damaged cartilage 90.

[0097] Preferably, a cut-out cavity 92 is pre-created on the surface of the damaged area 90 and the newly formed cartilage 12 is then implanted into the cut-out cavity 92 .

[0098] The term "cutting" is intended to mean a procedure that consists in eroding the unhealthy cartilage and exposing the subchondral bone. Cutting allows the damaged area of ​​cartilage to be cleaned. Furthermore, cutting can cause microbleeds, the influx of new blood vessels, and the local release of growth factors in the native subchondral bone.

[0099] The morphology of the newly formed cartilage 12 is controlled by the choice of the shape of the implantable device 1. Through the design of the device 1, and in particular depending on the shape of the walls that define the cell expression space, it is possible to obtain a cartilage that matches a given specific morphology of the joint cavity. To this end, the first part 2 and / or the second part 3 are preferably custom manufactured depending on the morphology of the damaged area 90 to be repaired.

[0100] Such custom manufacturing is carried out, for example, by 3D printing. It is possible to use any 3D printing technique using biocompatible materials, such as one or more of the techniques described in the publication Bioactive scaffolds for osteochondral regeneration, Deng, Chang, Wu, Journal of Orthopaedic Translation (2019) 17, pp. 15-25 (especially p. 22), printing by extrusion, laser printing, stereolithography, fused deposition modeling (FDM), selective laser sintering (SLS), electrospinning, etc.

[0101] The 3D printing of the implantable device 1 may be based on a three-dimensional model that takes into account the geometry of the area of ​​damaged cartilage 90 acquired by medical imaging.

[0102] Examples of medical imaging techniques that may be used for this purpose are magnetic resonance imaging (MRI) (T2 relaxation time MRI or T1rho MRI) and / or delayed gadolinium-enhanced MRI of articular cartilage (dGEMRIC) and / or standard radiography and / or arthroscopic scanners.

[0103] After harvesting one or more pieces of newly formed cartilage 12, said cartilage is implanted into the articular area 9. The implantation of the newly formed cartilage 12 is optionally performed arthroscopically, such a procedure being minimally invasive.

[0104] A notable advantage of the approach proposed here is that it allows the use of a cut-out of an area of ​​damaged cartilage 90 (in this case from the surface of the femoral condyle) after harvesting the newly formed cartilage 12.

[0105] It is therefore possible to control the quality and shape of the portion of newly formed cartilage 12 before cutting out the diseased area of ​​cartilage that has to be repaired. It is also possible to adapt the shape of the cut-out cavity 92 according to the shape to be obtained for the newly formed cartilage 12. Insofar as the cut-out involves the destruction of the original cartilage (albeit damaged) that is still in place, it is also possible to abandon the cut-out and, in case of insufficient production of the newly formed cartilage inside the device, the implantation procedure.

[0106] Examples of implantable devices aimed at promoting the formation of new cartilage are described below with reference to accompanying Figures 4a to 12. A removable implantable device according to any one of these examples may be used to perform the procedure described above with reference to Figure 3.

[0107] Example 1A - Translational mobilization to form two pieces of cartilage 4a shows diagrammatically a removable implantable device 1 according to a first exemplary embodiment, shown in perspective from above. The device 1 is preferably intended to be removably implanted in the intramuscular region and / or to be removably implanted in the subcutaneous region.

[0108] The device 1 has the general form of a closed housing. The device 1 comprises a first housing part 2 made of a biocompatible material and a second housing part 3 also made of a biocompatible material.

[0109] The first part 2 is shown in the upper part of Fig. 4a and the second part 3 is shown in the lower part of Fig. 4a. In this Fig. 4a the two housing parts are therefore separate from each other.

[0110] The first portion 2 and the second portion 3 are intended to define a cavity therebetween that forms a cell expression space 40 .

[0111] Accompanying Figure 4b shows the device 1, in which the first housing part 2 is assembled (e.g. via a slide 6, which is not shown in Figure 4b for ease of reading) with the second housing part 3. The cell expression space 40 is visible on one side at the right of Figure 4b.

[0112] The inside of the device 1, which is intended to receive the cellular repair matrix 4, is also visible in cross section in the accompanying Figure 5. In this cross section of Figure 5, as well as in Figures 7 and 9, the vertical gap between the inner surface 26 of the first portion 2 and the opposite inner surface 36 of the second portion 3 is not shown to scale and has been enlarged for ease of reading of these figures. The vertical gap is very small (e.g., less than 1 millimeter) compared to the dimensions of the first portion 2 and the second portion 3.

[0113] Space 40 is intended to receive osteochondrogenic cells, particularly cells derived from the expression of cellular repair matrix 4, and to allow proliferation of these cells.

[0114] The second housing part 3 is removably attached to the first housing part 2. The connection between the second part 3 and the first part 2 is sufficiently durable so as not to collapse during the loading of the device 1 by external mobilization means (described below) during the mobilization phase.

[0115] The second part 3 is movably attached to the first part 2, in this example the second part 3 is translationally movable relative to the first part 2 in a direction parallel to the longitudinal axis B of the housing.

[0116] The first part 2 and / or the second part 3 are preferably formed of a biocompatible material selected from a polymeric material (such as PTFE), an extracellular matrix, a bioceramic material, a biological glass or a biocompatible metal, or any mixture of these materials.

[0117] The first housing portion 2 is at least partially laterally defined by a first side 20 and a second side 22. The sides 20 and 22 are generally perpendicular to the longitudinal axis of the housing and extend along two generally parallel surfaces.

[0118] In this example, the first side 20 and the second side 22 each have a central hollow. Thus, a hollow channel is formed along the longitudinal axis B of the first portion 2 and connects the sides 20 and 22.

[0119] Additionally, the first housing portion 2 is externally defined by an outer surface 24 and internally defined by an inner surface 26. The outer surface 24 and the inner surface 26 extend over two generally parallel surfaces.

[0120] The inner surface 26 is placed opposite the second housing part 3. In this example, the inner surface 26 is hollowed out in its center (in a hollow channel between the sides 20 and 22) to allow for the expression of osteochondrogenic cells at the bottom of the first part 2.

[0121] The first housing part 2 further includes two inner walls 28 which laterally define a hollow channel. The inner walls 28 extend from a bottom wall located behind the outer face 24 towards the second part 3.

[0122] The second housing part 3 is laterally defined by a first side 30 and a second side 32. The sides 30 and 32 are generally perpendicular to the longitudinal axis of the housing and extend on two generally parallel surfaces. Again, the first side 30 and the second side 32 each include a central hollow. Thus, an additional hollow channel is formed along the longitudinal axis B of the second part 3, connecting the sides 30 and 32.

[0123] The second housing part 3 is defined externally by an outer surface 34 and internally by an inner surface 36. The outer surface 34 and the inner surface 36 extend over two generally parallel surfaces. The inner surface 36 is disposed opposite the first housing part 2.

[0124] The second housing part 3 further comprises two inner walls 38 which laterally define a hollow channel. The inner walls 38 extend from a bottom wall located behind the outer face 34 towards the second part 2.

[0125] In the present example, and as shown in FIG. 4b, when the housing constituting the device 1 is closed, the hollow channels of the first and second parts 2, 3 are placed opposite each other.

[0126] The attached FIG. 6, a longitudinal section of the device 1, corresponds to a section through the two hollow channels. FIG. 6 illustrates the first part 2 and the second part 3 during external mobilization of the device 1. A cell expression space 40 extends inside the two hollow channels. Said space 40 is defined laterally by the inner wall 28 of the first part 2 and by the inner wall 38 of the second part 3. The cell expression space 40 is also defined from above (according to the orientation of FIG. 4a) by the inner side of the outer face 34 and from below by the inner side of the outer face 24.

[0127] Hence, when the second part 3 is aligned with the first part 2, the cell expression space 40 provided inside the device 1 has an approximately parallelepipedal shape.

[0128] The function of the repair matrix 4 is to generate a large number of osteochondrogenic cells. The repair matrix 4 advantageously comprises a periosteal graft, the biological function of which has been recalled above.

[0129] Very advantageously (although not obligatory), the periosteal graft is a vascularized graft, for example a pedicled vascularized graft. Figure 4a illustrates a periosteal graft attached to a pedicle 44, which passes through a through hole 46 provided in the body of the first housing part 2. A non-vascularized graft is also possible, or optionally a combination of a non-vascularized and a vascularized graft is possible, if at least two different grafts are used.

[0130] Advantageously, the periosteal graft originates from an autologous transplant. In other words, the cells forming the periosteal graft are autologous cells originating from the same individual in whom the articular implant is to be 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 individual's body. Thus, cartilage regeneration is promoted more effectively and the risk of rejection is significantly limited.

[0131] In this example, the periosteal graft is derived from the periosteum of the tibia, the advantage being that the harvesting procedure for the tibia bone is easy and relatively minimally invasive.

[0132] Preferably, prior to action by the external mobilization means, the repair matrix 4 is in the form of a coherent solid element that is not necessarily integral with the device 1. For example, the repair matrix 4 is inserted (and optionally sutured) into the cell expression space 40 immediately prior to insertion of the device 1 into the intramuscular or subcutaneous region.

[0133] The advantage of the through holes 46 is that they allow vascularization of the repair matrix 4 throughout the entire mobilization phase by the external mobilization means. The openings allow the passage of at least one blood vessel from the outside of the implant so that the repair matrix 4 is vascularized during mobilization. Such vascularization is very relevant when the repair matrix 4 includes a periosteal graft, to ensure good cell expression.

[0134] Thus, following implantation of the implant (eg, in the intramuscular or subcutaneous region), osteochondrogenic cells proliferate in vivo from the repair matrix 4 .

[0135] 6 shows osteochondrophogenic cells filling the space 40 after proliferation inside the implant. If the first part 2 and / or the second part 3 comprises a cone-shaped tip 43, the osteochondrophogenic cells preferentially fill the compartment defined by the tip 43.

[0136] In this example, the second part 3 is configured to slide relative to the first part 2 along the inner side 26 during its translational movement by external mobilization of the device 1. The dashed line in FIG. 5 indicates the extension surface P of the inner side 26.

[0137] The device 1 comprises external mobilization means, allowing the movement of the second part 3 relative to the first part 2 to be forced. Thus, shear is generated between the second part 3 and the first part 2, particularly in this case near the extended surface P of the internal sliding surface 26. Thus, shear stress is generated in the cell expression space 40.

[0138] Such shear stress has the advantage of directing the differentiation of cells present near surface P within cell expression space 40. More specifically, cells closest to surface P are most exposed to shear stress. Thus, the cells will preferentially differentiate into cartilage surface cells (differentiation pathway C illustrated in FIG. 2).

[0139] Hence, external mobilization of the device 1 creates cleavage planes inside the cell expression space 40 to apply shear stress.

[0140] The shear stresses thus created are similar to those exerted on the moving surfaces of a joint, in this case between the femoral condyle and the tibial plateau.

[0141] The device 1 is preferably mobilized after the osteochondrogenic cells have begun to proliferate (see example illustrated in FIG. 6).

[0142] The external mobilisation means preferably comprise mechanical means. More preferably, said means comprise at least one mobilisation string attached to the second part 3, configured to enable towing the second part 3 relative to the first part 2.

[0143] The term "mobilization string" is intended to mean a fastener (thread, cable, belt, etc.) fixed to a part of the device 1 that can be pulled to force a relative movement, in this case a translational movement, of the second part 3 with respect to the first part 2. Preferably, said mobilization string is then fixed to an outer surface, typically one of the sides 30 and / or 32 of the second part 3.

[0144] In the example of figures 4a to 8, the external mobilisation means comprises a first mobilisation string 5A fixed to the side 30 and a second mobilisation string 5B fixed to the opposite side 32. The two mobilisation strings 5A and 5B are thus fixed to opposite outer sides of the second part 3. These links are not shown in figure 4b for the sake of readability.

[0145] As previously described in relation to FIG. 3, when the device 1 is implanted, the two mobilization strings 5A and 5B preferably have a subcutaneous internal length of thread and an external length of thread that is intended to remain outside the skin.

[0146] Using the mobilizing strings 5A and 5B, the second portion 3 can be towed from the left and then from the right side (according to the orientation of Figures 4a and 6) relative to the first portion 2 to create shear within the cell expression space.

[0147] The mobilization strings 5A and 5B are preferably made of semi-rigid strands of thread. The strings are preferably made of a polymeric material. For example, it is possible to use any material that is normally used for sutures.

[0148] Optionally, and advantageously, the device 1 further comprises a slide 6 for guiding the movement of the second part 3 relative to the first part 2. Thus, during loading of the device 1 by the external mobilization means 5, the second part 3 slides along the slide 6 such that the second part 3 does not move laterally relative to the first part 2.

[0149] Such a slide can be seen in figures 4a and 5. In this example, the slide 6 has at least one monorail fixed to the first part 2. The monorail is mechanically integral with the remainder of the first part 2. Said monorail projects from an inner face 26 which in this case is oriented opposite the second part 3. The second part 3 then has at its inner face 36 at least one groove 60 complementary to the monorail. For ease of reading the figures, the actual shape of the groove 60 is not illustrated in figures 4a and 4b.

[0150] As shown in FIG. 4a, the slide 6 preferably has two identical longitudinal monorails on two sides.

[0151] Alternatively, a slide having a similar action may be obtained by placing one or two monorails on inner surface 36 and one or more complementary grooves on inner surface 26 .

[0152] Such a slide 6 can be translated into a variant of the device 1 in which the external mobilisation means is electrical and not mechanical.

[0153] Furthermore, the device 1 optionally includes means for fixing the first portion 2 to the body, for example to the intramuscular or subcutaneous region in which the device 1 resides.

[0154] For this purpose, the device 1 preferably comprises at least one fixed link, and still more preferably a pair of fixed links. In Fig. 4a, the device 1 comprises a first fixed link 5C at side 30 and further comprises a second fixed link 5D at side 32. These links are not shown in Fig. 4b for the sake of readability.

[0155] The fixing links 5C and / or 5D are, for example, attached to the muscle 8 in which the device 1 is implanted. The fixing links 5C and 5D are, for example, sutured to the muscle 8 such that the first part 2 remains fixed while the second part 3 is moved in translation during the external mobilization phase. Alternatively, the fixing links 5C and 5D may have respective external lengths of thread that are intended to remain outside the skin, like the mobilization strings 5A and 5B. The fixing links 5C and 5D may then be immobilized, for example manually, in these external lengths of thread.

[0156] The fixed links 5C and 5D are preferably made of semi-rigid strands of thread. The links are preferably made of a polymeric material. For example, it is possible to use any material that is normally used for sutures.

[0157] The first portion 2 and / or the second portion 3 preferably have a hollow structure and form a hollow recess through which the cell expression space 40 extends.

[0158] In the example of Figures 4a to 8, the first portion 2 has a lattice 42 which forms such a hollow structure.

[0159] The lattice 42 extends from the inside of the outer surface 24 in a direction of extension (width) perpendicular to the outer surface 24. For ease of reading of the accompanying figures, the lattice 42 is not illustrated in Figures 4a and 4b.

[0160] The lattice 42 defines a plurality of cell growth through cavities that open to the interior of the device 1 in the direction of width (extension perpendicular to the outer surface 24 ).

[0161] The cell growth cavities are, in this case, defined between conical tips 43 formed in the lattice 42. The bases of the conical tips 43 are preferably oriented outwardly and the apexes of the conical tips 43 are oriented inwardly.

[0162] A hollow through section (e.g., a parallelepiped and / or honeycomb section) is formed between the conical tips 43. The internal space of the section is located in the extension of the area where the repair matrix 4 is placed. Thus, the internal space of the section extends the cell expression space 40. As illustrated in FIG. 5, the repair matrix 4 can then be embedded and / or fixed above the upper surface of the lattice 42 of the first part 2.

[0163] The growth cavity (in this case the inner compartment of the lattice 42) passes through two sides in this case: on the outside, it passes through the outer face 24 of the first part 2, and on the inside, it leads to the cell expression space 40.

[0164] The advantage of such a lattice 42 is that during translational movement of the second part 3 relative to the first part 2, the cells located near the outer surface 24 (which are the cells furthest from the cleavage plane P) are mechanically more stable than the cells near the cleavage plane P.

[0165] Thus, during external mobilization of the implantable device, a gradient of stiffness in shear is created inside the cell expression space 40. Cells located close to the external surface 24 are induced to preferentially form bone cells after differentiation (pathway A in FIG. 2). Thus, it is possible to obtain a layer of subchondral bone within the newly formed cartilage 12 obtained at the end of mobilization of the device 1.

[0166] Furthermore, the lattice 42 allows blood perfusion to reach the inside of the cell expression space 40 from the outside of the device 1 .

[0167] Additionally, an advantage of using a conical tip 43 to form the lattice 42 is that the separating walls of the lattice 42 now have a greater thickness at the base than their thickness at the surface, thereby enhancing the shear stiffness gradient.

[0168] To obtain the lattice 42, one or more cavities may be originally provided in the design of the first part 2. For example, the 3D model of the first part 2 may incorporate the cavities of the lattice 42 from its design. Alternatively, the cavities of the lattice 42 may be obtained by drilling after production.

[0169] An additional advantage of providing the lattice 42 in the first portion 2 is that it allows for interaction of the repair matrix 4 with the environment of the intramuscular area, and in particular, better vascularization of the repair matrix 4 .

[0170] In this example 1A, the second part 3 does not include a lattice. However, in this case, the second part 3 includes a conical tip 43 that forms a growth cavity in the extension of the cell expression space 40. Thus, the conical tip of the second part 3 faces the conical tip of the first part 2. Unlike the first part 2, the space between the conical tips 43 of the second part 3 does not form a through hole.

[0171] Alternatively, the second part 3 may also comprise through-perforations, for example similar to the lattice 42. However, it is advantageous that the outer surface 34 is not perforated and that the cavity formed between the conical tips 43 of the second part 3 is not perforated. In fact, the second part 3 is induced to move relative to the muscle area. The smooth outer surface 34 makes it possible to avoid friction or rubbing between the second part 3 and the muscle environment during the movement of the second part 3.

[0172] Optionally and advantageously, at least some of the conical tips 43 of the first part 2 and / or the second part 3 may have a recess at their base. The shape of the recess of the conical tip 43 is preferably selected so as not to interfere with the subsequent extraction of the newly formed osteochondral tissue.

[0173] By way of example, such a recess may have a triangular shape at the base of the conical tip 43 and extend in a pyramidal shape towards the apex of the cone (e.g. a triangular pyramid shape). Thus, the triangular recess created in the surface of the conical tip 43 preferably does not extend to the apex of said tip 43.

[0174] Such hollowed conical tips 43 are advantageous since they enlarge the total contact surface between the osteochondrogenic cells being formed and the biomaterial support inside the cell expression space. Furthermore, the stiffness of the first support part 2 and / or the second support part 3 is locally increased. To simplify the accompanying drawings, the conical tips 43 are not shown with such recesses in these figures.

[0175] Alternatively, the conical tip 43 of the device 1 does not have a recess.

[0176] Preferably, means for blocking translational movements are provided on the first part 2 and / or the second part 3. The translational blocking means make it possible to define the range of translational movements of the second part 3 relative to the first part 2.

[0177] In the present example, such translation blocking means comprises at least one protrusion 27 configured to abut against at least one wedge 37 .

[0178] Here, the first portion 2 includes a pair of upwardly projecting protrusions 27 on one side of the first portion 2. The protrusions 27 are preferably axially located near one another along the longitudinal axis B on one side of the longitudinal axis B. Each protrusion 27 includes, for example, a base and a rod protruding from the base with a spherical end.

[0179] Here, the second part 3 comprises a pair of wedges 37. The wedges 37 are located opposite each other on the same side of the longitudinal axis B. The distance between the inner faces of the wedges 37 along the longitudinal axis B is preferably exactly greater than the distance between the projections 27 along the longitudinal axis B.

[0180] Thus, when the first part 2 and the second part 3 are assembled as illustrated in Figure 4b, the projections 27 are inserted into their bases at the sides of the elements 2 inside the longitudinal space provided between the wedges 37. The range of translational movement of the second part 3 relative to the first part 2 is therefore limited by the abutment of the projections 27 on the inner sides of the wedges 37.

[0181] It should be understood that alternatively, the wedges and protrusions may be located on the other or both sides and / or one or more protrusions may be provided on the second portion 3 and / or one or more wedges may be provided on the first portion 2.

[0182] At the end of the mobilization of the device 1 by external mobilization means, which may optionally be repeated periodically during the mobilization phase, the osteochondrogenic cells in the space 40 differentiate into chondrocytes and subchondral bone. Thus, in Example 1A, two opposing portions of newly formed cartilage 12 are obtained, opposite each other, as illustrated in the attached FIG. 7.

[0183] At the surface of the lattice 42, the cells closest to the surface P preferentially differentiate into chondrocytes in order to obtain the cartilage surface 120.

[0184] At the base of the lattice 42 (near the lateral surfaces 24 and 34 on either side of the housing), the cells furthest from the surface P preferentially differentiate into subchondral bone cells to acquire the dermal subchondral region 122 .

[0185] 8 shows the disintegration of the device 1 after extraction of the device 1 to the subcutaneous or intramuscular region. In this example, a mechanical force is applied to separate the first portion 2 and the second portion 3. Thus, the slide 6 is broken, preferably at the monorail. For example, the base of the monorail remains at the first portion 2 and the distal portion of the monorail is carried away by the second portion 3.

[0186] Thus, two integrated pieces of cartilage are obtained, ready to be introduced into the joint cavity to repair the damaged cartilage section.

[0187] In this example, the damaged cartilage sections are located at the femoro-tibial joint. For example, one of the newly formed cartilage pieces 12 obtained is positioned on the femoral condyle and the other of the newly formed cartilage pieces 12 is positioned on the tibial plateau opposite the femoral condyle. Each newly formed cartilage piece is preferably implanted directly into the corresponding damaged section, e.g., within the respective cutout cavity.

[0188] The resulting newly formed cartilage 12 preferably conforms to the geometry of the damaged cartilage section to be repaired and, where appropriate, to the geometry of the cut-out cavity. After implantation of the newly formed cartilage 12, the surface of the cartilage preferably extends in continuity with the surface adjacent the damaged section of cartilage.

[0189] The steps of mobilization and separation of parts of the implantable device as described above for the example of accompanying Figures 4a-8 are transferred in a similar manner to other examples of removable implantable devices described below in connection with accompanying Figures 9-12.

[0190] The advantage of the implantable device according to the first example described above is that it allows the simultaneous formation of two sections of newly formed cartilage 12, preferably suitable for transplantation in two damaged cartilage sections belonging to two opposing surfaces of the same joint.

[0191] The average total thickness of cartilage in the human adult femoro-tibial joint is approximately 5 millimeters. Thus, the average thickness of newly formed cartilage 12 (perpendicular to the extended surface of the lateral surface of the cartilage) is, for example, 1 to 10 millimeters.

[0192] Example 1B - Translational Mobilization Using a Single Chondrogenic Compartment 9 illustrates diagrammatically an implantable device according to a second exemplary embodiment, the implantable device being seen in cross section, perpendicular to the longitudinal axis of extension.

[0193] The implantable device according to this second example has structural and functional features very close to the device according to the first example 1 described above, except for the structure of the first housing part 2. The second housing part 3 is translationally movable relative to the first housing part 2.

[0194] Unlike the preceding Example 1A, the first part 2 (preferably held fixedly against the intramuscular region) is not perforated and does not include a lattice 42. In this case, the first part 2 includes a solid inner side 26' facing the second part 3. If a slide 6 is included, the inner side 26' may extend between two longitudinal monorails of the slide 6.

[0195] Optionally and advantageously, a network of stiffening elements 7 is arranged on the inside of the first part 2. The stiffening elements 7 are placed on the inside of the first part 2, against the inner side 26'. The network of stiffening elements 7 preferably covers a majority of the extent of the inner side 26'.

[0196] The stiffening element 7 has, for example, a cross shape and is preferably fixed to the inner side 26'. The cross shape is, for example, obtained by 3D printing of a biomaterial. Such a stiffening element 7 is shown in FIG.

[0197] The advantage of the stiffening element 7 is that it increases the stiffness against shear at the bottom of the cell expression space 40, on the side of the first portion 2. Thus, the stiffness gradient is increased between the first portion 2 and the second portion 3.

[0198] In this second example, the periosteal graft preferably remains vascularized by the pedicle, and for this purpose a through-hole is preferably provided through the lower face of the first part 2 to allow the pedicle canal to pass through.

[0199] The second part 3 is translationally movable relative to the first part 2. For example, the slide 6 is integrally fixed to the inside of the first part 2 to guide the movement along a surface P including the inner side 26'. During the mobilization phase of the implantable device, the cells closest to the surface P tend to be subjected to shear, while the cells at the bottom of the conical tip 43 tend to move with the second part 3. The cells furthest from the surface P preferentially differentiate into subchondral bone.

[0200] After mobilization and cell expression, a complete newly formed osteochondral tissue, including the cartilage surface and the subchondral bone area, is typically obtained inside the first part 2, allowing the damaged joint area to be treated. After extraction of the implantable device according to this Example 1B from the body, the first part 2 and the second part 3 are separated from the osteochondral tissue. The conical tip 43 is not integrated into the newly formed osteochondral tissue.

[0201] The cartilage potentially generated on the side of the second part 3 where the stiffening element 7 is embedded will not be reused within the patient.

[0202] In a possible alternative, the stiffening element 7 can be positioned on the side of the mobile second part 3 (against the face 34), by replacing or combining with the conical tip 43. The stiffening element 7 is then, optionally, detached from the second part 3 upon extraction of the newly formed osteochondral tissue, remaining integrated with this newly formed tissue. In particular, incorporation of the stiffening element into the cartilage to be implanted is possible, if the stiffening element 7 is made of a bioabsorbable biomaterial, or a biomaterial that is very well tolerated over time inside the treated joint.

[0203] Example 2A - Rotational mobilization to form two pieces of cartilage Fig. 10 illustrates diagrammatically an implantable device according to a third exemplary embodiment. The device is preferably intended to be removably implanted in the intramuscular region of an individual and / or to be implanted in the subcutaneous region of an individual. Fig. 10 shows the device implanted inside the muscle 8, beneath the epidermis 82, viewed in cross section.

[0204] This third example differs from the examples described above mainly by the rotational movement of the second housing part 3 relative to the first housing part 2 , as well as by the structure of the first part 2 and the second part 3 .

[0205] In this case, the first portion 2 is open at the bottom (according to the orientation of FIG. 10) and is generally cylindrical about axis R. The first portion 2 includes a side wall 28 and a bottom wall 29. The bottom wall 29 is preferably disc-shaped. The side wall 28 extends downwardly from an annular end of the bottom wall 29.

[0206] The second portion 3 is also open at the top (according to the orientation of FIG. 10) and has a generally cylindrical shape about an axis R. The second portion 3 includes a side wall 38 and a bottom wall 39. The bottom wall 39 is disc shaped. The side wall 38 extends upwardly from an annular end of the bottom wall 39.

[0207] The second part 3 is removably attached to the first part 2 .

[0208] The first part 2 and / or the second part 3 preferably have rotational symmetry around the axis R. The first part 2 and the second part 3 closed to one another thus form a substantially cylindrical closed housing.

[0209] The outer diameter of the side wall 38 is advantageously smaller than the inner diameter of the side wall 28 so that the second part 3 is rotatable about the axis R inside the side wall 38 .

[0210] In a similar manner to the two previous examples, the second part 3 is configured to be moved relative to the first part 2, in particular under the influence during external mobilisation.

[0211] The device preferably comprises a slide 6 intended to induce a rotation of the second part 3 about an axis R relative to the first part 2 .

[0212] 10 and 11, the slide 6 preferably includes an annular rib extending radially (with respect to axis R) from the side wall 38 of the second part 3, near the free end of the side wall 38, and the first part 2 includes an annular groove oriented radially (with respect to axis R) from the side wall 28 towards the inside. It will be appreciated that alternatively the slide may be formed by an inwardly directed annular rib of the first part 2 complementary to the groove of the second part 3.

[0213] Optionally, the device comprises additional means for fixation and rotational guidance of the second part 3 relative to the first part 2 .

[0214] By way of example, the free end of the side wall 28 (pointed towards the second part 3) may have an external thread radially outwards. During mounting of the second part 3 to the first part 2, in order to obtain a closed housing, an additional fastening ring of a diameter larger than the outer diameter of the first part 2 may be mounted on the slide 6 and closed at the free end of the side wall 28. The fastening ring then preferably has, radially inwards, an internal thread complementary to the external thread of the side wall 28, allowing said ring to be screwed against said wall. Such a fastening ring is not shown in figures 10 to 12.

[0215] A cell expression space 40 is defined axially between the inside of the bottom wall 29 and the inside of the bottom wall 39. This cell expression space 40 can receive a repair matrix 4. This matrix has the characteristics already explained above. Said matrix preferably includes, in particular, a periosteal graft. Preferably, also in this third example, the periosteal graft remains vascularized by a pedicle. For this purpose, the first part 2 and / or the second part 3 can include a through-hole for the pedicle (not shown in the attached drawings).

[0216] As in the previous example, the function of the repair matrix 4 is to generate a large number of osteochondrogenic cells within the cell expression space 40. Preferably, after a certain cell expression time, the osteochondrogenic cells fill the inner space of the first portion 2 and the inner space of the second portion 3, as illustrated in FIG.

[0217] In a similar manner to the two previous examples, the external mobilisation means 5 is operable to move the second portion 3 relative to the first portion 2 so as to generate shear within the cell expression space 40.

[0218] In this example, the external mobilisation means 5 comprises a handle that can be rotated about a rotation axis R. In this case, the movable handle is fixed to the bottom wall 39. Here, the movable handle comprises a sleeve 54 extending from the bottom wall 39 along the axis R, and a gripping part 56 (in this case in the form of a wheel) extending outwardly from the sleeve 54.

[0219] The movable handle is integral with the second housing portion 3 in its rotation about axis R. Thus, when a practitioner or patient grasps the grip portion 56 and pivots said grip portion as illustrated in FIG. 11, the second portion 3 is rotated.

[0220] Preferably, during mechanical action of the second part 3, the first part 2 remains fixed relative to the muscle 8. Stabilization means of the first part 2, such as a fastener 83, are for example provided for this purpose.

[0221] Osteochondrogenic cells present in the volume located radially inward of side wall 38 tend to be driven by the rotational movement of second portion 3, whereas osteochondrogenic cells present in the volume located radially inward of side wall 28 tend to remain fixed.

[0222] A shear surface Z is presented at the interface between the inner space of side wall 28 and the inner space of side wall 38. During the rotational movement of second portion 3, shear stresses are generated, especially in cells located close to shear surface Z.

[0223] As explained above, such shear stress promotes directed differentiation of osteochondroprogenitor cells into chondrocytes. Expression of the cartilage surface is promoted near the shear surface Z.

[0224] Optionally and advantageously, to create a gradient of stiffness against shear inside the space 40 (high stiffness against shear near the bottom walls 29 and 39 and lower stiffness near the shear surface Z), the first housing part 2 and / or the second housing part 3 include a conical tip 43 extending from the bottom walls 29 and 39 of said two housing parts, respectively. The conical tips 43 form a compartment between them, for example in the form of a parallelepiped or honeycomb shape. The cell expression space 40 extends to the bottom of the compartment.

[0225] In this example, a conical tip 43 is provided on both the first part 2 and the second part 3. The advantage is to increase the gradient of stiffness against shear inside the cell expression space 40. Furthermore, the conical tip 43 forms a cavity that extends the cell expression space 40 between the first part 2 and the second part 3. Thus, the formation of a subchondral zone is promoted in the newly formed cartilage obtained.

[0226] In the first fixed part 2, the cavity formed between the conical tips 43 is preferably a through cavity. Thus, the lattice 42 is formed in the bottom wall 29 and is thereby induced to remain fixed.

[0227] In contrast, the bottom wall 39 is preferably not perforated. The outer surface of the bottom wall 39 is preferably smooth.

[0228] Optionally, and advantageously, the implantable device further comprises a means for stabilizing the first portion 2 relative to the region of the body in which the device is implanted, in this case the muscle 8. In this example, the device comprises a fastener 83. The fastener 83 securely connects the first portion 2 (e.g., the side wall 28) to the epidermis 82. The fastener 83 comprises, for example, two sutures, each of which is fixed at one end to the side wall 28 and at an opposite end to the epidermis 82. Thus, during mobilization of the second portion 3, the first portion 2 remains fixed relative to the muscle 8.

[0229] The advantage of the implantable device according to this third example is that the first part 2 and the second part 3 are not displaced axially relative to each other during mobilization. The two volumes of osteochondrogenic cells contained inside the first part 2 and the second part 3, respectively, remain in contact throughout the entire mobilization. This makes it possible to avoid insufficient shear stress at the edges.

[0230] The implantable device according to this third example allows for the simultaneous formation of two cartilages. After extraction of the newly formed osteochondral tissue, the conical tip 43 (if present) preferably does not incorporate the newly formed tissue.

[0231] In a possible alternative, the implantable device of this Example 2B may include one or more networks of stiffening elements 7 inside the housing. Stiffening elements 7 of similar structure to those described above are positioned, for example, against bottom wall 29 and / or bottom wall 39, preferably having a cross shape. Stiffening elements 7 preferably replace conical tips 43 and cover most of the area of ​​the corresponding bottom wall. Such stiffening elements 7 may be incorporated into the newly formed osteochondral tissue (especially if these stiffening elements are formed of a bioabsorbable biomaterial or another material that is well tolerated by the joint over time).

[0232] Example 2B - Rotational mobilization to create convex cartilage FIG. 12 shows an implantable device according to a fourth example that is structurally and functionally similar to the third example.

[0233] In this fourth example, the second part 3 is rotatable about axis R relative to the first part 2 via external mobilisation means 5. The device of the fourth example differs from that of the third example by certain structural features of the first part 2 and of the second part 3. For attachment of the second part 3 to the first part 2, an adjustable threaded fixing ring can be provided on the second part 3, as in the preceding examples.

[0234] In this fourth example, the bottom wall 39 of the second portion 3 is preferably smooth and not perforated. The bottom wall 29 of the first portion 2 is preferably perforated to form a lattice 42 that promotes vascularization of the repair matrix 4.

[0235] In this fourth example, the periosteal graft preferably remains vascularized by the pedicle, and for this purpose a through-hole is preferably provided through the first part 2 to allow the pedicle canal to pass through.

[0236] In this case, the bottom wall 29 of the first part 2 and / or the bottom wall 39 of the second part 3 do not have a flat geometry. Here, the two bottom walls 29 and 39 are curved. The convexity of the bottom walls 29 and 39 preferably corresponds to the convexity of the damaged area of ​​the cartilage to be repaired. The necessary convexity for the shape of the bottom walls 29 and 39 is determined, for example, from a 3D model of the cartilage stalk to be treated. The advantage is that it provides from the design of the implantable device the appropriate final shape for the newly formed cartilage obtained at the end of the mobilization phase.

[0237] It should be understood that such adaptation of the convex surface of the movable part is equally applicable to any of the other examples described above.

[0238] Additionally, in this case the implantable device of this Example 2B includes a stiffening element 7 positioned against the bottom wall 39. The stiffening element 7 preferably replaces the conical tip 43 of the second part 3 of the preceding Example 2A. The implantable device according to the fourth example is suitable for enabling the formation of a single newly formed cartilage on the side of the first part 2, for example to treat a single damaged area of ​​cartilage having a non-flat shape (convex shape in this Example 2B).

Claims

1. 1. A removable implantable device for generating articular cartilage, comprising: a first support (2) made of a biocompatible material; a second support part (3) made of a biocompatible material and movably attached to the first support part (2), the first support part (2) and the second support part (3) defining between them a cavity forming a cell expression space (40), the cell expression space (40) intended to receive osteochondrogenic cells proliferating within the cell expression space (40); - operable external mobilization means (5A, 5B) configured to move the second support (3) relative to the first support (2) in order to generate shear inside the cell expression space (40); 1. A removable implantable device comprising:

2. 2. The implantable device of claim 1, wherein at least one of the first support portion (2) and the second support portion includes a bottom support wall and two side support walls (28) extending from the bottom support wall, the two side support walls (28) defining the cell expression space (40).

3. The implantable device of claim 1, wherein the implantable device comprises a closed housing formed by the first support part (2) and the second support part (3), and the cell expression space (40) is defined inside the housing.

4. 2. The implantable device of claim 1, wherein the first support portion (2) includes an inner surface (26) facing the second support portion (3), and the second support portion (3) is configured to slide relative to the first support portion (2) along the inner surface (26).

5. 5. The implantable device according to claim 4, wherein the second support (3) is mounted so as to be translationally movable relative to the first support (2) in a direction parallel to the extension surface (P) of the inner side (26).

6. 2. The implantable device of claim 1, wherein the second support (3) is rotatably mounted relative to the first support (2) around an axis of rotation (R).

7. 7. The implantable device of claim 6, wherein at least one of the first support and / or the second support (3) comprises a cylindrical side surface (38) extending around the axis of rotation (R).

8. The implantable device as described in claim 7, wherein at least one of the first support portion and / or the second support portion (3) further includes a base (39) approximately perpendicular to the cylindrical side surface (38), and the external mobilization means (5) includes a handle (54) that is forced to rotate together with the base (39) and is rotatable around the rotation axis (R).

9. 2. The implantable device of claim 1, wherein the external mobilization means comprises at least one mobilization string (5A) attached to the second support (3) and configured to tow the second support (3).

10. 10. The implantable device of claim 9, wherein the mobilization string (5A) is attached to a first outer surface (30) of the second support (3), and the implantable device further comprises an additional mobilization link (5B) attached to a second outer surface (32) of the second support (3), the second outer surface (32) being opposite the first outer surface (30).

11. 10. The implantable device of claim 9, wherein the mobilization strings (5A, 5B) comprise semi-rigid strands, preferably strands made of a polymeric material.

12. 2. The implantable device of claim 1, comprising a slide (6) configured to guide movement of the second support part (3) relative to the first support part (2).

13. 2. The implantable device of claim 1, wherein at least one of the first support portion (2) and / or the second support portion (3) includes a lattice (42), the lattice (42) defining a plurality of cell growth cavities that open to the inside of the implantable device.

14. The implantable device of claim 1, wherein at least one of the first support portion (2) and / or the second support portion (3) comprises a network of stiffening elements (7) fixed to the at least one of the first support portion and / or the second support portion (3), and the stiffness against shear in the stiffening elements (7) is truly greater than the stiffness against shear in a central region of the cell expression space (40).

15. An implant for the formation of chondrocytes, comprising: - an implantable device (1) according to claim 1; a cellular repair matrix (4) interposed between a first support part (2) of the implantable device and a second support part (3) of the implantable device, the cellular repair matrix (4) comprising a large number of osteochondrogenic cells intended to proliferate in a cell expression space (40) of the implantable device; Including, implants.

16. 16. The implant of claim 15, wherein the cellular repair matrix (4) comprises at least one periosteal graft, preferably a vascularized periosteal graft.

17. 17. The implant of claim 16, wherein the periosteal graft is derived from the periosteum of the tibia.

18. 16. The implant of claim 15, wherein the implant is configured to be removably implanted in an intramuscular region of an individual and / or configured to be removably implanted in a subcutaneous region of an individual.

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