WO2001032229A1 - Reparation de tissus - Google Patents

Reparation de tissus Download PDF

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Publication number
WO2001032229A1
WO2001032229A1 PCT/GB2000/004166 GB0004166W WO0132229A1 WO 2001032229 A1 WO2001032229 A1 WO 2001032229A1 GB 0004166 W GB0004166 W GB 0004166W WO 0132229 A1 WO0132229 A1 WO 0132229A1
Authority
WO
WIPO (PCT)
Prior art keywords
implantable article
attaching
component
tissue
implantable
Prior art date
Application number
PCT/GB2000/004166
Other languages
English (en)
Inventor
Nicholas John Cotton
Original Assignee
Smith & Nephew Plc
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 Smith & Nephew Plc filed Critical Smith & Nephew Plc
Priority to CA002389694A priority Critical patent/CA2389694A1/fr
Priority to AU11539/01A priority patent/AU777374B2/en
Priority to JP2001534433A priority patent/JP2003512896A/ja
Priority to EP00972982A priority patent/EP1225928A1/fr
Publication of WO2001032229A1 publication Critical patent/WO2001032229A1/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
    • A61L27/38—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix containing added animal cells
    • A61L27/3804—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix containing added animal cells characterised by specific cells or progenitors thereof, e.g. fibroblasts, connective tissue cells, kidney cells
    • A61L27/3817—Cartilage-forming cells, e.g. pre-chondrocytes
    • 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
    • A61F2/08—Muscles; Tendons; Ligaments
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14—Macromolecular materials
    • A61L27/18—Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
    • A61L27/38—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix containing added animal cells
    • A61L27/3804—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix containing added animal cells characterised by specific cells or progenitors thereof, e.g. fibroblasts, connective tissue cells, kidney cells
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
    • A61L27/38—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix containing added animal cells
    • A61L27/3839—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix containing added animal cells characterised by the site of application in the body
    • A61L27/3843—Connective tissue
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
    • A61L27/38—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix containing added animal cells
    • A61L27/3839—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix containing added animal cells characterised by the site of application in the body
    • A61L27/3843—Connective tissue
    • A61L27/386—Ligaments, tendons
    • 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
    • A61F2220/00—Fixations or connections for prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
    • A61F2220/0025—Connections or couplings between prosthetic parts, e.g. between modular parts; Connecting elements
    • A61F2220/0075—Connections or couplings between prosthetic parts, e.g. between modular parts; Connecting elements sutured, ligatured or stitched, retained or tied with a rope, string, thread, wire or cable

Definitions

  • the present invention relates to an implantable article; to synthetic implants comprising the implantable article; to hybrid implants generated by culturing cells within synthetic implants according to the invention; to methods of manufacture of implants according to the invention and to methods of treatment employing the implants according to the invention.
  • Implantable articles, synthetic implants and hybrid implants according to the invention may be used for the partial or total replacement of tissue, particularly connective tissue, such as ligament, cartilage, bone, meniscus, tendon, skin and the like.
  • cruciate ligaments there are two types of treatment for injured ligaments, such as cruciate ligaments, namely tissue grafting or replacement by a synthetic device.
  • Ligament reconstruction with autograft tissue is the most common treatment, but the extent to which this may be practised is evidently limited by the amount of tissue available for grafting.
  • donor site morbidity and necrosis of the graft tissue following implantation are problems which have not yet been overcome.
  • Use of allogenic or xenogenic tissue is one possible alternative to the use of allograft, which eliminates the problems associated with the tissue harvesting procedure in the patient.
  • the perceived risk of disease transmission and immunogenic responses has limited the use of these types of tissue to a small fraction of ligament reconstructions.
  • Synthetic devices for the replacement of ligaments have generally failed to show successful long-term results, with failure commonly occurring over a 2-10 year period, due to synovitis, loosening or implant failure. Following implantation, continuous loading of the device and abrasion against joint tissues causes wear, creep and fatigue of the device until it ultimately fails.
  • an implantable article comprising a first component and a second component coupled thereto, wherein the first component comprises a fabric and the second component comprises a material capable of being seeded with and supporting the growth of cells.
  • the phrase "capable of being seeded with and supporting the growth of cells” means having a seeding efficiency of greater than 50% and preferably greater than 70%. Seeding efficiency may be determined in the following way: a 2mm x 10mm disc comprising the second component is soaked overnight in foetal calf serum. It is then seeded with four million HuFF (human foreskin fibroblast) cells, suspended in 1 ml of culture medium by pulling the cell suspension backwards and forwards through the disc five times, using a 1 ml. pipette. The proportion of cells adhering to the disc is determined (by DNA assay using Hoechst 33258TM dye) after which the seeding efficiency may be calculated as the percentage of cells adhering to the disc in relation to the total number of cells.
  • HuFF human foreskin fibroblast
  • the first component also be capable of being seeded with and supporting the growth of cells, but in this event it is preferred that the second component have a higher seeding efficiency than the first component, according to the above definition of seeding efficiency.
  • the second component may be incorporated within said first component, in which case it is preferably distributed evenly throughout. This has the advantage that cells, once seeded onto the second component, may proliferate evenly throughout the first component to generate a homogenous matrix.
  • the first component typically comprises first and second surfaces.
  • the second component may be attached to at least a portion of at least one of the first and second surfaces of said first component. Such an arrangement may be employed if integration is a localised region is important.
  • the second component is coupled to the first component so as to be co-extensive with one of the first and second surfaces of the first component. More preferably, coupling is by physical attachment.
  • the first component may be encased in the second component.
  • the first component according to the invention comprises a fabric. Fabrics which may be employed according to the invention are woven, non-woven, knitted, braided or crocheted materials or a mixture of these. If the first component comprises a woven or knitted material, it may comprise a spacer fabric. Such materials have an advantage that their three dimensional structure may be modified to give a specific architecture, allowing, in their turn, properties like percentage open volume, toughness and other characteristics to be accurately tailored to the specific application.
  • the first component comprises an elongate fabric tape comprising both warp and weft strands.
  • the tape comprises first elongate elements.
  • the first elongate elements may comprise woven, non-woven, knitted, braided or crocheted material.
  • the first elongate elements comprise braided material.
  • Braided material has the advantage of a favourable load to elongation relationship, i.e. high strength incorporating sufficient elasticity. Single fibres, for example, frequently do not fulfil this criterion and can fatigue and break in vivo.
  • the pick rate of the braided material may advantageously be in the range from 10 to 30 picks/cm and comprise between 4 and 64 yarns, preferably between 8 and 64 yarns.
  • the number of filaments per yarn is advantageously in the range 30 to 150 and the filaments preferably have a diameter in the range 8 - 20 ⁇ m.
  • the first elongate elements may be independently translatable in the warp direction with respect to each other and with respect to the weft strands but maintained in a spaced apart relationship with respect to each other in the weft direction.
  • the implantable article according to the invention may be heat sealed or sealed with a binder in order to prevent fraying at the edges. It is preferred to heat seal the implantable article if it comprises independently translatable first elongate elements to prevent them from becoming detached.
  • the first elongate elements may be maintained in a spaced apart relationship by the weft strands alone or, in addition, by non- translatable second elongate elements interspersed between the translatable first elongate elements.
  • the second elongate elements may comprise chain stitched, woven, non-woven, knitted, braided or crocheted material.
  • the second elongate elements comprise chain-stitched material.
  • a line of chain stitches has the advantage of fulfilling the task of being a spacer element while not occupying much space itself.
  • the elongate fabric tape comprises an upper and a lower layer, each layer comprising an open mesh structure comprising warp and weft yarns, wherein the first elongate elements are laid into the structure.
  • the warp and weft strands of the upper and lower layers may cooperate to maintain the first elongate elements in a spaced relationship in the weft direction. This may be achieved by attaching weft strands of the upper layer to corresponding weft strands of the lower layer at positions between adjacent first elongate elements moving along the weft. Attachment may be by various methods, for example spot fusing or by means of a warp strand linking the upper and lower weft strands.
  • the first component according to the invention may comprise bioresorbable materials or materials which do not resorb in vivo.
  • Reference herein to a material being bioresorbable means that it breaks down over a finite period of time due to the chemical/biological action of the body and the terms "resorption” and “resorb” are to be interpreted accordingly.
  • complete resorption occurs within about 5 years, more preferably within about 3 years.
  • This breakdown is at a rate allowing the implantable medical article to maintain sufficient integrity while the tissue repairs: surgical repair devices formed of materials which are resorbed too quickly may fail when compressive, tensile or flexural loads are placed on them when the tissue has fully healed.
  • Advantages of using bioresorbable materials over materials which do not bioresorb include that they encourage tissue repair and further surgery is not required to remove them.
  • the first component may comprise bioresorbable polymers or copolymers comprising the following monomers or mixtures of polymers and/or copolymers formed thereby: hydroxy acids, particularly lactic acid, glycolic acid; caprolactone; hydroxybutyrate; dioxanone; orthoesters; orthocarbonates; aminocarbonates.
  • Preferred bioresorbable materials according to the invention include poly(lactic acid), poly(glycolic acid), polydioxanone, polyhydroxybutyrate and poly(trimethylene carbonate) or mixtures thereof. It is particularly preferred to use poly(lactic acid). This material has the advantage that it has good mechanical strength and does not resorb too quickly in vivo allowing this strength to be retained for a sufficient time for tissue repair to occur at which point the repaired tissue can take over load-bearing functions.
  • Non-bioresorbable materials include polyesters, particularly aromatic polyesters, such as polyalkylene terephthalates, like polyethylene terephthalate and polybutylene terephthalates; polyamides; polyalkenes such as polyethylene and polypropylene; poly(vinyl fluoride), polytetrafluoroethylene carbon fibres, silk (natural or synthetic) and mixtures of these materials.
  • aromatic polyesters such as polyalkylene terephthalates, like polyethylene terephthalate and polybutylene terephthalates
  • polyamides such as polyethylene and polypropylene
  • poly(vinyl fluoride) polytetrafluoroethylene carbon fibres
  • silk natural or synthetic
  • the second component according to the invention advantageously comprises a solid material.
  • the second component comprises a fabric, such as a woven or non-woven (fleece) material, a foams, a sponge or a mixture of these.
  • the second component may comprise bioresorbable polymers or copolymers comprising the following monomers, or mixtures of the polymers and/or copolymers formed thereby: hydroxy acids, particularly lactic acid, glycolic acid; caprolactone; hydroxybutyrate; dioxanone; orthoesters; orthocarbonates; aminocarbonates.
  • Preferred bioresorbable materials according to the invention comprise poly(lactic acid), poly(glycolic acid), polydioxanone, polyhydroxybutyrate, polyaminocarbonates and poly(trimethylene carbonate). It is particularly preferred to use poly(glycolic acid). This material has the advantage that it has a relatively high resorption rate allowing rapid tissue regeneration in those areas where it is present.
  • Non-bioresorbable materials include polyesters, particularly aromatic polyesters, such as polyalkylene terephthalates, like polyethylene terephthalate and polybutylene terephthalates; polyamides; polyalkenes such as polyethylene and polypropylene; poly(vinyl fluoride), polytetrafluoroethylene carbon fibres, silk (natural or synthetic) and mixtures of these materials.
  • aromatic polyesters such as polyalkylene terephthalates, like polyethylene terephthalate and polybutylene terephthalates
  • polyamides such as polyethylene and polypropylene
  • poly(vinyl fluoride) polytetrafluoroethylene carbon fibres
  • silk natural or synthetic
  • the second component comprises a non-woven material.
  • the nonwoven material may be dry laid, wet laid, spun laid or melt blown.
  • the fibres are needled to give a random entanglement providing a large surface area for cell attachment/capture.
  • the void fraction of the nowoven may be in the range 50 to 99%, but is preferably in the range 90 to 99%.
  • the nonwoven will have a density in the range 25 to 100 g/m 2 and staple fibre lengths in the range 40-50mm, though values outside these ranges may also be employed.
  • the nonwoven is typically used in thicknesses of 0.25 to 5mm and preferably in thicknesses of 0.5 to 2 mm, though again, the thickness according to the invention is not limited to these ranges.
  • the seeding efficiency of the second component may be an inherent property of the material selected or may be the result of an additional treatment step.
  • Treatment steps which may be employed according to the invention to achieve the requisite seeding efficiency include those of surface-modification by application of a material, such as serum, fibronectin or RGD peptide; by a chemical method, such as acid hydrolysis, or by plasma treatment.
  • Appropriate methods according to the invention for coupling the second component to the first component are by stitching, preferably crocheting, by means of a binder, an adhesive or by heat sealing.
  • the implantable article according to the invention is suitable for implantation into tissue defects.
  • synthetic implants are provided, the synthetic implants comprising an implantable article according to the first aspect of the invention.
  • the synthetic implants according to the second aspect of the invention may comprise unmodified sections of implantable article, though cut, if necessary, to a suitable shape, such as a quadrilateral, a circle, a triangle or other appropriate form.
  • the synthetic implants according to the second aspect of the invention may be presented in a modified form suitable for different surgical applications.
  • a first alternative form of synthetic implant according to the second aspect of the invention comprises a plurality of superimposed, mutually connected implantable articles, as defined above, also cut to a relevant shape, if appropriate.
  • Suitable methods according to the invention for attaching the superimposed layers to one another include those methods detailed above for coupling of the second component to the first component.
  • a second alternative form of the synthetic implant according to the second aspect of the invention comprises a spirally wound (i.e. a "Swiss Roll”-type of arrangement) implantable article.
  • the synthetic implant may comprise a plurality of superimposed implantable articles which is then spirally wound to form a "Swiss Roll”.
  • the synthetic implant may comprise a plurality of "Swiss Rolls" aligned longitudinally, parallel to one another, plaited or twisted together.
  • a third alternative form of the synthetic implant according to the second aspect of the invention comprises a serpentine or
  • the synthetic implant may comprise a plurality of superimposed implantable articles, which is then formed into a serpentine arrangement.
  • a fourth form according of the synthetic implant according to the second aspect of the invention comprises a tube of the implantable article attached together along an edge or a plurality of mutually connected concentric tubes of this type.
  • the synthetic implant comprises an implantable article which has been spirally wound into a "Swiss Roll".
  • the windings may be interconnected to prevent unravelling by means of stitching, by impregnation with a binder, by use of an adhesive or by heat sealing.
  • the "Swiss Roll"-type arrangement is a procedurally efficient way of ensuring that the second component of the implantable article within which cells may be seeded is present throughout the synthetic implant.
  • the second component of the implantable article is coupled by physical attachment to the first component of the implantable article so as to be co-extensive with one of the surfaces of the first component.
  • the synthetic implant according to the invention comprises an implantable article comprising:
  • the second component being attached to one of the surfaces of the first component so as to be co-extensive with said surface, the implantable article being spirally wound into a "Swiss Roll" with the free end being secured to prevent unravelling.
  • the first component comprises poly(lactic acid) fibres and the second component comprises poly(glycolic acid) fibres.
  • synthetic implants in the form of a "Swiss Roll” have a diameter in the range 5-15 mm.
  • the end regions will have a reduced diameter in the range 9-11 mm, to enable them to be located within a bone tunnel, which will generally have a diameter in this range.
  • a plurality of "Swiss Rolls" of smaller diameter may be employed. In this case, they may be longitudinally aligned and plaited or arranged in a twisted fashion.
  • the synthetic implant according to the invention may be received within a porous sleeve comprising a resorbable material.
  • a resorbable material are those listed above in relation to the first and second components of the implantable article.
  • the sleeve may comprise a fabric, such as a knitted, woven, crocheted or braided material. Preferably, it is a braided material. This has the advantage of preventing abrasion damage when the implantable article is in vivo.
  • Synthetic implants according to the invention may comprise cells. Incorporation of cells may be carried out either before or after implantation, but is preferably carried out prior to implantation. If carried out before implantation, tissue growth may be carried out exclusively in vivo but may also be preceded by in vitro tissue culturing. Preferably there is a stage of in vitro tissue growth prior to implantation.
  • the cells are normally incorporated into synthetic implants according to the invention by means of a carrier medium.
  • the carrier medium may be a medium which is retained by the implantable medical article, for example a hydrogel, or one which substantially passes through the implantable medical article, such that, after seeding, it is substantially no longer present therein - the cells remaining within the article, particularly within the second component.
  • Examples of this type of carrier medium are cell culture media.
  • a cell culture medium is employed to seed the cells, for example DMEM (DULBECO'STM Modified Eagle's Medium containing 10% calcium).
  • the carrier medium is a hydrogel it may be incorporated within and/or on and/or around at least the second component.
  • the carrier medium is incorporated at least within the second component, since this efficiently utilises the available open volume for cellular growth. More preferably, the carrier medium occupies the entire open volume of the second component.
  • Hydrogels which may be used as carrier media according to the invention comprise positively charged, negatively charged and neutral hydrogels which may be saturated or unsaturated.
  • hydrogels which may be used according to the invention are TETRONICSTM and POLOXAMINESTM, which are poly(oxyethylene)-poly(oxypropylene) block copolymers of ethylene diamine; polysaccharides, chitosan, poly(vinyl amines), poly(vinyl pyridine), poly(vinyl imidazole), polyethylenimine, poly-L-lysine, growth factor binding or cell adhesion molecule binding derivatives, derivatised versions of the above, e.g.
  • polyanions polycations, peptides, polysaccharides, lipids, nucleic acids or blends, block-copolymers or combinations of the above or copolymers of the corresponding monomers; agarose, methylcellulose, hydroxyproylmethylcellulose, xyloglucan, acetan, carrageenan, xanthan gum/locust beangum, gelatine, collagen (particularly Type 1), PLURONICSTM, POLOXAMERSTM, POLY(N- isopropylacrylmide) and N-isopropylacrylmide copolymers.
  • the cells with which synthetic implants according to the invention may be seeded comprise cells which are terminally differentiated or capable of undergoing phenotypic change e.g. stem cells, pluripotent cells and other precursor cells. More specifically, mesenchymal, tenocytes, ligamentous and chondrocytic cells may be seeded into the synthetic implants according to the invention.
  • the synthetic implant additionally comprises a third component, wherein the third component comprises biological tissue.
  • the implantable medical article is seeded with cells and biological tissue is grown in vitro, then, if one or both of the first and second components comprises a resorbable material, then one or both of said first and second components, as the case may be, may be resorbed prior to implantation.
  • the second component is resorbable and is substantially resorbed prior to implantation.
  • a hybrid implant comprising a first component and a third component, coupled thereto, wherein the first component comprises a fabric and the third component comprises biological tissue generated by culturing a cell-seeded synthetic implant according to the second aspect of the invention, such that the second component has substantially resorbed.
  • the term “culturing” means supplying with nutrients and maintaining conditions (e.g. temperature, pH) which propagate cell growth.
  • a method of making an implantable article according to the first aspect of the invention comprising the steps of manufacturing a first component comprising a fabric having first and second surfaces; encasing the first component in, or incorporating within the first component, or attaching to at least a portion of at least one of the opposing surfaces of the first component a second component which comprises a material capable of being seeded with and supporting the growth of cells.
  • a method of making synthetic implants comprising the step of forming an implantable article made according to the fourth aspect of the invention by applying the step of:
  • a method of making hybrid implants comprising the step of seeding a synthetic implant made according to the fifth aspect of the invention with cells and culturing said seeded synthetic implant under conditions conducive to the growth of cells for a sufficient period of time to permit growth of a biological tissue.
  • the first and second components of the implantable article comprised within the synthetic implant comprises a resorbable material
  • one or both of said first and second components may be resorbed prior to implantation.
  • the second component comprises a resorbable material and becomes resorbed during the growth of the biological tissue to generate a hybrid implant according to the third aspect of the invention.
  • a synthetic implant according to the second aspect of the invention or a hybrid implant according to the third aspect of the invention is implanted into an wound site in a mammalian organism in clinical need thereof.
  • wound site means any site where a change in the tissue from its normal condition has occurred, for example a change as a result of traumatic insult or degenerative changes.
  • synthetic implants and hybrid implants according to the invention may be used for the partial or total replacement of tissue, particularly connective tissue such as ligament, cartilage, bone, meniscus, tendon, skin and the like.
  • Ligaments which may be totally or partially replaced include ⁇ e the medial and lateral collateral ligaments, the anterior and posterior cruciate ligaments (ACL and PCL respectively) and ligaments and tendons of the elbow and hand.
  • Tendons which may be totally or partially replaced include the achilles tendon and patellar tendon.
  • the present invention finds particularly effective application in total or partial ACL-replacement and in the toatal or partial replacement of the rotator cuff of the glenohumeral joint. Reference hereinafter to
  • implant includes reference to both synthetic and hybrid implants.
  • the rotator cuff comprises four tendons, the supraspinatus, infraspinatus, teres minor and subcapularis. Ruptures to the supraspinatus are the most common problem encountered.
  • an implant manufactured from the implantable article according to the invention may be shaped in a generally triangular configuration, as shown in EP 0 7 44 165 or in the short or long Y shape as ultilised in the RCRTM device commercially available from Merck Biomaterial, France. Alternatively, if reinforcement is the issue, an implant comprising a strip of implantable artilce may suffice.
  • Rotator cuff implants may be secured in place by any conventional means known to those skilled in the art, e.g. suturing, suture anchors, bone fixation devices and bone screws.
  • Implants according to the present invention may also be used to partially/totally replace or augment other tissues such as the achilles tendon, medial collateral ligament (MCL), posterior cruciate ligament (PCL), patella tendon, lateral collateral ligament (LCL) and ligaments and tendons of the elbow and hand.
  • MCL medial collateral ligament
  • PCL posterior cruciate ligament
  • LCL lateral collateral ligament
  • Implants described herein can be used to repair a patellar tendon harvest site.
  • a portion of the tendon e.g., the middle one third of the tendon
  • patella and tibial bone plugs integrally attached thereto are considered advantageous because the tissue is derived from the host patient and the implanted tendon readily allows rapid tissue ingrowth.
  • studies have shown that after a patellar tendon autograft, the tissue that replaces the harvested patellar tendon often does not have the histological characteristics of a normal patellar tendon. Moreover, even after healing, patients often experience discomfort and pain at the patellar tendon harvest site.
  • an implant according to the invention is implanted into the site following harvesting of the bone-patellar-tendon-bone graft and secured, e.g., by fixing the implant into the site.
  • the implant is disposed along the length of the patellar tendon and the implant is secured to the remaining natural patellar tendon, e.g., by suturing opposite sides of the implant to the tendon.
  • the implant is secured to the tibia and patella, e.g., by cementing, suturing, stapling or fixing with one or more screws.
  • Implants according to the invention may also be used to repair a ruptured or torn Achilles tendon.
  • the implant can be used to repair tears that occur within the Achilles tendon itself, severing the tendon, or the implant can be used to repair ruptures, which result from the tendon tearing off of the calcaneus.
  • the implant may be composed of elements that have load-bearing properties similar to the naturally occurring Achilles tendon and is designed so as to allow new Achilles tendon growth on the implant.
  • the implant preferably comprises a bioresorbable material that has the property of resorbing slowly in the body, e.g., PLA. The slow resorption allows retention of the mechanical properties of the implantable material until a time when the newly reconstructed Achilles tendon can take over the load-bearing functions of the implant.
  • standard surgical methods of identifying and locating the torn tendon can be used.
  • a longitudinal incision is made just medial to the Achilles tendon and the severed end(s) of the ruptured tendon identified.
  • the opposite ends of the implant are attached to each of the torn tendon ends, e.g., by suturing the first end of the implant to the first end of the torn Achilles tendon and suturing the second end of the implant to the second end of the torn Achilles tendon, thereby reattaching the first and second ends.
  • the surgical method includes attaching a first end of the implant to the calcaneus and the second end of the implant to the torn end of the Achilles tendon, e.g., by suturing, thereby reattaching the Achilles tendon to the calcaneus.
  • Figure 1 illustrates a synthetic implant according to an embodiment of the invention.
  • Figs.2-4 illustrate front and back views, made by SEM, of an implantable article made according to Example 1.
  • Figure 5 shows a synthetic implant according to Example 2, 3 months after implantation into an ovine stifle joint.
  • Figure 6 illustrates a biochemical analysis of synthetic implants, harvested after implantation, as described in Example 3. In particular, it compares the amount of DNA and GAG present in the harvested synthetic implants with that in a natural ACL.
  • Figure 7 illustrates a biochemical analysis of synthetic implants, harvested after implantation, as described in Example 3. In this case, it compares the amount of collagen and tissue found in the harvested synthetic implant as compared with a natural ACL.
  • Figure 8 is an H&E section through the femoral aspect of a synthetic implant harvested after implantation, as described in Example 3.
  • Figure 9 is a transverse H&E section through an aspect of a synthetic implant harvested after implantation, as described in Example 3, at higher magnification than the view shown in Figure 8.
  • Figure 10 illustrates a knee joint in which an implant comprising an implantable article has been implanted during an anterior cruciate ligament (ACL) reconstruction procedure.
  • ACL anterior cruciate ligament
  • a synthetic implant comprising an implantable article, in which the second component (1) is attached to the first component (2) so as to be co-extensive with one of the opposing surfaces of the first component, the implantable article being spirally wound to form the synthetic implant.
  • the first component (2) may, for example, comprise an elongate fabric tape comprising poly(lactic acid) fibres and the second component (1 ) may comprise a non- woven felt comprising poly(glycolic acid) fibres.
  • the second component is stitched onto one of the opposing surfaces of the first component.
  • EXAMPLE 1 MANUFACTURE OF IMPLANTABLE ARTICLE
  • PLA yarn (90 filament) is twisted at 200 turns/metre "S” direction, wound onto 16 braider spools and braided at 1680 picks per metre.
  • PLA yarn (40 filament) is twisted at 200 turns/metre "S” direction and wound onto 11 knitting spools, and two weft spools.
  • the implantable article is manufactured as follows.
  • n Number of braids.
  • Courses/metre are set at 535.
  • the felt is cut slightly too wide to insert into the knitting and the sides of the tape are trimmed later.
  • Fig.2 illustrates a view of one side of the implantable article, with the PGA-felt being visible on the far side of the fabric tape.
  • Fig.3 is a more magnified version of part of Fig.2.
  • Fig.4 illustrates the opposing side of the implantable medical article, showing the PGA-felt and the stitching attaching it to the PLA-tape.
  • EXAMPLE 2 MANUFACTURE OF SYNTHETIC IMPLANT
  • the implantable article made according to Example 1 was cut into the 280mm lengths and held at both ends of the outer braid.
  • the outer braid was twisted so that the scaffold rolled over itself to form a spiral section structure.
  • the lip formed by this process was attached to the rest of the scaffold by stitching PLA fibre through the scaffold and lip along the entire length of the device.
  • EXAMPLE 3 IMPLANTATION OF SYNTHETIC IMPLANT OF EXAMPLE 2 FOR ACL REPAIR
  • the lateral parapatellar incision was used to expose the joint.
  • the patella was dislocated medially.
  • the stifle joint was assessed visually to ensure the absence of gross pathology e.g. degenerative joint disease.
  • the stifle joint was flexed to expose the anterior cruciate ligament which was resected as close to its origin and insertion sites as possible. All visible particulate matter was be removed from the joint and flushed with sterile physiological saline.
  • a Kirschner wire (K-wire) was inserted from the medial border of the proximal tibia (approximately 1cm distal to the joint surface and midway between anterior and posterior aspects of the tibia) and directed in to the joint at the point of insertion of the resected anterior cruciate ligament.
  • An appropriately designed drill bit was slipped over the K- wire and a suitable bone tunnel, extending into the joint, was created. All resultant visible debris was removed and the articular borders of the bone tunnel smoothed to reduce abrasion of the device.
  • An orthopaedic cruciate 'hook' was inserted from between the femoral condyles and directed posteriorly towards the caudo-lateral aspect of the lateral condyle to exit lateral and proximal to the lateral fabella.
  • the 'hook' was used to guide a graft passer into the joint from the lateral aspect of the lateral condyle, around the posterior of the lateral condyle to exit in the inter-condylar space.
  • the synthetic implant was inserted from the anterior aspect of the inter-condylar space, between the condyles and around the caudo-lateral aspect of the lateral condyle to exit at the disto-lateral femur.
  • the femoral end of the synthetic implant was anchored to the disto-lateral femur with standard orthopaedic screws and washers.
  • a graft passer the tibial end of the synthetic implant was passed from the joint space into and through the tibial tunnel.
  • the tibial end of the synthetic implant was tensioned to ensure it has been inserted fully and was then anchored with standard orthopaedic RCI (round head cannulated inside-out) screws inserted into the tunnel from the medial aspect of the tibia and directed towards the joint.
  • standard orthopaedic RCI round head cannulated inside-out
  • the patella was relocated and the limb manipulated through the full range of normal motion approximately five times.
  • the intra-articular portion of the ligament was assessed for taughtness.
  • excess length of synthetic implant was removed from the medial aspect of the tibia.
  • the patella was relocated and the incisions sutured in the standard surgical manner.
  • Robert-Jones type dressings were applied and maintained for approximately 7 days post surgery.
  • Analgesia (buprenorphine - Vetergesic; Animalcare) was administered at completion of surgery and maintained for a minimum of 48 hours post surgery. Antibiotic cover was maintained for 4 days.
  • Samples were fixed in 10% formalin and embedded in paraffin. The samples were sectioned (approximately 6 ⁇ m) and stained with picro sirrus red and haematoxylin and eosin (H&E).
  • Figure 5 shows the intact ACL scaffold at 3 months. Tissue can be seen completely encapsulating the synthetic implant, indicated by pointer (3).
  • Figure 6 illustrates the DNA and GAG assay results. They show that the native ACL has low levels of DNA, as it is composed largely of extra cellular matrix and is generally acellular. The slightly higher levels in the implanted synthetic implants represent cells invading the device upon implantation. On the other hand, the GAG levels in the devices are comparable to that found in the natural ACL.
  • Figure 7 shows the collagen and % dry weight of tissue results found in the implanted synthetic implants. Even at this early time point, the synthetic implants already contained approximately half the level of collagen of the natural ACL. Histology
  • the synthetic implant was infiltrated with cellular fibrous tissue; alignment of collagen extending between braids and surrounding the braid was also observed when visualised under polarised light.
  • the arrangement of the braids was open allowing optimum incorporation of tissue.
  • the synthetic implant has been shown to support tissue ingrowth and it was apparent that the tissue was beginning to mature into a dense, ligamentous tissue.
  • Implants were generated by cutting implantable articles, manufactured as in Example 1 , into 20 x 15 mm lengths (of 1 mm thickness).
  • EXAMPLE 5 Use of an implant comprising the biocompatible, implantable material to repair the ACL
  • Implants comprising implantable articles described herein may be used for reconstructing a torn anterior cruciate ligament (ACL).
  • ACL anterior cruciate ligament
  • a knee joint is shown in which an implant (7) has been implanted during an ACL reconstruction procedure.
  • the implant (7) comprises elements that have load-bearing properties similar to the naturally occurring ACL.
  • An implant (7) for an ACL repair is designed to be porous so as to allow new ACL tissue growth theron/therewithin. It is important that the porosity does not collapse or decrease significantly when implant (7) is extended longitudinally.
  • the implant (7) preferably comprises the bioresorbable material PLA, which has two key features: PLA resorbs slowly, and it has load-bearing properties similar to the naturally occurring ACL. The slow resorption is important so as to allow retention of the mechanical properties until a time when the newly reconstructed ACL can take over load-bearing functions.
  • the surgeon Prior to surgically implanting the implant (7), the surgeon removes the torn ACL stump from the intercondylar notch and clears the ligament.
  • a notchplasty procedure is preferably performed to expand the intercondylar notch (8) of the femur (an example of such a notchplasty procedure is described in U.S. Patent 5,139, 520, the contents of which are incorporated herein by reference).
  • a femoral tunnel (9) for receiving one end of the implant (7) and a tibial tunnel (10) for receiving the other end of implant (7) are drilled.
  • the two tunnels should be formed so that they enter the joint at the proper anatomic attachment points. These points are preferably on the knee joint surfaces where the original ACL was attached.
  • the procedure for providing the femoral tunnel (9) and tibial tunnel (10) is described in greater detail in U.S. Patent 5,306,301 , the contents of which are incorporated herein by reference.
  • the implant (7) is inserted through the femoral tunnel (9) and exits an opening in the femur (11).
  • the femoral end of the implant (7) is attached to the femur by any of a number of different procedures known in the art, e.g., cementing, suturing, stapling, or fixing with a screw.
  • the tibial end of implant (7) is then passed from the joint space into the tibial tunnel (10).
  • the tibial end of the implant (7) is tensioned and attached within the tibial tunnel, e.g., by cementing, suturing, stapling, or fixing with a screw.

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  • General Health & Medical Sciences (AREA)
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  • Transplantation (AREA)
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  • Orthopedic Medicine & Surgery (AREA)
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  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Prostheses (AREA)
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Abstract

L'invention concerne des implants destinés à la réparation de tissus et notamment à la réparation de tissus conjonctifs tels que ligaments, cartilage, os, ménisques, tendons et peau. Elle concerne aussi des procédés de fabrication de ces implants ainsi que leur utilisation dans des procédés de traitement médical. Les implants peuvent comprendre un article implantable qui, à son tour, comprend un premier et un deuxième composants qui y sont couplés. Le premier composant comprend un tissu et le deuxième composant comprend un matériau pouvant être ensemencé avec des cellules de croissance et servir de support à ces cellules.
PCT/GB2000/004166 1999-11-04 2000-10-30 Reparation de tissus WO2001032229A1 (fr)

Priority Applications (4)

Application Number Priority Date Filing Date Title
CA002389694A CA2389694A1 (fr) 1999-11-04 2000-10-30 Reparation de tissus
AU11539/01A AU777374B2 (en) 1999-11-04 2000-10-30 Tissue repair
JP2001534433A JP2003512896A (ja) 1999-11-04 2000-10-30 組織修復
EP00972982A EP1225928A1 (fr) 1999-11-04 2000-10-30 Reparation de tissus

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB9926231.3 1999-11-04
GBGB9926231.3A GB9926231D0 (en) 1999-11-04 1999-11-04 Medical implants

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WO2001032229A1 true WO2001032229A1 (fr) 2001-05-10

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JP (1) JP2003512896A (fr)
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WO (1) WO2001032229A1 (fr)

Cited By (18)

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WO2004050133A2 (fr) * 2002-12-05 2004-06-17 Cardio Incorporated Implant biocompatible et son utilisation
WO2007092464A2 (fr) * 2006-02-07 2007-08-16 Tepha, Inc. Procedes et dispositifs pour la reparation de la coiffe des rotateurs
WO2008128304A1 (fr) * 2007-04-24 2008-10-30 The University Of Western Australia Échafaudages biologiques contenant des ténocytes et traitement les utilisant
FR2937243A1 (fr) * 2008-10-22 2010-04-23 Sofradim Production Implant de renfort
FR2937244A1 (fr) * 2008-10-22 2010-04-23 Sofradim Production Implant de remplacement de tendon a base de collagene
GB2466073A (en) * 2008-12-12 2010-06-16 Univ Manchester Tissue repair scaffold
WO2011031854A1 (fr) * 2009-09-11 2011-03-17 Allergan, Inc. Dispositif prothétique et son procédé de fabrication
WO2011062974A1 (fr) 2009-11-17 2011-05-26 Arsenal Medical, Inc. Fibres chargées en médicaments
US8287909B2 (en) 2007-12-19 2012-10-16 Tepha, Inc. Medical devices containing melt-blown non-wovens of poly-4-hydroxybutyrate and copolymers thereof
US8968626B2 (en) 2011-01-31 2015-03-03 Arsenal Medical, Inc. Electrospinning process for manufacture of multi-layered structures
US9034240B2 (en) 2011-01-31 2015-05-19 Arsenal Medical, Inc. Electrospinning process for fiber manufacture
US9194058B2 (en) 2011-01-31 2015-11-24 Arsenal Medical, Inc. Electrospinning process for manufacture of multi-layered structures
AU2013222002B2 (en) * 2005-09-09 2016-06-02 Cytex Therapeutics, Inc. Tissue engineering methods and compositions
US9655864B2 (en) 2013-02-04 2017-05-23 Arsenal Medical, Inc. Fibers comprising poorly soluble drugs and/or proteins
US9745670B2 (en) 2013-08-02 2017-08-29 Arsenal Medical, Inc. Patterned slit fixtures and surfaces for high throughput slit-surface electrospinning
EP2453837A4 (fr) * 2009-07-16 2018-01-17 Artimplant AB Implant pour reconstruction de tissus mous
WO2020194280A1 (fr) * 2019-03-28 2020-10-01 Universidade Do Porto Structure prothétique bio-fonctionnalisée dotée d'une architecture cœur-écorce pour la réparation partielle ou totale de tendons ou de ligaments humains
CN112972064A (zh) * 2021-01-25 2021-06-18 上海市第六人民医院 一种插销式软组织修复补片及其制备方法

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US8562633B2 (en) * 2004-08-02 2013-10-22 W. L. Gore & Associates, Inc. Tissue repair device with a bioabsorbable support member
JP2008529749A (ja) * 2005-02-18 2008-08-07 シンタソーム インコーポレーテッド 軟組織修復用合成構造物
JP2012205720A (ja) * 2011-03-29 2012-10-25 Gunze Ltd 腱板及び肩関節内構成体再生材料
EP3636292B1 (fr) * 2017-05-29 2023-03-01 Educational Foundation Of Osaka Medical And Pharmaceutical University Substrat de régénération du ménisque

Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0303496A1 (fr) * 1987-08-12 1989-02-15 Ethicon, Inc. Treillis chirurgical résorbable, prothèses réalisées à partir de ce treillis et leurs applications chirurgicales
US4942875A (en) * 1986-03-03 1990-07-24 American Cyanamid Company Surgical repair device having absorbable and nonabsorbable components
US5139520A (en) 1990-01-31 1992-08-18 American Cyanamid Company Method for acl reconstruction
US5197983A (en) * 1988-04-19 1993-03-30 W. L. Gore & Associates, Inc. Ligament and tendon prosthesis
US5306301A (en) 1993-02-11 1994-04-26 American Cyanamid Company Graft attachment device and method of using same
US5376118A (en) * 1989-05-10 1994-12-27 United States Surgical Corporation Support material for cell impregnation
US5458636A (en) * 1994-07-20 1995-10-17 U.S. Biomaterials Corporation Prosthetic device for repair and replacement of fibrous connective tissue
EP0744165A1 (fr) 1995-05-25 1996-11-27 Ellis Developments Limited Dispositif de réparation de la coiffe des rotateurs de l'épaule
US5595621A (en) * 1993-09-29 1997-01-21 Johnson & Johnson Medical, Inc. Method of making absorbable structures for ligament and tendon repair

Patent Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4942875A (en) * 1986-03-03 1990-07-24 American Cyanamid Company Surgical repair device having absorbable and nonabsorbable components
EP0303496A1 (fr) * 1987-08-12 1989-02-15 Ethicon, Inc. Treillis chirurgical résorbable, prothèses réalisées à partir de ce treillis et leurs applications chirurgicales
US5197983A (en) * 1988-04-19 1993-03-30 W. L. Gore & Associates, Inc. Ligament and tendon prosthesis
US5376118A (en) * 1989-05-10 1994-12-27 United States Surgical Corporation Support material for cell impregnation
US5139520A (en) 1990-01-31 1992-08-18 American Cyanamid Company Method for acl reconstruction
US5306301A (en) 1993-02-11 1994-04-26 American Cyanamid Company Graft attachment device and method of using same
US5595621A (en) * 1993-09-29 1997-01-21 Johnson & Johnson Medical, Inc. Method of making absorbable structures for ligament and tendon repair
US5458636A (en) * 1994-07-20 1995-10-17 U.S. Biomaterials Corporation Prosthetic device for repair and replacement of fibrous connective tissue
EP0744165A1 (fr) 1995-05-25 1996-11-27 Ellis Developments Limited Dispositif de réparation de la coiffe des rotateurs de l'épaule

Cited By (27)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004050133A3 (fr) * 2002-12-05 2004-08-12 Cardio Inc Implant biocompatible et son utilisation
WO2004050133A2 (fr) * 2002-12-05 2004-06-17 Cardio Incorporated Implant biocompatible et son utilisation
AU2013222002B2 (en) * 2005-09-09 2016-06-02 Cytex Therapeutics, Inc. Tissue engineering methods and compositions
US8016883B2 (en) 2006-02-07 2011-09-13 Tepha, Inc. Methods and devices for rotator cuff repair
WO2007092464A2 (fr) * 2006-02-07 2007-08-16 Tepha, Inc. Procedes et dispositifs pour la reparation de la coiffe des rotateurs
WO2007092464A3 (fr) * 2006-02-07 2008-07-03 Tepha Inc Procedes et dispositifs pour la reparation de la coiffe des rotateurs
WO2008128304A1 (fr) * 2007-04-24 2008-10-30 The University Of Western Australia Échafaudages biologiques contenant des ténocytes et traitement les utilisant
US9463263B2 (en) 2007-04-24 2016-10-11 Orthocell Pty Ltd Tenocyte containing bioscaffolds and treatment using the same
US8287909B2 (en) 2007-12-19 2012-10-16 Tepha, Inc. Medical devices containing melt-blown non-wovens of poly-4-hydroxybutyrate and copolymers thereof
FR2937244A1 (fr) * 2008-10-22 2010-04-23 Sofradim Production Implant de remplacement de tendon a base de collagene
FR2937243A1 (fr) * 2008-10-22 2010-04-23 Sofradim Production Implant de renfort
US9770529B2 (en) 2008-12-12 2017-09-26 The University Of Manchester Tissue repair scaffold
GB2466073A (en) * 2008-12-12 2010-06-16 Univ Manchester Tissue repair scaffold
US11534287B2 (en) 2009-07-16 2022-12-27 International Life Sciences LLC Implant for soft tissue reconstruction
EP2453837A4 (fr) * 2009-07-16 2018-01-17 Artimplant AB Implant pour reconstruction de tissus mous
WO2011031854A1 (fr) * 2009-09-11 2011-03-17 Allergan, Inc. Dispositif prothétique et son procédé de fabrication
WO2011062974A1 (fr) 2009-11-17 2011-05-26 Arsenal Medical, Inc. Fibres chargées en médicaments
EP2501369A1 (fr) * 2009-11-17 2012-09-26 Arsenal Medical, Inc. Fibres chargées en médicaments
EP2501369A4 (fr) * 2009-11-17 2013-10-02 Arsenal Medical Inc Fibres chargées en médicaments
US9194058B2 (en) 2011-01-31 2015-11-24 Arsenal Medical, Inc. Electrospinning process for manufacture of multi-layered structures
US9034240B2 (en) 2011-01-31 2015-05-19 Arsenal Medical, Inc. Electrospinning process for fiber manufacture
US8968626B2 (en) 2011-01-31 2015-03-03 Arsenal Medical, Inc. Electrospinning process for manufacture of multi-layered structures
US9655864B2 (en) 2013-02-04 2017-05-23 Arsenal Medical, Inc. Fibers comprising poorly soluble drugs and/or proteins
US9745670B2 (en) 2013-08-02 2017-08-29 Arsenal Medical, Inc. Patterned slit fixtures and surfaces for high throughput slit-surface electrospinning
WO2020194280A1 (fr) * 2019-03-28 2020-10-01 Universidade Do Porto Structure prothétique bio-fonctionnalisée dotée d'une architecture cœur-écorce pour la réparation partielle ou totale de tendons ou de ligaments humains
CN112972064A (zh) * 2021-01-25 2021-06-18 上海市第六人民医院 一种插销式软组织修复补片及其制备方法
CN112972064B (zh) * 2021-01-25 2024-06-28 上海市第六人民医院 一种插销式软组织修复补片及其制备方法

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GB9926231D0 (en) 2000-01-12
CA2389694A1 (fr) 2001-05-10

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