WO2019068660A1 - Bouchon de cartilage - Google Patents

Bouchon de cartilage Download PDF

Info

Publication number
WO2019068660A1
WO2019068660A1 PCT/EP2018/076690 EP2018076690W WO2019068660A1 WO 2019068660 A1 WO2019068660 A1 WO 2019068660A1 EP 2018076690 W EP2018076690 W EP 2018076690W WO 2019068660 A1 WO2019068660 A1 WO 2019068660A1
Authority
WO
WIPO (PCT)
Prior art keywords
bone
cartilage
scaffold portion
scaffold
kit
Prior art date
Application number
PCT/EP2018/076690
Other languages
English (en)
Inventor
Lobat TAYEBI
Hua Ye
Zhanfeng Cui
James Richardson
Original Assignee
Oxford University Innovation Limited
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Oxford University Innovation Limited filed Critical Oxford University Innovation Limited
Publication of WO2019068660A1 publication Critical patent/WO2019068660A1/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02—Prostheses implantable into the body
    • A61F2/30—Joints
    • A61F2/30756—Cartilage endoprostheses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02—Prostheses implantable into the body
    • A61F2/28—Bones
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02—Prostheses implantable into the body
    • A61F2/28—Bones
    • A61F2/2846—Support means for bone substitute or for bone graft implants, e.g. membranes or plates for covering bone defects
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02—Prostheses implantable into the body
    • A61F2/30—Joints
    • A61F2/3094—Designing or manufacturing processes
    • A61F2/30942—Designing or manufacturing processes for designing or making customized prostheses, e.g. using templates, CT or NMR scans, finite-element analysis or CAD-CAM techniques
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B33—ADDITIVE MANUFACTURING TECHNOLOGY
    • B33Y—ADDITIVE MANUFACTURING, i.e. MANUFACTURING OF THREE-DIMENSIONAL [3-D] OBJECTS BY ADDITIVE DEPOSITION, ADDITIVE AGGLOMERATION OR ADDITIVE LAYERING, e.g. BY 3-D PRINTING, STEREOLITHOGRAPHY OR SELECTIVE LASER SINTERING
    • B33Y80/00—Products made by additive manufacturing
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02—Prostheses implantable into the body
    • A61F2/30—Joints
    • A61F2002/30001—Additional features of subject-matter classified in A61F2/28, A61F2/30 and subgroups thereof
    • A61F2002/30003—Material related properties of the prosthesis or of a coating on the prosthesis
    • A61F2002/3006—Properties of materials and coating materials
    • A61F2002/30062—(bio)absorbable, biodegradable, bioerodable, (bio)resorbable, resorptive
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02—Prostheses implantable into the body
    • A61F2/30—Joints
    • A61F2002/30001—Additional features of subject-matter classified in A61F2/28, A61F2/30 and subgroups thereof
    • A61F2002/30316—The prosthesis having different structural features at different locations within the same prosthesis; Connections between prosthetic parts; Special structural features of bone or joint prostheses not otherwise provided for
    • A61F2002/30535—Special structural features of bone or joint prostheses not otherwise provided for
    • A61F2002/30604—Special structural features of bone or joint prostheses not otherwise provided for modular
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02—Prostheses implantable into the body
    • A61F2/30—Joints
    • A61F2/30756—Cartilage endoprostheses
    • A61F2002/30757—Cartilage endoprostheses made of a sheet covering the natural articular surface, e.g. cap
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02—Prostheses implantable into the body
    • A61F2/30—Joints
    • A61F2/30756—Cartilage endoprostheses
    • A61F2002/30761—Support means for artificial cartilage, e.g. cartilage defect covering membranes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02—Prostheses implantable into the body
    • A61F2/30—Joints
    • A61F2/30756—Cartilage endoprostheses
    • A61F2002/30766—Scaffolds for cartilage ingrowth and regeneration
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02—Prostheses implantable into the body
    • A61F2/30—Joints
    • A61F2/30767—Special external or bone-contacting surface, e.g. coating for improving bone ingrowth
    • A61F2002/3092—Special external or bone-contacting surface, e.g. coating for improving bone ingrowth having an open-celled or open-pored structure
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02—Prostheses implantable into the body
    • A61F2/30—Joints
    • A61F2/3094—Designing or manufacturing processes
    • A61F2/30942—Designing or manufacturing processes for designing or making customized prostheses, e.g. using templates, CT or NMR scans, finite-element analysis or CAD-CAM techniques
    • A61F2002/30962—Designing or manufacturing processes for designing or making customized prostheses, e.g. using templates, CT or NMR scans, finite-element analysis or CAD-CAM techniques using stereolithography
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02—Prostheses implantable into the body
    • A61F2/30—Joints
    • A61F2/3094—Designing or manufacturing processes
    • A61F2002/30985—Designing or manufacturing processes using three dimensional printing [3DP]

Definitions

  • This invention relates to a kit of parts for forming a joint plug, for example a knee plug, for use in the treatment of damaged cartilage and an assembled implant for the same.
  • Cartilage is a thin, elastic tissue that protects the bone of a joint, and allows supple movement of the joint by ensuring that the surfaces within the joint can slide easily over each other.
  • Cartilage tissue lacks a neural network. Accordingly, when cartilage is damaged and partly removed, the joint can become painful as the neural network of the underlying bone becomes exposed. In addition, cartilage has very limited capacity for self- restoration.
  • surgeons may remove damaged cartilage and underlying bone tissue from the damaged joint, and stimulate growth of tissue in the damaged area by cell therapy or other methods.
  • surgeons may take bone from other parts of the patient's body (autograft) and apply the autograft to the damaged area of the joint (e.g. knee). They may also use allografts.
  • autograft bone can cause morbidity of other parts of the body, while allografts can sometimes transfer disease.
  • Figure 1 a provides a schematic view of the kit according to an embodiment of the present invention
  • Figure 1 b provides a schematic view of the kit of Figure 1 a assembled as a joint plug and located within a bone layer and cartilage layer of a damaged knee joint;
  • Figure 2 is a graph showing the growth of osteoblasts on a bone scaffold portion of a kit according to an embodiment of the present invention
  • Figure 3 is a graph showing the rate of degradation of a cartilage scaffold portion of a kit according to an embodiment of the present invention.
  • Figure 4 is a graph showing the proliferation rate of chondrocytes on a cartilage scaffold portion of a kit according to an embodiment of the present invention. DESCRIPTION
  • a kit of parts for assembly into a joint plug is for insertion within an opening of a bone layer in a joint and through a cartilage layer on the bone layer.
  • the kit of parts comprises a bone scaffold portion for accommodating bone tissue therein.
  • the bone scaffold portion is configured for insertion into the opening of the bone layer.
  • the kit of parts further comprises a cartilage scaffold portion for accommodating cartilage tissue therein.
  • the cartilage scaffold portion is configured to be positioned over the bone scaffold portion.
  • the kit of parts further comprises a permeable membrane portion configured to be provided over the cartilage scaffold portion.
  • the kit of parts further comprises engagement means for mounting the cartilage scaffold portion on the bone scaffold portion.
  • a joint plug for insertion within an opening of a bone layer in a joint and through a cartilage layer on the bone layer.
  • the joint plug is for treatment of damaged cartilage.
  • the joint plug comprises a bone scaffold for accommodating bone tissue therein, said bone scaffold portion configured for insertion into the opening of the bone layer.
  • the joint plug further comprises a cartilage scaffold portion for accommodating cartilage tissue therein, said cartilage scaffold portion being configured to be positioned over the bone scaffold portion.
  • the joint plug further comprises a permeable membrane portion configured to be provided over the cartilage scaffold portion.
  • the joint plug further comprises engagement means for mounting the cartilage scaffold portion on the bone scaffold portion.
  • the joint plug may comprise any of the features of the kit of parts described herein.
  • the kit of parts can be assembled to form a joint plug for the treatment of damaged cartilage in a joint.
  • the joint plug of the present invention may be used in ACI (autologous chondrocyte implantation), for example as a knee-plug.
  • bone tissue can grow in the bone scaffold portion when the joint plug is inserted within the opening of the bone layer.
  • the bone scaffold may be configured to accommodate osteoblasts as they propagate to form bone tissue.
  • the bone scaffold portion may be provided with openings or pores for accommodating osteoblasts. Accordingly, once positioned within the bone layer, the scaffold can facilitate growth of bone tissue within the bone layer. Thus, bone tissue can grow into the bone layer of the joint, so as to secure the joint plug in place.
  • the cartilage scaffold portion is configured to accommodate cartilage tissue.
  • the cartilage scaffold portion may comprise openings or pores for accommodating chondrocytes.
  • chondrocytes present in the cartilage scaffold portion can propagate and form a cartilage layer over the bone.
  • the cartilage scaffold portion may facilitate cartilage growth within the cartilage layer and retain chondrocytes within the layer, improving cell differentiation between the bone layer and the cartilage layer.
  • the permeable membrane portion is positioned over the cartilage scaffold portion to help to retain cartilage tissue within the cartilage layer, while allowing nutrients to diffuse through the membrane portion into the cartilage scaffold portion to facilitate cell propagation and growth.
  • the membrane portion may also facilitate sliding of the joint, for example the knee joint.
  • the permeable membrane portion may also cover an area of the surrounding joint tissue.
  • the permeable membrane portion may be attached to the surrounding joint tissue, for example by suturing or stitching.
  • the kit of parts of the present disclosure may be assembled into a joint plug that can be used for joint repair.
  • the joint plug can be used to support bone tissue growth and/or cartilage growth, while maintaining good cell differentiation between the bone and cartilage layers.
  • the kit of parts may also simplify the surgical procedure employed for joint repair, as the bone scaffold portion and the cartilage scaffold portion may be seeded with cells ex-vivo and the seeded portions inserted into the joint, for example, together as a unit.
  • the permeable membrane portion may be placed over the cartilage scaffold portion before insertion, again potentially simplifying the surgical procedure as the assembled plug may be inserted into the joint.
  • the joint plug may be a knee plug.
  • the joint plug may be for use at the elbow, ankle, hips, wrists or other joints of the body.
  • the joint plug is a knee plug or ankle plug.
  • a bone scaffold portion for the kit of parts for assembly into the joint plug as described herein, the bone scaffold portion for accommodating bone tissue therein and for having a cartilage scaffold portion of the joint plug provided thereon.
  • cartilage scaffold portion for the kit of parts for assembly into the joint plug as described hereinbefore, the cartilage scaffold portion for accommodating cartilage tissue therein and configured to be provided on a bone scaffold portion of the joint plug.
  • a method of forming the bone scaffold portion for the kit of parts for assembly into the joint plug comprises receiving sensor data from a sensor device.
  • the sensor data is indicative of the shape of the opening of the bone layer into which the bone scaffold portion will be inserted.
  • the method further comprises determining a bone scaffold portion shape based on the obtained sensor data, and forming the bone scaffold portion having the bone scaffold portion shape using a three-dimensional (3D) printing device.
  • bone scaffold portions for joint plugs can be manufactured to be
  • kits of parts in accordance with the present invention may be formed with a controlled structure.
  • the bone scaffold layer and/or the cartilage scaffold layer may be formed using 3D printing, such that they correspond to the size of the opening in the bone layer in which they are to be inserted.
  • 3D printing also provides controllability of the size of the pores within the bone scaffold layer and/or the cartilage scaffold layer. This is important for the growth of new tissues such as bone tissue and cartilage tissue.
  • the pore size of the bone scaffold layer may be tailored to accommodate osteoblasts and other cells for bone tissue growth.
  • the pore size of the cartilage scaffold layer may be tailored to support chondrocytes.
  • a gradient in the pore size within the bone scaffold layer and/or the cartilage scaffold layer may be present. This may facilitate cell seeding and growth.
  • the method may further comprise seeding the bone scaffold portion with bone cells.
  • the method may further comprise determining a cartilage scaffold portion shape based on the obtained sensor data, and forming the cartilage scaffold portion having the cartilage scaffold portion shape using the or a further three-dimensional (3D) printing device.
  • a method of preparing a joint plug for insertion into an opening in a bone layer of a body is for treatment of a damaged cartilage layer covering the bone layer.
  • the joint plug comprises a bone scaffold portion for accommodating bone tissue therein, said bone scaffold portion being configured for insertion into the opening of the bone layer.
  • the joint plug further comprises a cartilage scaffold portion for accommodating cartilage tissue therein, said cartilage scaffold portion being configured to be positioned over the bone scaffold portion.
  • the joint plug yet further comprises a permeable membrane portion configured to be provided over the cartilage scaffold portion.
  • the method comprises: seeding the bone scaffold portion with bone tissue; seeding the cartilage scaffold portion with cartilage tissue; and assembling the joint plug by providing the cartilage scaffold portion over the bone scaffold portion and providing the permeable membrane portion over the cartilage scaffold portion.
  • the cartilage scaffold portion is provided between the bone scaffold portion and the permeable membrane portion in the assembled joint plug, which is also a seeded joint plug and ready for insertion into the body for treatment of damaged cartilage in or around a joint.
  • the joint plug may be assembled after seeding of the bone scaffold portion with bone tissue.
  • the joint plug may be assembled before seeding of the bone scaffold portion with bone tissue.
  • the bone scaffold portion may be seeded with bone tissue as part of assembly of the joint plug.
  • the joint plug may be assembled after seeding of the cartilage scaffold portion with cartilage tissue.
  • the joint plug may be assembled before seeding of the cartilage scaffold portion with cartilage tissue.
  • the cartilage scaffold portion may be seeded with cartilage tissue as part of assembly of the joint plug.
  • the kit of parts may further comprise bone scaffold engagement means for mounting the cartilage scaffold portion on the bone scaffold portion.
  • the engagement means may take the form of a plurality of protrusions or legs extending from either the bone scaffold portion or the cartilage scaffold portion, or from both of the bone and cartilage scaffold portions.
  • the cartilage scaffold portion may be secured to the bone scaffold portion. This can restrict the position of the bone scaffold portion relative to the cartilage scaffold portion, which, in turn, can facilitate cell differentiation, as bone tissue growth and cartilage growth may be substantially constrained in their respective parts.
  • Engagement between the cartilage scaffold portion and the bone scaffold portion may also allow the two portions to be coupled together prior to insertion into the joint. This may simplify the surgical procedure.
  • the kit of parts may further comprise membrane portion engagement means for mounting the permeable membrane portion on the cartilage scaffold portion.
  • the permeable membrane portion may be secured to the cartilage scaffold portion.
  • the juxtaposition of the membrane portion relative to the cartilage scaffold portion can help to prevent migration of chondrocytes away from the cartilage layer, keeping the chondrocytes in place within the cartilage scaffold portion.
  • the membrane may also facilitate sliding of the joint, for example, while the cartilage layer is still undergoing repair.
  • Engagement between the membrane portion and the cartilage scaffold portion may also allow the two portions to be coupled together prior to insertion into the joint. This may, in some circumstances, simplify the surgical procedure, particularly if the bone scaffold portion is also coupled to the cartilage layer as the assembled plug may be inserted as an integral unit.
  • the kit of parts may further comprise a barrier portion to be provided in the bone scaffold portion to substantially prevent passage of cartilage tissue from the cartilage scaffold portion beyond the barrier portion within the bone scaffold portion.
  • the barrier portion may comprise pores that are sized to prevent the passage of cartilage tissue or chondrocytes form the cartilage layer into the bone scaffold portion.
  • the barrier portion is devoid of pores.
  • the barrier portion may be integral with the bone scaffold portion or may be a separate layer.
  • the barrier portion may be configured to be provided less than 500 micrometres from an interface between the cartilage scaffold portion and the bone scaffold portion.
  • the barrier portion may be provided by a portion of the bone scaffold portion.
  • the barrier portion may be provided by a layer of the bone scaffold portion.
  • the bone scaffold portion may be formed from a biodegradable material.
  • the biodegradable material may be configured to degrade in less than 80 days, or less than 65 days, for example in less than 50 days.
  • the bone scaffold may be formed from a suitable material that is not degradable.
  • the bone scaffold portion may be formed from a ceramic or composite material.
  • the bone scaffold portion may be formed from at least one of the following materials: bioactive glasses, biodegradable magnesium alloys, biocompatible ceramics, biodegradable synthetic polymers, and biodegradable natural polymers.
  • biocompatible ceramics include ⁇ -tri-calcium phosphate, tricalcium phosphate, aluminium oxide, calcium oxide, tribasic calcium phosphate, zirconium oxide, bioactive hydroxyapatite, and pyrolitic carbon ((LTI)Pyrolitic carbon).
  • the bone scaffold portion may be in the form of a composite.
  • biodegrable synthetic polymers examples include poly(a-esters),
  • the porous film may be formed from a synthetic material selected from proteins and poly(amino acids), and polysaccharides.
  • proteins and poly(amino acids) include collagen, poly(amino acids), elastin, elastin-like peptides, albumin and fibrin.
  • the polysaccharide may be of human origin or of non-human origin.
  • the bone scaffold portion may be formed from a mixture of tricalcium phosphate (TCP) and hydroxyapatite (HA).
  • TCP tricalcium phosphate
  • HA hydroxyapatite
  • the tricalcium phosphate is sintered tricalcium phosphate.
  • the ratio of TCP to HA may be 2:1 to 10:1 , preferably, 3:1 to 6:1 , for example 4:1 to 5:1.
  • the mixture of TCP and HA may additionally include, for example, sodium tripolyphosphate and /or carboxymethylcellulose.
  • the bone scaffold portion can be formed from a paste material suitable to be formed by a 3D printing process, which enables direct matching of the shape of the bone scaffold portion to the opening in the bone layer.
  • the present disclosure may also provide a 3D printing ink composition comprising tricalcium phosphate (TCP), hydroxyapatite (HA) and a liquid carrier.
  • TCP tricalcium phosphate
  • HA hydroxyapatite
  • the ratio of TCP to HA may be 2:1 to 10:1 , preferably, 3:1 to 6:1 , for example 4:1 to 5:1 .
  • the ink may additionally include, for example, sodium tripolyphosphate and /or carboxymethylcellulose.
  • the bone scaffold portion comprises bone tissue accommodation means to accommodate bone tissue therein.
  • the bone scaffold portion may comprise pores having a large pore size.
  • the pores have a diameter of between 300 ⁇ - 1 mm, preferably between 400 - 800 ⁇ , for example between 500 - 700 ⁇ .
  • the pores may be regularly shaped.
  • the pores may define chambers or tunnels extending through at least a portion of the bone scaffold portion.
  • the bone scaffold portion may take the form of a matrix.
  • the bone scaffold portion takes the form of a matrix comprising a plurality of pores.
  • the pores may be regularly spaced and, in some embodiments, take the form of regularly spaced chambers or tunnels extending through at least part of the bone scaffold portion.
  • the bone scaffold portion may be configured to support the cartilage scaffold portion thereon.
  • the bone scaffold portion may include
  • the bone scaffold engagement means may comprise one or more protrusions for mechanical engagement between the bone scaffold portion and the cartilage scaffold portion when the kit of parts is assembled into the joint plug.
  • the one or more protrusions may be one or more legs extending between the bone scaffold portion and the cartilage scaffold portion when the kit of parts is assembled into the joint plug.
  • the one or more legs may extend from the cartilage scaffold portion within the bone scaffold portion when the kit of parts is assembled into the joint plug to mount the cartilage scaffold portion to the bone scaffold portion.
  • the one or more protrusions may be a plurality of protrusions.
  • the bone scaffold portion may be coupled to the cartilage scaffold portion by other means, for example, by an adhesive, stitching or stapling.
  • the bone scaffold portion may be in the form of granules or a powder matrix that supports bone tissue growth.
  • the cartilage scaffold portion may be formed from a biodegradable material.
  • the biodegradable material may be configured to degrade in less than 80 days, or less than 65 days, for example in less than 50 days.
  • the cartilage scaffold may be formed from a suitable material that is not degradable.
  • the cartilage scaffold portion may be formed from a hydrogel, biodegradable polymer, or a composite material.
  • the cartilage scaffold portion may be formed from a synthetic material selected from poly(oesters), polyurethanes, poly(ester amides), poly(ortho esters), poly(ortho esters), polyanhydrides, poly(anhydride-co-imide), cross-linked polyanhydrides, poly(propylene fumarate), pseudo poly(amino acid), poly(alkyl cyanoacrylates), polyphosphazenes and polyphosphoesters.
  • poly(a-esters) include polyglycolide, polylactides, poly(lactide-co-glycolide), polydioxanone,
  • the cartilage scaffold portion may be formed from a synthetic material selected from proteins and poly(amino acids), and polysaccharides.
  • proteins and poly(amino acids) include collagen, poly(amino acids), elastin, elastin-like peptides, albumin and fibrin.
  • the polysaccharide may be of human origin or of non-human origin.
  • the cartilage scaffold portion comprises at least one of gelatin, elastin and sodium hyaluronate.
  • the cartilage scaffold portion comprises gelatin.
  • the cartilage scaffold portion comprises gelatin and elastin.
  • the cartilage scaffold portion comprises gelatin, elastin and sodium hyaluronate.
  • the ratio of gelatin to elastin may be 1 :1 to 10:1 , preferably 2:1 to 8:1 , for example, 3:1 to 4:1.
  • the ratio of gelatin to sodium hyaluronate may be 10:1 to 30:1 , for example 12:1 to 20:1 .
  • the material may, in certain embodiments, be desirable for the material to be printable e.g. by 3D printing.
  • the cartilage scaffold portion may be in the form of a composite comprising two or more of said synthetic or natural materials.
  • any suitable method may be used to attach the cartilage scaffold portion to the bone scaffold portion and/or the membrane portion.
  • the cartilage scaffold portion may comprise one or more legs or protrusions that extend from the cartilage scaffold portion to mechanically interlock with the bond scaffold portion.
  • the cartilage scaffold portion may be suturable or stitchable to at least one of the bone scaffold portion and the membrane portion.
  • chemical methods may be used to attach the cartilage scaffold portion to the bone scaffold portion and/or the membrane portion.
  • the cartilage scaffold portion is positioned on top of the bone scaffold portion.
  • the cartilage scaffold portion comprises cartilage tissue accommodation means to accommodate cartilage tissue therein.
  • the cartilage tissue accommodation means may comprise openings or pores. The openings may have a diameter of between 300 - 600 ⁇ , preferably 400 - 500 ⁇ .
  • the cartilage tissue accommodation means may be seeded with chondrocytes.
  • the cartilage tissue accommodation means may be seeded with chondrocytes prior to assembly of the joint plug.
  • the pore size and pore profile of the cartilage scaffold portion may be tailored to accommodate chondrocytes and cartilage growth.
  • the pore size adjacent the bone scaffold portion may be tailored so as to reduce the risk of chondrocytes falling into the bone scaffold portion. For instance, the pore size at the interface with the bone scaffold portion may be smaller than the pore size in the remainder of the cartilage scaffold portion.
  • the cartilage scaffold portion is formed as a substrate having one or more openings defined therein.
  • the cartilage tissue accommodation means is provided by a plurality of openings defined within the substrate.
  • the substrate can be substantially planar.
  • the substrate may be a single layer or multiple layer substrate.
  • the substrate may be irregular or regular in form.
  • the substrate may include through-voids and/or internal voids.
  • the cartilage scaffold portion takes the form of a lattice, wherein the lattice has a regularly repeating shape.
  • the lattice may have openings provided at regular intervals.
  • the growth of the cartilage tissue accommodated within the cartilage scaffold portion can be encouraged or improved by nutrients provided through the permeable membrane portion.
  • the cartilage scaffold portion may be for accommodating chondrocytes therein.
  • chondrocytes are to be understood as a form of cartilage tissue.
  • cartilage tissue should be understood to mean any biological material naturally present in cartilage in the body, or which results in the formation of cartilage.
  • the kit of parts may further comprise a source of chondrocytes. The source of chondrocytes may be provided in the cartilage scaffold portion.
  • the membrane portion is configured to be provided over the cartilage scaffold portion.
  • the membrane portion comprises a porous film.
  • the permeable membrane portion is permeable due to a plurality of through-holes defined within the permeable membrane portion.
  • the membrane portion comprises small pores for nutrient and gas delivery, for example for delivery to the propagating cells within the cartilage scaffold portion and/or bone scaffold portion.
  • the maximum pore diameter may be less than 100 ⁇ .
  • a maximum pore size of the porous film may be less than 50 micrometres or less than 25 ⁇ .
  • the membrane portion comprises pores having a diameter of between 5-25 ⁇ .
  • the pore diameter may be less than 15 micrometres, for example, the pore size may be about 10 ⁇ .
  • he membrane portion allows retention of the growing cartilage within the cartilage layer.
  • the membrane portion is suturable or stitchable.
  • the membrane portion may be stitched to the surrounding joint tissue.
  • the membrane portion may be sutured or stitched to the cartilage scaffold portion.
  • the membrane portion may be formed from a hydrogel, biodegradable polymer, or a composite material.
  • the permeable membrane portion may be a porous degradable or non- degradable membrane.
  • the permeable membrane portion may be formed from a biodegradable material.
  • the permeable membrane portion may be arranged to dissolve or otherwise degrade in the body in time.
  • the permeable membrane portion may be formed to degrade naturally in the body within less than 80 days.
  • the membrane portion may be formed from a synthetic material selected from poly(a-esters), polyurethanes, poly(ester amides), poly(ortho esters), poly(ortho esters), polyanhydrides, poly(anhydride-co-imide), cross-linked polyanhydrides, poly(propylene fumarate), pseudo poly(amino acid), poly(alkyl cyanoacrylates), polyphosphazenes and polyphosphoesters.
  • poly(a-esters) include polyglycolide, polylactides, poly(lactide-co-glycolide), polydioxanone,
  • the porous film may be formed from a synthetic material selected from proteins and poly(amino acids), and polysaccharides.
  • proteins, poly(amino acids) and polysaccharides include polyvinyl alcohol, collagen, poly(amino acids), gelatin, alginate, elastin, elastin-like peptides, albumin and fibrin.
  • the polysaccharide may be of human origin or of non-human origin.
  • the membrane portion may be in the form of a composite comprising two or more of said synthetic or natural materials.
  • the membrane portion comprises polycaprolactone.
  • the permeable membrane portion may be biocompatible, mechanically strong, porous and substantially degradable.
  • the membrane portion may comprise membrane portion engagement means for mounting the membrane portion on the cartilage portion.
  • the membrane portion may be provided with an inner surface for facing the cartilage scaffold portion when the membrane portion is provided on the cartilage scaffold portion, and wherein the inner surface of the membrane portion is hydrophilic.
  • the membrane portion may be provided with an outer surface for facing away from the cartilage scaffold portion when the membrane portion is provided on the cartilage scaffold portion, wherein the outer surface of the membrane portion is hydrophobic.
  • the hydrophobicity of the membrane's surface may be altered by surface treatment.
  • the hydrophobicity may be controlled by surface treatment with a hydroxide, for example, sodium hydroxide.
  • the kit of parts may further comprise a barrier portion.
  • the barrier portion may be provided within the bone scaffold portion and may be integral with it.
  • the barrier portion may be provided at a distance of less than 500 ⁇ microns from the top of the bone portion, preferably less than 250 ⁇ , for example less than 100 ⁇ from the top of the bone portion.
  • the barrier portion is provided by a layer of the bone scaffold portion.
  • the barrier portion may substantially prevent passage of cartilage tissue from the cartilage scaffold portion beyond the barrier portion within the bone scaffold portion. Some chondrocytes and osteoblasts can still interact at the interface between the bone portion and scaffold portion.
  • the pore size of the pores within the bone scaffold portion may be smaller at the top of the bone scaffold portion, i.e. in the part of the bone scaffold portion that is nearest to the cartilage scaffold portion.
  • the pore size may be reduced in the region of less than 500 ⁇ microns from the top of the bone portion, preferably less than 250 ⁇ , for example less than 100 ⁇ from the top of the bone portion.
  • the pore size is reduced within at least one layer of the bone scaffold portion.
  • the maximum diameter of the pores within the at least one layer may be less than 100 ⁇ , or less than 50 ⁇ , or less than 25 ⁇ . In one embodiment, the pore diameter is substantially zero.
  • Each of the bone scaffold portion, cartilage scaffold portion and porous membrane may be formed by any suitable method.
  • suitable methods include injection molding, freeze drying, solvent casting, particulate leaching, gas foaming, porogen leaching, self-assembly methods, phase separation, 3D printing (for example rapid prototyping), melt molding, fiber bonding, fiber mesh, membrane lamination, and molding.
  • the bone scaffold portion is formed using a 3D printing method.
  • the method for forming the bond scaffold portion using 3D printing may comprise a first step of receiving sensor data from a sensor device, the sensor data being indicative of the shape of the opening of the bone layer into which the bond scaffold portion will be inserted.
  • the shape of the bone scaffold portion may then be determined based on the obtained sensor data.
  • a bone scaffold portion having the shape determined using the obtained sensor data may then be formed using a 3D printing device.
  • the cartilage portion is formed by a 3D printing method.
  • the cartilage portion may be formed by the same 3D printing method described for forming the bone scaffold portion.
  • the porous membrane is formed using a moulding method.
  • Figure 1 a provides a schematic view of the kit according to an embodiment of the present invention.
  • Figure 1 b provides a schematic view of the kit of Figure 1 a assembled as a joint plug and located within a bone layer and cartilage layer of a damaged knee joint.
  • Figure 1 a shows a kit 10 of parts for assembly into a joint plug.
  • the kit 10 comprises a bone scaffold portion 12 for accommodating bone tissue therein.
  • the bone scaffold portion 12 is configured for insertion into an opening of the bone layer.
  • the bone scaffold portion 12 comprises openings for accommodating osteoblasts and for growth of bone tissue.
  • the openings may be regularly spaced and may define tunnels or longitudinal chambers that extend through the length of the bone scaffold portion 12.
  • the kit 10 further comprises a cartilage scaffold portion 14 for accommodating cartilage tissue therein.
  • the cartilage scaffold portion 14 takes the form of a lattice having openings for accommodating chondrocytes and supporting the growth of cartilage tissue.
  • the cartilage scaffold portion 14 comprises protrusions 16 for securement of the cartilage scaffold portion 14 to the bone scaffold portion 12. The protrusions 16 can be received within openings in the bone scaffold portion 12, thus securing the cartilage scaffold portion 14 to the bone scaffold portion 12.
  • the kit 10 of parts further comprises a permeable membrane portion 18 configured to be provided over the cartilage scaffold portion.
  • the kit 10 of parts may further comprise optional barrier layer 20.
  • Figure 1 b shows the kit 10 of Figure 1 a mounted within a joint.
  • the bone scaffold portion 12 is received within a bone layer (B), while the cartilage scaffold portion 14 is received within a cartilage layer (C).
  • the permeable membrane portion 18 is positioned over the cartilage scaffold portion 14 and permits the flow of nutrients to the underlying cells in the cartilage and bone tissue.
  • Tricalcium phosphate (TCP), hydroxyapatite (HA), polycaprolactone (PCL, Mn 80000), polyethylene glycol (PEG, Mn 2000) and gelatin (Type A, from porcine skin) were purchased from Sigma (USA).
  • Carboxymethylcellulose (CMC), sodium tripolyphosphate (TPP), 1 -Ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) and N-Hydroxysuccinimide (NHS) were purchased from Alfa Aesar (USA).
  • Elastin with a molecular weight of 60 KDa (Elastin-Soluble, No. ES12) was purchased from Elastin Products Company, Inc.
  • Sodium Hyaluronate (Research Grade, 500-749KDa) was obtained from Lifecore Biomedical. All the solvents were of reagent grade.
  • a printable paste composed of TCP, HA, CMC and TPP was used to print the bone portion.
  • 12 g TCP, 3 g HA, 0.5 g TPP and 0.075 g CMC were added to 5.75 ml water and homogenized at 2000 rpm for 2 min using a centrifugal mixer (Thinky, USA).
  • the viscosity and applied stress was measured as a function of shear rate at different temperatures.
  • a shear rheometer Kerexus, Malvern, UK
  • a stainless steel parallel-plate geometry 20 mm in diameter and a Peltier temperature control was used.
  • the viscometry of the samples was conducted, applying a gap distance of 0.5 mm at temperatures in decreasing 2°C increments, ranging from 28°C to 20°C.
  • the shear rate varied logarithmically in ramp mode from 0 to 50 s "1 and then back to 0 s "1 .
  • the ink was loaded into standard Nordson cartridges and printed using the parameters presented in Table 1.
  • Table 1 Applied parameters to 3D-print the bone part of the plug.
  • the resulted constructs were allowed to air-dry overnight before being transferred to a furnace.
  • the samples were heated up to 600°C with a rate of 3°C/min and held at this temperature for 2 h to eliminate the organic additives.
  • the temperature was then raised to 1 100°C at a rate of 5°C/min and kept at this temperature for 4 h to ensure complete sintering of the ceramic scaffolds.
  • Table 2 Applied parameters to 3D-print the cartilage part of the plug.
  • the printed constructs were then cross-linked using a solution of 6 mg/ml EDC and 0.75 mg/ml NHS in 70% v/v ethanol for 4 h. To remove the residual cross-linker, the constructs were washed carefully through soaking in a large amount of Dl water. The prepared constructs were stored in pure ethanol inside a -20°C freezer to be used after rehydration, when needed.
  • porous PCL films were prepared using the combination of film casting and sacrificial material leaching methods. Briefly, 1 g PCL was dissolved in 15 ml 2,2,2-Trifluoroethanol, and varying amounts of PEG (0, 0.2, 0.4, 1 and 1 .5 g) were added to the solution. After complete dissolution, the solution was casted and the solvent was allowed to evaporate overnight. The obtained films were soaked in water to eliminate PEG, whereas the porous films were achieved by sacrificing PEG. In other words, the PEG is dispersed in the polymer and then removed (i.e. sacrificed) to form pores.
  • the prepared films were allowed to float on 10% w/v NaOH overnight. The films were finally rinsed with copious amount of water to remove residual NaOH.
  • Electromechanical Precision Universal Tester (AGS-X 5 kN, Shimadzu, Japan). The samples were tested in compression mode using a 5 kN load cell and crosshead speed of 1 mm/min.
  • Human osteoblasts (HOB, Cell Applications, USA) were cultured under standard aseptic conditions. The cells were cultured in standard flasks and nourished with Dulbecco Modified Eagle Medium (DMEM) supplemented with 10% v/v fetal bovine serum (FBS), 100 U/mL penicillin, 100 ⁇ g/mL streptomycin and 0.25 ⁇ g/mL amphotericin every 2 days until a confluency of 90% was reached. The cells were trypsinized using TrypLE (Gibco, US) and sub-cultured. The cells of the third passage were used to seed the scaffolds at a density of 2500 cells/mm 2 .
  • DMEM Dulbecco Modified Eagle Medium
  • FBS v/v fetal bovine serum
  • Sample degradation rate was measured by monitoring the weight of samples over time. Samples were immersed in PBS and kept at 37°C in a shaker incubator (IKA KS 3000) for 60 days. At certain times, samples were taken out, weighed and returned to the container. The ratio of the recorded weight to the initial weight at each time point was reported as a function of time.
  • chondrocytes Normal human chondrocytes (Cell Applications Inc, USA) were cultured and sub- cultured under standard aseptic condition. At the confluency of 90%, chondrocytes were trypsinized and suspended in fetal bovine serum (FBS, Sigma-Aldrich, USA). Scaffolds were disinfected using 70% ethanol, washed and seeded with a density of 3 x 10 5 cells/scaffold in 12-well culture plates. The scaffolds were submerged after 30 min and incubated at 37°C, 5% CO2, using a chondrocyte growth medium (Cell Applications Inc, USA). The media were changed every other day.
  • FBS fetal bovine serum
  • Prestoblue assay was used to measure the proliferation rate of chondrocytes on the scaffold. At certain time intervals (i.e. 4, 7, 14, 21 days), the media of the wells were replaced with 10% v/v prestoblue. The plates were then incubated for 1 .5h at 37°C and 5% CO2. The fluorescence intensity was measured at an excitation wavelength of 540 nm and emission wavelength of 590 nm. The same procedure was performed on the first day, after complete attachment of the cells to the scaffolds. The number of cells at each time point (N) to the initial number of the cells (No) was calculated by dividing the corresponding intensity value by the absorbance value of the first day.
  • Scanning electron microscopy was used to investigate cell attachment. Scaffold- cell complexes were washed using PBS and immersed in Karnovsky's fixative for 1 .5 h. The complexes were then submerged in 1 % w/v osmium tetroxide for 1.5 h. Ethanol series (30, 50, 75, 95 and 100% v/v) were used to dehydrate the samples. The samples were then air-dried and sputter-coated with gold. SEM imaging was performed at accelerating voltages between 1 -5 kV with different magnifications.
  • scaffolds were fixed in formalin solution (10%, neutral buffered) for H&E staining.
  • the cells on the scaffold were fixed overnight and stained using Eosin and Hematoxylin. The color was adjusted using 1 % v/v acidic alcohol, ethanol and bluing agent, according to standard histology protocols.
  • Laser microscopy (Lext, Olympus) and fluorescence microscopy (Evos Fl, Life Technologies) were employed for monitoring cell growth on the scaffold and extracellular matrix (ECM) secretion by chondrocytes.
  • Fluorescein sodium salt was selected as the model probe to quantify the permeability of the films.
  • concentration side transferred to a 96-well plate and the fluorescence intensity was recorded at excitation/emission wavelengths of 540/590 nm using a micro-plate reader.
  • the diffusion kinetics were reported as the variation in the ratio of concentration at each specific time to the equilibrium concentration over time.
  • control standard cell culture plate (control group)
  • the number of cells on the scaffold is higher than the control group at all other time points. Furthermore, the cells seem to grow and proliferate faster on the scaffold as the slope of the TCP-HA graph increases.
  • the number of the cells on the scaffold persistently increased from day 1 to day 21. After 21 days, the number of cells was more than 5 times that of the initial number, seeded on the first day.
  • Table 3 represents the mechanical properties and suture retention strength of the prepared films compared to solid PCL film fabricated with addition of no PEG.
  • the porous PCL film was found to have lower modulus and ultimate strength, but higher elongation at break. Having a porous structure, as well as the plasticizing effect of the residual PEG, might account for lower stiffness and strength, along with more flexibility.
  • the suture retention strength was 9.04 ⁇ 0.92 N for the porous PCL film, which is about half of the corresponding value for solid film.
  • Table 3 The mechanical properties and suture retention strength of porous PCL film compared to a solid film.

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Abstract

Un kit de pièces pour assemblage dans un bouchon d'articulation, le bouchon d'articulation pour l'insertion à l'intérieur d'une ouverture d'une couche d'os dans une articulation et à travers une couche de cartilage sur la couche d'os, le kit de pièces comprenant : une partie d'échafaudage d'os destinée à recevoir un tissu osseux à l'intérieur de celle-ci, ladite partie d'échafaudage d'os étant conçue pour être insérée dans l'ouverture de la couche d'os; une partie d'échafaudage de cartilage destinée à recevoir un tissu cartilagineux, ladite partie d'échafaudage de cartilage étant conçue pour être positionnée sur la partie d'échafaudage d'os; une partie de membrane perméable conçue pour être disposée sur la partie d'échafaudage de cartilage; et comprenant en outre des moyens de mise en prise d'échafaudage d'os pour monter la partie d'échafaudage de cartilage sur la partie d'échafaudage d'os.
PCT/EP2018/076690 2017-10-04 2018-10-01 Bouchon de cartilage WO2019068660A1 (fr)

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