WO2020133668A1 - Conduit nerveux de structure tissée composite de filament de magnésium et de soie et procédé de préparation pour conduit nerveux - Google Patents

Conduit nerveux de structure tissée composite de filament de magnésium et de soie et procédé de préparation pour conduit nerveux Download PDF

Info

Publication number
WO2020133668A1
WO2020133668A1 PCT/CN2019/076010 CN2019076010W WO2020133668A1 WO 2020133668 A1 WO2020133668 A1 WO 2020133668A1 CN 2019076010 W CN2019076010 W CN 2019076010W WO 2020133668 A1 WO2020133668 A1 WO 2020133668A1
Authority
WO
WIPO (PCT)
Prior art keywords
silk
catheter
nerve
magnesium
solution
Prior art date
Application number
PCT/CN2019/076010
Other languages
English (en)
Chinese (zh)
Inventor
李刚
张淑军
郑兆柱
王晓沁
Original Assignee
南通纺织丝绸产业技术研究院
苏州大学
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 南通纺织丝绸产业技术研究院, 苏州大学 filed Critical 南通纺织丝绸产业技术研究院
Priority to JP2021523697A priority Critical patent/JP2022506369A/ja
Publication of WO2020133668A1 publication Critical patent/WO2020133668A1/fr

Links

Images

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
    • A61L27/14—Macromolecular materials
    • A61L27/26—Mixtures of macromolecular compounds
    • 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
    • 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
    • A61L27/02—Inorganic materials
    • A61L27/04—Metals or alloys
    • A61L27/047—Other specific metals or alloys not covered by A61L27/042 - A61L27/045 or A61L27/06
    • 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
    • A61L27/22—Polypeptides or derivatives thereof, e.g. degradation products
    • A61L27/227—Other specific proteins or polypeptides not covered by A61L27/222, A61L27/225 or A61L27/24
    • 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
    • A61L27/383—Nerve cells, e.g. dendritic cells, Schwann 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
    • A61L27/3878—Nerve tissue, brain, spinal cord, nerves, dura mater
    • 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
    • A61L27/52—Hydrogels or hydrocolloids
    • 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
    • A61L27/56—Porous materials, e.g. foams or sponges
    • 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
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
    • A61L2300/30—Compounds of undetermined constitution extracted from natural sources, e.g. Aloe Vera
    • 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
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/412—Tissue-regenerating or healing or proliferative agents
    • 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
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/412—Tissue-regenerating or healing or proliferative agents
    • A61L2300/414—Growth factors
    • 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
    • A61L2430/00—Materials or treatment for tissue regeneration
    • A61L2430/32—Materials or treatment for tissue regeneration for nerve reconstruction

Definitions

  • the invention belongs to the technical field of biomedical materials, and in particular relates to a magnesium-silk silk composite braided structure nerve catheter and a preparation method thereof.
  • Peripheral nerve injury is a common clinical condition.
  • the use of biomaterials and tissue engineering techniques to promote the repair and regeneration of defective nerves is a research hotspot in the field of neuroscience.
  • Ideal biological materials, appropriate physical and mechanical guidance and suitable biological microenvironment are the key factors to promote the recovery of sensory, motor and other biological functions of damaged nerves.
  • the most researched nerve catheters are the use of model casting method, electrostatic nano-spinning method, 3D bioprinting and other technologies, and the use of biodegradable materials such as silk fibroin, chitosan and collagen to produce physical guides. Hollow catheters, but the neural catheters produced by these techniques have poor mechanical mechanics and flexibility.
  • a kind of nerve catheter using silk fibroin nanofiber directional guidance function uses condensation-induced silk fibroin solution to form nano-micropores as physical guidance, but the micropores formed in this invention are difficult to control the shape size and direction, and the radial compression of the catheter General performance, bending flexibility is not considered;
  • another example is to use nano-oriented fibers to make films with different degradation concentrations and then roll them into a neural tube with a tubular structure.
  • This neural tube has excellent physical guidance to cells, but its mechanical properties are relatively good. Poor, there is less space for nerve regeneration inside;
  • another example is the use of 3D bioprinting, which has greater restrictions on materials, and the current resolution is lower, which is about 1 ⁇ 300mPa/s.
  • magnesium is one of the important elements necessary for the human body. It participates in protein synthesis in the brain and central nervous system, activates various enzymes in the body, and regulates neuromuscular activity.
  • metal magnesium ions have various biological functions such as anti-inflammatory, anti-oxidation, anti-apoptosis, and regulation of mitochondrial calcium buffer.
  • the latest research shows that magnesium ions can promote the proliferation of Schwann cells under the appropriate microenvironment, such as secretion of growth factors, extracellular matrix (ECM), etc., which play a role in supporting and protecting neurons.
  • Silkworm silk is a natural animal protein synthesized and secreted by the silkworm. It has a wide range of sources.
  • Silk fibroin is the main component of silk, accounting for 70%-80% of the quality of silk. The remaining main components are sericin and carbohydrates.
  • Silk fibroin contains a variety of amino acids, of which the more common alanine (Ala), glycine (Gly), and serine (Ser) account for about 85% of the total composition.
  • Silk fibroin itself has good physical and chemical properties, breathable moisture, biocompatibility, can be degraded into peptides and free amino acids in the body can be absorbed by the body to promote the growth of nerve cells.
  • the nerve duct made of silk fibroin has low inflammatory response in the body, is biodegradable, and can promote the functional recovery of peripheral nerve injury.
  • the present invention proposes a magnesium silk silk composite braided structure nerve catheter and a preparation method thereof.
  • the purpose of the present invention is to provide a magnesium silk silk composite braided structure neural catheter and a preparation method thereof, which can improve the order of nerve regeneration and the mechanical strength of the nerve catheter to solve the above problems.
  • a nerve conduit with a composite braided structure of magnesium silk and silk comprising an outer layer of a nerve conduit, an intermediate layer of a nerve conduit, and an inner layer of a nerve conduit, the middle layer of the nerve conduit covers the outside of the inner layer of the nerve conduit, and the outer layer of the nerve conduit
  • the outer layer of the nerve catheter is a porous sponge structure formed by mixing silk fibroin solution and chitosan solution, and the thickness of the outer layer of the nerve catheter is 0.5-1.5mm ,
  • the pore diameter is 20-150 ⁇ m, the porosity is 75%-90%
  • the middle layer of the nerve conduit is a three-dimensional braided structure, the thickness of the middle layer of the nerve conduit is 0.3-1mm, and the braid angle of the three-dimensional braided structure is 45 -60°
  • the inner layer of the nerve conduit is a porous gel structure
  • the diameter of the inner layer of the nerve conduit is 1.8-5 mm.
  • the three-dimensional braided structure is any one of a diamond braided structure, a regular braided structure and a Hergliss braided structure.
  • the three-dimensional braided structure is a three-dimensional structural catheter skeleton formed by compound braiding of magnesium wire as the shaft yarn and degummed silk as the braided yarn.
  • the diameter of the magnesium wire is 0.1-0.25 mm and the number of wires is 4-16.
  • the distance between two adjacent magnesium wires is 200-2000 ⁇ m, and the linear density of the degummed silk is 20-120D.
  • the porous gel structure is a composite gel layer composed of silk fibroin gel, Schwann cells and nerve growth factor, the silk fibroin gel is frozen to form a mesh fiber, the Schwann cell and nerve
  • the growth factor is set in the mesh fiber, the diameter of the mesh fiber is 10-1000 nm, and the pore diameter is 10-500 ⁇ m.
  • a method for preparing a nerve conduit of magnesium silk and silk composite braided structure includes the following steps:
  • a vertical spindle braiding machine with a core function is used to prepare the skeleton structure of the nerve catheter, which is composite braided with magnesium wire as the shaft yarn and degummed silk as the woven yarn;
  • a silk fibroin solution with a concentration of 0.01-0.5% cultured Schwann cells is injected into the hollow structure of the outer layer of the neural catheter, and it is left at a temperature of 37°C for 12 hours to form Gelation catheter; insert the gelation catheter vertically into a liquid nitrogen tank, freeze slowly at a speed of 0.1-1 mm/s along the axis of the gelation catheter, and then put it into the freeze dryer It was freeze-dried in medium for 24-48 hours to obtain magnesium silk silk composite braided structure neural catheter.
  • the preparation method of the silk fibroin solution in step (2) is as follows: weigh silkworm raw silk to degumme in boiling Na 2 CO 3 aqueous solution for 30 minutes, stir with a glass rod every 10 minutes, and use deionized water After the second rinse, place it in a fume hood overnight and dry it naturally to obtain dried silkworm silk fibers. Dissolve the dried silkworm silk fibers in the LiBr solution and dissolve them in an oven at 60°C for 4 hours. Ensure that the dissolution is complete, obtain the first mixed solution, centrifuge the first mixed solution after dialysis to obtain the silk fibroin solution, and place it in a refrigerator at 4 °C for use.
  • the dialysis in step (2) is: pouring the first mixed solution into a dialysis bag with a molecular weight cut-off of 3500D, dialyzing in deionized water for 36 hours, and changing the water every 4 hours.
  • step (2) centrifuging twice at 9000 r/min in a high-speed centrifuge for 20 minutes each time.
  • the preparation method of the chitosan solution in step (2) is: weigh out chitosan with a degree of deacetylation of 80-95%, dissolve in 0.5-4% acetic acid solution, and stir for 4-12 hours To make a chitosan solution with a mass percentage of 1-5%.
  • the invention provides a magnesium-silk silk composite braided structure nerve catheter and a preparation method thereof, and its advantages are:
  • the catheter has good biocompatibility, surface activity and permeability, can promote the adhesion, growth and proliferation of neuronal cells, and accelerate the regeneration of damaged nerves;
  • the degradation rate of the catheter can be adjusted to provide a suitable growth space for nerve regeneration
  • the magnesium wire in the catheter can stimulate and guide nerve growth.
  • the magnesium ions generated during degradation can help to increase the activity of neuronal cells.
  • FIG. 1 is a schematic structural view of a magnesium silk silk composite braided structure neural catheter according to the present invention in Example 1;
  • FIG. 2 is a schematic structural view of a magnesium silk silk composite braided structure neural catheter according to the present invention in Example 2;
  • Example 3 is a schematic structural diagram of a magnesium silk silk composite braided structure nerve catheter according to the present invention in Example 1;
  • FIG. 4 is a braid angle of a neural catheter with an inner diameter of 2 mm and 3 mm made of magnesium silk composite braided structure prepared with different parameters according to Example 1 of the present invention
  • FIG. 5 is a load-tensile strain curve of a neural catheter with an inner diameter of 2 mm and 3 mm prepared by using different parameters of a composite braided structure of magnesium silk and silk according to Example 1 of the present invention.
  • 1 is the outer layer of the nerve conduit
  • 2 is the middle layer of the nerve conduit
  • 3 is the inner layer of the nerve conduit
  • 4 is the shaft yarn
  • 5 is the braided yarn
  • 6 is the silk fibroin gel
  • 7 is the Schwann cell
  • 8 is the nerve Growth factor
  • 9 is titanium, nickel alloy wire.
  • the invention provides a magnesium silk silk composite braided structure neural catheter.
  • the catheter is divided into three layers, including: the outer layer 1 of the neural catheter is a porous sponge formed by mixing silk fibroin solution and chitosan solution Structure, the thickness is 0.5-1.5mm, the pore size is 20-150 ⁇ m, the porosity is 75%-90%, the middle layer 2 of the neural catheter is a three-dimensional braided structure, which can be diamond braided (1/1 interwoven), regular braided (2/ 2 interweave) and Hercules (3/3 interweave) any one of the three braided structures, the thickness is 0.3-1mm, the braid angle is 45-60°, and the inner layer 3 of the nerve conduit is a porous gel structure , Diameter is 1.8-5mm, its degradation time is 1-5 days.
  • the middle layer 2 of the nerve catheter is made of magnesium wire as the shaft yarn 4, its diameter is 0.1-0.25mm, the number is 4-16, the spacing between the magnesium wires is 200-2000 ⁇ m, and the degummed silk is woven yarn 5, and its thread Density of 20-120D, composite braided three-dimensional structure catheter skeleton; nerve catheter inner layer 3 is composed of silk fibroin gel 6, Schwann cell 7 and nerve growth factor 8 composite gel layer, which guides the directed growth of nerve cells Effect.
  • Nerve growth factor 8 is a protein molecule necessary for the growth and survival of neurons.
  • the diameter of the network fibers formed by freezing is 10-1000 nm, and the pore diameter is 10-500 ⁇ m.
  • the catheter structure has excellent flexibility and flexibility, and can well adapt to the complex stress environment of the body.
  • the preparation method of the above-mentioned magnesium silk silk composite braided structure nerve catheter includes the following steps:
  • the first mixed solution was taken out and poured into a dialysis bag (molecular weight cut off 3500D), dialyzed in deionized water for 36 hours, and the water was changed every 4 hours.
  • the dialyzed solution was centrifuged twice in a high-speed centrifuge at 9000r/min for 20 minutes each time to remove impurities, and finally a silk fibroin solution was obtained, which was placed in a 4°C refrigerator for use.
  • the "one embodiment” or “embodiments” referred to herein refer to specific features, structures, or characteristics that can be included in at least one implementation of the present invention.
  • the appearances of "in one embodiment” in different places in this specification do not all refer to the same embodiment, nor are they separate or selective embodiments mutually exclusive with other embodiments.
  • This example shows a structure and preparation method of a nerve catheter with a composite braided structure of magnesium silk and silk.
  • the nerve catheter has three layers in which the shaft yarn 4 of the middle layer 2 of the nerve catheter is magnesium wire and the middle of the nerve catheter
  • the braided yarn 5 of layer 2 is degummed silk
  • the outer layer 1 of the nerve conduit is a porous sponge layer made by mixing silk fibroin and chitosan solution
  • the mass ratio of silk fibroin to chitosan is 10:1
  • chitosan solution The concentration is 3-6 mg/mL
  • the silk fibroin aqueous solution concentration is 5-10% (w/v).
  • the inner layer 3 of the nerve conduit is a porous silk fibroin gel layer made of an aqueous solution of silk fibroin at a concentration of 5-10% (w/v).
  • the preparation process is as follows:
  • the braid angle of the magnesium wire and silk composite braided structure neural catheter varies between 40-55°.
  • the angle is stable; as can be seen in Figure 5, the first peak represents the breaking peak of the braided yarn, at this time the tensile strain is 8%, the load is up to 35N, and the second peak represents the breaking peak of the shaft yarn, when the load is greater than 65N, indicating that the shaft
  • the addition of yarn greatly enhances the tensile properties of the nerve catheter.
  • This example shows a structure and preparation method of a nerve catheter with a composite braided structure of magnesium silk and silk.
  • the nerve catheter has a total of three layers.
  • the shaft yarn 4 of the middle layer 2 of the nerve catheter is magnesium wire and braided yarn.
  • the outer layer 1 of the nerve catheter is a porous sponge made of chitosan solution with a concentration of 3-6mg/mL
  • the layer has a solution concentration of 3-6 mg/mL
  • the inner layer 3 of the neural catheter is a silk fibroin gel made of a silk fibroin aqueous solution with a concentration of 5-10% (w/v).
  • the preparation process is as follows:
  • the raw material is 20-100D degummed silk silk, magnesium wire and titanium, nickel alloy wire with a diameter of 0.05-0.2mm
  • This example shows a structure and preparation method of a nerve conduit with a composite braided structure of magnesium silk and silk.
  • the nerve conduit has three layers, in which the shaft yarn 4 of the middle layer 2 of the nerve conduit is magnesium wire and degummed silk Interweaving, braided yarn 5 is degummed silk, the outer layer 1 of the nerve conduit is a porous sponge layer prepared from an aqueous solution of silk fibroin with a concentration of 5-10% (w/v); the inner layer 3 of the nerve conduit is a concentration of 5-10 A porous silk fibroin gel layer made of% (w/v) silk fibroin aqueous solution.
  • the preparation process is as follows:
  • the present invention discloses a magnesium silk silk composite braided structure nerve catheter and a preparation method thereof.
  • the medical metal magnesium wire with strong mechanical properties is used as a shaft yarn to be added to the silk braided structure, which serves as a longitudinal guide It can also improve the radial compression performance of the braided skeleton.
  • the magnesium wire can slowly degrade, promote the growth and proliferation of Schwann cells, and is conducive to the recovery of damaged nerves; the braided yarn is degummed silk with a good biological phase Capacitive, while ensuring good mechanical properties, create a biological microenvironment that promotes nerve regeneration.

Abstract

La présente invention concerne un conduit nerveux ayant une structure tissée composite d'un filament de magnésium et de soie ainsi qu'un procédé de préparation du conduit nerveux.Le conduit nerveux comprend une couche externe à la structure spongieuse poreuse formée par mélange d'une solution de fibroïne de soie avec une solution de chitosane, une couche intermédiaire de squelette à la structure tridimensionnelle formée par tissage composite d'un filament de magnésium en tant que fil axial et de soie décreusée en tant que fil de tressage, et une couche interne à la structure de gel poreux. La structure tissée composite de filament de magnésium et de soie peut améliorer la résistance à la pression radiale, se dégrader lentement pour favoriser la croissance et la prolifération de cellules de Schwann, faciliter la récupération de nerfs endommagés et présente une bonne biocompatibilité.
PCT/CN2019/076010 2018-12-29 2019-02-25 Conduit nerveux de structure tissée composite de filament de magnésium et de soie et procédé de préparation pour conduit nerveux WO2020133668A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
JP2021523697A JP2022506369A (ja) 2018-12-29 2019-02-25 マグネシウムワイヤー・シルク複合編組構造の神経カテーテル及びその製造方法

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN201811638025.9 2018-12-29
CN201811638025.9A CN109513041B (zh) 2018-12-29 2018-12-29 一种镁丝蚕丝复合编织结构神经导管及其制备方法

Publications (1)

Publication Number Publication Date
WO2020133668A1 true WO2020133668A1 (fr) 2020-07-02

Family

ID=65798765

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2019/076010 WO2020133668A1 (fr) 2018-12-29 2019-02-25 Conduit nerveux de structure tissée composite de filament de magnésium et de soie et procédé de préparation pour conduit nerveux

Country Status (3)

Country Link
JP (1) JP2022506369A (fr)
CN (1) CN109513041B (fr)
WO (1) WO2020133668A1 (fr)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113634048A (zh) * 2021-09-10 2021-11-12 武汉纺织大学 天然蚕丝微纳米纤维复合多孔材料及其应用
CN114470325A (zh) * 2022-03-24 2022-05-13 合肥工业大学 一种可缝裁单面导电抗菌的甲壳素水凝胶神经导管材料的制备方法
CN114983622A (zh) * 2022-06-01 2022-09-02 奥精医疗科技股份有限公司 一种神经导管的制备方法及神经导管
CN116899014A (zh) * 2023-07-24 2023-10-20 上海工程技术大学 一种三维拓扑结构多通道神经导管及其制备方法

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109513041B (zh) * 2018-12-29 2023-10-03 南通纺织丝绸产业技术研究院 一种镁丝蚕丝复合编织结构神经导管及其制备方法
CN110251732B (zh) * 2019-06-18 2020-10-27 南通纺织丝绸产业技术研究院 一种多层复合编织的可降解神经导管结构及其制备方法
CN110786965B (zh) * 2019-11-14 2021-04-30 苏州大学 变锭编织法制备多通道抗菌神经导管的方法
CN111281599A (zh) * 2020-03-19 2020-06-16 中国海洋大学 一种增强型人工神经导管及其制备方法和应用
CN111297513A (zh) * 2020-03-19 2020-06-19 中国海洋大学 一种负载营养因子的人工神经导管及其制备方法和应用

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1987850A1 (fr) * 2000-12-21 2008-11-05 Ethicon, Incorporated Implants de tissu renforcés, leurs procédés de fabrication et leur utilisation
CN102274089A (zh) * 2011-05-24 2011-12-14 苏州大学 一种丝素蛋白管状支架及其制备方法
CN104107096A (zh) * 2014-07-18 2014-10-22 上海交通大学 可弯曲全降解镁合金神经导管及其制备方法
CN104548205A (zh) * 2014-12-29 2015-04-29 东莞颠覆产品设计有限公司 一种动物源神经支架及其制备方法
WO2015142631A1 (fr) * 2014-03-17 2015-09-24 University Of Pittsburgh-Of The Commonwealth System Of Higher Education Échafaudages contenant un composite de magnésium pour amplifier la régénération tissulaire
CN105748171A (zh) * 2016-02-21 2016-07-13 新乡医学院 生物型神经导管
CN109513041A (zh) * 2018-12-29 2019-03-26 南通纺织丝绸产业技术研究院 一种镁丝蚕丝复合编织结构神经导管及其制备方法

Family Cites Families (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2580349C (fr) * 2004-09-14 2014-06-17 Neurotex Limited Procedes et appareil de croissance amelioree de nerfs peripheriques et des tissus nerveux
JP4982887B2 (ja) * 2007-02-20 2012-07-25 北海道曹達株式会社 神経再生チューブ及びその製造方法
KR101116237B1 (ko) * 2009-08-12 2012-03-09 서울대학교산학협력단 실크 나노섬유 신경도관 및 이의 제조방법
CN102688076B (zh) * 2011-03-25 2014-09-10 广州迈普再生医学科技有限公司 一种神经导管及其制备方法
JP2014155622A (ja) * 2013-02-15 2014-08-28 Terumo Corp 管状体
CN103083720B (zh) * 2013-02-28 2015-01-21 苏州大学 一种丝素蛋白管及其制备方法
CN103598927A (zh) * 2013-10-17 2014-02-26 上海交通大学 用于神经缺损修复的可降解镁合金神经导管及其制备方法
ES2577883B2 (es) * 2014-12-16 2016-11-21 Universitat Politècnica De València Biohíbrido para su uso en la regeneración de tractos neurales
CN110461382A (zh) * 2017-01-25 2019-11-15 B.布劳恩梅尔松根股份公司 腔内装置
CN108853587B (zh) * 2017-05-10 2021-08-03 上海交通大学 镁合金与高分子丝材混编复合补片及其用途

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1987850A1 (fr) * 2000-12-21 2008-11-05 Ethicon, Incorporated Implants de tissu renforcés, leurs procédés de fabrication et leur utilisation
CN102274089A (zh) * 2011-05-24 2011-12-14 苏州大学 一种丝素蛋白管状支架及其制备方法
WO2015142631A1 (fr) * 2014-03-17 2015-09-24 University Of Pittsburgh-Of The Commonwealth System Of Higher Education Échafaudages contenant un composite de magnésium pour amplifier la régénération tissulaire
CN104107096A (zh) * 2014-07-18 2014-10-22 上海交通大学 可弯曲全降解镁合金神经导管及其制备方法
CN104548205A (zh) * 2014-12-29 2015-04-29 东莞颠覆产品设计有限公司 一种动物源神经支架及其制备方法
CN105748171A (zh) * 2016-02-21 2016-07-13 新乡医学院 生物型神经导管
CN109513041A (zh) * 2018-12-29 2019-03-26 南通纺织丝绸产业技术研究院 一种镁丝蚕丝复合编织结构神经导管及其制备方法

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113634048A (zh) * 2021-09-10 2021-11-12 武汉纺织大学 天然蚕丝微纳米纤维复合多孔材料及其应用
CN114470325A (zh) * 2022-03-24 2022-05-13 合肥工业大学 一种可缝裁单面导电抗菌的甲壳素水凝胶神经导管材料的制备方法
CN114983622A (zh) * 2022-06-01 2022-09-02 奥精医疗科技股份有限公司 一种神经导管的制备方法及神经导管
CN116899014A (zh) * 2023-07-24 2023-10-20 上海工程技术大学 一种三维拓扑结构多通道神经导管及其制备方法
CN116899014B (zh) * 2023-07-24 2024-05-07 上海工程技术大学 一种三维拓扑结构多通道神经导管及其制备方法

Also Published As

Publication number Publication date
JP2022506369A (ja) 2022-01-17
CN109513041B (zh) 2023-10-03
CN109513041A (zh) 2019-03-26

Similar Documents

Publication Publication Date Title
WO2020133668A1 (fr) Conduit nerveux de structure tissée composite de filament de magnésium et de soie et procédé de préparation pour conduit nerveux
CN103341209B (zh) 一种丝素蛋白纳米纤维膜及其制备方法
CN110251732B (zh) 一种多层复合编织的可降解神经导管结构及其制备方法
Zhao et al. Preparation of nanofibers with renewable polymers and their application in wound dressing
Han et al. A review: Current status and emerging developments on natural polymer‐based electrospun fibers
CN101879330B (zh) 一种小口径丝素蛋白管状材料及其制备方法
Wang et al. Fabrication of the FGF1-functionalized sericin hydrogels with cell proliferation activity for biomedical application using genetically engineered Bombyx mori (B. mori) silk
CN106237381B (zh) 一种丝素蛋白微纳米纤维多孔支架及其制备方法
Ma et al. Piezoelectric conduit combined with multi-channel conductive scaffold for peripheral nerve regeneration
KR20110016581A (ko) 실크 나노섬유 신경도관 및 이의 제조방법
Tavakoli et al. Coaxial electrospun angiogenic nanofiber wound dressing containing advanced platelet rich-fibrin
CN106310380A (zh) 一种纳米纤维化丝素蛋白凝胶及其制备方法
CN107982580A (zh) 一种基于编织和涂层技术的丝素蛋白组织工程支架及其制备方法和应用
CN108114315A (zh) 一种双丝素蛋白神经移植物
Li et al. Tough and VEGF-releasing scaffolds composed of artificial silk fibroin mats and a natural acellular matrix
CN114732954B (zh) 一种载药型人工皮肤及其制备方法
CN106243377A (zh) 一种多孔蚕丝纤维材料及其制备方法
CN102247184B (zh) 管内具有平行导向纱的编织型神经导管支架及其制备方法
WO2021227255A1 (fr) Procédé de préparation de greffon nerveux de fibroïne de soie fusionné avec nt3
CN110464881A (zh) 具有层级结构的丝素多孔支架及其制备方法
Mohammadzadehmoghadam et al. Electrospinning of silk fibroin-based nanofibers and their applications in tissue engineering
Das et al. Silk fiber composites in biomedical applications
CN209564438U (zh) 一种镁丝蚕丝复合编织结构神经导管
CN110615913B (zh) 一种丝蛋白多孔海绵及其制备方法
CN106729981A (zh) 一种丝素蛋白纳米纤维及其制备方法和应用

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: 19903207

Country of ref document: EP

Kind code of ref document: A1

ENP Entry into the national phase

Ref document number: 2021523697

Country of ref document: JP

Kind code of ref document: A

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 19903207

Country of ref document: EP

Kind code of ref document: A1