WO2013178229A1 - Treillis non tissé biodégradable avec points de colle - Google Patents

Treillis non tissé biodégradable avec points de colle Download PDF

Info

Publication number
WO2013178229A1
WO2013178229A1 PCT/DK2013/050162 DK2013050162W WO2013178229A1 WO 2013178229 A1 WO2013178229 A1 WO 2013178229A1 DK 2013050162 W DK2013050162 W DK 2013050162W WO 2013178229 A1 WO2013178229 A1 WO 2013178229A1
Authority
WO
WIPO (PCT)
Prior art keywords
mesh
glue points
fibres
lactide
biodegradable
Prior art date
Application number
PCT/DK2013/050162
Other languages
English (en)
Inventor
Monica Ramos Gallego
Jakob Vange VANGE
Original Assignee
Coloplast A/S
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 Coloplast A/S filed Critical Coloplast A/S
Publication of WO2013178229A1 publication Critical patent/WO2013178229A1/fr

Links

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
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L31/148—Materials at least partially resorbable by the body
    • 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
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/54—Biologically active materials, e.g. therapeutic substances
    • 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
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/58—Materials at least partially resorbable by the body
    • 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
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L31/16—Biologically active materials, e.g. therapeutic substances
    • D—TEXTILES; PAPER
    • D04—BRAIDING; LACE-MAKING; KNITTING; TRIMMINGS; NON-WOVEN FABRICS
    • D04H—MAKING TEXTILE FABRICS, e.g. FROM FIBRES OR FILAMENTARY MATERIAL; FABRICS MADE BY SUCH PROCESSES OR APPARATUS, e.g. FELTS, NON-WOVEN FABRICS; COTTON-WOOL; WADDING ; NON-WOVEN FABRICS FROM STAPLE FIBRES, FILAMENTS OR YARNS, BONDED WITH AT LEAST ONE WEB-LIKE MATERIAL DURING THEIR CONSOLIDATION
    • D04H3/00—Non-woven fabrics formed wholly or mainly of yarns or like filamentary material of substantial length
    • D04H3/02—Non-woven fabrics formed wholly or mainly of yarns or like filamentary material of substantial length characterised by the method of forming fleeces or layers, e.g. reorientation of yarns or filaments
    • D04H3/04—Non-woven fabrics formed wholly or mainly of yarns or like filamentary material of substantial length characterised by the method of forming fleeces or layers, e.g. reorientation of yarns or filaments in rectilinear paths, e.g. crossing at right angles

Definitions

  • a biodegradable non-woven mesh with glue points A biodegradable non-woven mesh with glue points
  • the present invention relates to a mesh suitable for medical application.
  • the present invention relates to biocompatible composite non-woven mesh useful for medical application.
  • Scaffolds are structures, such as synthetic polymer structures used to guide the organization, growth and differentiation of cells in the process of forming new functional tissue at the site of a tissue defect or wound, typically used in conjunction with surgical intervention.
  • scaffolds must meet some specific requirements.
  • a high porosity and an adequate pore size are necessary to facilitate cell growth and diffusion throughout the whole structure of both cells and nutrients.
  • Biodegradability is essential since scaffolds need to be absorbed by the surrounding tissues without the necessity of a surgical removal.
  • Electrospun meshes may be suitable for use as scaffolds. Electrospinning is a technique for making structures of non-woven nano- or microfibre. Because of the fibrous structure and the large surface area these structures can be useful as scaffolds for tissue regeneration. When made from a biodegradable polymer, scaffolds can first support formation of new tissue in-vivo and then disappear by being resorbed. Because electrospun mesh is non-woven, the strength is mostly achieved by friction between the fibres. When implanted into living tissue, cells will migrate into the structure and reduce this cohesion by lifting the fibres apart thereby weakening the scaffold.
  • One object of the present invention is to provide a mesh having improved strength and sustainability that contribute to the ease of the handling of an implant comprising said mesh under surgical implantation such as general prolapse surgery, pelvic organ prolapse, incontinence (sling) and hernia.
  • a further object of the present invention is to provide a mesh having improved strength that contribute to the support of tissue in applications such as general prolapse surgery, pelvic organ prolapse, incontinence (sling), hernia and enabling efficient cells migration into and within the mesh and adherence of the cells to the mesh.
  • biocompatible non-woven mesh comprising
  • fibres are interconnected by the glue points.
  • the fibres have an in vivo degradation time that is higher than an in vivo degradation time of the glue points.
  • the fibres have an in vivo degradation time of 2-48 months. In some aspects the glue points have an in vivo degradation time of 1 -52 weeks.
  • the biodegradable fibre material comprises homo- or co-polymers of glycolide, L-lactide, DL-lactide, D-lactide,meso-lactide, ⁇ -caprolactone, ⁇ - valerolactone, 1 ,4-dioxan-2-one, trimethylene carbonate, block-copolymers of MPEG or PEG and one or more of the monomers mentioned above, degradable polyurethanes, degradable polyurethane-urea, polypeptides, degradable polyesters, poly(3- hydroxybutyrate), polyhydroxyalkanoate and polyesterdiol-based polyurethane.
  • the biodegradable polymer of the glue points comprises homo- or copolymers of glycolide, L-lactide, DL-lactide, D-lactide,meso-lactide, ⁇ -caprolactone, ⁇ - valerolactone, 1 ,4-dioxan-2-one, trimethylene carbonate, block-copolymers of MPEG or PEG and one or more of the monomers mentioned above, degradable polyurethanes, degradable polyurethane-urea, polypeptides, degradable polyesters, poly(3- hydroxybutyrate), polyhydroxyalkanoate and polyesterdiol-based polyurethane.
  • the fibres are electrospun fibres.
  • the amount of glue points in the mesh is 1-70% (w/w). In some aspects the mesh has an area density in the range 2-20 mg/cm 2 .
  • the fibres have an average diameter size of 0.1 ⁇ -10 ⁇ .
  • said mesh further comprises a component that facilitates cell adhesion and/or migration into the mesh.
  • said mesh further comprises a component selected from the group consisting of estrogen, estrogen derivatives, thrombin, ECM (Extra Cellular Matrix) powder, chondroitin sulfate, hyaluronan, Hyaluronic Acid (HA), heparin sulfate, heparan sulfate, dermatan sulfate, growth factors, such as Insulin-like growth factors (IGFs), such as IGF-1 or IGF-2, or Transforming Growth Factors (TGFs), such as TGF-alpha or TGF- beta, or Fibroblast Growth Factors (FGFs), such as FGF-1 or FGF-2, or 20 Platelet- Derived Growth Factors (PDGFs), such as PDGF-AA, PDGF-BB or PDGF-AB, or Mechano Growth Factor (MGF), or Nerve Growth Factor (NGF), or Human Growth
  • IGFs Insulin-like growth factors
  • TGFs Transforming Growth Factors
  • HGH Hormone
  • fibrin such as collagen type I and/or type II, type III, type IV, type V and/or type VII, gelatin, and aggrecan, or any other suitable extracellular matrix component.
  • fibronectin such as collagen type I and/or type II, type III, type IV, type V and/or type VII, gelatin, and aggrecan, or any other suitable extracellular matrix component.
  • elastin such as collagen type I and/or type II, type III, type IV, type V and/or type VII, gelatin, and aggrecan, or any other suitable extracellular matrix component.
  • said non-woven mesh is suitable for supporting, augmenting and regenerating soft tissue.
  • the mesh is for use in the treatment of pelvic organ prolapse, stress urinary incontinence or hernia.
  • the glue points are in the form of substantially non-fibrous domains.
  • non-fibrous means that the biodegradable polymer making up the glue point is not in fibre form.
  • substantially non-fibrous means that less than 5% (v/v) of the glue point is in fibrous form.
  • the glue point may in some embodiments be entirely non-fibrous.
  • the glue points may comprise less than 25% (v/v) fibrous material, such as less than 20% (v/v) fibrous material, such as less than 15% (v/v) fibrous material, such as less than 10% (v/v) fibrous material, such as less than 5% (v/v) fibrous material, such as less than 2% (v/v) fibrous material, such as less than 1 % (v/v) fibrous material.
  • the glue points are distributed homogeneously in the mesh.
  • biodegradable surgical implant for supporting, augmenting and regenerating soft tissue, where said implant comprises
  • said implant is suitable for the treatment of pelvic organ prolapse, stress urinary incontinence or hernia.
  • the solution in step (b) comprises a solvent selected from the group consisting of ethyl acetate (EtOAc); isopropyl acetate (iPrOAc); a mixture of EtOAc and methanol (MeOH); and a mixture of iPrOAc and MeOH.
  • EtOAc ethyl acetate
  • iPrOAc isopropyl acetate
  • MeOH a mixture of EtOAc and methanol
  • MeOH a mixture of iPrOAc and MeOH.
  • said solvent is EtOAc.
  • Biocompatible material In the context of the present invention, a biocompatible material refers to a material that interacts with the surrounding tissue without eliciting any undesirable local or adverse systemic effects in the recipient or beneficiary of that therapy.
  • biocompatible mesh or surgical implant refers to a mesh or surgical implant, which does not have undesirable local or adverse systemic effects in the recipient to which it is applied.
  • glue points are herein meant domains of a non-fibre forming polymer distributed in the mesh thereby gluing the fibres together sporadically.
  • the glue points may be in the form of droplets and/or irregular domains connecting adjacent fibres.
  • the glue points are substantially non-fibrous, i.e. less than 5% v/v of the glue points are in the form of fibres.
  • Biodegradable refers to the capacity of a material to decompose over time as a result of biological activity, such as by enzymatic degradation or through simple hydrolysis. The material disappears over time; is biodegraded and vanish from the implantation site and the body within a given time. This is a huge clinical advantage as there is no remaining material to remove or to make complication afterwards.
  • An example of a polymer, which is not biodegradable, is polyethylene oxide (PEO).
  • low molecular weight PEO ⁇ 40 kDa
  • Higher (>40 kDa) such as 100 kDa PEO is not excreted and tends to accumulate in the kidney.
  • the degradation time of a material is the time it takes for that material to be degraded.
  • the in vivo degradation time is the time it takes for a given material to be degraded when said material is placed in vivo.
  • biodegradable implants will degrade over time when implanted into an animal.
  • a short degradation time means that the material degrades quickly, whereas a long degradation time means that the material degrades slowly.
  • Composite materials may have different degradation times for the different components.
  • the fibre material of the instant biodegradable meshes may have a degradation timer that is different from the glue points of the same meshes.
  • Non-woven mesh refers to a sheet made from a layer of fibres bonded by random entanglement and/or physical, mechanical or chemical means as opposed to weave or knitted fabrics where the entanglements are highly ordered.
  • the orientation of the fibres in a non-woven can be either random or have some degree of order.
  • the bonds in non-woven formed by electrospinning are entanglement and sometimes connecting points between fibres formed by incomplete evaporation of spinning solvents when fibres hit the collector, causing the fibres to fuse where they touch each other.
  • Mesh refers to a material (such as a sheet) providing a semi-permeable barrier.
  • the mesh of the present invention is biocompatible.
  • the term “mesh” refers to a material being porous and fibrous, preferably in the form of a layer or sheet, but may also have a more three-dimensional structure suitable for implants.
  • Fibre material refers to a material in the form of fibre of a uniform fibre thickness, or a range of thicknesses.
  • Electrospinning Electrospinning (or E-spinning) is a technique where a solution of polymer is stretched into a thin fibre by applying a voltage between solution and collector, typically resulting in an electrical field of 0.5-2 kV/cm. As the solution is stretched, the solvent evaporates, resulting in a fibre.
  • the fibre can be collected as a non-woven fabric, either with a random orientation of the fibres, or with special setups, some degree of order.
  • the technique can be used to form fibres with diameter ranging from ⁇ 100nm to >10 ⁇ .
  • the fibres are deposited randomly on the collector.
  • the fibres are deposited on the collector with a preferred direction. This can be done with special techniques, e.g air-gap e-spinning, or with a rapidly spinning collector.
  • Youngs modulus is the slope of the stress-strain curve for the elastic deformation of a sample.
  • ⁇ ( ⁇ - ⁇ 0 )/ ⁇ .
  • I is the initial length of the sample and (l-l 0 ) is the elongation of the sample, ⁇ is the stress obtained by dividing force with cross section of sample.
  • Area density refers to the weight of a given area of material. In one embodiment of the present invention, the area density is in the range of 0.1-50 mg/cm 2 .
  • Surgical implant refers to a medical device manufactured to replace a missing biological structure, support a damaged biological structure, or enhance an existing biological structure. In the present context, the surgical implant is a biocompatible material that interacts with the surrounding tissue to perform the desired function with respect to a medical therapy, after which it is degraded and the metabolites are cleared of the body.
  • tissue refers to a solid living tissue which is part of a living mammalian individual, such as a human being.
  • the tissue may be a hard tissue (e.g. bone, joints and cartilage) or soft tissue including tendons, ligaments, fascia, fibrous tissues, fat, synovial membranes, muscles, nerves and blood vessels.
  • a biocompatible non-woven mesh comprising fibres of a biodegradable fibre material and glue points in the form of domains of biodegradable polymer wherein the fibres are interconnected by the glue points.
  • the glue points may be in the form of non- fibrous domains.
  • the biodegradable polymer forming the glue points may be a non-fibre forming biodegradable polymer.
  • the mesh of the present invention allows migration of cells into the mesh and adherence of the mesh in concert with the regeneration and augmentation of the tissue surrounding the implanted mesh, while retaining the strength needed for supporting the tissue.
  • the effect is accomplished by applying a non-woven biodegradable mesh with glue points.
  • the fibres and the glue points may have different in vivo degradation times, one fast degrading and one slow degrading.
  • the glue points contribute to the strength of the mesh by gluing fibres together.
  • the fast degrading elements are degraded and disappear from the mesh leaving only the slow degrading elements in a more porous configuration allowing better cell in-growth and vascularisation.
  • the newly formed tissue is not fully matured, but the slow degrading elements are still there to contribute strength while the newly formed tissue matures.
  • the biodegradable fibre material may be made of homo- or co-polymers of glycolide, L- lactide, DL-lactide, D-lactide, meso-lactide, ⁇ -caprolactone, 5-valerolactone, 1 ,4-dioxan-2- one, trimethylene carbonate, block-copolymers of MPEG or PEG and one or more of the monomers mentioned above, degradable polyurethanes, degradable polyurethane-urea, polypeptides, degradable polyesters, poly(3-hydroxybutyrate), polyhydroxyalkanoate and polyesterdiol-based polyurethane.
  • the biodegradable glue points may be made of homo- or co-polymers of glycolide, L- lactide, DL-lactide, D-lactide,meso-lactide, ⁇ -caprolactone, 5-valerolactone, 1 ,4-dioxan-2- one, trimethylene carbonate, block-copolymers of MPEG or PEG and one or more of the monomers mentioned above, degradable polyurethanes, degradable polyurethane-urea, polypeptides, degradable polyesters, poly(3-hydroxybutyrate), polyhydroxyalkanoate and polyesterdiol-based polyurethane.
  • the fibres degrade faster than the glue points.
  • the fibres When the fibres are degraded as cells populate the mesh, it is secured that the added strength of the glue points is maintained through the period of degradation. Because these glue points reduce the porosity of the scaffold and therefore has the potential to reduce cell in-growth, it can be advantageous to make the glue points of a polymer that degrades faster than the fibres. This will ensure that the porosity of the scaffold increases over time as the glue points are degraded.
  • the in vivo degradation time of the fibres may be 1-48 months.
  • the in vivo degradation time of the fibres may be 5-10 months, 10-20 months, 20-30 months, 30-40 months, 40-48 months, 5-20 months, 5-30 months, 5-40 months, 10-30 months, 10-40 months, 10-48 months, 20-40 months, 20-48 months, or 30-48 months.
  • the in vivo degradation time of the glue points may be 1-52 weeks.
  • the in vivo degradation time of the glue points may be 1-10 weeks, 10-20 weeks, 20-30 weeks, 30-40 weeks, 40-52 weeks, 1-20 weeks, 1-30 weeks, 1-40 weeks, 1-52 weeks, 10-30 weeks, 10-40 weeks, 10-52 weeks, 20-40 weeks, 20-52 weeks, or 30-52 weeks.
  • the in vivo degradation time of the fibres may be selected from the group consisting of 1-48 months, 5-10 months, 10-20 months, 20-30 months, 30-40 months, 40-48 months, 5-20 months, 5-30 months, 5- 40 months, 10-30 months, 10-40 months, 10-48 months, 20-40 months, 20-48 months, and 30-48 months, while at the same time the in vivo degradation time of the glue points is selected from the group consisting of 1-52 weeks, 1-10 weeks, 10-20 weeks, 20-30 weeks, 30-40 weeks, 40-52 weeks, 1-20 weeks, 1-30 weeks, 1-40 weeks, 1-52 weeks, 10-30 weeks, 10-40 weeks, 10-52 weeks, 20-40 weeks, 20-52 weeks, and 30-52 weeks.
  • the fibres degrade slower than the glue points.
  • the glue points When the glue points are degraded first, the porosity of the mesh is increased. Generally, having the glue points will lead to a slower in-growth of cells as compared to meshes without glue points. In order to ensure stability of the mesh during the entire in-growth of cells, it may be advantageous to have a relatively slow initial in-growth. Such a slow initial in-growth will help prevent newly in-growing cells from compromising the structure of the mesh before the newly formed tissue is strong enough. For instance, the glue points may ensure that newly in-growing cells do not push apart the fibres of the mesh and thereby compromise the strength of the mesh before a strong new tissue is formed by the in-growing cells.
  • the stability of the mesh is ensured by the glue points during the early stages of cell in-growth.
  • the faster degrading glue points will gradually degrade, thus gradually allowing faster in-growth without compromising the integrity of the mesh at a too early stage.
  • After the glue points have been degraded, at least part of the fibres will remain to ensure a structured formation of the new tissue that is to replace the mesh once also the fibres have degraded.
  • the glue points degrade at least twice as fast as the fibres, such as at least 3 times as fast, such as at least 4 times as fast, such as at least 5 times as fast, such as at least 10 times as fast, such as at least 15 times as fast.
  • the mesh degrades at the same pace as the glue points. This may be obtained by making the glue-points of the same polymer as the mesh. Meshes of this kind are advantageous if maximum strength is required for the full duration of the treatment.
  • the mesh is made of electrospun fibres. Electrospinning is a superior way to produce fibres with a diameter of ⁇ 10 ⁇ to nanoscale.
  • the amount of glue points can vary from 1-70 %(w/w) of the mesh.
  • the glue points may comprise 1-70% (w/w), such as 2-50% (w/w), such as 5-50% (w/w), such as 10-30% (w/w) of the mesh.
  • the glue points may comprise at least 1 % (w/w) of the mesh, such as at least 2% (w/w) of the mesh, such as at least 5%(w/w) of the mesh, such as at least 10%(w/w) of the mesh, such as at least 20%(w/w) of the mesh, such as at least 30%(w/w) of the mesh, such as at least 40%(w/w) of the mesh, such as at least 50%
  • the glue points may comprise no more than 70% (w/w) of the mesh, such as no more than 60% (w/w) of the mesh, such as no more than 50% (w/w) of the mesh, such as no more than 40% (w/w) of the mesh, such as no more than 30% (w/w) of the mesh, such as no more than 20% (w/w) of the mesh, such as no more than 10% (w/w) of the mesh, such as no more than 5% (w/w) of the mesh, such as no more than 2% (w/w) of the mesh, such as no more than 1 % (w/w) of the mesh.
  • the mesh may have an area density in the range 2-20 mg/cm 2 , such as 5-20 mg/cm 2 , such as 5-15 mg/cm 2 , such as 5-10 mg/cm 2 .
  • the fibre material may be composed of fibres having an average diameter in the range of 0.1-10 ⁇ . In one embodiment, the fibre material is a fibre having an average diameter in the range of 2-20 ⁇ .
  • the mesh may be a non-aligned non-woven mesh.
  • the mesh may further comprise a component that facilitates cell adhesion and/or migration into the mesh. Such cell migration into the mesh is sometimes referred to as ingrowth.
  • the mesh may further comprise a component selected from the group consisting of estrogen, estrogen derivatives, thrombin, ECM (Extra Cellular Matrix) powder, chondroitin sulfate, hyaluronan, Hyaluronic Acid (HA), heparin sulfate, heparan sulfate, dermatan sulfate, growth factors, such as Insulin-like growth factors (IGFs), such as IGF-1 or IGF-2, or Transforming Growth Factors (TGFs), such as TGF-alpha or TGF-beta, or Fibroblast Growth Factors (FGFs), such as FGF-1 or FGF-2, or 20 Platelet-Derived Growth Factors (PDGFs), such as PDGF-AA, PDGF-BB or PDGF-AB, or Mechano Growth Fact
  • the glue points may be formed by introducing droplets, for example by spraying into the fibre mesh.
  • the resulting glue points may be in the form irregular domains connecting the adjacent fibres.
  • the glue points may preferably have an average diameter of 1-200 ⁇ , such as 10-150 ⁇ , such as 50-100 ⁇ .
  • the glue points can be applied to the fibre material in different ways, for example:
  • the invention also relates to a method of preparing a non-woven mesh by electro spinning, said method comprising the steps of dispensing a biodegradable fibre-forming solution on a collector (rotating cylinder), and simultaneously or subsequently dispensing drops of a biodegradable polymer solution by electrospraying.
  • Nozzle 1 dispenses the fibre-forming solution in a layer on a collector 2
  • nozzle 3 dispenses small drops of a non-fibre forming polymer solution by
  • the invention further relates to a biodegradable surgical implant for supporting, augmenting and regenerating soft tissue, where said implant comprises biodegradable fibre material and glue points in the form of domains of biodegradable polymer wherein the fibres are interconnected by the glue points.
  • the surgical implant may be suitable for the treatment of pelvic organ prolapse, stress urinary incontinence or hernia. Examples
  • Example 1 Preparation of an electrospun mesh with glue points.
  • Fibre-forming solution 27 g PCL (polycaprolactone), 165 g acetone, 12.5 g 1.3-dioxolane, 4.5 g methanol, sealed in a closed flask, was heated to 60°C overnight and stirred until homogeneous.
  • Glue point forming solution 2,5 g methoxypolyethylene glycol-co-poly(DL-lactide-co- glycolide) 2-40 kDa with 85%(mol) DL-lactide, 20 g acetone and 5 g butanone sealed in a closed flash, was heated to 60°C overnight and shaken until homogeneous.
  • Fibre-forming nozzle (-28 kV, 20 cm from collector) fed with 25 mL/h of fibre-forming solution.
  • Glue point nozzle (+8.77 kV, 3 cm from collector) fed with 5 mL/h of glue point forming solution.
  • the collector was a rotating cylinder 025cm (0 kV), 1.3 s "1 , covered with an embossed PE- film (poly ethylene).
  • the nozzles were mounted on a linear bearing moving slowly back and forth along the axis of the rotating cylindrical collector, thereby depositing the composite on the PE-film.
  • Both nozzles were dual feed coaxial: A 19 gauge inner needle and a 17 gauge outer needle.
  • the inner needle was fed with the polymer containing solution and the outer needle was fed with a slow stream of pure solvent (1 ml_/h of 10% 1.3-dioxolane in acetone) to avoid clogging.
  • Figure 7 is shown the modulus of e-spun PCL reinforced with glue points after coculturing with fibroblasts for 3 and 8 weeks. Control samples kept in media without cells. From Figure 6 and 7 it is seen that the mesh reinforced with glue points have a higher modulus after 3 weeks both when grown with cells and when kept in media without cells. At 8 weeks the modulus is comparable.
  • PLGA 2-40 85DL. All solutions were dyed with 0.2 mg Dil (1 , 1 '-Dioctadecyl-3,3,3',3'- tetramethylindocarbocyanine perchlorate).
  • the PET films with glue points are imaged with a Leica DMI 4000B CLSM and analyzed with ImageJ. Images are analyzed with ImageJ (lower cutoff limit 200 ⁇ 2 ) and areas are transformed to spherical diameters.
  • Glue points containing Dil fluorescent dye were sprayed onto PET-film at different flows (7-10 mL/h) and different voltages (10-24 kV). The samples were analyzed with fluorescence microscopy and size distributions were determined using image processing.
  • the s-Nozzles are the nozzles normally used for spinning fibres. A voltage is applied to these inactive nozzles to mimic the electrical fields that would be present when spinning a mesh with glue points. Results are displayed in the table below. The size increases with flow and decreases with voltage. The higher voltages (>3 kV/cm) give a more unstable and narrrow jet making them less advantageous for our purposes.
  • the purpose of this study was to do a preliminary test of the PCL and PCL-GP implants in two rats.
  • the model is a full thickness defect model in rats done according to M.L.
  • the implants were cut into 2.5 cm x 4.0 cm pieces. All implants and mesh were tested as sterilized products. The following products were tested:
  • the rats were anesthetized with Hypnorm/Dormicum, 0.3 ml/ 100g s.c. and supplemented with half the dose every 20-30 min thereafter. All rats received peri-operativt Rimadyl
  • the rats were given Rimadyl (0.1 ml/ 100g) s.c. the following 2 days after the operation and Buprenorphin (0.03 mg/kg) mixed into a chocolate paste (Nutella) every 12 hours for the first 3 days after operation. The rats were trained to eat the chocolate before the operation.
  • the abdominal area was shaved and disinfected by ethanol and iodide.
  • a midline incision was made and by blunt dissection the skin was loosened from the abdominal muscle in the right side of the rats.
  • a 1.5 cm x 3.0 cm full thickness defect was made in the abdominal muscle layer.
  • the defect was afterwards repaired by the respective implant or mesh with a 0.5 cm overlap in all directions.
  • the corners of the implants or mesh were independently fixated with suture followed by a continuously suture all the way around the implant or mesh.
  • the suture in the corners was permanent Prolene 5-0 suture (Ethicon) in order to be able to find the implant and the continuously suture was Vicryl 4-0 (Ethicon).
  • the skin was afterwards closed by skin staples.
  • the rats were inspected at least once a week in order to observe the rats for hernia or other complications.
  • the 2 rats were killed by cervical dislocation and a midline incision was made in each animal and the implant-area dissected free from the skin.
  • the implantations areas were inspected for signs of herniation, fluid-collection, infection, erosion, rejection or other signs of discrepancies. Digital pictures of the implantation areas were taken and the area was measured. Explants were harvested compromising the implantation area with surrounding tissue. This area was divided into four sections each 1 cm x 2.5 cm. The two midsections were saved for mechanical testing by placing the tissue in phosphate buffered saline (PBS) until testing later the same day of explantation.
  • PBS phosphate buffered saline
  • the two outer sections were divided further into 3-4 pieces, fixated in formalin buffered saline pH 7.4, embedded in paraffin and cut into 4 ⁇ sections using a Leica RM 2255 microtome.
  • the sections were stained with Meyer's Haematoxylin and eosin (HE).
  • the tensile test was performed using a TA-XT plus, Stable Micro Systems.
  • the samples for mechanical testing were stored in PBS after explantation and until testing.
  • the two samples from each rat were measured by respectively having the grips placed at the ends of the implants or by having the grips in the tissue surrounding the implants.
  • the grips were modified with 1 mm rubber sheet and 3M Safety-Walk grip paper.
  • the grip pressure was set to 3 bar, the gauge length was respectively 10 or 30 mm for the placement of the grips and the thickness and width of the samples were measured before the test.
  • the implants were 2.5 x 4 cm (10 cm 2 ) when they were implanted in the rats. At explantation the implants were 2.2 x 3.5 cm (7.7 cm 2 ) and 2.5 x 3.7 cm (9.1 cm 2 ), respectively.
  • the reason for the smaller implants 8 weeks after implantation is due to folds in the implants as seen in the pictures in Figure 1 (se appendix). There were no indications of an increase or decrease in the size of the implants which could be related to failure of the implants.
  • the explants were compared to healed partial defects of the muscle layer.
  • the tensile test of the explanted PCL and PCL-GP implants showed a comparable strength to the partial healed muscle layer.
  • the histology shows a good tissue integration of both types of implants. Both implant types have areas in the middle of the implants where the in-growth of cells seems to be reduced. In the PCL-GP implants these low in-growth areas are more pronounced compared to the PCL implants. The PCL-GP implants have small areas in the full thickness of the implants where there are no in-growth. These areas correspond to the glue points.
  • a generally good biocompatibility was found for both implant types.
  • a reduced in-growth at 8 weeks was found in the areas with the glue points and in middle of the PCL-GP implants compared to the PCL implants.
  • Slower in-growth in the PCL-GP implants may contribute to higher stability of the implants by not allowing the in-growing cells to push apart the individual fibres of the implants.
  • the glue points may help maintain stability of the implant during in-growth.
  • Figure 1 shows a typical example of an electrospun structure (polycaprolactone fibres).
  • Figure 2a and 2b show a scaffold during implantation (Figure 2a) and after 3 weeks of implantation ( Figure 2b).
  • Figure 3 shows cross section of setup for an electrospinning process with addition of glue points.
  • Figure 4 shows electrospun polycaprolactone fibres bonded with glue points of MPEG- PLGA.
  • Figure 5 shows the result of a creep test of mesh.
  • Figure 6 and 7 show E-modulus of mesh.

Abstract

L'invention concerne un treillis non tissé biocompatible comprenant des fibres biodégradables et des points de colle sous la forme de domaines de polymère biodégradable, les fibres étant interconnectées par les points de colle. Le treillis convient comme échafaudage dans le traitement d'un prolapsus d'organe pelvien (POP), une incontinence urinaire d'effort (SUI), ou une hernie.
PCT/DK2013/050162 2012-05-30 2013-05-29 Treillis non tissé biodégradable avec points de colle WO2013178229A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DKPA201270287 2012-05-30
DKPA201270287 2012-05-30

Publications (1)

Publication Number Publication Date
WO2013178229A1 true WO2013178229A1 (fr) 2013-12-05

Family

ID=48576169

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/DK2013/050162 WO2013178229A1 (fr) 2012-05-30 2013-05-29 Treillis non tissé biodégradable avec points de colle

Country Status (1)

Country Link
WO (1) WO2013178229A1 (fr)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105688275A (zh) * 2014-11-25 2016-06-22 上海市第六人民医院 用于盆底重建的纳米弹性补片材料的制备方法
EP3706858A4 (fr) * 2017-11-09 2021-08-25 Neuronano AB Stabilisation de position de dispositifs médicaux implantés dans un tissu
CN113599578A (zh) * 2021-08-11 2021-11-05 上海海洋大学 含dHAM的复合静电纺丝纤维膜及其制备方法和应用
US11944723B2 (en) 2018-03-13 2024-04-02 Institut Quimic De Sarria Cets Fundacio Privada Vascular repair patch

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0334046A2 (fr) * 1988-03-24 1989-09-27 American Cyanamid Company Structure chirurgicale composite contenant des composants absorbables et non absorbables
US20080160859A1 (en) * 2007-01-03 2008-07-03 Rakesh Kumar Gupta Nonwovens fabrics produced from multicomponent fibers comprising sulfopolyesters
WO2010039865A2 (fr) * 2008-10-01 2010-04-08 Cornell University Système biodégradable d'administration d'agent chimique
US7824601B1 (en) * 2007-11-14 2010-11-02 Abbott Cardiovascular Systems Inc. Process of making a tubular implantable medical device

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0334046A2 (fr) * 1988-03-24 1989-09-27 American Cyanamid Company Structure chirurgicale composite contenant des composants absorbables et non absorbables
US20080160859A1 (en) * 2007-01-03 2008-07-03 Rakesh Kumar Gupta Nonwovens fabrics produced from multicomponent fibers comprising sulfopolyesters
US7824601B1 (en) * 2007-11-14 2010-11-02 Abbott Cardiovascular Systems Inc. Process of making a tubular implantable medical device
WO2010039865A2 (fr) * 2008-10-01 2010-04-08 Cornell University Système biodégradable d'administration d'agent chimique

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
M.L. KONSTANTINOVIC ET AL., NEUROUROLOGY AND URODYNAMICS, vol. 29, 2010, pages 488 - 493

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105688275A (zh) * 2014-11-25 2016-06-22 上海市第六人民医院 用于盆底重建的纳米弹性补片材料的制备方法
CN105688275B (zh) * 2014-11-25 2019-05-03 上海市第六人民医院 用于盆底重建的纳米弹性补片材料的制备方法
EP3706858A4 (fr) * 2017-11-09 2021-08-25 Neuronano AB Stabilisation de position de dispositifs médicaux implantés dans un tissu
US11944723B2 (en) 2018-03-13 2024-04-02 Institut Quimic De Sarria Cets Fundacio Privada Vascular repair patch
CN113599578A (zh) * 2021-08-11 2021-11-05 上海海洋大学 含dHAM的复合静电纺丝纤维膜及其制备方法和应用
CN113599578B (zh) * 2021-08-11 2022-10-04 上海海洋大学 含dHAM的复合静电纺丝纤维膜及其制备方法和应用

Similar Documents

Publication Publication Date Title
Catto et al. Small diameter electrospun silk fibroin vascular grafts: Mechanical properties, in vitro biodegradability, and in vivo biocompatibility
Feng et al. Bioresorbable electrospun gelatin/polycaprolactone nanofibrous membrane as a barrier to prevent cardiac postoperative adhesion
RU2538688C2 (ru) Биоразлагаемый каркас для регенерации мягких тканей и его применение
Zhang et al. Electrospun PDLLA/PLGA composite membranes for potential application in guided tissue regeneration
Zhao et al. Biological augmentation of rotator cuff repair using bFGF-loaded electrospun poly (lactide-co-glycolide) fibrous membranes
Hong et al. An elastomeric patch electrospun from a blended solution of dermal extracellular matrix and biodegradable polyurethane for rat abdominal wall repair
US20080109070A1 (en) Biodegradable elastomeric scaffolds containing microintegrated cells
US9345486B2 (en) Nanofibrous conduits for nerve regeneration
EP2125050B1 (fr) Fibres et tissus d'albumine et leurs procédés de génération et d'utilisation
US20190046689A1 (en) Wet-Electrospun Biodegradable Scaffold and Uses Therefor
US20160325016A1 (en) Biohybrid Composite Scaffold
He et al. Fabrication of fibrinogen/P (LLA‐CL) hybrid nanofibrous scaffold for potential soft tissue engineering applications
Chung et al. Three‐layered scaffolds for artificial esophagus using poly (ɛ‐caprolactone) nanofibers and silk fibroin: An experimental study in a rat model
Fan et al. Tissue engineered esophagus scaffold constructed with porcine small intestinal submucosa and synthetic polymers
Sun et al. A synthetic bridging patch of modified co-electrospun dual nano-scaffolds for massive rotator cuff tear
Mohammadalizadeh et al. Synthetic-based blended electrospun scaffolds in tissue engineering applications
WO2008100534A2 (fr) Echafaudage de nanofibres biomimétique pour la réparation, l'augmentation et le remplacement d'un tissu mou et d'un tissu mou-os
JP6118905B2 (ja) 心臓修復パッチの新しいスキャフォールド
CN110193098B (zh) 一种多层梯度生物膜及其制备方法
Rao et al. A multi-walled silk fibroin/silk sericin nerve conduit coated with poly (lactic-co-glycolic acid) sheath for peripheral nerve regeneration
Huang et al. Preparation of composite tubular grafts for vascular repair via electrospinning
Yang et al. A smart scaffold composed of three-dimensional printing and electrospinning techniques and its application in rat abdominal wall defects
WO2013178229A1 (fr) Treillis non tissé biodégradable avec points de colle
Niu et al. Urethral reconstruction using an amphiphilic tissue-engineered autologous polyurethane nanofiber scaffold with rapid vascularization function
Mao et al. Comparative study on nanofiber containing polypropylene-based composite mesh for abdominal wall hernia repair

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 13726675

Country of ref document: EP

Kind code of ref document: A1

DPE1 Request for preliminary examination filed after expiration of 19th month from priority date (pct application filed from 20040101)
122 Ep: pct application non-entry in european phase

Ref document number: 13726675

Country of ref document: EP

Kind code of ref document: A1