Implantable device with external mobilization agents for joint cartilage formation

Description

FIELD OF INVENTION

[0001] The present invention relates to an implantable device intended to stimulate the formation of articular cartilage, preferably adapted to the morphology of deteriorated articular cartilage in an individual, in order to replace said area of ​​deteriorated cartilage.

[0002] The invention relates in particular to an implantable device adapted to promote the formation of specific cellular layers of articular cartilage. The implantable device is associated with a cellular repair matrix. The repair matrix preferably comprises a periosteal graft. STATE OF THE ART

[0003] Chondropathy manifests as the disintegration of one or more cartilage surfaces, which lose their mechanical properties of protecting bone surfaces and cushioning the mechanical stresses of a joint. Untreated chondropathy in humans can degenerate into advanced osteoarthritis, causing significant chronic pain and potentially leading to severe disability, particularly in elderly patients.

[0004] In the example of the knee, during natural movements such as walking or squatting, the pressure exerted on the knee joint between the femur and tibia is very significant. If the mobility and shock-absorbing function of the articular cartilage is not maintained, these natural movements become painful.

[0005] Such lesions of the articular cartilage can be located on only one of the two opposing articular surfaces, but both opposing articular cartilage surfaces can also be affected. Joint lesions originate either from age-related cartilage wear (osteoarthritis) or from joint trauma due to impacts or accidents, particularly in young individuals. In current medical practice, the severity of chondropathies is assessed clinically using the ICRS functional score and radiologically (MRI) using the ICRS grade or the Outerbridge classification.

[0006] The current state of knowledge includes numerous therapeutic approaches for patients with chondropathy. In early stages of osteoarthritis, treatment is offered using systemic or local injections of anti-inflammatory drugs. Intra-articular injections are also available, such as hyaluronic acid injections (referred to as "viscosupplementation") or platelet-rich plasma injections. Relatively minimally invasive arthroscopic approaches can also be used, such as joint lavage with debridement, the Pridie microperforation technique, the microfracture technique, or the use of three-dimensional matrices composed of collagen and hydroxyapatite.

[0007] However, the aforementioned approaches often provide transient clinical results and are inconclusive for the formation of new cartilage. Histologically, the cartilage thus formed is of poor quality.

[0008] Another known approach involves directly implanting one or more healthy osteochondral segments, taken from a joint of the individual being treated, into the joint segment to be treated in the same individual (via "osteochondral autograft"). In this case, osteochondral cores are harvested, for example, from non-weight-bearing areas of the joint to be treated and transferred to the segment requiring repair.

[0009] We have represented on the Figure 1a an osteochondral autograft at the level of a femoral condyle, to treat the knee joint of a human individual (Resumption of sport after mosaic osteochondral autograft of the femoral condyles:) 25 case at 9 years average decline,Cognault, Seurat, Chaussard, lonescu, Saragaglia, Journal of orthopedic and trauma surgery 101 (2015) pp. 215-220).

[0010] There Figure 1a This illustrates a "mosaicplasty" technique. A plurality of cores (here, four cores) previously harvested from the same individual are implanted, in a mosaic pattern, into the damaged articular surface. Each core comprises a cartilaginous surface and an underlying layer of subchondral bone. Preferably, the cores have a diameter of approximately 7 or 8 millimeters and a length of approximately 15 millimeters.

[0011] However, the number of "donor" sites—that is, suitable non-joint-bearing areas for core sampling—is limited. This mosaicplasty autografting technique is therefore intended for treating joint lesions with a limited surface area (typically less than 3 square centimeters).

[0012] Another approach, known as "osteochondral allografting," involves using a healthy osteochondral segment from a different individual than the one being treated. This technique is suitable for treating larger joint lesions, utilizing larger osteochondral grafts.

[0013] However, this technique is difficult to implement in routine practice, as the osteo-cartilaginous sampling must be carried out on a human organism that died less than 12 hours after death.

[0014] There Figure 1b This represents an example of an osteochondral core 13bis, intended, for example, for an osteochondral articular allograft. Core 13bis is shown here in isolation, after harvesting and before implantation in the patient. The length of core 13bis is approximately 4 centimeters.

[0015] Given the limitations of the approaches presented above in relation to Figures 1a and 1bIn humans, arthroplasty (joint replacement) has been proposed as a treatment for advanced osteoarthritis. Joints frequently treated in this way include the hip and knee. For advanced chondropathy of the knee, surgical implantation of a definitive unicompartmental or total knee prosthesis, permanently fixed under anesthesia, is common.

[0016] US document 2001 / 0014473 describes an in vitro cartilage tissue production device that defines a cellular space and is intended to be introduced into a culture environment.

[0017] The international patent application published under number WO 2005 / 016175 A2 describes a permanent joint prosthesis made of a rigid, biocompatible material, implanted directly into the affected joint cavity, to restore the expected mechanical properties of the joint. However, with such a permanent joint prosthesis, extensive joint rehabilitation is necessary. Significant medical care in a specialized center, including physiotherapy and supportive care, is often required.

[0018] In addition, there are significant risks of loss of mechanical functionality of the joint prosthesis over time, due to mechanical wear of the prosthesis components, and / or infection of the prosthetic material.

[0019] It follows from the above that, as things stand, current surgical practices and approaches do not allow for a fully satisfactory, sufficiently high-quality, and durable repair of articular cartilage, and / or present risks of infection and / or mechanical wear of the implanted devices. Furthermore, some of these treatments, based on current best practices, require extensive medical and surgical intervention.

[0020] Therefore, known approaches do not adequately address public health issues concerning the treatment of joint pain and joint mobility disorders related to cartilage damage. GENERAL DESCRIPTION OF THE INVENTION

[0021] There is therefore a need for an implantable device capable of promoting the generation of a new area of ​​articular cartilage, in order to replace an area of ​​deteriorated cartilage in a joint, particularly in the knee (femoro-tibial, or femoropatellar joint) or in the hip joint in humans.

[0022] The desired device must allow the formation of new osteo-cartilaginous tissue, advantageously comprising a sector of articular cartilage and a layer of subchondral bone.

[0023] To obtain good quality osteocartilaginous tissue, the newly formed cartilage must contain the different layers of chondrocytes (superficial, transitional, radial, and calcified cartilage layers) characteristic of articular cartilage. 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.

[0024] The desired device must exhibit excellent surgical maneuverability and not require overly complex medical intervention for its implantation. Preferably, the device should allow for the repair of larger joint areas compared to osteochondral autograft techniques, while also being easy to implant.

[0025] Ideally, the desired device should stimulate the formation of a new cartilage segment whose geometry is well-suited to the specific morphology of the joint being treated. The surface of the repaired cartilage should have a geometry very close to that of the native cartilage, thereby meeting the geometric criteria for optimal function and preventing further wear of the patient's cartilage after treatment.

[0026] A secondary objective is to provide a device enabling the production and placement of portions of newly formed cartilage in two areas of damaged cartilage, on the two opposite sides of the same injured joint.

[0027] To meet the aforementioned needs, a first aspect of the invention relates to a removable implantable device for the production of articular cartilage, comprising: a first support part made of biocompatible material, a second support part made of biocompatible material mounted movably on the first support part, the first support part and the second support part defining between them a cavity forming a cell development space, the cell development space being intended to receive osteochondrogenic cells multiplying in the cell development space, and actionable external mobilization means configured to move the second support part relative to the first support part, so as to generate shear within the cell development space.

[0028] The implantable device as defined above is intended to allow the formation of autologous osteo-cartilaginous tissue, after being implanted in an anatomical region preferably different from the joint to be treated.

[0029] This implantable device is removable, and is transiently implanted in a recipient tissue space, preferably an intramuscular or subcutaneous region of the individual which is therefore preferentially separated from the joint to be treated.

[0030] One advantage of such a device is that, following a phase of external mobilization, it allows the formation of osteo-cartilaginous tissue with a geometry adapted to the surface of the cartilage to be repaired. The formed tissue can then be extracted from the biocompatible scaffolds used in its production and implanted into the joint to be treated.

[0031] The osteo-cartilaginous tissue formed is, for example, implanted into the joint to be treated in a similar way to the autograft or allograft techniques mentioned above.

[0032] Optionally and without limitation, the implantable device according to this first aspect may have the following characteristics, taken alone or in any of the technically possible combinations: The device comprises a closed housing, formed by the first support part and the second support part, with the cell development space defined within the housing. The first support part includes an inner face facing the second support part, the second support part being configured to slide relative to the first support part along the inner face. The second support part is mounted to move in translation relative to the first support part, along a direction parallel to an extension surface of the inner face. The second support part is mounted to move in rotation relative to the first support part about an axis of rotation. At least one of the first and / or second support parts includes a cylindrical lateral face extending around the axis of rotation.The support portion further includes a base substantially perpendicular to the lateral face. The external mobilization means include a handle fixed to the base for rotation and movable for rotation about the axis of rotation. The external mobilization means include at least one mobilization cord mounted on the second support portion, configured to pull the second support portion. The mobilization cord is mounted on a first external face of the second support portion. The device includes an additional mobilization link mounted on a second external face of the second support portion, the second external face being opposite the first external face. The mobilization cord includes a semi-rigid strand, preferably a strand made of polymer material. The device includes a slide configured to guide movement of the second support portion relative to the first support portion.At least one of the first support part and / or the second support part includes a grid. The grid defines a plurality of cell growth cavities opening onto an interior side of the device. At least one of the first support part and / or the second support part includes an array of stiffening elements attached to said support part. The shear stiffness at the stiffening elements is strictly greater than the shear stiffness at a central area of ​​the cell growth space.

[0033] A second aspect of the invention relates to an implant for the formation of cartilage cells, the implant comprising: an implantable device as defined above; a repair cell matrix, interposed between the first support part of the implantable device and the second support part of the implantable device, the repair cell matrix comprising a volume of osteochondrogenic cells intended to multiply in the cell development space of the implantable device.

[0034] Optionally and without limitation, the implant according to this second aspect may have the following characteristics, taken alone or in any of the technically possible combinations: The cellular repair matrix includes at least one periosteal graft. The periosteal graft is vascularized. The periosteal graft is derived from a tibial periosteum. The implant is configured for removable implantation in an intramuscular region of an individual. The implant is configured for removable implantation in a subcutaneous region of an individual. GENERAL DESCRIPTION OF THE FIGURES

[0035] Other features, purposes, and advantages of the implant will become apparent from the following description, which is purely illustrative and not exhaustive and should be read in conjunction with the attached drawings, among which, in addition to the Figure 1a and of the Figure 1b already commented on: There Figure 2This schematically illustrates three differentiation pathways of mesenchymal stem cells: towards bone, fibrous, or articular cartilage tissue, depending on the mechanical stresses exerted on the mesenchymal stem cells. Figure 3 This schematically illustrates several successive stages of implanting an implant, according to an example of the invention, into an intramuscular region, followed by mobilization of said implant using external links to promote the formation of new cartilage, then explantation of the device and transfer of the resulting osteo-cartilaginous structure to the recipient joint. Figure 4aThis is a schematic top-view perspective of an implantable device according to a first embodiment. The device has a general parallelepiped-shaped casing, with a first portion and a second portion of the device shown separately. A pedicled periosteal graft is mounted on the first portion. Figure 4b This illustrates the same implantable device seen in the closed position, with the first and second portions fitted one on top of the other. Figure 5 is a schematic cross-sectional view (along plane AA shown on the Figure 4b ) of the device of the Figure 4b , whereas a periosteal graft is placed in the space for cell development. The Figure 6 is a schematic longitudinal cross-sectional view (along the BB plane shown on the Figure 4a ) of the device of the Figure 4billustrating a relative movement of the first and second supporting portions, as well as the development of osteochondrogenic cells. Figure 7 is a schematic cross-sectional view of the device of the Figure 4b Following mechanical mobilization of the implantable device, two portions of osteocartilaginous tissue were produced within the device, one convex and the other concave. Figure 8 schematically illustrates the dissociation of a first support portion, a second support portion, and two newly formed portions of osteocartilaginous tissue extracted from the two support portions, the implantable device conforming to the example of Figures 4a and 4b . There Figure 9is a schematic cross-sectional view of an implantable device according to a second embodiment, the device having a parallelepiped-shaped casing with curves, and intended to produce a single portion of osteocartilaginous tissue with a concave surface at the upper element. Figure 10 This is a schematic longitudinal cross-sectional view of an implantable device according to a third embodiment, at the time of its implantation. The device has a general cylindrical housing shape and is implanted in a muscle. This device is designed to produce two newly formed, flat portions of osteocartilaginous tissue opposite each other. Figure 11 is a schematic longitudinal cross-sectional view of the device of the Figure 10 during its mechanical mobilization, while osteochondrogenic cells developed. Figure 12This is a schematic longitudinal cross-sectional view of an implantable device according to a fourth embodiment, the device having a general shape of a quasi-cylindrical housing with one convex base and the other concave base. The device is intended to produce a single portion of newly formed osteocartilaginous tissue with a convex surface at the lower element. DETAILED DESCRIPTION OF SEVERAL METHODS OF IMPLEMENTING THE INVENTION

[0036] The examples of implantable devices described below are preferentially intended for the formation of new cartilage which will be subsequently implanted at the knee (femoro-tibial, or femoropatellar joint), or at the hip joint, particularly in humans.

[0037] The various examples of implantable devices described below are, however, adaptable to promote the generation of a new cartilage sector for any joint surface of the human or animal body.

[0038] The following examples involve the use of a periosteal graft as a repair matrix to generate osteochondrogenic cells within a space created in the implantable device. As will be seen below, the periosteal graft used is preferably harvested from the same individual and may or may not be vascularized.

[0039] It should be noted, however, that other types of cell repair matrices known in tissue engineering can be used. The repair matrix may or may not be associated with substances or compositions that aid growth and differentiation toward cartilage cells, such as proteins, growth factors, etc.

[0040] Throughout the attached figures and the description below, similar elements bear identical alphanumeric references. General principles relating to the formation of new articular cartilage

[0041] Articular cartilage is a flexible connective tissue found in joints, providing mechanical functions such as protecting bone ends, cushioning the pressure of loads exerted on bone ends, and allowing for the smooth gliding of opposing articular surfaces.

[0042] Articular cartilage is primarily composed of cells called chondrocytes and an extracellular matrix (collagens, glycosaminoglycans). Chondrocytes are responsible for the synthesis and maintenance of cartilage tissue. They are located in small compartments, each containing one or more chondrocytes. These compartments are called chondroplasts. Areas of cartilage can be damaged by various pathologies affecting the cartilage. The natural repair of articular cartilage is very limited. The progression of cartilage lesions involves cartilage fissures, a decrease in its thickness, and damage to the subchondral bone. This progression can lead to complete cartilage loss with exposure of the subchondral bone (eburnation).

[0043] Articular cartilage is found particularly on the epiphyseal surfaces of long bones. Chondrocytes originate from the cellular differentiation of stem cells located in the outermost layer of articular cartilage in adults. However, chondrocyte renewal is very slow, as this tissue repairs itself very poorly.

[0044] Long bones, with the exception of cartilage areas, are covered on the surface by a membrane called "periosteum" which ensures bone repair in case of fracture.

[0045] The periosteum is particularly rich in skeletal tissue repair stem cells (osteochondrogenic mesenchymal stem cells). For a detailed description of the composition and role of the periosteum, see the following publication: 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] Given the body's difficulty in spontaneously repairing articular cartilage in damaged areas of the joint surface, the device proposed here aims to reconstitute osteocartilaginous tissue in the damaged area that is qualitatively and geometrically equivalent to native articular cartilage (as it was initially before deterioration). This osteocartilaginous tissue reconstitution is performed using osteochondrogenic cells (typically derived from an autologous periosteal graft, as will be discussed below).

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

[0048] As an illustration, we have schematically represented on the Figure 2 attached three pathways A, B and C of mesenchymal stem cell differentiation.

[0049] From a volume of still immature osteochondrogenic cells 10, it is possible to influence the differentiation pathway and therefore the phenotype and future functionality of the newly formed tissue, through mechanical constraints exerted in the cell volume.

[0050] In pathway A, cells are "free" and no mechanical stress (or minimal stress) is exerted. Osteochondrogenic cells then preferentially give rise to 11A bone cells (osteocytes). A clinical illustration of pathway A is the fate of a bone fracture site properly stabilized by a cast or orthopedic cast. The fracture site (fracture callus), within which osteochondrogenic cells from the periosteum or bone marrow are present early on, will differentiate into bone (generally after a phase in the endochondral cartilage stage).

[0051] In pathway B, stretching forces (FB) are exerted along a preferred direction. This leads to the formation of fibrous tissue (11B), the constituent tissue of ligaments. A clinical example of pathway B is the surgical reconstruction of the lateral ankle ligament using a periosteal flap harvested from the fibula.

[0052] Finally, on "pathway C," shear forces FC are applied: the upper part of the osteochondrogenic cell volume is displaced to the left, and the lower part of said volume is displaced to the right. To the Applicant's knowledge, this pathway C of differentiation, which promotes osteochondrogenesis, has not yet been isolated, either naturally or in medical-surgical practice. The proposed device thus relies on shear movements applied to the cell volume, promoting directed differentiation of osteochondrogenic cells toward the formation of chondrocytes, ultimately resulting in areas of articular cartilage.

[0053] Following directed differentiation of osteochondrogenic cells via the C pathway, new cartilaginous surfaces 11C are obtained here extending on either side along the cleavage plane.

[0054] The various examples of implantable devices described below aim to promote the directed differentiation of immature osteochondrogenic cells, in a cell differentiation pathway similar to the aforementioned pathway C.

[0055] As will be seen below, the implantable device of the invention defines a space for cellular development in which immature osteochondrogenic cells are induced to multiply. A repair matrix, typically comprising a periosteal graft (preferably autologous), is placed within this space. Mechanical stresses are generated, by external mobilization, within this space, resulting in shearing of the cellular repair matrix along a precise cleavage plane, reproducible identically with each movement.

[0056] In order to ensure the development of osteochondrogenic cells and the directed differentiation of said cells towards chondrocytes (pathway C), it is proposed here to place the implantable device, temporarily, directly into the body of the individual to be treated, in a tissue space favorable to this cell development.

[0057] The selected space (for example, a muscular or subcutaneous region) nourishes the repair cell matrix located within the implantable device, promoting the development of osteochondrogenic cells. Implanting the device in an environment capable of nourishing the repair cell matrix in this way is particularly relevant when the latter includes a non-vascularized periosteal graft.

[0058] Preferably, an implantable device conforming to any of the examples described below is not initially implanted in or near the joint to be treated. Instead, it is proposed to temporarily place said implantable device in another region of the individual's body.

[0059] It is highly advantageous to place said implantable device in a removable manner in an intramuscular region of the individual, or in a subcutaneous region of the individual, during the phase of growth and directed differentiation of osteochondrogenic cells.

[0060] The intramuscular region presents a biological environment particularly favorable to the growth of new osteochondrogenic cells. Regarding the interactions between the environment of the intramuscular region and the growth of osteochondrogenic cells, we can cite the following publication: 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, Anaïs Julien, Jaselle Perry, Catia Pereira, Frédéric Relaix, Théodore Miclau, Ralph Marcucio, Céline Colnot, Stem Cells, May 2015, 33(5):1501-11.These two scientific publications show that the intramuscular region not only has high vascularization allowing for an influx of blood nourishing the graft, but also contains progenitor cells contributing directly to bone repair.

[0061] It is therefore advantageous to use a periosteal graft as a repair matrix within the implantable device, and to place the implantable device within an intramuscular region. The combined action of periosteal cells and neighboring myogenic cells creates a particularly favorable environment for the multiplication and directed differentiation of osteochondrogenic cells, to form the osteocartilaginous tissue comprising the new cartilage segment and the subchondral bone.

[0062] The main steps in the placement of an implantable device and the creation of a new cartilage area are described below, using an example.

[0063] Placement of an implant and mechanical mobilization to promote cartilage formation We have represented on the Figure 3 The appended diagram details the successive steps of placement, here in an intramuscular region 80 of a muscle 8 of a human individual, of an implant comprising a removable implantable device 1 and a cellular repair matrix 4, followed by external mobilization of said implant. Finally, the newly formed cartilage 12 is extracted from device 1 and implanted into a sector of the articular surface (here in the debridement cavity 92) of a damaged cartilage sector 90 of the same individual.

[0064] The implantable device 1 shown here has a parallelepiped-shaped casing. For example, it conforms to either of Examples 1A and 1B described below. The same procedure steps could be performed using a different implantable device.

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

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

[0067] To begin the procedure, the intramuscular region 80 is exposed. For example, an incision is made in muscle 8. The practitioner creates sufficient space within the muscle for the insertion of device 1.

[0068] Device 1 is then inserted into the intramuscular region 80. Device 1 is associated with a repair matrix (not shown in the diagram). Figure 3 ) inserted into a cell development space within device 1, forming an implant for cartilage formation. Device 1 is typically closed around the repair matrix.

[0069] One role of the repair matrix is ​​to provide intended osteochondrogenic cells, after directed multiplication and differentiation, to differentiate into chondrocytes and form newly formed cartilage 12. Very preferentially, the repair matrix includes a periosteal graft.

[0070] The periosteal graft, preferably autologous, was for example taken from a bone surface of the individual. In the present example, the periosteal graft is taken from the anterior aspect of the tibia. For example, the periosteal graft is a rectangular flap, very thin, with a width, for example, between 1 centimeter and 5 centimeters and a length between 5 centimeters and 10 centimeters. Alternatively, the periosteal graft can be taken from any other bone of the individual. It may or may not be associated with a pedicle 44 (in which case it will be referred to as a periosteal "flap");

[0071] Device 1 is associated with means of external mobilization, allowing the displacement of a first portion 2 of device 1 relative to a second portion 3 of device 1 to be forced. A shear is thus generated between the two said portions, to generate shear stresses within the cellular repair matrix.

[0072] In the present example, the external mobilization means include mobilization links 5. Here, a first pair of mobilization links 5 is fixed to each side of the second portion 3, and a second pair of links is fixed to each side of the first portion 2.

[0073] This second pair of ties stabilizes the first portion 2 in place relative to the intramuscular region, while the mobilization ties of the first pair are used to mobilize the second portion 3. To stabilize the ties of the second pair relative to the intramuscular region (particularly during mobilization of device 1), preferably, fasteners 53 secure said ties to the skin. These fasteners 53 are preferably made during closure of the muscle incision 8, for example, by sutures.

[0074] The use of more than two pairs of stabilization or mobilization links may be considered, if necessary.

[0075] Back to the Figure 3 To allow for subsequent mobilization after suturing of the intramuscular region 80, the mobilization ligations 5 here comprise an internal subcutaneous portion 52 and an external portion 50 intended to remain outside the individual's skin. Mobilization ligations 5 are chosen to be of sufficient length to provide external portions 50 of sufficient length for easy manipulation.

[0076] Here, the mobilization links 5 preferably include semi-rigid strands, preferably plasticized threads and / or suture threads.

[0077] The incision in muscle 8 is then closed so as to leave the external parts 50 outside. The external parts 50 pass through incision points 51 made in the skin, preferably above muscle 8. The attachments 53 are then made if necessary.

[0078] Device 1 is formed from one or more biocompatible materials, and the repair matrix is ​​preferably autologous. Therefore, the risks of rejection of device 1 by the body are limited.

[0079] At this stage, the implantable device 1 is preferably left immobile, permanently in the intramuscular region 80, in a context of muscle immobility. One advantage is that it allows time for osteochondrogenic cells to multiply within the cell development space inside device 1. The osteochondrogenic cells then multiply without any mechanical shear stress, until they "colonize" the cell development space.

[0080] In a subsequent step, device 1 is mobilized (preferably mechanically) to move the second portion 3 of the housing relative to the first portion 2 of the housing. Before mobilization, the osteochondrogenic cells are generally in a relatively immature state, allowing for their directed differentiation.

[0081] In the example shown on the Figure 3 , during the external mobilization phase: The first portion 2 of the housing remains fixed relative to muscle 8. For example, the mobilization straps 5 are held attached to the first portion 2 to force the first portion 2 to remain fixed relative to the muscle. The second portion 3 of the housing is displaced relative to muscle 8 and relative to portion 2. via the mobilization links 5 attached to the second section 3. For example, a mobilization link 5 located on one side of the second section 3 is pulled, for example along the mobilization direction D illustrated on the Figure 3 , then alternatively a mobilization link 5 located on an opposite side of the second portion 3.

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

[0083] One advantage of using electromechanical and / or electromagnetic mobilization means, associated for example with a control unit integrated into the implantable device 1, is to allow control of external mobilization of device 1 using control signals, which eliminates the need to pull on mobilization links during the mobilization phase.

[0084] The external mobilization of device 1 is preferably controlled in real time by the practitioner using medical imaging techniques, for example, ultrasound, so as to monitor the actual movements. Optionally, device 1 can be equipped with one or more sensors to detect displacement and / or velocity and / or acceleration of the second portion 3 relative to the first portion 2. Device 1 includes, for example, one or more accelerometers.

[0085] Preferably, the periosteal graft remains vascularized by a pedicle 44 (if a vascularized graft is used), particularly in the case where, during external mobilization of device 1, the lower face of portion 2 is immobilized.

[0086] Accordingly, a through-hole 46 is preferably provided through the lower face of the first portion 2 of the casing, so as to allow passage of the vessels of the pedicle 44 of the periosteal graft. The through-hole 46 here passes through the external wall 24 of the first portion 2, as shown in the Figure 4a The passage opening 46 is arranged here in a central area of ​​the grid 42 present on the first portion 2.

[0087] Preferably, the passage opening 46 is small. This allows the pedicled periosteum graft (which is preferably thin and flexible) to be temporarily rolled up to slide through the small passage opening 46. The vascularized periosteum can then be unrolled and inserted into the cell development space.

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

[0089] The external mobilization phase of the implantable device 1 can be repeated as many times as necessary, for a duration sufficient to generate shear stresses within the device. For example, mobilization lasting a few minutes can be performed daily, for a duration ranging from one to ten minutes.

[0090] At a later stage, once the newly formed cartilage(s) 12 have been obtained in the cell development space inside the device 1, the device 1 is extracted from the organism and disassembled, so as to recover the newly formed cartilage(s) 12.

[0091] The intramuscular region 80 is reopened to extract device 1 from the muscle, then the first portion 2 is separated from the second portion 3 (an example of dismantling a device 1 is described below in relation to the Figure 8 attached).

[0092] As illustrated at the bottom of the Figure 3 , the newly formed cartilage 12 obtained preferably comprises a cartilaginous surface 120 (here convex in shape) on the surface, and a zone of newly formed subchondral bone 122 underlying the cartilaginous surface 120.

[0093] We also represented on the Figure 3 a joint area 9 to be repaired, including the damaged cartilage sector 90.

[0094] The newly formed cartilage 12 is then implanted in place of the damaged area, at the level of the debridement cavity 92, after debridement of this cavity. In this example, the articular area 9 is a femoral condyle. The treated joint is a tibiofemoral joint.

[0095] It is understood, however, that newly formed cartilage could also be implanted to repair damaged cartilage in another joint. The implantation of newly formed cartilage is specifically considered for the patellofemoral joint, the talocrural joint, the glenohumeral joint, the acromioclavicular joint, and the hip joint.

[0096] The newly formed cartilage 12 obtained is, very advantageously, precisely adapted to the geometry of the damaged cartilage sector 90 to be repaired. Thus, the newly formed cartilage 12 is precisely shaped to the damaged cartilage sector 90.

[0097] Preferably, a trimming cavity 92 has been previously made on the surface of the damaged sector 90, the newly formed cartilage 12 then being implanted in the trimming cavity 92.

[0098] The term "trimming" refers to a procedure that involves eroding unhealthy cartilage and exposing the subchondral bone. Trimming allows for the removal of cartilage from the damaged area. Furthermore, trimming can generate micro-bleeding, an influx of new blood vessels, and a local release of growth factors into the native subchondral bone.

[0099] The morphology of the newly formed cartilage 12 is controlled by the choice of shape of the implantable device 1. By designing the device 1, and in particular by shaping the walls delimiting the space for cell development, it is possible to obtain cartilage adapted to a specific morphology of the joint cavity. Therefore, the first portion 2 and / or the second portion 3 are preferably custom-made, according to the morphology of the damaged area 90 to be repaired.

[0100] Such custom manufacturing is, for example, achieved through 3D printing. Any 3D printing technique using biocompatible materials can be employed, for example, one or more of the techniques described (particularly on page 22) in the publication Bioactive scaffolds for osteochondral regeneration,Deng, Chang, Wu, Journal of Orthopaedic Translation (2019) 17, pp.15-25, extrusion printing, laser printing, stereolithography, fused deposition modeling (FDM), selective laser sintering (SLS), electrospinning, etc.

[0101] The 3D printing of the implantable device 1 can be based on a three-dimensional model taking into account the geometry of the damaged cartilage sector 90, obtained by medical imaging.

[0102] Examples of medical imaging techniques that can be used for this purpose are magnetic resonance imaging (MRI) (T2 relaxation time MRI or T1RHO MRI) and / or MRI with so-called "dGEMRIC" acquisition sequences (delayed Gadolinium-Enhanced MRI of articular Cartilage) and / or standard radiography and / or arthro-CT scan.

[0103] After retrieving the newly formed cartilage(s) 12, said cartilage is implanted on the joint area 9. The placement of the newly formed cartilage 12 is possibly carried out by arthroscopy; such a procedure is quite minimally invasive.

[0104] A notable advantage of the approach proposed here is to allow the implementation of the trimming of the damaged cartilage sector 90 (here of the surface of the femoral condyle) posterior to the obtaining of the newly formed cartilage 12.

[0105] It is thus possible to control the quality and shape of the newly formed cartilage portion 12 before debriding the damaged area of ​​the cartilage to be repaired. The shape of the debriding cavity 92 can also be adapted according to the shape obtained for the newly formed cartilage 12. Debriding can also potentially be omitted, since it involves the destruction of the remaining (albeit damaged) native cartilage, and the implantation procedure can be abandoned if insufficient newly formed cartilage is produced within the device.

[0106] Examples of implantable devices designed to promote the formation of new cartilage are described below in relation to Figures 4a to 12 attached. Removable implantable devices according to any of these examples may be used to implement the procedure described above in relation to the Figure 3 . Example 1A - Translational mobilization to form two portions of cartilage

[0107] There Figure 4aThis schematically illustrates a removable implantable device 1 according to a first embodiment, shown in top perspective. Device 1 is preferably designed to be removably implanted in an intramuscular region, and / or designed to be removably implanted in a subcutaneous region.

[0108] Device 1 has a general closed housing shape. Device 1 comprises a first portion 2 of a housing made of biocompatible material and a second portion 3 of a housing made of biocompatible material.

[0109] The first portion 2 is represented on an upper part of the Figure 4a , and the second portion 3 is represented on a lower part of the Figure 4a On this Figure 4a , the two parts of the casing are therefore separated from each other.

[0110] The first portion 2 and the second portion 3 are designed to define a cavity between them, which forms a space 40 for cell development.

[0111] We have represented on the Figure 4b attached the same device 1, the first portion 2 of the housing being fitted with the second portion 3 of the housing (for example via a slide 6, which has not been shown on the Figure 4b (for greater clarity of the figure). Cell development space 40 is visible from the side, on a right-hand side of the Figure 4b .

[0112] The interior of device 1, designed to receive a 4-cell repair matrix, is also visible in cross-section on the Figure 5 attached. On the cross-sectional view of this Figure 5 , and on the Figures 7 And 9The vertical gap between the inner face 26 of the first portion 2 and the opposite inner face 36 of the second portion 3 is not shown to scale and has been enlarged for clarity. This vertical gap is very small (for example, less than one millimeter) compared to the dimensions of the first portion 2 and the second portion 3.

[0113] Space 40 is designed to receive osteochondrogenic cells (including cells from the development of the cellular repair matrix 4) and to allow the multiplication of these cells.

[0114] The second portion 3 of the housing is removably mounted on the first portion 2 of the housing. The connection of the second portion 3 to the first portion 2 is sufficiently strong to prevent failure during stress on the device 1 by the external mobilization means (which will be described below) during the mobilization phase.

[0115] The second portion 3 is mounted movable on the first portion 2; in the present example, the second portion 3 is movable in translation relative to the first portion 2 along a direction parallel to a longitudinal axis B of the housing.

[0116] The first portion 2 and / or the second portion 3 are preferably formed from a biocompatible material chosen from polymer materials (such as PTFE), extracellular matrices, bioceramic materials, bio-glasses or biocompatible metals, or from any mixture of these materials.

[0117] The first portion 2 of the housing is at least partially delimited laterally by a first lateral face 20 and a second lateral face 22. The lateral faces 20 and 22 are substantially perpendicular to the longitudinal axis of the housing, and extend along two substantially parallel surfaces.

[0118] In this example, the first lateral face 20 and the second lateral face 22 each include a central hollow. A hollow channel is thus formed along the longitudinal axis B of the first portion 2, connecting the lateral faces 20 and 22.

[0119] The first portion 2 of the housing is further delimited externally by an external face 24, and internally by an internal face 26. The external face 24 and the internal face 26 extend over two substantially parallel surfaces.

[0120] The inner face 26 is positioned opposite the second portion 3 of the housing. In this example, the inner face 26 is hollowed out in its center (at the level of the hollow channel between the lateral faces 20 and 22) to allow the development of osteochondrogenic cells to the bottom of the first portion 2.

[0121] The first portion 2 of the housing further comprises two internal lateral walls 28 that laterally delimit the hollow channel. The internal lateral walls 28 extend towards the second portion 3 from a bottom wall located behind the external face 24.

[0122] The second portion 3 of the housing is laterally delimited by a first lateral face 30 and a second lateral face 32. The lateral faces 30 and 32 are substantially perpendicular to the longitudinal axis of the housing and extend over two substantially parallel surfaces. Here too, the first lateral face 30 and the second lateral face 32 each include a central recess. An additional hollow channel is thus formed along the longitudinal axis B of the second portion 3, connecting the lateral faces 30 and 32.

[0123] The second portion 3 of the housing is delimited externally by an outer face 34, and internally by an inner face 36. The outer face 34 and the inner face 36 extend over two substantially parallel surfaces. The inner face 36 is positioned opposite the first portion 2 of the housing.

[0124] The second portion 3 of the housing further comprises two internal lateral walls 38 that laterally delimit the hollow channel. The internal lateral walls 38 extend towards the first portion 2 from a bottom wall located behind the external face 34.

[0125] In this example, and as shown on the Figure 4b , when the housing constituting the device 1 is closed, the respective hollow channels of the first portion 2 and the second portion 3 are placed opposite each other.

[0126] There Figure 6 The attached figure, which is a longitudinal cross-sectional view of device 1, corresponds to a cross-sectional plane passing through said two hollow channels. Figure 6 illustrates the first portion 2 and the second portion 3 during the external mobilization of device 1. The cell development space 40 extends inside the two hollow channels. This space 40 is delimited laterally by the inner lateral walls 28 of the first portion 2, and by the inner lateral walls 38 of the second portion 3. The cell development space 40 is further delimited from above (depending on the orientation of the Figure 4a by the inner side of the outer face 34, and is delimited from below by the inner side of the outer face 24.

[0127] Thus, when the second portion 3 is aligned with the first portion 2, the cell development space 40 provided inside the device 1 has a general parallelepiped shape.

[0128] The function of repair matrix 4 is to generate a multitude of osteochondrogenic cells. Repair matrix 4 advantageously includes a periosteal graft, the biological function of which has been described above.

[0129] Very advantageously (but not necessarily), the periosteal graft is a vascularized graft, for example, a vascularized pedicled graft. Figure 4a Figure 44 illustrates a periosteal graft attached to a pedicle, the pedicle passing through the opening 46 provided in the body of the first portion 2 of the housing. A non-vascularized graft can also be considered, or possibly a combination of a non-vascularized and a vascularized graft in cases where at least two different grafts are used.

[0130] Advantageously, the periosteal graft results from an autograft. In other words, the cells forming the periosteal graft are autologous cells, originating from the same individual in whom the joint implant is placed. The use of autologous cells promotes 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 more effectively promoted and the risk of rejection is greatly reduced.

[0131] In this example, the periosteal graft is taken from a tibial periosteum. One advantage is that the procedure for harvesting it from the tibial bone is easy and relatively non-invasive.

[0132] Preferably, before activation by means of external mobilization, the repair matrix 4 takes the form of a solid cohesive element, not necessarily attached to the device 1. For example, the repair matrix 4 is inserted (and possibly sutured) into the cell development space 40 just before insertion of the device 1 into the intramuscular or subcutaneous region.

[0133] One advantage of the access port 46 is that it allows vascularization of the repair matrix 4 throughout the mobilization phase using external mobilization methods. The port allows the passage of at least one blood vessel from outside the implant, ensuring that the repair matrix 4 is vascularized during mobilization. Such vascularization is particularly important when the repair matrix 4 includes a periosteal graft, to guarantee proper cell development.

[0134] Thus, after the implant is placed (for example in the intramuscular or subcutaneous region), osteochondrogenic cells multiply. in vivo based on repair matrix 4.

[0135] We have represented on the view of the Figure 6 Osteochondrogenic cells fill space 40 after multiplying inside the implant. In cases where the first portion 2 and / or the second portion 3 include conical tips 43, the osteochondrogenic cells preferentially fill the locules defined by the tips 43.

[0136] In this example, the second portion 3 is configured to slide relative to the first portion 2 along the inner face 26 during its translational movement, by external mobilization of the device 1. This is represented by a dashed line on the Figure 5 a surface P of extension of the inner face 26.

[0137] Device 1 includes external mobilization means, enabling the displacement of the second portion 3 relative to the first portion 2. This generates shear stress between the second portion 3 and the first portion 2, particularly in the vicinity of the extension surface P of the internal sliding surface 26. Shear stresses are thus generated within the cell development space 40.

[0138] Such shear stresses have the advantage of directing the differentiation of cells located near the P surface within the cell development space 40. Indeed, the cells closest to the P surface are the most exposed to shear stresses. The cells will therefore differentiate preferentially towards cartilage surface cells (differentiation pathway C illustrated in the diagram). Figure 2 ).

[0139] Thus, the external mobilization of device 1 materializes a cleavage plane within the cell development space 40, to exert shear stresses.

[0140] The shear stresses thus created are similar to the stresses exerted on a plane of mobility of a joint, here between a femoral condyle and a tibial plateau.

[0141] Device 1 is preferably activated after osteochondrogenic cells have begun to multiply (see illustrated example on the Figure 6 ).

[0142] Preferably, the external mobilization means include mechanical means. More preferably, said means include at least one mobilization loop mounted on the second portion 3, configured to allow the second portion 3 to be pulled relative to the first portion 2.

[0143] The term "mobilization loop" refers to a fastener (wire, cable, strap, etc.) attached to a part of the device 1, which can be pulled to force a relative movement of the second portion 3 with respect to the first portion 2, in this case a translational movement. Preferably, the mobilization loop is then attached to an external face, typically to one of the lateral faces 30 and / or 32 of the second portion 3.

[0144] In the example of Figures 4a à 8 The external mobilization means include a first mobilization loop 5A fixed to the lateral face 30 and a second mobilization loop 5B fixed to the opposite lateral face 32. Thus, the two mobilization loops 5A and 5B are fixed to opposite external faces of the second portion 3. These links have not been shown in the Figure 4b for greater readability.

[0145] As described previously in relation to the Figure 3 , when device 1 is implanted, the two mobilization laces 5A and 5B preferably include an inner length of thread subcutaneously and an outer length of thread intended to remain outside the skin.

[0146] Using the mobilization laces 5A and 5B, the second section 3 can be pulled from the left side and then from the right side (depending on the orientation of the Figures 4a And 6 ) relative to the first portion 2, so as to create a shear within the cell development space.

[0147] Preferably, the mobilization laces 5A and 5B are made with semi-rigid thread strands. Preferably, these laces are made of a polymer material. For example, any material commonly found in suture threads may be used.

[0148] Optionally and advantageously, the device 1 further includes a slide 6 guiding the movement of the second portion 3 relative to the first portion 2. Thus, when the device 1 is activated by the external mobilization means 5, the second portion 3 slides along the slide 6, so that the second portion 3 does not move in a transverse direction relative to the first portion 2.

[0149] Such a slide is visible on the Figure 4a as well as on the Figure 5 In this example, the slide 6 includes at least one monorail fixed to the first section 2. The monorail is mechanically attached to the rest of the first section 2. This monorail projects from its inner face 26, which faces the second section 3. The second section 3 then includes, on its inner face 36, at least one groove 60 complementary to the monorail. For clarity, the actual shape of the groove 60 is not shown in the figures. Figures 4a et 4b .

[0150] Preferably, the slide 6 has two identical longitudinal monorails on both sides, as shown in the Figure 4a .

[0151] Alternatively, a slide with a similar function could be obtained by placing one or two monorails at the level of the inner face 36 and one or two complementary grooves at the level of the inner face 26.

[0152] Such slides 6 are transposable to a variant of device 1 where the means of external mobilization would be electrical and not mechanical.

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

[0154] As such, device 1 preferably includes at least one fastening link, and even more preferably a pair of fastening links. On the Figure 4a The device 1 includes a first fixing link 5C on the lateral face 30, and further includes a second fixing link 5D on the lateral face 32. These links have not been shown in the Figure 4b for greater readability.

[0155] The fixation sling 5C and / or fixation sling 5D are, for example, attached to a muscle 8 into which the device 1 is implanted. The fixation slings 5C and 5D are, for example, sutured to the muscle 8, so that the first portion 2 remains fixed while the second portion 3 is moved in translation during the external mobilization phase. Alternatively, the fixation slings 5C and 5D may have respective external thread lengths intended to remain outside the skin, similar to the mobilization laces 5A and 5B. The fixation slings 5C and 5D can then be immobilized, for example, manually, at these external thread lengths.

[0156] Preferably, the 5C and 5D fixation links are made of semi-rigid thread strands. Preferably, these links are made of a polymer material. For example, any material commonly found in suture threads may be used.

[0157] Preferably, the first portion 2 and / or the second portion 3 comprise a hollow structure, forming hollow housings which extend the cell development space 40.

[0158] In the example of Figures 4a à 8 , the first portion 2 presents a grid 42 forming such a hollow structure.

[0159] The grid 42 extends from the inside of the outer face 24, along a direction of extension (width) perpendicular to the outer face 24. For clarity in the accompanying figures, the grid 42 has not been illustrated in the Figures 4a et 4b .

[0160] The grid 42 defines, in the width direction (extension direction perpendicular to the external face 24), a plurality of through-cell growth cavities opening from an internal side of the device 1.

[0161] Cell growth cavities are defined here between conical points 43 formed in the grid 42. Preferably, one base of the conical points 43 is oriented outwards and one apex of the conical points 43 is oriented inwards.

[0162] Hollow locules (e.g., parallelepiped and / or alveolar locules) are formed between the conical points 43. The interior spaces of the locules are an extension of the area where the repair matrix 4 is placed. Thus, the interior spaces of the locules extend the cell development space 40. The repair matrix 4 can then be placed and / or fixed above an upper surface of the grid 42 of the first portion 2, as illustrated in the Figure 5 .

[0163] The growth cavities (here the cells inside the grid 42) are through-holes on both sides. On the outside, the cells pass through the outer face 24 of the first portion 2, and on the inside, the cells join the cell development space 40.

[0164] One advantage of such a grid 42 is that during the translational movement of the second portion 3 relative to the first portion 2, the cells located in the vicinity of the outer face 24 (which are the cells furthest from the cleavage surface P) are more mechanically stable than the cells in the vicinity of the cleavage surface P.

[0165] During external mobilization of the implantable device, a stiffness gradient against shear is thus created within the cell development space 40. Cells located near the external face 24 are preferentially directed to form bone cells after differentiation (pathway A of the Figure 2 ). It is thus possible to obtain layers of subchondral bone in the newly formed cartilage 12 obtained after the mobilization of device 1.

[0166] In addition, grid 42 allows blood irrigation to reach the inside of the cell development space 40, from outside the device 1.

[0167] In addition, an advantage of using conical points 43 to form the grid 42 is that the separating walls of the grid 42 then have a thickness at the base greater than their thickness at the surface, which accentuates the stiffness gradient against shear.

[0168] To obtain grid 42, one or more cavities can be incorporated natively into the design of the first portion 2. For example, a 3D model of the first portion 2 can integrate the grid 42 cavities from its design stage. Alternatively, the grid 42 cavities can be created by perforation after manufacturing.

[0169] An additional advantage of providing a grid 42 at the level of the first portion 2 is to allow intercommunication between the repair matrix 4 and the environment of the intramuscular region, and in particular better vascularization of the repair matrix 4.

[0170] In this Example 1A, the second portion 3 does not include a grid. However, the second portion 3 here includes conical tips 43 forming growth cavities extending from the cell development space 40. Thus, the conical tips of the second portion 3 are opposite the conical tips of the first portion 2. Unlike the first portion 2, the spaces between the conical tips 43 of the second portion 3 do not form through perforations.

[0171] Alternatively, the second portion 3 could also have through perforations, for example, like the grid 42. However, it is advantageous for the outer surface 34 not to be perforated and for the cavities formed between the conical points 43 of the second portion 3 not to be through perforations. Indeed, the second portion 3 is intended to be displaced relative to the muscular region. The smooth outer surface 34 prevents friction between the second portion 3 and the surrounding muscular environment during its displacement.

[0172] Optionally and advantageously, at their base, at least some of the conical tips 43 of the first portion 2 and / or the second portion 3 may have recesses. Preferably, the shape of the recesses in the conical tips 43 is selected so as not to hinder the subsequent extraction of the newly formed osteocartilaginous tissue.

[0173] For 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 (for example, in the shape of a three-sided pyramid). Preferably, the triangular recess thus formed in the surface of the conical tip 43 does not extend to the apex of said tip 43.

[0174] Such hollowed conical tips 43 are advantageous because they increase the total contact area between the formed osteochondrogenic cells and the biomaterial scaffold within the cell development space. Furthermore, the rigidity of the first scaffold portion 2 and / or the second scaffold portion 3 is locally increased. To simplify the accompanying figures, the conical tips 43 have not been shown with such hollows in these figures.

[0175] As an alternative, the conical points 43 of device 1 do not have recesses.

[0176] Preferably, means of blocking in translation are provided on the first portion 2 and / or on the second portion 3. The means of blocking in translation allow the range of translational displacement of the second portion 3 to be defined relative to the first portion 2.

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

[0178] Here, the first portion 2 includes a pair of protuberances 27 projecting upwards, on one side of the first portion 2. The protuberances 27 are preferably placed axially close to each other along the longitudinal axis B, on one side of the longitudinal axis B. Each protuberance 27 includes, for example, a base, and a stem projecting from the base with a spherical termination.

[0179] The second portion 3 includes here, for its part, a pair of wedges 37. The wedges 37 are placed opposite each other, on the same side of the longitudinal axis B. Preferably, the distance between the inner faces of the wedges 37 along the longitudinal axis B is strictly greater than the distance between the protrusions 27 along the longitudinal axis B.

[0180] Thus, when the first portion 2 and the second portion 3 were fitted together as illustrated on the Figure 4b The protrusions 27 are inserted in their bases on the lateral face of the element 2 inside the longitudinal space provided between the wedges 37. The range of translational displacement of the second portion 3 relative to the first portion 2 is then limited by the butting of the protrusions 27 against the internal faces of the wedges 37.

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

[0182] Following mobilization of device 1 by external mobilization methods, which may be repeated regularly during a mobilization phase, the osteochondrogenic cells of space 40 differentiate into cartilage and subchondral bone cells. Thus, in Example 1A, two adjacent portions of newly formed cartilage 12 are obtained, as illustrated in the Figure 7 attached.

[0183] On the surface of grid 42, the cells closest to surface P preferentially differentiated into cartilage cells, to obtain cartilaginous surfaces 120.

[0184] At the base of grid 42 (in the vicinity of the external faces 24 and 34 on both sides of the case), the cells furthest from the surface P preferentially differentiated into subchondral bone cells, to obtain subchondral zones 122.

[0185] We have represented on the Figure 8 Dismantling of device 1 after extraction of said device from the subcutaneous or intramuscular region. In the present example, a mechanical force is applied to separate the first portion 2 and the second portion 3. This breaks the slide 6, preferably at the level of the monorail. For example, one base of the monorail remains on the first portion 2, and a distal part of the monorail is carried away by the second portion 3.

[0186] This results in two intact cartilages, ready to be assimilated into the joint cavity in order to repair the damaged areas of cartilage.

[0187] In this example, the damaged cartilage areas are located in a femorotibial joint. For example, one of the 12 newly formed cartilages is positioned at a femoral condyle, and the other is positioned at a tibial plateau facing the femoral condyle. Each newly formed cartilage is preferably embedded directly into the corresponding damaged area, for example, in a respective debridement cavity.

[0188] Preferably, the newly formed cartilages 12 conform to the geometries of the damaged cartilage areas to be repaired, and where applicable, to the geometries of the debridement cavities. After placement of the newly formed cartilage 12, the cartilage surface extends preferentially in continuity with the surfaces adjacent to the damaged cartilage area.

[0189] The steps for mobilizing and dissociating the portions of the implantable device as described above, for example, the Figures 4a à 8 annexed, are transposed in a similar manner to the other examples of removable implantable devices described below in relation to the Figures 9 à 12 attached.

[0190] An advantage of an implantable device according to the first example described above is to allow the simultaneous formation of two sectors of newly formed cartilage 12, adapted for implantation in two damaged sectors of cartilage belonging preferentially to two surfaces facing the same joint.

[0191] The average total thickness of the cartilage in an adult human femorotibial joint is approximately 5 millimeters. Thus, the average thickness of newly formed cartilage 12 (perpendicular to an extension surface of the outer face of the cartilage) is, for example, between 1 millimeter and 10 millimeters. Exemple 1B - Translational mobilization with a unique cartilage formation site

[0192] There Figure 9 This schematically illustrates an implantable device according to a second embodiment. The implantable device is seen in cross-section, perpendicular to a longitudinal extension axis.

[0193] The implantable device according to this second example has structural and functional characteristics very similar to device 1 according to the first example described above, with the exception of the structure of the first portion 2 of the housing. The second portion 3 of the housing is translationally mobile relative to the first portion 2 of the housing.

[0194] Unlike the previous Example 1A, the first portion 2 (which is preferably kept fixed relative to the intramuscular region) is not perforated and does not include a grid 42. The first portion 2 here includes a solid inner face 26', opposite the second portion 3. In the case where a slide 6 is included, the inner face 26' can extend between two longitudinal monorails of the slide 6.

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

[0196] The stiffening elements 7, for example, have a cross-shaped form and are preferably fixed to the inner face 26'. A cross-shaped form is obtained, for example, by 3D printing of biomaterial. Such stiffening elements 7 are shown on the Figure 9 .

[0197] One advantage of the stiffening elements 7 is to increase the stiffness against shear at the bottom of the cell development space 40, on the side of the first portion 2. This increases the stiffness gradient between the first portion 2 and the second portion 3.

[0198] Preferably, in this second example, the periosteal graft remains vascularized by a pedicle. To this end, a through-hole is preferably created through the inferior surface of the first portion 2, in order to allow the vessels of the pedicle to pass through.

[0199] The second portion 3 is translationally mobile relative to the first portion 2. For example, a slide 6 is fixed rigidly inside the first portion 2 to guide movement along the surface P, which includes the inner face 26'. During the mobilization phase of the implantable device, cells closest to the surface P tend to undergo shearing, while cells at the base of the conical tips 43 tend to move with the second portion 3. Cells furthest from the surface P preferentially differentiate into subchondral bone.

[0200] After mobilization and cell development, a complete newly formed osteocartilaginous tissue, comprising a cartilage surface and a subchondral bone region, is typically obtained within the first portion 2 and allows for the treatment of the damaged joint area. After extraction of the implantable device according to this Example 1B from the body, the first portion 2 and the second portion 3 are dissociated from the osteocartilaginous tissue. The conical tips 43 are not integrated into the newly formed osteocartilaginous tissue.

[0201] The cartilage possibly generated on the side of the second portion 3, in which the stiffening elements 7 are embedded, is not reused in the patient here.

[0202] In one possible variation, stiffening elements 7 could be positioned on the side of the second mobile portion 3 (against face 34), either replacing or in combination with the conical tips 43. The stiffening elements 7 are then optionally detached from the second portion 3 during the extraction of the newly formed osteocartilaginous tissue and remain integrated within this newly formed tissue. Integration of the stiffening elements 7 into the cartilage to be implanted is particularly feasible if the stiffening elements 7 are formed from a bioresorbable biomaterial, or from a biomaterial that is very well tolerated in the long term within the treated joint. Exemple 2A - Rotational mobilization to form two portions of cartilage

[0203] There Figure 10 This schematically illustrates an implantable device according to a third embodiment. This device is preferably designed to be removably implanted in an intramuscular region of an individual, and / or designed to be implanted in a subcutaneous region of an individual. Figure 10 represents the device implanted inside a muscle 8, under the epidermis 82, seen in longitudinal section.

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

[0205] The first portion 2 here presents a general cylindrical shape around the axis R, open at the bottom (according to the orientation of the Figure 10 The first portion 2 comprises a side wall 28 and a bottom wall 29. The bottom wall 29 is preferably disc-shaped. The side wall 28 extends downwards from an annular edge of the bottom wall 29.

[0206] The second portion 3 also has a general cylindrical shape around the axis R, open at the top (depending on the orientation of the Figure 10 The second portion 3 comprises a side wall 38 and a bottom wall 39. The bottom wall 39 is disc-shaped. The side wall 38 extends upwards from an annular edge of the bottom wall 39.

[0207] The second portion 3 is mounted in a removable manner on the first portion 2.

[0208] Preferably, the first portion 2 and / or the second portion 3 have rotational symmetry around the axis R. The first portion 2 and the second portion 3 closed on each other thus form a closed case of general cylindrical shape.

[0209] The external diameter of the side wall 38 is advantageously smaller than the internal diameter of the side wall 28, so that the second portion 3 is mobile in rotation around the axis R inside the side wall 38.

[0210] Similar to the two previous examples, the second portion 3 is configured to be moved relative to the first portion 2, notably under the effect of an external mobilization.

[0211] Preferably, the device includes a slide 6 intended to guide the rotation of the second portion 3 around the axis R relative to the first portion 2.

[0212] In the example of Figures 10 And 11The slide 6 includes an annular rib extending radially from the outside (with respect to axis R) from the side wall 38 of the second portion 3, preferably in the vicinity of a free edge of the side wall 38. The first portion 2 then includes an annular groove oriented radially inwards (with respect to axis R) from the side wall 28. It will be understood that, alternatively, a slide can be formed by an annular rib of the first portion 2 directed inwards, complementary to a groove of the second portion 3.

[0213] Optionally, the device includes additional means for fixing and guiding the rotation of the second portion 3 relative to the first portion 2.

[0214] As an example, the free edge of the side wall 28 (facing the second portion 3) may have external threads on its radially outer side. When mounting the second portion 3 onto the first portion 2 to obtain a closed housing, an additional retaining ring with a diameter larger than the outer diameter of the first portion 2 may be placed over the slide 6 and closed onto the free edge of the side wall 28. The retaining ring then preferably has, on its radially inner side, internal threads that complement the external threads of the side wall 28, allowing the ring to be screwed against the wall. Such a retaining ring is not shown in the diagrams. Figures 10 à 12 .

[0215] A cell development space 40 is defined axially between the inner side of the basement wall 29 and the inner side of the basement wall 39. This cell development space 40 can receive a repair matrix 4. This matrix has the characteristics already described above. The matrix preferably includes a periosteal graft. Preferably, again in this third example, the periosteal graft remains vascularized by a pedicle. Accordingly, the first portion 2 and / or the second portion 3 may include an opening for the passage of the pedicle (not shown in the accompanying figures).

[0216] As in the previous examples, the repair matrix 4 functions to generate a multitude of osteochondrogenic cells in the cell development space 40. Preferably, after a certain period of cell development, the osteochondrogenic cells fill the interior space of the first portion 2 and the interior space of the second portion 3, as illustrated in the Figure 11 .

[0217] Similar to the two previous examples, external mobilization means 5 can be actuated to move the second portion 3 relative to the first portion 2, so as to generate shear within the cell development space 40.

[0218] In the present example, the external mobilization means 5 include a movable handle rotating about the axis of rotation R. The movable handle is here fixed to the bottom wall 39. The movable handle here includes a handle 54 extending from the bottom wall 39 along the axis R and a gripping part 56 (here in the form of a steering wheel) extending outwards from the handle 54.

[0219] The movable handle is fixed to the second portion 3 of the housing, in its rotation around the axis R. Thus, if a practitioner or the patient grasps the gripping part 56 and pivots said part as illustrated in the Figure 11 , the second portion 3 is driven in rotation.

[0220] Preferably, during the mechanical stress on the second portion 3, the first portion 2 remains fixed relative to the muscle 8. Means of stabilizing the first portion 2 are provided for this purpose, such as attachments 83.

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

[0222] We have represented a shear surface Z, at the interface between the space inside the lateral wall 28 and the space inside the lateral wall 38. During the rotational movement of the second portion 3, shear stresses are generated in particular at the level of the cells located in the vicinity of the shear surface Z.

[0223] As described above, such shear stresses promote the directed differentiation of osteochondrogenic cells towards cartilage cells. The development of cartilaginous surfaces near the Z shear surface is favored.

[0224] Optionally and advantageously, to create a shear stiffness gradient within the space 40 (high shear stiffness near the bottom walls 29 and 39, and lower stiffness near the shear surface Z), the first portion 2 of the housing and / or the second portion 3 of the housing include conical tips 43 extending from the respective bottom walls 29 and 39 of the two said housing portions. The conical tips 43 form locules among themselves, for example, parallelepiped-shaped or honeycomb-shaped. The cell development space 40 extends to the bottom of the locules.

[0225] In this example, conical tips 43 are provided in both the first portion 2 and the second portion 3. One advantage is to increase the stiffness gradient against shear within the cell development space 40. In addition, the conical tips 43 form cavities that extend the cell development space 40 between the first portion 2 and the second portion 3. This promotes the formation of a subchondral zone in the newly formed cartilage.

[0226] On the first fixed portion 2, the cavities formed between the conical points 43 are preferably through cavities. Thus, a grid 42 is formed on the bottom wall 29, which is intended to remain fixed.

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

[0228] Optionally and advantageously, the implantable device further includes means for stabilizing the first portion 2 relative to the area of ​​the body in which the device is implanted, here muscle 8. In this example, the device includes attachments 83. The attachments 83 securely connect the first portion 2 (for example, the lateral wall 28) to the epidermis 82. The attachments 83 include, for example, two suture threads, each fixed at one end to the lateral wall 28 and at the opposite end to the epidermis 82. Thus, during mobilization of the second portion 3, the first portion 2 remains fixed relative to muscle 8.

[0229] One advantage of an implantable device like this third example is that the first portion 2 and the second portion 3 are not axially displaced relative to each other during mobilization. The two volumes of osteochondrogenic cells contained within the first portion 2 and the second portion 3 remain in contact throughout the mobilization. This prevents insufficient shear stress at the edges.

[0230] The implantable device described in this third example allows for the simultaneous formation of two cartilages. After extraction of the newly formed osteo-cartilaginous tissues, the conical tips (if present) are preferentially not integrated into the newly formed tissues.

[0231] In one possible variant, the implantable device of this Example 2B may include one or more arrays of stiffening elements 7 within the housing. The stiffening elements 7, similar in structure to that described above, are positioned, for example, against the base wall 29 and / or against the base wall 39, and preferably have a cross-shaped form. Preferably, the stiffening elements 7 replace the conical tips 43 and cover a major portion of the corresponding base wall. Such stiffening elements 7 may be integrated into the newly formed osteocartilaginous tissues (particularly if these stiffening elements are made of bioresorbable material or another material well tolerated by the joint in the long term). Exemple 2B - Rotational mobilization to form a convex-shaped cartilage

[0232] We have represented on the Figure 12 an implantable device according to a fourth example, similar structurally and functionally to the third example.

[0233] In this fourth example, the second portion 3 is mobile in rotation around the axis R relative to the first portion 2, via means of external mobilization 5. The device of the fourth example differs from the device of the third example by certain structural characteristics of the first portion 2 and the second portion 3. For the mounting of the second portion 3 on the first portion 2, an adjustable threaded fixing ring can be provided on the second portion 3, as in the previous example.

[0234] In this fourth example, the base wall 39 of the second portion 3 is preferably smooth and not perforated. The base wall 29 of the first portion 2, on the other hand, is preferably perforated, so as to form a grid 42 promoting the vascularization of the repair matrix 4.

[0235] Preferably, in this fourth example, the periosteal graft remains vascularized by a pedicle. For this reason, a through-through opening is preferably provided through the first portion 2, in order to allow the vessels of the pedicle to pass through.

[0236] The base wall 29 of the first portion 2 and / or the base wall 39 of the second portion 3 do not have a planar geometry here. Both base walls 29 and 39 are curved. Preferably, a convexity of the base walls 29 and 39 corresponds to a convexity of the damaged area of ​​cartilage to be repaired. The convexity required for the shape of the base walls 29 and 39 is determined, for example, from a 3D model of a cartilage area to be treated. One advantage is that, from the design stage of the implantable device, a suitable final shape can be anticipated for the newly formed cartilage obtained at the end of the mobilization phase.

[0237] It will be understood that such an adaptation of the convexity of the moving portions is also applicable to any of the other examples described above.

[0238] Furthermore, the implantable device in this Example 2B includes stiffening elements 7 positioned against the base wall 39. Preferably, the stiffening elements 7 replace the conical tips 43 of the second portion 3 of the preceding Example 2A. An implantable device according to the fourth example is adapted to allow the formation of a single newly formed cartilage on the side of the first portion 2, to treat a single damaged area of ​​cartilage having, for example, a non-flat shape (convex in the present Example 2B).

Claims

1. A removable implantable device intended for the production of articular cartilage, comprising: • a first support part (2) made of biocompatible material, • a second support part (3) made of biocompatible material and movably mounted on the first support part (2), the first support part (2) and the second support part (3) defining therebetween a cavity that forms a cell-development space (40), the cell-development space (40) being intended to receive osteochondrogenic cells which multiply in the cell-development space (40), • operable external mobilisation means (5A, 5B) configured to move the second support part (3) relative to the first support part (2) so as to generate shear inside the cell-development space (40).

2. The device according to claim 1, wherein at least one of the first support part (2) and the second support part comprises a bottom support wall and comprises two side support walls (28) extending from the bottom support wall, said two side support walls (28) delimiting the cell-development space (40).

3. The device according to any one of claims 1 or 2, wherein the device comprises a closed housing, formed by the first support part (2) and the second support part (3), the cell-development space (40) being defined inside the housing.

4. The device according to any one of claims 1 to 3, wherein the first support part (2) comprises an internal face (26) facing the second support part (3), the second support part (3) being configured to slide relative to the first support part (2) along the internal face (26), preferably wherein the second support part (3) is movably mounted in translation relative to the first support part (2), in a direction parallel to an extension surface (P) of the internal face (26).

5. The device according to any one of claims 1 to 4, wherein the second support part (3) is rotatably mounted relative to the first support part (2) around an axis of rotation (R).

6. The device according to claim 5, wherein at least one of the first support part and / or the second support part (3) comprises a cylindrical side face (38) extending around the axis of rotation (R), preferably wherein said support part (3) further comprises a base (39) substantially perpendicular to the side face (38), the external mobilisation means (5) comprising a handle (54) constrained to rotate with the base (39) and rotatable around the axis of rotation (R).

7. The device according to any one of claims 1 to 6, wherein the external mobilisation means comprise at least one mobilisation lace (5A) mounted on the second support part (3), configured to tow the second support part (3).

8. The device according to claim 7, wherein the mobilisation lace (5A) is mounted on a first external face (30) of the second support part (3), the device further comprising an additional mobilisation link (5B) mounted on a second external face (32) of the second support part (3), the second external face (32) being opposite the first external face (30).

9. The device according to any one of claims 7 or 8, wherein the mobilisation lace (5A, 5B) comprises a semi-rigid strand, preferably a strand made of polymer material.

10. The device according to any one of claims 1 to 9, the device comprising a slide (6) configured to guide a movement of the second support part (3) relative to the first support part (2).

11. The device according to any one of claims 1 to 10, wherein at least one of the first support part (2) and / or the second support part (3) comprises a grid (42), the grid (42) defining a plurality of cell-growth cavities opening on an inner side of the device.

12. The device according to any one of claims 1 to 11, wherein at least one of the first support part (2) and / or the second support part (3) comprises a network of rigidifying elements (7) fixed to said support part, a rigidity against shear at the rigidifying elements (7) being strictly greater than a rigidity against shear in a central region of the cell-development space (40).

13. An implant for the formation of cartilage cells, the implant comprising: • an implantable device (1) according to any one of claims 1 to 12, • a cellular repair matrix (4), interposed between the first support part (2) of the implantable device and the second support part (3) of the implantable device, the cellular repair matrix (4) comprising a volume of osteochondrogenic cells intended to multiply in the cell-development space (40) of the implantable device.

14. The implant according to claim 13, wherein the cellular repair matrix (4) comprises at least one periosteal graft, preferably a vascularised periosteal graft, preferably wherein the periosteal graft comes from a periosteum of the tibia.

15. The implant according to any one of claims 13 or 14, wherein the implant is configured to be removably implanted in an intramuscular region of an individual and / or is configured to be removably implanted in a subcutaneous region of an individual.