WO2023035767A1 - Endoprothèse bionique 3d à plusieurs branches, son procédé de préparation et son application - Google Patents

Endoprothèse bionique 3d à plusieurs branches, son procédé de préparation et son application Download PDF

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WO2023035767A1
WO2023035767A1 PCT/CN2022/105551 CN2022105551W WO2023035767A1 WO 2023035767 A1 WO2023035767 A1 WO 2023035767A1 CN 2022105551 W CN2022105551 W CN 2022105551W WO 2023035767 A1 WO2023035767 A1 WO 2023035767A1
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branch
fiber
tube
fiber tubes
tubes
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PCT/CN2022/105551
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Chinese (zh)
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陈仕国
杜冰
赵世光
吴佳宁
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深圳大学
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    • 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
    • A61L27/02—Inorganic materials
    • A61L27/025—Other specific inorganic materials not covered by A61L27/04 - A61L27/12
    • 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
    • A61L27/16—Macromolecular materials obtained 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
    • A61L27/14—Macromolecular materials
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    • 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
    • A61L27/20—Polysaccharides
    • 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
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    • A61L27/22—Polypeptides or derivatives thereof, e.g. degradation products
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    • A—HUMAN NECESSITIES
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    • 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
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    • 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
    • A61L27/507—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials for artificial blood vessels
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    • 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
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    • 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
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B33—ADDITIVE MANUFACTURING TECHNOLOGY
    • B33Y—ADDITIVE MANUFACTURING, i.e. MANUFACTURING OF THREE-DIMENSIONAL [3-D] OBJECTS BY ADDITIVE DEPOSITION, ADDITIVE AGGLOMERATION OR ADDITIVE LAYERING, e.g. BY 3-D PRINTING, STEREOLITHOGRAPHY OR SELECTIVE LASER SINTERING
    • B33Y10/00—Processes of additive manufacturing
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B33—ADDITIVE MANUFACTURING TECHNOLOGY
    • B33Y—ADDITIVE MANUFACTURING, i.e. MANUFACTURING OF THREE-DIMENSIONAL [3-D] OBJECTS BY ADDITIVE DEPOSITION, ADDITIVE AGGLOMERATION OR ADDITIVE LAYERING, e.g. BY 3-D PRINTING, STEREOLITHOGRAPHY OR SELECTIVE LASER SINTERING
    • B33Y70/00—Materials specially adapted for additive manufacturing
    • B33Y70/10—Composites of different types of material, e.g. mixtures of ceramics and polymers or mixtures of metals and biomaterials
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B33—ADDITIVE MANUFACTURING TECHNOLOGY
    • B33Y—ADDITIVE MANUFACTURING, i.e. MANUFACTURING OF THREE-DIMENSIONAL [3-D] OBJECTS BY ADDITIVE DEPOSITION, ADDITIVE AGGLOMERATION OR ADDITIVE LAYERING, e.g. BY 3-D PRINTING, STEREOLITHOGRAPHY OR SELECTIVE LASER SINTERING
    • B33Y80/00—Products made by additive manufacturing
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    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/0062—General methods for three-dimensional culture
    • A—HUMAN NECESSITIES
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    • 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
    • A61L2430/00—Materials or treatment for tissue regeneration
    • A61L2430/32—Materials or treatment for tissue regeneration for nerve reconstruction
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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    • C12N2535/00—Supports or coatings for cell culture characterised by topography

Definitions

  • the invention belongs to the technical field of biomedicine, and in particular relates to a 3D multi-branch bionic scaffold and its preparation method and application.
  • Tissue engineering is a cutting-edge interdisciplinary science. Its basic principle is: by constructing a three-dimensional complex of cells and scaffolds in vitro, simulating the environment in vivo, and cultivating and training them to obtain tissues with repair or replacement functions.
  • Biomimetic scaffolds for tissue engineering provide mechanical support for cells through biomimetic extracellular matrix, and promote cell adhesion, growth, proliferation, migration and metabolism, which is one of the key factors in tissue engineering.
  • vascularization is necessary for tissue repair.
  • tissues with vigorous metabolism such as myocardium and liver, because the cells have a high level of substance and energy metabolism, and the transmission distance of oxygen and nutrients in the scaffold is limited, how to establish an effective vascular network and solve the problem of hypoxic necrosis of inner cells It has always been an important problem in tissue engineering.
  • the existing methods of perfusion culture, increasing the oxygen content of the surrounding environment, adding oxygen carriers, and in vivo transplantation can make the thickness of the artificial tissue living cell layer reach 500 ⁇ m.
  • adding substances such as endothelial cells and pro-angiogenic growth factors can promote the formation of capillary-like tissues after transplantation in vivo.
  • the above method does not form a branched vascular network similar to hierarchical penetration, and cannot fundamentally solve the problem of oxygen supply to cells inside the scaffold.
  • the present invention provides a 3D multi-branch bionic scaffold and its preparation method and application.
  • design-manufacture-assemble hollow directional fiber tubes of different sizes are designed and prepared, and then assembled to form a A 3D multi-branch bionic scaffold with a complex hierarchical structure, which can provide effective mechanical support for defective tissue, and its interpenetrating network framework is conducive to the directional arrangement of cells, osmotic growth, and ingrowth of blood vessels and nerves. It is convenient for the transfer of nutrients and metabolic waste, and the 3D multi-branch bionic scaffold has low preparation cost, strong production operability and high flexibility, and has ideal promotion and application value in the fields of biomedical materials and tissue engineering.
  • the first aspect of the present invention provides a 3D multi-branch bionic scaffold, wherein the 3D multi-branch bionic scaffold includes: a trunk fiber tube, one end of the trunk fiber tube communicates with at least two primary branch fiber tubes, each The ends of each primary branch fiber tube are communicated with secondary branch fiber tubes; the cross-sectional area of the trunk fiber tube is equal to the sum of the cross-sectional areas of all the primary branch fiber tubes connected thereto, and the trunk fiber tube.
  • the tube wall, the tube wall of the primary branch fiber tube and the tube wall of the secondary branch fiber tube all have a pore structure.
  • the cross-sectional area of a single branch fiber tube is equal to the sum of the cross-sectional areas of all the next-level branch fiber tubes connected to it.
  • the 3D multi-branch bionic scaffold further includes a sleeve, and the sleeve is used to reinforce the connection between different fiber tubes.
  • the diameter of the fiber is 0.1-25 mm, and the diameter of the pore is 0.01-100 ⁇ m.
  • a second aspect of the present invention provides a method for preparing the 3D multi-branched bionic scaffold of the present invention, which includes the following steps:
  • the mixed ink includes biodegradable polymer material A, biodegradable polymer material B and solvent;
  • the multiple fiber tubes are spliced and assembled by self-adhesion to obtain the 3D multi-branch bionic scaffold.
  • the biodegradable polymer material A is silk protein, chitosan, hyaluronic acid, collagen, sodium alginate, gelatin, polylactide-glycolide, polyvinyl alcohol, polycaprolactone, One or a combination of two or more polylactic acids;
  • the biodegradable polymer material B is one or two or more of tannic acid, polyacrylamide, polyvinyl alcohol, positive metal salts, borax, cyclodextrin, and dimethylglyoxime combination;
  • the solvent is one or a combination of two or more of water, formic acid, acetic acid, hexafluoroisopropanol, tetrahydrofuran, dimethylformamide, and dimethyl sulfoxide.
  • the total biodegradable polymer material accounts for 1 to 35% w/v, and the mass ratio of the biodegradable polymer material A to the biodegradable polymer material B is 1:4 ⁇ 19:1.
  • the step of making the mixed ink into a plurality of fiber tubes by using 3D direct writing or electrospinning specifically includes:
  • the distance from the syringe needle of the 3D direct writer to the receiver is 0.1-1.5 cm, the pressure is 10-100 kPa, the electric field is 0.5-1.5 kV, and the flow rate is 1-30 mm/s;
  • the distance from the syringe needle of the electrospinning machine to the receiver is 5-30 cm, the electric field is 15-25 kV, and the flow rate is 0.1-10 ml/h.
  • the post-treatment is drying, removing impurities, One or a combination of spraying and hole making.
  • the method further includes a step of reinforcing the joints between different fiber tubes with sleeves.
  • the third aspect of the present invention provides the application of the 3D multi-branch biomimetic scaffold of the present invention as or preparation of tissue engineering scaffold material.
  • the advantages of the present invention at least include:
  • the present invention realizes the formation of multi-branched and network-structured biomimetic scaffolds, which can not only obtain the multi-branched extracellular matrix simulation structure in natural tissues on demand, but also overcome the direct The technical bottleneck of forming complex microchannel structures.
  • the 3D multi-branch bionic scaffold can provide effective mechanical support for defective tissue, and its interpenetrating network framework is conducive to the directional arrangement of cells, osmotic growth, and ingrowth of blood vessels and nerves, and also facilitates the delivery of nutrients and metabolic waste.
  • the preparation cost of the 3D multi-branch bionic scaffold is low, the production operability is strong, and the flexibility is high, and it has ideal promotion and application value in the field of biomedical materials and tissue engineering;
  • the present invention uses biodegradable polymer materials as raw materials for preparing 3D multi-branch bionic scaffolds, which are safe, non-toxic, and have good biocompatibility.
  • the materials can be automatically degraded; due to biodegradable Polymer material A and biodegradable polymer material B can be self-adhesive through hydrogen bonding or metal complexation, so the obtained fiber tubes have self-adhesion function, and no additional adhesive is required for 3D multi-branch bionic scaffold assembly
  • the direct connection of different fiber tubes can be realized; when different biodegradable polymer materials are mixed, not only can the precise design and manufacture of tissue engineering scaffolds be realized according to the defect repair requirements, but also the mechanical properties of the scaffold materials (such as elasticity, Hardness, strength, etc.) and degradation rate can be effectively regulated, and it has outstanding advantages in the design and preparation of tissue engineering scaffolds;
  • the diameter of the fibers prepared by 3D direct writing or electrospinning in the present invention is equivalent to that of the microfilaments in the extracellular matrix.
  • the tiny pore structure composed of fibers and better pipeline connectivity can well simulate natural
  • the extracellular matrix structure provides an ideal microenvironment for cell growth.
  • Fig. 1 is a schematic structural diagram of a 3D multi-branched bionic scaffold provided by an embodiment of the present invention.
  • Fig. 2 is a schematic structural diagram of a 3D multi-branched brachial plexus bionic scaffold for brachial plexus structural repair in Example 1 of the present invention.
  • Fig. 3 is a schematic structural diagram of a 3D multi-vessel biomimetic stent used for repairing branch structures of vascular tissue engineering in Example 2 of the present invention.
  • An embodiment of the present invention provides a 3D multi-branch bionic scaffold
  • the 3D multi-branch bionic scaffold includes: a trunk fiber tube, one end of the trunk fiber tube is connected with at least two primary branch fiber tubes, each primary branch fiber The end of the pipe is communicated with a secondary branch fiber tube; the cross-sectional area of the main fiber tube is equal to the sum of the cross-sectional areas of all the first-level branch fiber tubes connected to it, the tube wall of the main fiber tube, the Both the tube wall of the primary branch fiber tube and the tube wall of the secondary branch fiber tube have a pore structure.
  • the 3D multi-branch bionic scaffold in this embodiment is not limited to include first-level branched fiber tubes and second-level branched fiber tubes, but may also include third-level branched fiber tubes and fourth-level branched fiber tubes. . .
  • m-level branched fiber tubes the number of stages of branched fiber tubes is determined according to needs.
  • one end of a single branch fiber tube may be connected with several next-level branch fiber tubes, and the number may be one, two, three or four.
  • the cross-sectional area of a single branch fiber tube is equal to the sum of the cross-sectional areas of all the next-level branch fiber tubes connected to it.
  • the 3D multi-branch bionic scaffold further includes a sleeve, and the sleeve is used to reinforce the connection between different fiber tubes.
  • the fiber has a diameter of 0.1-25 mm, and the pore has a diameter of 0.01-100 ⁇ m, which is conducive to cell osmotic growth, ingrowth of blood vessels and nerves, and also facilitates the transfer of nutrients and metabolic waste.
  • the 3D multi-branch bionic scaffold includes a main fiber tube 1 and branch fiber tubes, and the branch fiber tubes include a primary branch fiber tube 2, a secondary branch fiber tube 3, a tertiary branch fiber tube 4,
  • the primary branch fiber tube 2 includes a primary branch fiber tube 21 and a primary branch fiber tube 22
  • the secondary branch fiber tube 3 includes a secondary branch fiber tube 31, a secondary branch fiber tube Tube 32, secondary branch fiber tube 33, secondary branch fiber tube 34 and secondary branch fiber tube 35
  • the tertiary branch fiber tube 4 includes a tertiary branch fiber tube 41 and a tertiary branch fiber tube 42
  • the first-level branch fiber tube 5 includes a fourth-level branch fiber tube 51 and a fourth-level branch fiber tube 52; one end of all first-level branch fiber tubes 2 is connected to the same end of the main fiber tube 1, and the second-level branch fiber tube 3 It is connected with the other end of the primary branch fiber tube 2; the cross-sectional area of the
  • the 3D multi-branch bionic support also includes a sleeve 6, which is used to fix the joints of different fiber tubes.
  • the embodiment of the present invention provides a method for preparing a 3D multi-branch bionic scaffold, which includes the following steps:
  • mixed ink described mixed ink comprises biodegradable polymer material A, biodegradable polymer material B and solvent;
  • the advantages of this embodiment at least include:
  • this example realizes the formation of multi-branched and network-structured biomimetic scaffolds, which can not only obtain the multi-branched extracellular matrix simulation structure in natural tissues on demand, but also overcome the Technical bottleneck of direct molding complex microchannel structures.
  • the 3D multi-branch bionic scaffold can provide effective mechanical support for defective tissue, and its interpenetrating network framework is conducive to the directional arrangement of cells, osmotic growth, and ingrowth of blood vessels and nerves, and also facilitates the delivery of nutrients and metabolic waste.
  • the preparation cost of the 3D multi-branch bionic scaffold is low, the production operability is strong, and the flexibility is high, and it has ideal promotion and application value in the field of biomedical materials and tissue engineering;
  • this embodiment uses biodegradable polymer materials as raw materials for preparing 3D multi-branch biomimetic scaffolds, which are safe, non-toxic, and have good biocompatibility.
  • the materials can be automatically degraded;
  • the degradable polymer material A and the biodegradable polymer material B can be self-adhesive through hydrogen bonding or metal complexation, so the obtained fiber tubes have self-adhesive function, and no additional bonding is required for the assembly of 3D multi-branch bionic scaffolds
  • the direct connection of different fiber tubes can be realized by using the same agent; when different biodegradable polymer materials are used in combination, not only can the precise design and manufacture of tissue engineering scaffolds be realized according to the needs of defect repair, but also the mechanical properties (such as elasticity) of the scaffold materials can be adjusted. , hardness, strength, etc.) and degradation rate can be effectively regulated, which has outstanding advantages in the design and preparation of tissue engineering scaffolds;
  • the diameter of the fiber prepared by 3D direct writing or electrospinning in this example is equivalent to that of the microfilament in the extracellular matrix, coupled with the tiny pore structure composed of the fiber, and better pipeline connectivity, it can well simulate The natural extracellular matrix structure provides an ideal microenvironment for cell growth.
  • the type of liquid supply in the preparation process such as changing the type of biodegradable polymer material
  • the mold of the receiving device and designing the corresponding parameters (ie, parameters such as pressure, electric field, and flow rate)
  • different tensile strain rates and The nano-scale fiber tubes with oriented structure can meet different cell growth requirements, and can promote cell adhesion, spreading and proliferation.
  • the hydroxyl group (-OH), carboxyl group (-COOH) and ester group (-COOR) in the biodegradable polymer material A and the positive metal ion contained in the metal salt in the biodegradable polymer material B (such as Ca 2+ , Fe 3+ ions) constitute the metal complexation, so that different fiber tubes have a self-adhesive function.
  • the biodegradable polymer material A can be silk protein, chitosan, hyaluronic acid, collagen, sodium alginate, gelatin, polylactide-glycolide, polyvinyl alcohol, poly One or a combination of two or more of caprolactone, polylactic acid, etc.
  • the biodegradable polymer material B is one or both of tannic acid, polyacrylamide, polyvinyl alcohol, positive metal salts, borax, cyclodextrin, and dimethylglyoxime. more than one combination.
  • the mixed ink can be prepared by the following method:
  • the first solvent is one or more of water, formic acid, acetic acid, hexafluoroisopropanol, tetrahydrofuran, dimethylformamide, and dimethyl sulfoxide The combination.
  • the second solvent is one or more of water, formic acid, acetic acid, hexafluoroisopropanol, tetrahydrofuran, dimethylformamide, and dimethyl sulfoxide The combination.
  • step S13 in one embodiment, in the mixed ink, the total biodegradable polymer material (that is, the sum of the mass of biodegradable polymer material A and biodegradable polymer material B) accounts for 1-35% w/v, the mass ratio of the biodegradable polymer material A to the biodegradable polymer material B is 1:4-19:1.
  • step S2 specifically includes:
  • the distance from the syringe needle of the 3D direct writer to the receiver is 0.1-1.5 cm
  • the pressure is 10-100 kPa
  • the electric field is 0.5-1.5 kV
  • the flow velocity is 1-30 mm /s.
  • step S2 specifically includes:
  • the distance from the syringe needle of the electrospinning machine to the receiver is 5-30 cm, the electric field is 15-25 kV, and the flow rate is 0.1-10 ml/h.
  • the diameter of the fibers is 0.1-25 mm, and the diameter of the pores formed between the fibers is 0.01-100 ⁇ m, which is conducive to the osmotic growth of cells, the ingrowth of blood vessels and nerves, and the convenience of nutrients and metabolism. delivery of waste.
  • step S3 in one embodiment, before the step of splicing and assembling the plurality of fiber tubes by self-adhesion, the step of post-processing the plurality of fiber tubes is also included.
  • the treatment is one or a combination of drying, impurity removal, spraying and pore making.
  • the step of reinforcing the joints between different fiber tubes with sleeves is further included. That is, after the fiber tubes of different sizes are self-repairing and self-adhesive, the casing is further reinforced.
  • the embodiment of the present invention provides the application of the 3D multi-branch biomimetic scaffold as or preparation of tissue engineering scaffold material.
  • the preparation method of the 3D multi-branch bionic scaffold of the present embodiment comprises the following steps:
  • silk protein is carried out extraction pretreatment (5g silk protein powder is added in the degumming agent sodium carbonate aqueous solution of 0.02M after boiling, after washing, drying obtains protein fiber; Then protein fiber is dissolved in 9.3M LiBr solution, in Stir at 60°C for 4 hours, after cooling, go through repeated dialysis to remove metal ions, and finally freeze-dry); disperse the pretreated silk protein in deionized water, and prepare 80ml of A solution with a concentration of 5% w/v; then 1.6 ml of tannic acid aqueous solution B with a concentration of 50% w/v was added dropwise into solution A to prepare a mixed ink with a total solute concentration of 7% w/v;
  • Example 1 the size parameters of fiber tubes of different sizes are shown in Table 1.
  • the fiber tube obtained by 3D direct writing from the above-mentioned biodegradable polymer material was further tested.
  • the tensile strength of a single fiber tube is about 5-10MPa, the tensile modulus is 120-180MPa, and the elongation at break is about 10-20%;
  • Adsorption capacity test The adsorption capacity of fiber tubes to proteins varies from 5 ⁇ 1.20 ⁇ g to 15 ⁇ 4.20 ⁇ g depending on the size.
  • Biocompatibility test CCK-8 cell proliferation test was used to evaluate the biocompatibility of the fiber tube.
  • the specific method is as follows: mMSCs (mouse bone marrow mesenchymal stem cells) were inoculated on the surface of the 3D multi-branched biomimetic scaffold at a concentration of 2 ⁇ 10 4 cells/cm 2 , and samples were taken for detection after 1, 4 and 7 days of culture respectively.
  • the structure of the brachial plexus is simulated, and the above-mentioned fiber tubes of different sizes are assembled according to the structure of the brachial plexus to obtain a 3D multi-branched brachial plexus bionic scaffold for the repair of the brachial plexus structure.
  • the preparation method of the 3D multi-branch bionic scaffold of the present embodiment comprises the following steps:
  • silk protein is carried out extraction pretreatment (5g silk protein powder is added in the degumming agent sodium carbonate aqueous solution of 0.02M after boiling, after washing, drying obtains protein fiber; Then protein fiber is dissolved in 9.3M LiBr solution, in Stir at 60°C for 4 hours, after cooling, remove metal ions through repeated dialysis, and finally lyophilize); disperse the pretreated silk protein in deionized water, prepare 80ml of A solution with a concentration of 5% w/v, and add to Add 0.887g of calcium chloride to the A solution, and stir well; then, add 1.6ml of 50% w/v tannic acid aqueous solution B dropwise into the A solution containing calcium chloride to prepare a mixed ink ;
  • the branch structure of vascular tissue engineering is simulated, and the above-mentioned fiber tubes of different sizes are assembled according to the branch structure of vascular tissue engineering to obtain a 3D multi-branched vascular bionic scaffold for repairing the branch structure of vascular tissue engineering.
  • the preparation method of the 3D multi-branch bionic scaffold of the present embodiment comprises the following steps:
  • silk protein is carried out extraction pretreatment (5g silk protein powder is added in the degumming agent sodium carbonate aqueous solution of 0.02M after boiling, after washing, drying obtains protein fiber; Then protein fiber is dissolved in 9.3M LiBr solution, in Stirring at 60°C for 4 hours, cooling, repeated dialysis to remove metal ions, and finally freeze-drying); dispersing the pretreated silk protein in deionized water, and preparing a solution A with a concentration of 30% w/v; then, According to the mass ratio of silk protein to polyacrylamide 3:2, the polyacrylamide B aqueous solution with a concentration of 15% w/v is mixed with the A solution and diluted with deionized water to prepare a mixture with a total solute concentration of 18% w/v ink;
  • the preparation method of the 3D multi-branch bionic scaffold of the present embodiment comprises the following steps:
  • silk protein is carried out extraction pretreatment (5g silk protein powder is added in the degumming agent sodium carbonate aqueous solution of 0.02M after boiling, after washing, drying obtains protein fiber; Then protein fiber is dissolved in 9.3M LiBr solution, in Stir at 60°C for 4 hours, after cooling, go through repeated dialysis to remove metal ions, and finally freeze-dry); after the chitosan is pretreated for impurity removal, the pretreated silk protein and chitosan are mixed in a mass ratio of 4:1 Add it into the formic acid solution, fully stir it evenly, and prepare 80ml of a mixed solution whose total biodegradable polymer material accounts for 15% w/v; then add 0.887g of calcium chloride to the mixed solution, stir well, and prepare mixed ink;
  • the preparation method of the 3D multi-branch bionic scaffold of the present embodiment comprises the following steps:
  • silk protein is carried out extraction pretreatment (5g silk protein powder is added in the degumming agent sodium carbonate aqueous solution of 0.02M after boiling, after washing, drying obtains protein fiber; Then protein fiber is dissolved in 9.3M LiBr solution, in Stir at 60°C for 4 hours, after cooling, go through repeated dialysis to remove metal ions, and finally freeze-dry); disperse the pretreated silk protein in deionized water, and prepare A solution with a concentration of 15% w/v, take 20ml A solution of 80ml is mixed with 50% w/v polyvinyl alcohol B aqueous solution to prepare a mixed ink with a silk protein concentration of 3% w/v;
  • the preparation method of the 3D multi-branch bionic scaffold of the present embodiment comprises the following steps:
  • the above 15 kinds of fiber tubes of different sizes are dried and post-processed, and then spliced and assembled.
  • the self-healing properties of the fibers at the joints are adhered to each other, and the joints are reinforced with sleeves, and finally a 3D multi-branch bionic scaffold is obtained.
  • the preparation method of the 3D multi-branch bionic scaffold of the present embodiment comprises the following steps:
  • the above 12 fiber tubes of different sizes are dried and post-processed, and then spliced and assembled.
  • the self-healing properties of the fibers at the joints are adhered to each other, and the joints are reinforced with sleeves, and finally a 3D multi-branch bionic scaffold is obtained.
  • the preparation method of the 3D multi-branch bionic scaffold of the present embodiment comprises the following steps:

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Abstract

L'invention concerne une endoprothèse bionique 3D à plusieurs branches, son procédé de préparation et son application. L'endoprothèse bionique 3D à plusieurs branches comprend : un tube de fibre principal, une extrémité du tube de fibre principal étant raccordée à au moins deux tubes de fibre de branche primaire, et l'extrémité de chaque tube de fibre de branche primaire étant raccordée à un tube de fibre de branche secondaire ; la surface de section transversale du tube de fibre principal est équivalente à la somme des surfaces de section transversale de tous les tubes de fibre de branche primaire qui lui sont raccordés ; et la paroi du tube de fibre principal, les parois du tube de fibre de branche primaire et les parois du tube de fibre de branche secondaire présentent toutes des structures de pores. L'endoprothèse bionique 3D à plusieurs branches peut fournir un support mécanique efficace pour les tissus défectueux, et sa structure en réseau interconnecté facilite la disposition directionnelle des cellules, la croissance osmotique et la croissance des vaisseaux sanguins et des nerfs, et facilite également le transfert des substances nutritives et des déchets métaboliques. L'endoprothèse présente de faibles coûts de production et une grande opérabilité de production, et est très flexible.
PCT/CN2022/105551 2021-09-10 2022-07-13 Endoprothèse bionique 3d à plusieurs branches, son procédé de préparation et son application WO2023035767A1 (fr)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN115386133A (zh) * 2022-09-22 2022-11-25 诺一迈尔(苏州)生命科技有限公司 一种关节软骨纳米纤维微球支架及其制备方法

Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20080125870A1 (en) * 2006-11-06 2008-05-29 Carmichael Ralph W Nerve regeneration device
CN102631709A (zh) * 2012-04-13 2012-08-15 清华大学 一种带分支血管网络的复杂器官前体的制备方法
CN204890256U (zh) * 2015-08-13 2015-12-23 长沙医学院 一种周围神经修复用组织工程诱导支架
CN105311683A (zh) * 2015-11-16 2016-02-10 清华大学 一种含内通道网络和定向孔隙结构的仿生组织工程支架及其制备方法与应用
CN106584836A (zh) * 2016-11-30 2017-04-26 广州博敏科技有限公司 复合3d打印成型系统、成型方法及血管支架
CN107693846A (zh) * 2017-09-29 2018-02-16 清华大学 一种具有多层血管结构的仿生血管化软组织及其制备方法
CN111346264A (zh) * 2020-03-10 2020-06-30 南通大学 用于组织修复的多分叉型空心生物材料导管的制备方法
CN112292221A (zh) * 2018-05-21 2021-01-29 悉尼大学 制造铸件的方法
CN113288534A (zh) * 2021-05-14 2021-08-24 胡佳 拼接式血管支架

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7101391B2 (en) * 2000-09-18 2006-09-05 Inflow Dynamics Inc. Primarily niobium stent
WO2013078051A1 (fr) * 2011-11-21 2013-05-30 Johnson Jed K Échafaudages fibreux utilisables dans des prothèses trachéennes
CN104939946B (zh) * 2015-06-29 2017-01-11 上海大学 中空水凝胶纤维的制备及构建分支血管单元的方法
EP3315147A1 (fr) * 2016-10-28 2018-05-02 Bioengineering Laboratories S.r.l. Échafaudage hybride permettant de régénérer des tissus et procédé de production
US20190142571A1 (en) * 2017-11-13 2019-05-16 Derrick Chu Branching covered stent-grafts and related deployment systems and methods

Patent Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20080125870A1 (en) * 2006-11-06 2008-05-29 Carmichael Ralph W Nerve regeneration device
CN102631709A (zh) * 2012-04-13 2012-08-15 清华大学 一种带分支血管网络的复杂器官前体的制备方法
CN204890256U (zh) * 2015-08-13 2015-12-23 长沙医学院 一种周围神经修复用组织工程诱导支架
CN105311683A (zh) * 2015-11-16 2016-02-10 清华大学 一种含内通道网络和定向孔隙结构的仿生组织工程支架及其制备方法与应用
CN106584836A (zh) * 2016-11-30 2017-04-26 广州博敏科技有限公司 复合3d打印成型系统、成型方法及血管支架
CN107693846A (zh) * 2017-09-29 2018-02-16 清华大学 一种具有多层血管结构的仿生血管化软组织及其制备方法
CN112292221A (zh) * 2018-05-21 2021-01-29 悉尼大学 制造铸件的方法
CN111346264A (zh) * 2020-03-10 2020-06-30 南通大学 用于组织修复的多分叉型空心生物材料导管的制备方法
CN113288534A (zh) * 2021-05-14 2021-08-24 胡佳 拼接式血管支架

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN115386133A (zh) * 2022-09-22 2022-11-25 诺一迈尔(苏州)生命科技有限公司 一种关节软骨纳米纤维微球支架及其制备方法
CN115386133B (zh) * 2022-09-22 2023-11-14 诺一迈尔(苏州)生命科技有限公司 一种关节软骨纳米纤维微球支架及其制备方法

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