WO2010092065A1

WO2010092065A1 - Endo-prosthesis for cartilage lesions

Info

Publication number: WO2010092065A1
Application number: PCT/EP2010/051618
Authority: WO
Inventors: Christian Jorgensen; Danièle NOEL
Original assignee: INSERM (Institut National de la Santé et de la Recherche Médicale)
Priority date: 2009-02-11
Filing date: 2010-02-10
Publication date: 2010-08-19

Abstract

The present invention relates to an endo-prosthesis for repairing lesions of the cartilage wherein said endo-prosthesis comprises a flexible gridded sheet.

Description

ENDO-PROSTHESIS FOR CARTILAGE LESIONS

FIELD OF THE INVENTION

The present invention relates to an endo-prosthesis and a method for repairing lesions of the cartilage.

BACKGROUND OF THE INVENTION

In the field of rheumatology, articular cartilage injury and degenerative pathologies such as arthrosis represent common affections which impact the patient both in terms of pain and of functional handicap. Arthrosis affects 16% of the population above 65 years of age. Polyarthritis affects 0.3% of the population. Also, many traumatic lesions of the cartilage resulting from sport injuries require surgery. These articular cartilage conditions therefore have a significant socio-economic impact. To date, the main therapeutic approaches are palliative treatments, such as analgesics, anti-inflammatory drugs or local infiltrations of corticoids or hyaluronic acid.

Other available alternatives include surgical treatments which consist in the use of prostheses. Existing surgical treatments comprise for example the implantation of chondrocytes into the lesion. The chondrocytes can be covered by a periosteal graft, or placed within a hydrogel or a biocompatible polymer.

EP 1 273 312 discloses a porous scaffold for supporting chondrocytes or their progenitor cells differentiating thereto comprising a composite material which in turn comprises a mesh or porous sponge of a biodegradable synthetic polymer and a porous sponge of naturally derived polymer formed on and/or in the mesh or porous sponge.

WO 2005 110278 discloses a sterile cartilage defect implant material comprising milled lyophilized allograft cartilage pieces in a bio-absorbable carrier.

However, such treatments require extensive surgery and are limited to small surface lesions, since the implant tends to collapse within the lesion. Moreover, patients must be immobilized over long periods because physical activity aggravates the problem of implant collapsus.

Thus, there is still an existing need for an efficient and long-lasting therapy for articular cartilage lesions.

SUMMARY OF THE INVENTION

The present invention thus provides an endo-prosthesis for repairing lesions of the cartilage wherein said endo-prosthesis comprises a flexible gridded sheet, preferably with at least one anchorage device for anchoring the sheet into the cartilage.

The present invention also relates to an endo-prosthesis comprising a flexible gridded sheet with at least one anchorage device.

The present invention also relates to a method for repairing lesions of the cartilage comprising the step of placing an endo-prosthesis comprising a flexible gridded sheet onto a lesion of the cartilage.

DETAILED DESCRIPTION OF THE INVENTION

The present invention relates to an endo-prosthesis for repairing lesions of the cartilage wherein said endo-prosthesis comprises a flexible gridded sheet. The endo-prosthesis according to the invention can also be referred to as a chondral stent.

In the cardiovascular field, an endovascular stent or vascular stent is a tube that reinforces a weak spot or is used to re-open coronary arteries that have become narrowed as a result of coronary artery disease. The tube is delivered as a small diameter tube to the relevant site via a catheter and is subsequently expanded to a large diameter tube, typically by natural expansion (in the case of self-expanding stents). Accordingly, the tube is expanded and keeps the artery open or reinforced. The grid structure of the stent tube allows the expansion. A major difference between the endo-prosthesis according to the invention and a vascular stent lies in the fact that a vascular stent is an expandable tube, whereas the device according to the invention is a sheet. The endo-prosthesis of the invention is a flexible sheet which can be rolled up to facilitate implantation, but which opens up in order to fit the shape of the cartilage lesion to be repaired. The endo-prosthesis of the invention, when in use, is placed onto the cartilage where it covers the lesion of the cartilage, thus providing protection of the underlying substrate.

The term "flexible" as used herein refers to the capacity of the gridded sheet to be easily bent or rolled up without presenting any risk of rupture. As will be detailed below, such properties are conferred both by the material which the gridded sheet is made of and by the gridding, which also improves the elasticity of the endo-prosthesis.

In an embodiment, the flexible gridded sheet comprises a thin resiliently deformable mesh, said mesh being configured to extend generally in a plane in the absence of external stress. The mesh may comprise a plurality of wires extending generally parallel to each other, and a plurality of bridges connecting the wires to each other.

Each wire may extend generally along a mean line between the two ends of said wire. Said wire may present a series of waves extending generally transversally with respect to said mean line, the waves of said wire being arranged in the plane of the mesh in the absence of external stress. In a similar manner, each bridge may have at least one wave extending generally in a direction parallel to the wires, the wave of each bridge being arranged in the plane of the mesh in the absence of external stress. Besides, each bridge may extend generally transversally between two adjacent wires and connect said two adjacent wires to each other. Manufacturing of the endo-prosthesis of the invention can be carried out by adapting any method known in the art for manufacturing vascular stents in order to obtain a sheet rather than a tube. Typically, the endoprosthesis according to the invention can be made according to the method disclosed in US 2004/0162605 without performing the final steps. This document discloses a method for manufacturing a stent, whereby a flat metal sheet is first made, which is subsequently deformed in order to form a cylinder. Alternatively, the endo-prosthesis according to the invention may be made according to methods used for making cylindrical tubes, followed by an additional step of cutting the vascular stent cylinder along the long axis in order to obtain a sheet.

Two types of methods are generally employed and are known by the skilled person for the manufacture of vascular stents. The endo-prosthesis can comprise wires woven together in a Z or zig-zag shape or in the form of diamonds, and optionally welded, soldered or glued together. The endoprosthesis may also be made from a sheet of metal onto which a pattern is made by etching or laser cutting. The material of the endo-prosthesis is selected among the materials commonly employed for the manufacture of vascular stents.

Preferably, the endo-prosthesis of the invention is made of metal wire, such as inox, titanium, tantalum or alloys such as nitinol (a composition of nickel and titanium). Typically, the endo-prosthesis may be made of a material which inhibits excessive vascularisation, such as titanium.

As used herein, the expression "made of when referring to an endoprosthesis means that said endo-prosthesis predominantly consists of a given material. Typically, an endo-prosthesis made of a given material consists of at least 50%, preferably at least 60%, 70%, 80%, 90% 95%, or 99% of said material.

The diameter of the stent wire can be between 0.05 mm and 0.2 mm, preferably between 0.1 and 0.2 mm.

In a preferred embodiment, the endo-prosthesis is covered with an inorganic layer such as carbon, titanium oxide, nitride, cobalt-chromium, platinum, polymers or silicon.

In another embodiment, the endo-prosthesis of the invention is made of biocompatible polymer such as those employed for manufacturing bioabsorbable stents. Typically, the endo-prosthesis of the invention can be made of poly L-lactide, poly (D, L-lactide/glycolide copolymer), polycaprolactone, poly (hydroxybutyrate-hydroxyvalerate), or polyorthoester (described for example in Colombo and Carvouni, Circulation, 2000, 102: 371 ). The gridding of the endoprosthesis according to the invention can be that conventionally used for vascular stents. Preferably, the gridding is such that it enables the passage of small molecules such as nutrients on either side of the gridded sheet, but not the passage of cells. Preferably, the gridding of the gridded sheet is impermeable to chondrocytes. Advantgeously, the gridding of the gridded sheet also participates in the flexible properties of the endo-prosthesis.

The dimensions of the endo-prosthesis according to the invention depend on the shape of the lesion to be repaired. Typically, the dimensions of endo-prosthesis according to the invention range between 0.5 cm² and 25 cm². The area of the endo-prosthesis shall be at least equal to the area of the lesion. Preferably, the area of the endo-prosthesis shall be superior to the area of the lesion plus an additional 0.1 cm on each side.

In one embodiment, the endo-prosthesis is a rectangular-shaped grid. The dimensions of the endo-prosthesis are preferably comprised between 10 and 20 mm by 10 and 20 mm. The surgeon may shape the gridded sheet according to needs, depending on the shape and size of the lesion to be repaired.

The endo-prosthesis according to the invention can comprise at least one anchorage device. The anchorage device can be any device known in the art of cartilage repair for anchoring an implant to the cartilage surrounding the lesion. It can comprise, for example, hooks, pins, grapplers, pitons, surgical screws, biocompatible glue such as fibrin glue, anchoring loops for suturing etc. In particular, the flexible gridded sheet may present two opposite edges, the anchorage device being arranged at said opposite edges.

The anchorage device can be made of metal or any other material commonly used in orthopaedic surgery. For example, suitable pins can include Ortho-Pin (a commercially available lactide copolymer pin, Ed., Geistlich Sonne, Switzerland). Alternatively, the anchorage device can be biocompatible glue, such as organic fibrin glue sold as Tisseel by Baxter (Austria), or such as fibrin glue prepared in the surgical theatre using autologous blood samples.

In a preferred embodiment, the anchorage device can include one or several hooks, preferably one or several metal hooks made out of the same material as the gridded sheet. Typically, the hook(s) should be placed on the edge of the gridded sheet and facing the same side of the sheet. The term

"hook" as used herein refers to an expansion of the gridded sheet which forms an angle of at least 30° compared to the grid. Preferably, the angle formed by the hook is at least 45°, preferably at least 60°, even more preferably 90°. The length of the hook can vary between 0.2 to 2 mm.

Preferably, the length of the hook is comprised between 0.5 and 1 mm.

In a preferred embodiment, the endo-prosthesis of the invention is coated with a layer of biological agents such as anti-angiogenic agents, anti- inflammatory agents, agents inducing chondrogenesis.

Examples of anti-angiogenic agents include bevacizumab, ATF peptide, and angiostatin. Preferably, an anti-angiogenic drug according to the invention is angiostatin.

Anti-inflammatory agents include indomethacin, prednisone and diclofenac. Preferably, an anti-inflammatory agent according to the invention is indomethacin.

Agents inducing chondrogenesis can be selected from the group consisting of FGF-2, FGF-5, IGF-1 , TGF-beta1-3, BMP-2, BMP-7, PDGF and

VEGF. In a preferred embodiment, the agent inducing chondrogenesis is TGF- beta. Even more preferably, the agent inducing chondrogenesis is

TGF-beta 3.

Those factors can be placed within a biogel which coats the endoprosthesis, or can be incorporated into the endo-prosthesis itself when it is made out of a material forming nanopores. Different methods for coating an endo-prosthesis are known in the field of "coated stents" or "drug-eluting stents" and can be applied for coating the endo-prosthesis of the invention. Such methods are disclosed, for example in WO 1997 037617 and WO 2005 016187 and in the references incorporated therein.

In a preferred embodiment, the endo-prosthesis of the invention further comprises cells such as chondrocytes and/or a mixture of chondrocyte progenitors and differentiation factors which will induce their differentiation into chondrocytes. The chondrocytes can be derived from autograft material, allograft material, or from an in vitro culture after differentiation of progenitor cells into chondrocytes. A method for obtaining suitable cells is described in Mrugala D, Bony, C, Neves, N, Caillot, L, Fabre, S, Moukoko D., Jorgensen, C, and Noel D. Phenotypic and functional characterization of ovine mesenchymal stem cells; application to a cartilage defect model. Ann Rheum dis, 2007, JuI 20 (E-Pub ahead of print).

In one embodiment, the endo-prosthesis of the invention can be directly coated with chondrocytes and/or progenitor cells differentiating thereto. For example, US2007213801 discloses methods for producing a stent, coated with a biocompatible matrix which incorporates antibodies, antibody fragments, or small molecules, which recognize, bind to and/or interact with a progenitor endothelial cell surface antigen to immobilize the endothelial cells at the surface of the device. The method can be transposed to the endo-prosthesis of the invention by using molecules which bind to the surface of chondrocytes, such as hyaluronic acid, in order to immobilize chondrocytes on the surface of the endo-prosthesis. Alternatively, the endoprosthesis of the invention can be coated with a biogel which comprises chondrocytes or progenitor cells differentiating thereto, such as mesenchymal stem cells.

The invention also relates to a kit for repairing a lesion of the cartilage comprising an endo-prosthesis as defined above and chondrocytes or progenitor cells differentiating thereto. The invention thus relates to: a) an endo-prosthesis comprising a gridded sheet and b) chondrocytes or progenitor cells differentiating thereto. In one embodiment, the chondrocytes and/or progenitor cells differentiating thereto are included in an implant. According to this embodiment, said cells are associated with a biocompatible matrix. The matrix can be made of polypeptides or proteins such as gelatin or collagen. It can be made of other biological molecules such as sodium hyaluronate, hyaluronic acid and its derivatives, chitosan, and alginate Alternatively, the matrix can be made of biodegradable synthetic polymers such as those described in EP 1 273 312.

The invention therefore relates to the use of an endo-prosthesis comprising a flexible gridded sheet for repairing lesions of the cartilage.

Any lesion of the articular cartilage can be repaired using the endoprosthesis according to the invention. Conditions which can advantageously be treated using the endo-prosthesis of the invention include arthritic lesions of the knee, the hip or the shoulder. They can comprise lesions of bearing or non-bearing articulations of variable extension. The endo-prosthesis according to the invention can be used in the case of traumatic loss of cartilaginous substance. It can also be used for cartilage repair in the case of inflammatory articular diseases such as chondrocalcinosis, psoriatic arthritis and rheumatoid arthritis. The endo-prosthesis according to the invention can be used as an implant for repairing a lesion of the cartilage. The surgeon can implant the endo-prosthesis according to surgical procedures known in the art for treating lesions of the cartilage. Preferably, the surgical procedure involves arthroscopy. A small incision (about the size of a buttonhole) is made to insert the arthroscope. Several other incisions are made in order to insert the miniaturized surgical instruments and the endo-prosthesis. The endo-prosthesis is guided to the correct location in order to cover the lesion of the cartilage. It is then unfolded, positioned correctly and anchored down into the healthy cartilage surrounding the lesion. The endo-prosthesis according to the invention can be used alone or in combination with other implants conventionally used for repairing cartilage. Several endo-prostheses according to the invention can be used in combination if the lesion is very wide or if it has a very irregular surface.

The invention also relates to an endo-prosthesis comprising a flexible girded sheet, which is particularly adapted for use in repairing lesions of the cartilage.

In a preferred embodiment, said endo-prosthesis is made of metal wire, preferably titanium.

In a preferred embodiment, said endo-prosthesis further comprises at least one anchorage device. In a preferred embodiment, said endo-prosthesis is coated with at least one biological factor, selected from the group consisting of anti- angiogenic agents, anti-inflammatory agents and agents inducing chondrongenesis.

Without wishing to be bound by any theory, it is believed that the endo-prosthesis of the invention provides a good protection of the underlying cells and tissue against physical aggression due to mechanical forces in the joint, whilst enabling exchange of fluids on either side of the gridded sheet.

The endo-prosthesis both protects the underlying chondral lesion, stimulates endogenous progenitors and maintains a 3D structure that enables mesenchymal stem cells to differentiate to chondrocytes.

The endo-prosthesis of the invention possesses several advantages for use in repairing lesions of the cartilage.

Due to the material which the flexible gridded sheet is made of, the endo-prosthesis of the invention is resistant and biocompatible. Moreover, it possesses elastic properties which render it self- expanding, i.e. if introduced into a lesion in a rolled form it will expand out into a sheet form. Thus, the endo-prosthesis according the invention can be implanted easily into the cartilage, by a minimally invasive technique.

Due to the possible presence of the anchorage device, the endo- prosthesis of the invention possesses an excellent adhesion capacity and can be anchored into the healthy cartilage surrounding the lesion. Thus, the endo-prosthesis of the invention, once implanted to the site of the lesion, provides a long-term repair of the lesion.

The endo-prosthesis according to the invention is easy to make, and can be manufactured at relatively low cost. The endo-prosthesis of the invention can be easily handled in industrial chains, since it can be manufactured in existing facilities designed for manufacturing vascular stents, with only minor modifications, which will be easily carried out by the skilled person.

The endo-prosthesis according to the invention is easy to use, since it can be inserted by minimally invasive surgery.

Moreover, the endoprothesis offers the advantage of being able to maintain on site the cells (chondrocytes and/or progenitor cells differentiating thereto such as mesenchymal stromal cells trapped in a suitable matrix) in the cartilage lesions, with the possible release of appropriate growth factor such as TGFbeta3 or BMPs.

The invention also relates to a method for repairing lesions of the cartilage comprising the step of placing the endo-prosthesis according to the invention onto a lesion of the cartilage. In a preferred embodiment, the endoprosthesis is implanted by a minimally invasive procedure, preferably arthroscopy.

The invention also relates to a method for repairing lesions of the cartilage further comprising the step of designing a customized endoprosthesis according to the invention to enable a better fit onto the lesion. The shape of the endo-prosthesis can be adapted to the shape of the lesion. The additional agents and the presence of cells can also be adapted to the gravity of the lesion, depending on its depth, on its precise location etc.

In a preferred embodiment, the method of the invention comprises the steps of :

-determining the shape (surface dimensions and depth) of the cartilage lesion and

- shaping of an adaptable endo-prosthesis to fit the shape of the lesion; - implanting the endo-prosthesis.

Examples on techniques for determining the shape of the lesion include, but are not limited to X-ray radiology, Magnetic Resonance Imaging and diagnostic arthroscopy. In another embodiment, the method of the invention comprises the additional step of placing an implant comprising chondrocytes and/or progenitor cells differentiating thereto prior to implantation of the endoprosthesis.

FIGURE LEGENDS

The invention will further be illustrated in view of the figures and examples.

Figure 1 : Chondral stent

Figure 1 illustrates the endo-prosthesis, and an enlarged part thereof, according to the invention as defined in Example 1.

Figure 2: Cartilage lesion covered with the chondral stent

Figure 2 represents the endo-prosthesis of Example 1 when placed onto a cartilage in a female sheep model of lesion (Example 2), covering the two 0.5 mm diameter lesions performed in the condyle cartilage and filled with mesenchymal cells and polymeric scaffolds.

EXAMPLES

Example 1 : Manufacture of a chondral stent

On Figure 1 , the endo-prosthesis comprises a grid formed of a thin resiliently deformable mesh as flexible gridded sheet. The mesh, for example of rectangular shape, is represented in a flat configuration in which it extends generally in a plane.

The mesh comprises an arrangement in two dimensions of a plurality of wires and a plurality of bridges connecting the wires. As can be seen on Figure 1 , each wire extends generally parallel to a first direction of the plane between two opposite ends. The opposite ends of the wires are arranged in correspondence to define opposite edges of the mesh. Each wire extends generally along a fictive mean line, parallel to the first direction in the flat configuration, between the two opposite ends. Each wire presents a series of waves extending transversally with respect to the mean line. In the flat configuration, the waves of each wire are arranged in the plane, generally along a second direction of the plane, perpendicular to the first direction. In particular, the waves of each wire, for example having a U-shape or, as represented, a V-shape, are alternated and present respective summits arranged alternately on either sides of the mean line. As represented, the series of waves of two adjacent wires can be offset so that the respective summits of the adjacent wires alternately approach each other and move away from each other to form a diamond pattern between the adjacent wires.

The bridges connect the wires to each other. In particular, each bridge extends generally transversally between two adjacent wires and connects the respective summits of the two adjacent wires to each other, where these summits are close to each other. As can be seen on Figure 1 , each bridge has at least one wave extending generally in a direction parallel to the mean line of the wires. In the flat configuration, the bridges extend generally in the second direction whereas the waves of the bridges are arranged in the plane of the mesh, generally along the first direction.

The endo-prosthesis comprises an anchorage device adapted to secure the mesh to a body part. In Figure 1 , the anchorage device is made of hooks arranged at the opposite edges of the mesh. In particular, each hook is attached, for example welded, to the ends in correspondence of two adjacent wires.

Thanks to the above described structure, the endo-prosthesis can remain in or resiliently return to the flat configuration in the absence of external stress, especially as long as it is not deformed for introduction within the body or attachment to a body part, for example a cartilage, through the hooks. This structure however allows the endo-prosthesis to be flexible so as to permit its introduction within the body and the attachment to the body part. As an example, a vascular stent from Hexacath, France, was used to manufacture a chondral stent according to the invention (see Figure 1 ). A Titan2 Helistent of 10mm long and 4mm diameter, covered with titanium oxynitride, was cut along the longitudinal axis into a rectangular gridded sheet of approximately 25 mm x 10 mm. Twenty-five 1 mm-long titanium hooks were soldered onto the long edge with a spacing of 0.2mm. They formed a 90° angle with the gridded sheet. The sheet was then cut along the long edge to form squares of 10 mm x 10 mm.

Example 2: Use of the endo-prosthesis in a female sheep model of cartilage lesion

4 female sheep under general anaesthesia were laid down in lateral position, one knee bent to a 90° angle. The knee joint was exposed and a lateral luxation of the knee cap was performed. Two endochondral lesions of 0.5 cm diameter and 0.5 cm depth were performed using a Punch and a scalpel. The lesions were filled with autologous ovine labelled mesenchymal cells, expanded for 3 weeks ex vivo after selection by plastic adherence, in DMEM and betaFGF medium according to the procedure described in Mrugala D, Bony, C, Neves, N, Caillot, L, Fabre, S, Moukoko D., Jorgensen, C, and Noel D. Phenotypic and functional characterization of ovine mesenchymal stem cells; application to a cartilage defect model. Ann Rheum dis, 2007, JuI 20 (E-Pub ahead of print).

The chondral stent of Example 1 , without the hooks, was introduced by arthrotomy and, after expansion, was placed onto the lesion using tweezers. A gentle lateral pressure was exerted in order to implant the stent into the healthy cartilage surrounding the lesion (see Figure 2). The knee cap was placed back into a physiological position. After verifying that a correct bending and stretching of the knee could be performed and extensive washing, the joint capsule was sealed. The fascia and the skin were sutured. A thorough and widespread washing with Betadine was performed. The entire procedure was performed under strict surgical aseptic conditions. After waking, the sheep were placed under local monitoring for 24 hours in order to check for any discharge or any infection. The sheep were then allowed to stand and placed back in a field.

After 2 weeks, the knee joint was opened and the cells tracked through cell visio endoscope. The cartilage was further analysed, and the protective effect of the prosthesis evaluated.

No inflammatory reaction was observed around the endo-prosthesis, indicating that there was no toxicity. No degradation of the lesion was observed. Two weeks after surgery, the endo-prosthesis was still in place and had not moved compared to the implantation site. The grafted mesenchymal cells were still in place and were viable.

In conclusion, the endo-prosthesis is suitable for covering lesions of the cartilage, and provides a protective effect on the underlying cartilage.

Example 3: Use of the endo-prosthesis covered with mesenchymal cells in a female sheep model of cartilage lesion

The procedure described in Example 2 is performed on 4 female sheep using the chondral stent of Example 1 which has previously been covered with ovine mesenchymal cells. The endo-prosthesis is covered with 106 autologous mesenchymal stem cells pre-differentiated to chondrocytes with TGFb3 for 24h. The prosthesis is implanted after lateral incision on the knee joint of the sheep and after washing with serum, the wound is closed and the sheep allowed to stand after recovery from anaesthesia. Similar studies are performed in parallel with chondrocyte-coated endo-prostheses and uncoated endo-prostheses. The sheep are evaluated 1 month (batch n°1 ), 2 months (batch n°2) and up to 6 months (batch n°3) after implanting the chondral stent. The sheep are sacrificed, the knee joint is opened up, and the lesions are evaluated in several manners. First, a macroscopic evaluation is performed. Then, a scanographic evaluation of the radiographic lesions is performed. Finally, a histological analysis is carried out in order to assess the chondrogenesis below the stent. Example 4: Coating of the endroprothesis

The endoprosthesis of the invention was coated with multiple films of Poly(L-lysine) / Hyaluronane labelled by FITC. Observation under binoculars or by fluorescence microscopy revealed that the coating of the endoprosthesis was homogenous. The coating can also include growth factors such as TGFb3 or BMPs. All the documents cited are hereby incorporated by reference.

Claims

1. An endo-prosthesis comprising a flexible gridded sheet.

2. An endo-prosthesis according to claim 1 , wherein the flexible gridded sheet comprises a thin resiliently deformable mesh, said mesh being configured to extend generally in a plane in the absence of external stress.

3. An endo-prosthesis according to claim 2, wherein the mesh comprises a plurality of wires extending generally parallel to each other, and a plurality of bridges connecting the wires to each other.

4. An endo-prosthesis according to claim 3, wherein each wire extends generally along a mean line between the two ends of said wire, said wire presenting a series of waves extending generally transversally with respect to said mean line, the waves of said wire being arranged in the plane of the mesh in the absence of external stress.

5. An endo-prosthesis according to claim 3 or 4, wherein each bridge extends generally transversally between two adjacent wires and connects said two adjacent wires to each other.

6. An endo-prosthesis according to any of claims 3 to 5, wherein each bridge has at least one wave extending generally in a direction parallel to the wires, the wave of each bridge being arranged in the plane of the mesh in the absence of external stress.

7. An endo-prosthesis according to any of claims 1 to 6, specially adapted for use in treating lesions of the cartilage.

8. An endo-prosthesis according to any of claims 1 to 7, wherein the flexible gridded sheet is made of titanium.

9. An endo-prosthesis according to any one of claims 1 to 8, wherein the gridding of the flexible gridded sheet is impermeable to chondrocytes.

10. An endo-prosthesis according to any one of claims 1 to 9, further comprising an anchorage device.

11. An endo-prosthesis according to claim 10, wherein the anchorage device comprises one or several hooks, grapplers, pitons, loops for suturing or biocompatible glue.

12. An endo-prosthesis according to claim 10 or 11 , wherein the flexible gridded sheet presents two opposite edges, the anchorage device being arranged at said opposite edges.

13. An endo-prosthesis according to any one of claims 1 to 12, wherein the flexible gridded sheet is coated with at least one biological agent.

14. An endo-prosthesis according to claim 13, wherein the biological agent is selected from the group consisting of anti-angiogenic agents, anti-inflammatory agents and agents inducing chondrogenesis.

15. An endo-prosthesis according to any one of claims 1 to 14, further comprising chondrocytes and/or progenitor cells differentiating thereto.

16. A method for repairing lesions of the cartilage comprising the step of placing an endo-prosthesis according to any one of claims 1 to 15 onto a lesion of the cartilage.

17. A method according to claim 16, wherein said endo-prosthesis is implanted by arthroscopy.