WO2019144741A1 - 一种复合支架材料及其制备方法和用途 - Google Patents

一种复合支架材料及其制备方法和用途 Download PDF

Info

Publication number
WO2019144741A1
WO2019144741A1 PCT/CN2018/123280 CN2018123280W WO2019144741A1 WO 2019144741 A1 WO2019144741 A1 WO 2019144741A1 CN 2018123280 W CN2018123280 W CN 2018123280W WO 2019144741 A1 WO2019144741 A1 WO 2019144741A1
Authority
WO
WIPO (PCT)
Prior art keywords
group
acid
fiber
electrospinning
biocompatible
Prior art date
Application number
PCT/CN2018/123280
Other languages
English (en)
French (fr)
Inventor
刘光万
邵莹华
赵芳
曲洪媛
宋德利
Original Assignee
苏州博创同康生物工程有限公司
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 苏州博创同康生物工程有限公司 filed Critical 苏州博创同康生物工程有限公司
Priority to US16/964,198 priority Critical patent/US20230191003A1/en
Publication of WO2019144741A1 publication Critical patent/WO2019144741A1/zh

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
    • A61L27/50—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
    • A61L27/40—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
    • A61L27/44—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix
    • 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
    • A61L27/40—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
    • A61L27/44—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix
    • A61L27/48—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix with macromolecular fillers
    • 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
    • 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
    • A61L27/28—Materials for coating prostheses
    • A61L27/34—Macromolecular materials
    • 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
    • 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
    • D04H1/00—Non-woven fabrics formed wholly or mainly of staple fibres or like relatively short fibres
    • D04H1/40—Non-woven fabrics formed wholly or mainly of staple fibres or like relatively short fibres from fleeces or layers composed of fibres without existing or potential cohesive properties
    • D04H1/42—Non-woven fabrics formed wholly or mainly of staple fibres or like relatively short fibres from fleeces or layers composed of fibres without existing or potential cohesive properties characterised by the use of certain kinds of fibres insofar as this use has no preponderant influence on the consolidation of the fleece
    • D04H1/4326—Condensation or reaction polymers
    • D04H1/435—Polyesters
    • 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
    • D04H1/00—Non-woven fabrics formed wholly or mainly of staple fibres or like relatively short fibres
    • D04H1/70—Non-woven fabrics formed wholly or mainly of staple fibres or like relatively short fibres characterised by the method of forming fleeces or layers, e.g. reorientation of fibres
    • D04H1/72—Non-woven fabrics formed wholly or mainly of staple fibres or like relatively short fibres characterised by the method of forming fleeces or layers, e.g. reorientation of fibres the fibres being randomly arranged
    • D04H1/728—Non-woven fabrics formed wholly or mainly of staple fibres or like relatively short fibres characterised by the method of forming fleeces or layers, e.g. reorientation of fibres the fibres being randomly arranged by electro-spinning
    • 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
    • A61L2300/252—Polypeptides, proteins, e.g. glycoproteins, lipoproteins, cytokines
    • 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

Definitions

  • the invention relates to the technical field of medicine, in particular to a composite scaffold material, a preparation method thereof and use thereof.
  • PLGA polylactic acid glycolic acid copolymer
  • PLA polylactic acid
  • PCL polycaprolactone
  • biocompatibility is poor, the tissue cell adhesion performance and the biological induction activity are weak, and thus the regeneration and repair of the defect tissue are not well induced and promoted, and the volume shrinkage of these stents in the body fluid further affects the use effect. If the acellular matrix material is used, the immunogenicity is not completely removed, which may cause immune rejection.
  • Biopolymer materials, such as collagen sponge have good biocompatibility, but mechanical properties such as mechanical strength are poor, and the structure is easy to collapse.
  • the implanted body degrades too fast, and the tissue is not completely repaired when the degradation is complete.
  • the polymer material is cast film, the surface is dense, and the host cells are difficult to migrate to the inside of the material, and can only adhere to the surface of the material, resulting in a decrease in the repair effect.
  • Most tissues repair the regenerative scaffold, which is prone to rupture and stratification, resulting in separation or volumetric contraction after implantation in the body, which affects the therapeutic effect.
  • Most tissue repair patches cross-link cross-linking, which can improve the mechanical properties after cross-linking. Prolong the degradation time, but the use of excessive cross-linking agent in addition to a certain degree of tissue toxicity, it is easy to lead to calcification.
  • a first aspect of the present invention provides a composite scaffold material comprising a charged fiber skeleton material coated with alternating positively charged biocompatibility by electrostatic attraction Sexual materials and negatively charged biocompatible materials.
  • the fiber skeleton material generally comprises fibers.
  • the fibers constituting the fiber skeleton material may be fibers formed by electrospinning and/or 3D printing, constituting the fiber skeleton material.
  • the fibers are generally evenly distributed throughout the composite scaffolding material. Those skilled in the art can adjust the shape of the fiber skeleton material as needed, so that the shape of the composite stent material can be adjusted.
  • the fiber skeleton material can be stacked from fibers, and for example, the fiber skeleton material and/or the composite stent material can generally be Various regular or irregular shapes such as a layer body, a sphere, a cylinder (hollow or non-hollow), and the formed structure may be various two-dimensional or three-dimensional rules or irregularities such as a film shape, a tube shape, a spherical shape, and the like. shape.
  • the fibrous framework material may be a flat layer (e.g., a film, etc.).
  • the diameter (thickness) of the fibers constituting the fiber skeleton material may be 3 nm to 20,000 nm, 3 nm to 10 nm, 10 nm to 20 nm, 20 nm to 30 nm, 30 nm to 50 nm, 50 nm to 70 nm, 70 nm to 100 nm, 100 nm to 150 nm, and 150 nm.
  • the fiber may comprise 20%-90%, 20%-30%, 30%-40%, 40%-50%, 50%-60% by volume of the fiber skeleton material. 60%-70%, 70%-80% or 80%-90%.
  • the fibers constituting the fiber skeleton material usually have a charge (the charge may be a positive charge and/or a negative charge), and the fiber may be a fiber having its own charge, or may be
  • the charged fiber is treated by charge modification, so that the positively-charged biocompatible material and the negatively-charged biocompatible material can be alternately coated on the fiber skeleton material by electrostatic attraction.
  • the charge modification treatment generally refers to the modification of the fiber by certain physical methods and/or chemical methods (for example, adhesion or addition of a charged substance to the fiber, or modification or plasma modification of the surface of the fiber)
  • the resulting fiber thus has a positive and/or negative charge treatment.
  • the material obtained by the charge modification treatment may carry a positively charged group or a negatively charged group, so that the fibers constituting the fiber skeleton material are charged, and the positively charged group may be including but not limited to A combination of one or more of an amino group, a quaternary ammonium group, and the like, which may be a combination of one or more of, for example, but not limited to, a mercapto group, a carboxyl group, a sulfonic acid group, a phosphoric acid group, and the like.
  • the fibers constituting the fiber skeleton material are generally biocompatible materials, and the biocompatibility generally means that the material (for example, an inactive material) has a good phase with the host.
  • Capacity, for example, biocompatibility for fiber matrix materials generally refers to good affinity, small immune response, no cytotoxicity after implantation into human tissues, and specifically refers to conformity with International Standards Organization (ISO) 10993. And/or materials specified in the national standard GB/T16886.
  • the fiber constituting the fiber skeleton material may be a polymer material, and the polymer material generally means a compound (generally, a compound having a relative molecular mass (for example, a weight average molecular weight) of ⁇ 1000, ⁇ 1500 or ⁇ 2000).
  • the material consisting of the matrix may be a polymer material, and the polymer material generally means a compound (generally, a compound having a relative molecular mass (for example, a weight average molecular weight) of ⁇ 1000, ⁇ 1500 or ⁇ 2000).
  • the material consisting of the matrix.
  • the polymer material may be a natural biopolymer material and/or an organic synthetic polymer material, and the natural polymer material generally refers to a polymer material existing in animals, plants and other organisms, and may specifically include but not limited to Polylysine, polyglutamic acid, collagen, silk fibroin, soy protein, elastin, hyaluronic acid, chitosan, carboxymethyl chitosan, carboxymethyl dextran, carboxymethyl glucose, a combination of one or more of heparin, alginic acid, chondroitin sulfate, carboxymethyl starch, carboxymethyl cellulose, or other various modifying materials; the organic synthetic polymer material generally refers to by chemistry
  • the polymer material obtained by the synthetic method may specifically include, but not limited to, polylactic acid, polyglycolic acid, polycaprolactone, polylactic acid glycolic acid copolymer, polylactic acid caprolactone copolymer polyoxycyclohexanone, Sanya.
  • the fiber is doped with a charged doping material, so that the doped fiber carries a stronger charge
  • the doped material may be a natural biopolymer material. Specifically, it may be a natural biopolymer material as described above.
  • the doping material can be mixed with the fiber in any ratio, and for example, the doping material can account for no more than 1 wt% of the total mass of the doped fiber, 1- 5 wt%, 5-10 wt%, 10-20 wt%, 20-30 wt%, 30-40 wt%, 40-50 wt%, 50-60 wt%, 60-70 wt%, 70-80 wt%, 80-90 wt% or higher Percentage of mass.
  • a functional factor and/or a functional polypeptide may be added to the fibrous scaffold material.
  • the functional factor generally refers to a substance that can regulate the function of the human body by activating the activity of the enzyme or other means.
  • the functional factors in the fibrous matrix material may be, but not limited to, fibronectin, laminin, vascular endothelial growth factor, One of fibrinogen, epidermal growth factor, fibroblast growth factor, transforming growth factor, bone morphogenetic protein, insulin-like growth factor, platelet-derived growth factor, hydroxyapatite, barium chloride, thrombin, or the like
  • the functional factor in the fiber skeleton material may be added in an amount of not more than 10% by weight, not more than 20% by weight, not more than 30% by weight, not more than 40% by weight, not more than 50% by weight, not more than 1% by weight, 1 -2 wt%, 2-4 wt%, 4-6 wt%, 6-8 wt%, 8-10 wt%, 10-15 wt%, 15-20 wt%, 20-25 wt%, 25-30 wt%, 30-35 wt%, 35 -40 wt%, 40-45 wt% or 45
  • the functional polypeptide generally refers to a class of functional factors which may be polypeptides.
  • the functional polypeptide in the fibrous framework material may be a polypeptide including, but not limited to, an RGD polypeptide and an arginine-glycine-aspartate-containing polypeptide.
  • the functional polypeptide in the fibrous matrix material may be added in an amount of not more than 10% by weight, not more than 20% by weight, not more than 30% by weight, not more than 40% by weight, and not more than 50% by weight.
  • % not more than 1 wt%, 1-2 wt%, 2-4 wt%, 4-6 wt%, 6-8 wt%, 8-10 wt%, 10-15 wt%, 15-20 wt%, 20-25 wt%, 25-30 wt %, 30-35 wt%, 35-40 wt%, 40-45 wt% or 45-50 wt%.
  • the positively-charged biocompatible material and the negatively-charged biocompatible material coated on the skeleton material by electrostatic attraction can be realized by electrostatic self-assembly.
  • the manner of assembly should be known to those skilled in the art, for example, positively charged biocompatible materials and/or negatively charged biocompatible materials can be dissolved in an appropriate amount of solvent by spraying and/or soaking. The method of self-assembly.
  • the positively charged biocompatible material and/or the negatively charged biocompatible material are generally biocompatible materials, for example, for positively charged biocompatible materials and/or Biocompatibility of negatively charged biocompatible materials generally refers to good affinity, small immune response, no cytotoxicity, etc. after implantation into human tissues, and specifically refers to compliance with International Standards Organization (ISO) 10993 and / Or the relevant materials specified in the national standard GB/T16886.
  • the positively charged biocompatible material may be a positively charged material, and the positively charged material generally refers to a material having a positive charge, and may specifically include, but not limited to, polylysine, collagen, silk fibroin, fibronectin.
  • the negatively charged biocompatible material may be a negatively charged material, the negatively charged material generally being referred to as having a negative charge
  • the material may specifically include, but not limited to, polyglutamic acid, collagen, silk fibroin, fibronectin, laminin, fibrinogen (protein is an ampholyte, which can be charged by adjusting the pH of the solution), and transparent One or more of acid, carboxymethyl chitosan, carboxymethyl dextran, carboxymethyl glucose, heparin, alginic acid, chondroitin sulfate, carboxymethyl starch, carboxymethyl cellulose, and the like combination.
  • a functional factor and/or a functional polypeptide may be added to the positively charged biocompatible material and/or the negatively charged biocompatible material.
  • functional factors in positively charged biocompatible materials and/or negatively charged biocompatible materials can include, but are not limited to, fibronectin, laminin, vascular endothelial growth factor, fibrinogen, nerve growth factor, One or a combination of epidermal growth factor, fibroblast growth factor, transforming growth factor, bone morphogenetic protein, insulin-like growth factor, platelet-derived growth factor, hydroxyapatite, barium chloride, thrombin, and the like.
  • the amount of the functional factor added in the positively-charged biocompatible material and/or the negatively-charged biocompatible material may be not more than 10% by weight, not more than 20% by weight, not more than 30% by weight, not more than 40% by weight, and not more than 50 wt%, not more than 1 wt%, 1-2 wt%, 2-4 wt
  • a functional polypeptide in a positively charged biocompatible material and/or a negatively charged biocompatible material can be a polypeptide including, but not limited to, an RGD polypeptide, an arginine-glycine-aspartate-containing, -proline-glycine-valine-alanine-valine-glycine-polypeptide or polypeptide containing -isoleucine-lysine-valine-alanine-valine-, etc.
  • a combination of one or more of the above, and, for example, the functional polypeptide in the positively-charged biocompatible material and/or the negatively-charged biocompatible material may be added in an amount of not more than 10% by weight, not more than 20% by weight, or not more than 30 wt%, not more than 40 wt%, not more than 50 wt%, not more than 1 wt%, 1-2 wt%, 2-4 wt%, 4-6 wt%, 6-8 wt%, 8-10 wt%, 10-15 wt%, 15- 20 wt%, 20-25 wt%, 25-30 wt%, 30-35 wt%, 35-40 wt%, 40-45 wt% or 45-50 wt%.
  • the positively-charged biocompatible material and the negatively-charged biocompatible material may form a layer of alternating positively-charged biocompatible material and a layer of negatively-charged biocompatible material
  • a person skilled in the art can adjust parameters such as thickness, number of layers, and the like of a positively charged biocompatible material layer and/or a negatively charged biocompatible material layer, for example, a positively charged biocompatible material layer and/or a negatively charged organism.
  • the thickness of each layer of compatible material layer may be 0.1-100 microns, 0.1-1 microns, 1-5 microns, 5-10 microns, 10-20 microns, 20-40 microns, 40-60 microns, 60-80 microns. Or 80-100 microns, the total number of layers of alternating positively charged biocompatible material layers and negatively charged biocompatible material layers may be 2-200 layers, 2-10 layers, 10-30 layers, 30-50 layers , 50-100 layers, 100-150 layers or 150-200 layers.
  • the fiber skeleton material can occupy 5-95%, 5-15%, 15-25%, 25-35%, 35-45%, 45-55%, 55-65%, 65-75%, 75-85% of the total mass of the composite scaffold material Or 85-95%; for another example, the positively charged biocompatible material may comprise 5-95%, 5-15%, 15-25%, 25-35%, 35-45% of the total mass of the composite scaffold material.
  • the negatively charged biocompatible material may comprise 5-95% of the total mass of the composite scaffold material 5-15%, 15-25%, 25-35%, 35-45%, 45-55%, 55-65%, 65-75%, 75-85% or 85-95%; for example, The positively charged biocompatible material and the negatively charged biocompatible material account for 5-95%, 5-15%, 15-25%, 25-35%, 35-45%, 45- of the total mass of the composite scaffold material. 55%, 55-65%, 65-75%, 75-85% or 85-95%.
  • a second aspect of the invention provides a method for preparing the composite scaffold material, comprising:
  • the polymeric biocompatible material is formed into a fibrous matrix material by electrospinning and/or 3D printing, and the positively charged biocompatible material and the negatively charged biocompatible material are alternately coated by electrostatic self-assembly.
  • electrospinning and/or 3D printing can generally be carried out in the presence of a solvent, and the polymeric biocompatible material can be dissolved in a suitable solvent for electrospinning and/or 3D printing
  • electrospinning and Solvents used in / or 3D printing include, but are not limited to, formic acid, acetic acid, ethanol, acetone, dimethylformamide, dimethylacetamide, tetrahydrofuran, dimethyl sulfoxide, hexafluoroisopropanol, trifluoroethanol a combination of one or more of dichloromethane, chloroform, methanol, chloroform, dioxane, trifluoroethane, trifluoroacetic acid, water, physiological saline, various buffer solutions, etc.; for example, static
  • 3D printing speed 0.001-100mm/min, 0.001-0.01mm/min, 0.01-0.1mm/min, 0.1-1mm/min, 1-5mm/min, 5-10mm/min, 10-20mm/min, 20- 30 mm/min, 30-40 mm/min, 40-50 mm/min, 50-60 mm/min, 60-70 mm/min, 70-80 mm/min, 80-100 mm/min.
  • 3D printing temperature (such as organic polymer material can be 3D printing in solvent or molten state) can be -20-400 ° C, -20-10 ° C, -10-0 ° C, 0-10 ° C, 10-20 ° C 20-30 ° C, 30-40 ° C, 40-50 ° C, 50-60 ° C, 60-70 ° C, 70-80 ° C, 80-90 ° C, 90-100 ° C, 100-200 ° C, 200-300 ° C , 300-400 ° C.
  • those skilled in the art can alternately coat the positively charged biocompatible material and the negative charge by electrostatic self-assembly according to the type and parameters of the fibers to be formed and the appropriate process conditions.
  • Biocompatible materials For example, electrostatic self-assembly can be sprayed and/or immersed, and a method of drying and sterilizing can be advanced to alternately coat the surface of the material with a positively charged biocompatible material and a negatively charged biocompatible material.
  • Electrostatic self-assembly is carried out in the presence of a solvent, and the positively-charged biocompatible material and/or the negatively-charged biocompatible material can be dissolved in an appropriate amount of solvent to perform electrostatic self-assembly, a solvent used in electrostatic self-assembly.
  • a solvent used in electrostatic self-assembly A combination of one or more of, but not limited to, a formic acid solution, an acetic acid solution, a hydrochloric acid solution, a phosphoric acid solution, a sulfuric acid solution, water, an alkali solution, physiological saline, various salt solutions, and a buffer solution.
  • drying and/or sterilization during the preparation process, and specific drying methods include, but not limited to, freeze drying, drying, vacuum drying or natural drying, etc. Methods include, but are not limited to, radiation sterilization and/or chemical sterilization of ethylene oxide.
  • a third aspect of the invention provides the use of the composite scaffold material in the preparation of a biocompatible material.
  • the composite scaffold material provided by the invention has good biocompatibility, and can be used for preparing materials such as carrier materials, tissue engineering scaffold materials and the like.
  • the carrier material generally refers to a carrier that can be used to load other substances, and particularly can include, but is not limited to, a pharmaceutical carrier material, which can generally be used to load various drugs;
  • the tissue engineering scaffold material generally refers to capable The material to be implanted into the living body, so that it can be combined with the living cells of the tissue, and can have certain functional materials according to the specific replacement tissue, and specifically includes but not limited to artificial meninges, artificial blood vessels, nerve repair catheters, bone repair stents. Medical materials such as artificial skin and patches.
  • the composite scaffold material provided by the present invention overcomes the hydrophilicity of the existing scaffold material by coating the fiber skeleton material with electrostatically attractive alternating positively charged biocompatible materials and negatively charged biocompatible materials. Defects such as poor sex, poor biocompatibility, tissue cell adhesion and weak bio-inducing activity, which are better suited when used for tissue adhesion, sealing, plugging, hemostasis, isolation, repair, prevention of adhesion, etc. It can also be used as a carrier for preparing drugs (for example, a sustained-release carrier) and a tissue engineering scaffold material, and has a wide range of uses.
  • the composite scaffold material provided by the invention combines organic synthetic polymer materials and bio-polymer materials to simulate extracellular matrix, provides living space for cell berthing, growth and reproduction, acquires nutrition, carries out metabolism, and optimizes through materials.
  • the addition of functional factors and functional structural peptides in the composite scaffold material contributes to cell adhesion and extension, and achieves multifunctional use of the material in repairing and regenerating damaged tissues, and has high biological induction activity, and the polyelectrolyte is alternately stacked by materials.
  • the nano-scale material obtained by the preparation method makes the physical and chemical properties of the product beneficial to cell adhesion and gene expression, in particular, strengthens the mechanical properties of the material, is not easy to be deformed and shrunk, avoids excessive use of cross-linking agents, and can be used according to different uses.
  • the parts are produced with different requirements, and the preparation and operation are convenient, and the industrialization prospect is good.
  • Example 10 is a schematic view showing the results of scanning electron microscope test of Example 10 of the present application.
  • one or more of the method steps recited in the present invention are not exclusive of other method steps that may be present before or after the combination step, or that other method steps can be inserted between the steps specifically mentioned, unless otherwise It should be understood that the combined connection relationship between one or more devices/devices referred to in the present invention does not exclude that other devices/devices may exist before or after the combined device/device or Other devices/devices can also be inserted between the two devices/devices unless otherwise stated.
  • each method step is merely a convenient means of identifying the various method steps, and is not intended to limit the order of the various method steps or to limit the scope of the invention, the relative In the case where the technical content is not substantially changed, it is considered to be a scope in which the present invention can be implemented.
  • the film A was continuously electrospun on the carboxymethyl dextran film, and a layer of carboxymethyl dextran film B was assembled on the electrospinning film A, and the stacking was repeated 20 times. It was washed with water for injection, lyophilized, and the product was sterilized by ethylene oxide.
  • a rotatable hollow tube as an electrospinning receiver, (washed, sterilized and depyrogenated) dried; weigh 1g of PLGA and 0.2g of collagen, add 10ml of hexafluoroisopropanol, and prepare degradable polymer material PLGA And an electrospinning A solution with a cationic group material; the above solution is added to a syringe of an electrospinning device, the bolus rate of the micro syringe pump is adjusted to 0.2 mm/min, the positive voltage is adjusted to 10 V, the negative voltage is 1 V, and the receiving device is adjusted. The receiving distance was 15 cm, and a tubular electrospinning film was obtained.
  • a rotating roller as an electrospinning receiver, wrapped with a layer of aluminum foil (washed, sterilized and depyrogenated), dried; weighed 1 g of PLGA and 0.2 g of collagen, and added 10 ml of hexafluoroisopropanol to prepare for degradation.
  • Polymer material PLGA and electrospinning A solution with cationic group material the above solution is added into the syringe of the electrospinning device, the bolus rate of the micro syringe pump is adjusted to 0.4 mm/min, the positive voltage is adjusted to 15 V, and the negative voltage is 2 V.
  • the receiving distance of the receiving device was adjusted to 15 cm, and the fiber was received as a film-like structure, which was peeled off from the aluminum foil to prepare an electrospinning film A.
  • 0.5 g of collagen was weighed and dissolved in an aqueous solution of acetic acid to prepare a C solution having a cationic group; the solution was poured into a Petri dish, soaked, dried to form a film, and a layer of collagen was electrostatically assembled on the film B.
  • the liquid B liquid was alternately superimposed 20 times and then electrospun superposed A; the mixture was alternately repeated 5 times, rinsed with water for injection, freeze-dried, and the product was sterilized by ethylene oxide.
  • 0.1 g of collagen was weighed and dissolved in an aqueous solution of acetic acid to prepare a C solution having a cationic group; the above 3D printed film was placed in a solution C to be immersed, dried to form a film, and a layer of collagen was electrostatically assembled on the film B.
  • B liquid C liquid is alternately superimposed 20; rinsed with water for injection, freeze-dried, and the product is irradiated and sterilized.
  • the sample prepared according to the examples was tested for its hydrophilicity, mechanical property evaluation, immersion shrinkage and scanning electron microscope.
  • the preparation method of the PLGA electrospinning film used in this example was as described in Example 10 for electrospinning. Method for preparing membrane A.
  • test results show that the composite stent material of all the examples obtained by this technique has a contact angle of less than 90°, and the contact angle of the single PLGA electrospinning film is 140°, which is changed from a highly hydrophobic stent material to a hydrophilic stent material.
  • test sample was placed in physiological saline, placed in a constant temperature incubator, and the surface area change rate was measured at 10 min, 20 min, 30 min, 2 h, and 24 h.
  • the test results are shown in Table 3:
  • the present invention effectively overcomes various shortcomings in the prior art and has high industrial utilization value.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Dermatology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Transplantation (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Textile Engineering (AREA)
  • Materials Engineering (AREA)
  • Composite Materials (AREA)
  • Biomedical Technology (AREA)
  • Molecular Biology (AREA)
  • Dispersion Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Materials For Medical Uses (AREA)

Abstract

一种复合支架材料及其制备方法和用途。该复合支架材料包括带有电荷的纤维骨架材料，在该纤维骨架材料上通过静电引力包覆有交替叠加的正电荷生物相容性材料和负电荷生物相容性材料。该复合材料提高了亲水性、生物相容性、组织细胞粘附性和生物诱导活性，适用于组织黏附、封闭、堵漏、止血、隔离、修复、防止粘连，还可以用于制备药物载体及组织工程支架材料。

Description

一种复合支架材料及其制备方法和用途 技术领域
本发明涉及医药技术领域，特别是涉及一种复合支架材料及其制备方法和用途。
背景技术
常见的体内植入的可吸收支架材料，如可降解高分子材料聚乳酸羟基乙酸共聚物(PLGA)、聚乳酸(PLA)、聚己内酯(PCL)静电纺丝支架，其亲水性能差，生物相容性较差，组织细胞粘附性能及生物诱导活性弱，因而不能很好地诱导及促进缺损组织的再生修复，并且这些支架在体液中体积收缩较大进一步影响使用效果。再如采用脱细胞基质材料，免疫原性去除不彻底，会引起免疫排斥反应；采用生物高分子材料，如胶原海绵，虽然生物相容性好，但力学强度等机械性能差，结构易坍塌，植入人体降解速度过快，降解完全时组织还没有完全修复；采用高分子材料流延膜，表面致密，宿主细胞较难迁移至材料内部，只能在材料表面附着，导致修复效果下降。多数组织修复再生支架，容易出现断裂分层，导致使用过程中出现分离或者植入体内后体积收缩，影响治疗效果；多数组织修复补片进行交联剂交联，交联后能提高力学性能，延长降解时间，但使用过多的交联剂除有一定的组织毒性外，还容易导致钙化形成。
发明内容
鉴于以上所述现有技术的缺点，本发明的目的在于提供一种复合支架材料及其制备方法和用途，用于解决现有技术中的问题。
为实现上述目的及其他相关目的，本发明第一方面提供一种复合支架材料，包括带有电荷的纤维骨架材料，所述纤维骨架材料上通过静电引力包覆有交替叠加的正电荷生物相容性材料和负电荷生物相容性材料。
本发明所提供的复合支架材料中，所述纤维骨架材料通常包括纤维，例如，构成纤维骨架材料的纤维可以是由静电纺丝和/或3D打印所形成的纤维，构成所述纤维骨架材料的纤维通常可以在复合支架材料中均匀分布。本领域技术人员可根据需要调整纤维骨架材料的形状，从而可以调整复合支架材料的形状，例如，纤维骨架材料可以由纤维堆积而成，再例如，纤维骨架材料和/或复合支架材料通常可以是层体、球体、柱体(中空或非中空的)等各种规则或不规则的形状，所形成的结构可以是例如膜状、管状、球状等各种二维或三维的规则或不规则的形状。在本发明一具体实施方式中，所述纤维骨架材料可以是平坦的层体(例如，膜 等)。再例如，构成纤维骨架材料的纤维的直径(粗细)可以为3nm-20000nm、3nm-10nm、10nm-20nm、20nm-30nm、30nm-50nm、50nm-70nm、70nm-100nm、100nm-150nm、150nm-200nm、200nm-250nm、250nm-300nm、300nm-350nm、350nm-400nm、400nm-450nm、450nm-500nm、500nm-1000nm、1000nm-5000nm、5000nm-10000nm、10000nm-20000nm、20000nm-30000nm、30000nm-40000nm、40000nm-50000nm、50000nm-60000nm；再例如，纤维占纤维骨架材料的体积百分数可以为20％-90％、20％-30％、30％-40％、40％-50％、50％-60％、60％-70％、70％-80％或80％-90％。
本发明所提供的复合支架材料中，构成所述纤维骨架材料的纤维通常带有电荷(电荷可为正电荷和/或负电荷)，所述纤维可以是本身带有电荷的纤维，也可以是通过电荷改性处理后带有电荷的纤维，从而可以使正电荷生物相容性材料和负电荷生物相容性材料可以通过静电引力交替叠加地包覆于纤维骨架材料上。所述电荷改性处理通常指采用一定的物理方法和/或化学方法对纤维进行修饰(例如，在纤维中粘附或添加带电荷物质，也可以是对纤维表面进行修饰或等离子体改性)从而使所得纤维具有正电荷和/或负电荷的处理方法。本领域技术人员可根据纤维的种类、改性后携带电荷的种类等，选择合适的改性方法对纤维进行电荷改性处理，这些方法对于本领域技术人员来说应该是已知的。例如，经过电荷改性处理所得的材料上可以携带有正电荷基团或负电荷基团，从而使构成所述纤维骨架材料的纤维带有电荷，所述正电荷基团可以是包括但不限于氨基、季铵基等中的一种或多种的组合，所述负电荷基团可以是包括但不限于巯基、羧基、磺酸基、磷酸基等中的一种或多种的组合。
本发明所提供的复合支架材料中，构成所述纤维骨架材料的纤维通常为生物相容性材料，所述生物相容通常指材料(例如，对非活性材料)与宿主之间具有良好的相容性，例如，对于纤维骨架材料的生物相容通常指植入人体组织后亲和性好、免疫反应小、无细胞毒性等，具体可以是指符合国际标准化组织(International Standards Organization，ISO)10993和/或国家标准GB/T16886中相关规定的材料。构成所述纤维骨架材料的纤维可以为高分子材料，所述高分子材料通常指由高分子化合物(一般指相对分子质量(例如，重均分子量)≥1000、≥1500或≥2000的化合物)为基体所构成的材料。所述高分子材料可以是天然生物高分子材料和/或有机合成高分子材料，所述天然高分子材料通常指存在于动物、植物及其他生物体内的高分子物质，具体可以是包括但不限于聚赖氨酸、聚谷氨酸、胶原蛋白、丝素蛋白、大豆蛋白、弹性蛋白、透明质酸、壳聚糖、羧甲基壳聚糖、羧甲基葡聚糖、羧甲基葡萄糖、肝素、海藻酸、硫酸软骨素、羧甲基淀粉、羧甲基纤维素等材料或其他各种改性材料等中的一种或多种的组合；所述有机合成高分子材料通常指通过化学合成方法制备获得的高分子材料，具体可 以是包括但不限于聚乳酸、聚羟基乙酸、聚己内酯、聚乳酸乙醇酸共聚物、聚乳酸己内酯共聚物聚对氧环己酮、三亚甲基碳酸酯、聚乙烯、聚丙烯、聚四氟乙烯、聚氨酯、聚乙二醇、聚乙烯吡咯烷酮等中的一种或多种的组合。
本发明所提供的复合支架材料中，所述纤维中掺杂有带电荷的掺入材料，从而使掺杂后的纤维带有更强的电荷，所述掺入材料可以是天然生物高分子材料，具体可以是如上所述的天然生物高分子材料。本领域技术人员可根据需要选择合适的掺入比例，例如，掺入材料可以与纤维以任意比例进行混合，再例如，掺入材料可以占掺杂后纤维总质量的不大于1wt％、1-5wt％、5-10wt％、10-20wt％、20-30wt％、30-40wt％、40-50wt％、50-60wt％、60-70wt％、70-80wt％、80-90wt％或更高的质量百分比。
本发明所提供的复合支架材料中，所述纤维骨架材料中可以添加有功能因子和/或功能多肽。所述功能因子通常指可以通过激活酶的活性或其他途径，调节人体机能的物质，例如，纤维骨架材料中的功能因子可以是包括但不限于纤连蛋白、层粘连蛋白、血管内皮生长因子、纤维蛋白原、表皮生长因子、成纤维细胞生长因子、转化生长因子、骨形态发生蛋白、类胰岛素生长因子、血小板衍生生长因子、羟基磷灰石、氯化锶、凝血酶等中的一种或多种组合，再例如，纤维骨架材料中的功能因子的添加量可以是不大于10wt％、不大于20wt％、不大于30wt％、不大于40wt％、不大于50wt％、不大于1wt％、1-2wt％、2-4wt％、4-6wt％、6-8wt％、8-10wt％、10-15wt％、15-20wt％、20-25wt％、25-30wt％、30-35wt％、35-40wt％、40-45wt％或45-50wt％。所述功能多肽通常指一类可以是多肽类物质的功能因子，例如，纤维骨架材料中的功能多肽可以是包括但不限于RGD多肽、含-精氨酸-甘氨酸-天冬氨酸-的多肽、含-缬氨酸-甘氨酸-缬氨酸-丙氨酸-脯氨酸-甘氨酸-的多肽或含-异亮氨酸-赖氨酸-缬氨酸-丙氨酸-缬氨酸-的多肽等中的一种或多种的组合，再例如，纤维骨架材料中的功能多肽的添加量可以是不大于10wt％、不大于20wt％、不大于30wt％、不大于40wt％、不大于50wt％、不大于1wt％、1-2wt％、2-4wt％、4-6wt％、6-8wt％、8-10wt％、10-15wt％、15-20wt％、20-25wt％、25-30wt％、30-35wt％、35-40wt％、40-45wt％或45-50wt％。
本发明所提供的复合支架材料中，可以通过静电自组装的方式实现所述骨架材料上通过静电引力包覆有交替叠加的正电荷生物相容性材料和负电荷生物相容性材料，静电自组装的方式对于本领域技术人员来说应该是已知的，例如，可以将正电荷生物相容性材料和/或负电荷生物相容性材料溶于适量的溶剂中，采用喷涂和/或浸泡的方法实现自组装。
本发明所提供的复合支架材料中，所述正电荷生物相容性材料和/或负电荷生物相容性材料通常为生物相容性材料，例如，对于正电荷生物相容性材料和/或负电荷生物相容性材料的 生物相容通常指植入人体组织后亲和性好、免疫反应小、无细胞毒性等，具体可以是指符合国际标准化组织(International Standards Organization，ISO)10993和/或国家标准GB/T16886中相关规定的材料。所述正电荷生物相容性材料可以是正电荷材料，所述正电荷材料通常指带有正电荷的材料，具体可以是包括但不限于聚赖氨酸、胶原蛋白、丝素蛋白、纤连蛋白、层粘连蛋白、纤维蛋白原、壳聚糖等中的一种或多种的组合；所述负电荷生物相容性材料可以是负电荷材料，所述负电荷材料通常指带有负电荷的材料，具体可以是包括但不限于聚谷氨酸、胶原蛋白、丝素蛋白、纤连蛋白、层粘连蛋白、纤维蛋白原(蛋白质为两性电解质，可通过调节溶液pH带上不同电荷)、透明质酸、羧甲基壳聚糖、羧甲基葡聚糖、羧甲基葡萄糖、肝素、海藻酸、硫酸软骨素、羧甲基淀粉、羧甲基纤维素等中的一种或多种的组合。
本发明所提供的复合支架材料中，所述正电荷生物相容性材料和/或负电荷生物相容性材料中可以添加有功能因子和/或功能多肽。例如，正电荷生物相容性材料和/或负电荷生物相容性材料中的功能因子可以是包括但不限于纤连蛋白、层粘连蛋白、血管内皮生长因子、纤维蛋白原、神经生长因子、表皮生长因子、成纤维细胞生长因子、转化生长因子、骨形态发生蛋白、类胰岛素生长因子、血小板衍生生长因子、羟基磷灰石、氯化锶、凝血酶等中的一种或多种组合，再例如，正电荷生物相容性材料和/或负电荷生物相容性材料中功能因子的添加量可以是不大于10wt％、不大于20wt％、不大于30wt％、不大于40wt％、不大于50wt％、不大于1wt％、1-2wt％、2-4wt％、4-6wt％、6-8wt％、8-10wt％、10-15wt％、15-20wt％、20-25wt％、25-30wt％、30-35wt％、35-40wt％、40-45wt％或45-50wt％。再例如，正电荷生物相容性材料和/或负电荷生物相容性材料中的功能多肽可以是包括但不限于RGD多肽、含-精氨酸-甘氨酸-天冬氨酸-的多肽、含-缬氨酸-甘氨酸-缬氨酸-丙氨酸-脯氨酸-甘氨酸-的多肽或含-异亮氨酸-赖氨酸-缬氨酸-丙氨酸-缬氨酸-的多肽等中的一种或多种的组合，再例如，正电荷生物相容性材料和/或负电荷生物相容性材料中功能多肽的添加量可以是不大于10wt％、不大于20wt％、不大于30wt％、不大于40wt％、不大于50wt％、不大于1wt％、1-2wt％、2-4wt％、4-6wt％、6-8wt％、8-10wt％、10-15wt％、15-20wt％、20-25wt％、25-30wt％、30-35wt％、35-40wt％、40-45wt％或45-50wt％。
本发明所提供的复合支架材料中，所述正电荷生物相容性材料和负电荷生物相容性材料可以形成交替叠加正电荷生物相容性材料层和负电荷生物相容性材料层，本领域技术人员可根据需要调整正电荷生物相容性材料层和/或负电荷生物相容性材料层的厚度、层数等参数，例如，正电荷生物相容性材料层和/或负电荷生物相容性材料层每层的厚度可以是0.1-100微米、0.1-1微米、1-5微米、5-10微米、10-20微米、20-40微米、40-60微米、60-80微米或80-100 微米，交替叠加正电荷生物相容性材料层和负电荷生物相容性材料层的总层数可以是2-200层、2-10层、10-30层、30-50层、50-100层、100-150层或150-200层。
本发明所提供的复合支架材料中，本领域技术人员可根据需要适当调整纤维骨架材料、正电荷生物相容性材料、负电荷生物相容性材料所占的比例，例如，纤维骨架材料可以占复合支架材料总质量的5-95％、5-15％、15-25％、25-35％、35-45％、45-55％、55-65％、65-75％、75-85％或85-95％；再例如，所述正电荷生物相容性材料可以占复合支架材料总质量的5-95％、5-15％、15-25％、25-35％、35-45％、45-55％、55-65％、65-75％、75-85％或85-95％；再例如，所述负电荷生物相容性材料可以占复合支架材料总质量的5-95％、5-15％、15-25％、25-35％、35-45％、45-55％、55-65％、65-75％、75-85％或85-95％；再例如，所述正电荷生物相容性材料和负电荷生物相容性材料占复合支架材料总质量的5-95％、5-15％、15-25％、25-35％、35-45％、45-55％、55-65％、65-75％、75-85％或85-95％。
本发明第二方面提供所述复合支架材料的制备方法，包括：
将高分子生物相容性材料通过静电纺丝和/或3D打印形成纤维骨架材料，通过静电自组装交替包覆正电荷生物相容性材料和负电荷生物相容性材料。
本发明所提供的复合支架材料的制备方法中，本领域技术人员可根据所需形成纤维的种类和参数，选择合适的工艺条件制备纤维骨架材料。例如，静电纺丝和/或3D打印通常可以在溶剂存在的条件下进行，高分子生物相容性材料可以被溶于适当的溶剂中从而进行静电纺丝和/或3D打印，静电纺丝和/或3D打印中所使用的溶剂包括但不限于甲酸、乙酸、乙醇、丙酮、二甲基甲酰胺、二甲基乙酰胺、四氢呋喃、二甲基亚砜、六氟异丙醇、三氟乙醇、二氯甲烷、三氯甲烷、甲醇、氯仿、二噁烷、三氟乙烷、三氟乙酸、水、生理盐水、各种缓冲溶液等中的一种或多种的组合；再例如，静电纺丝中推注速度可以为0.001-90mm/min、0.001-0.01mm/min、0.01-0.1mm/min、0.1-1mm/min、1-5mm/min、5-10mm/min、10-20mm/min、20-30mm/min、30-40mm/min、40-50mm/min、50-60mm/min、60-70mm/min、70-80mm/min或80-90mm/min；再例如，静电纺丝中高压发生器的正电压可以为0.1-40kv、0.1-0.5kv、0.5-1kv、1-5kv、5-10kv、10-15kv、15-20kv、20-25kv、25-30kv、30-35kv或35-40kv；再例如，静电纺丝中高压发生器的负电压为0.1-10kv、0.1-0.5kv、0.5-1kv、1-3kv、3-5kv或5-10kv；再例如，静电纺丝中纺丝注射器与接收装置的距离为3-30cm、3-5cm、5-10cm、10-15cm、15-20cm、20-25cm或25-30cm。3D打印的速度0.001-100mm/min、0.001-0.01mm/min、0.01-0.1mm/min、0.1-1mm/min、1-5mm/min、5-10mm/min、10-20mm/min、20-30mm/min、30-40mm/min、40-50mm/min、50-60mm/min、60-70mm/min、70-80mm/min、80-100mm/min。3D打印温度(如 有机高分子材料可在溶剂中或熔融状态下进行3D打印)可以为-20-400℃、-20-10℃、-10-0℃、0-10℃、10-20℃、20-30℃、30-40℃、40-50℃、50-60℃、60-70℃、70-80℃、80-90℃、90-100℃、100-200℃、200-300℃、300-400℃。
本发明所提供的复合支架材料的制备方法中，本领域技术人员可根据所需形成纤维的种类和参数，选择合适的工艺条件通过静电自组装交替包覆正电荷生物相容性材料和负电荷生物相容性材料。例如，静电自组装可以采用喷涂和/或浸泡，还可以进步一进行干燥、灭菌的方法，交替地在材料表面包覆正电荷生物相容性材料和负电荷生物相容性材料。静电自组装在溶剂存在的条件下进行，正电荷生物相容性材料和/或负电荷生物相容性材料可以被溶于适量的溶剂中从而进行静电自组装，静电自组装中所使用的溶剂包括但不限于甲酸溶液、乙酸溶液、盐酸溶液、磷酸溶液、硫酸溶液、水、碱溶液、生理盐水、各种盐溶液及缓冲溶液等中的一种或多种的组合。本领域技术人员可选择合适的方法在制备过程中进行干燥和/或灭菌，具体可采用的干燥方法包括但不限于冷冻干燥、烘干、真空干燥或自然干燥等，具体可采用的灭菌方式包括但不限于辐照灭菌和/或环氧乙烷化学灭菌等。
本发明第三方面提供所述复合支架材料在制备生物相容性材料中的用途。
本发明所提供的复合支架材料具有良好的生物相容性，其可以用于制备载体材料、组织工程支架材料等材料。所述载体材料通常指可以用于负载其他物质的载体，具体可以是包括但不限于药物载体材料等，所述药物载体材料通常可以用于负载各种药物；所述组织工程支架材料通常指能够被植入生物体的材料，从而可以与组织活体细胞结合，并能根据具体替代的组织从而具备一定功能的材料，具体可以是包括但不限于人工脑膜、人工血管、神经修复导管、骨修复支架、人工皮肤及补片等医用材料。
本发明所提供的复合支架材料通过在纤维骨架材料上通过静电引力包覆有交替叠加的正电荷生物相容性材料和负电荷生物相容性材料的方式，克服了现有的支架材料亲水性差、生物相容性差、组织细胞粘附性能力及生物诱导活性弱等缺陷，当用于组织的黏贴、封闭、堵漏、止血、隔离、修复、防止粘连等处理时具有更好的适用性，还可以用于制备药物的载体(例如，缓释载体)及组织工程支架材料等材料，用途非常广泛。本发明所提供的复合支架材料通过有机合成高分子材料和生物高分子材料的复合，模拟细胞外基质，为细胞的停泊、生长、繁殖提供生存空间及获取营养、进行新陈代谢，且通过材料的优化组合调控材料的体内降解速率。复合支架材料中功能因子及功能结构多肽的添加有助于细胞的黏附、伸展，实现材料在损伤组织的修复、再生等方面的多功能用途，具有高生物诱导活性，通过材料交替叠加聚电解质的制备方法所得纳米级材料使产品的理化性质利于细胞的粘附与基因表达，特 别是强化了材料的力学性能，不易变形、收缩，避免过多使用交联剂的毒副作用，且可根据不同使用部位生产不同需求的产品，制备操作方便，具有很好的产业化前景。
附图说明
图1所示为本申请实施例10扫描电子显微镜试验结果示意图。
具体实施方式
以下通过特定的具体实例说明本发明的实施方式，本领域技术人员可由本说明书所揭露的内容轻易地了解本发明的其他优点与功效。本发明还可以通过另外不同的具体实施方式加以实施或应用，本说明书中的各项细节也可以基于不同观点与应用，在没有背离本发明的精神下进行各种修饰或改变。
须知，下列实施例中未具体注明的工艺设备或装置均采用本领域内的常规设备或装置。
此外应理解，本发明中提到的一个或多个方法步骤并不排斥在所述组合步骤前后还可以存在其他方法步骤或在这些明确提到的步骤之间还可以插入其他方法步骤，除非另有说明；还应理解，本发明中提到的一个或多个设备/装置之间的组合连接关系并不排斥在所述组合设备/装置前后还可以存在其他设备/装置或在这些明确提到的两个设备/装置之间还可以插入其他设备/装置，除非另有说明。而且，除非另有说明，各方法步骤的编号仅为鉴别各方法步骤的便利工具，而非为限制各方法步骤的排列次序或限定本发明可实施的范围，其相对关系的改变或调整，在无实质变更技术内容的情况下，当亦视为本发明可实施的范畴。
实施例1
准备一直径12cm的培养皿(经洗涤、灭菌及除热原处理)，干燥，作为静电纺丝接收器；称取1gPLGA和0.2g胶原，加入10ml六氟异丙醇，配制可降解高分子材料PLGA和带阳离子基团材料的静电纺丝A溶液；将上述溶液加入静电纺装置的注射器中，调节微量注射泵的推注速率0.1-0.3mm/min，调节正电压15V，负电压2V，调节接收装置的接收距离为15厘米，并将纤维接收为膜状结构，制得静电纺丝膜A。
称取0.5g羧甲基葡聚糖，加入水中溶解，调节pH＝6，配制成带阴离子基团的B溶液；将上述溶液倒入制得静电纺丝膜A的培养皿，浸泡，干燥成膜，在静电纺丝膜A上组装一层羧甲基葡聚糖膜B。
继续在羧甲基葡聚糖膜上静电纺丝膜A，在静电纺丝膜A上组装一层羧甲基葡聚糖膜B，不断重复叠加20次，用注射用水冲洗，冷冻干燥，揭膜，产品经过辐照灭菌。
实施例2
准备一直径12cm的培养皿(经洗涤、灭菌及除热原处理)，干燥，作为静电纺丝接收器；称取1gPLA和0.2g壳聚糖，加入10ml六氟异丙醇，配制可降解高分子材料PLA和带阳离子基团材料的A溶液；将上述溶液加入静电纺装置的注射器中，调节微量注射泵的推注速率0.5mm/min，调节正电压15V，负电压2V，调节接收装置的接收距离为10厘米，静电纺丝20层静电纺丝膜A。
称取0.5g羧甲基葡聚糖，加入水中溶解，调节pH＝6，配制成带阴离子基团材料的B溶液。将上述溶液倒入制得静电纺丝膜A的聚丙烯培养皿，浸泡，干燥成膜。产品经过环氧乙烷灭菌。
实施例3
准备一直径12cm的培养皿(经洗涤、灭菌及除热原处理)，干燥；称取0.5g透明质酸，加入水中溶解，调节pH＝6，配制阴离子基团材料A溶液。将上述A溶液喷涂在培养皿上，干燥成膜A；称取0.5g壳聚糖，加入水中溶解，调节pH＝4，配制成阳离子基团材料B溶液，喷涂在膜A上，使其在静电力的作用下组装，不断静电组装叠加20次,制得静电组装膜。称取1gPCL和0.2g聚赖氨酸，加入10ml六氟异丙醇，配制可降解高分子材料PCL和带阳离子基团材料静电纺丝C溶液；将上述溶液加入静电纺装置的注射器中，调节微量注射泵的推注速率1.0mm/min，调节正电压15V，负电压3V，调节接收装置的接收距离为20厘米，并将静电纺丝纤维包裹在制备好的静电组装膜上，冷冻干燥。产品经过辐照灭菌。
实施例4
准备一直径12cm的聚丙烯培养皿(经洗涤、灭菌及除热原处理)，干燥，作为静电纺丝接收器；称取1gPLGA和0.2g透明质酸，加入10ml六氟异丙醇，配制可降解高分子材料PLGA和带阴离子基团材料的静电纺丝A溶液；将上述溶液加入静电纺装置的注射器中，调节微量注射泵的推注速率0.3mm/min，调节正电压15V，负电压2V，调节接收装置的接收距离为15厘米，并将纤维接收为膜状结构，制得静电纺丝膜A。
称取0.5g胶原，加入水中溶解，调节pH＝6，配制成带阳离子基团的B溶液；将上述溶液倒入制得静电纺丝膜A的培养皿，浸泡，干燥成膜，在静电纺丝膜A上组装一层胶原膜B。继续在胶原膜上静电纺丝膜A，在静电纺丝膜A上组装一层胶原膜B，不断重复叠加50次，用注射用水冲洗，冷冻干燥，揭膜，产品经过辐照灭菌。
实施例5
准备一直径12cm的培养皿(经洗涤、灭菌及除热原处理)，干燥，作为静电纺丝接收器；称取1gPLA和0.2g羧甲基葡聚糖，加入10ml六氟异丙醇，配制可降解高分子材料PLA和带阴离子基团材料的A溶液；将上述溶液加入静电纺装置的注射器中，调节微量注射泵的推注速率0.1-0.3mm/min，调节正电压15V，负电压2V，调节接收装置的接收距离为15厘米，静电纺丝50层静电纺丝膜A。
称取0.5g壳聚糖，加入水中溶解，调节pH＝4，配制成带阳离子基团材料的B溶液。将上述溶液倒入制得静电纺丝膜A的培养皿，浸泡，干燥成膜。产品经过环氧乙烷灭菌。
实施例6
准备一直径12cm的培养皿(经洗涤、灭菌及除热原处理)，干燥，作为静电纺丝接收器；称取1gPLA和0.2g透明质酸，加入10ml六氟异丙醇，配制可降解高分子材料PLA和带阴离子基团材料的A溶液；将上述溶液加入静电纺装置的注射器中，调节微量注射泵的推注速率2.5mm/min，调节正电压20V，负电压4V，调节接收装置的接收距离为25厘米，静电纺丝20层静电纺丝膜A。
称取0.5g胶原，加入醋酸水溶液中溶解，调节pH＝6，配制成带阳离子基团材料的B溶液，在B液加入10％的凝血酶(浓度：2000IU/ml)。将上述溶液倒入制得静电纺丝膜A的培养皿，浸泡，干燥成膜。产品经过辐照灭菌。
实施例7
准备一直径12cm的培养皿(经洗涤、灭菌及除热原处理)，干燥，作为静电纺丝接收器；称取1gPLGA和0.2g胶原，加入10ml六氟异丙醇，配制可降解高分子材料PLGA和带阳离子基团材料的静电纺丝A溶液，在A液中加入RGD多肽；将上述溶液加入静电纺装置的注射器中，调节微量注射泵的推注速率0.8mm/min，调节正电压12V，负电压2V，调节接收装置的接收距离为10厘米，并将纤维接收为膜状结构，制得静电纺丝膜A。
称取0.5g羧甲基葡聚糖，加入水中溶解，调节pH＝6，配制成带阴离子基团的B溶液；将上述溶液倒入制得静电纺丝膜A的培养皿，浸泡，干燥成膜，在静电纺丝膜A上组装一层羧甲基葡聚糖膜B。
继续在羧甲基葡聚糖膜上静电纺丝膜A，在静电纺丝膜A上组装一层羧甲基葡聚糖膜B，不断重复叠加20次。用注射用水洗涤，冷冻干燥，产品经过环氧乙烷灭菌。
实施例8
采用可旋转的空心导管做静电纺丝接收器，(经洗涤、灭菌及除热原处理)干燥；称取1gPLGA和0.2g胶原，加入10ml六氟异丙醇，配制可降解高分子材料PLGA和带阳离子基团材料的静电纺丝A溶液；将上述溶液加入静电纺装置的注射器中，调节微量注射泵的推注速率0.2mm/min，调节正电压10V，负电压1V，调节接收装置的接收距离为15厘米，制得管状静电纺丝膜。
称取0.5g透明质酸，加入水中溶解，调节pH＝6，配制成带阴离子基团的B溶液；将上述静电纺丝导管浸泡在B溶液中静电组装，干燥成膜，用注射用水冲洗，冷冻干燥，产品经过辐照灭菌。
实施例9
采用转辊做静电纺丝接收器，在上面包裹一层铝箔(经洗涤、灭菌及除热原处理)，干燥；称取1gPLGA和0.2g胶原，加入10ml六氟异丙醇，配制可降解高分子材料PLGA和带阳离子基团材料的静电纺丝A溶液；将上述溶液加入静电纺装置的注射器中，调节微量注射泵的推注速率0.4mm/min，调节正电压15V，负电压2V，调节接收装置的接收距离为15厘米，并将纤维接收为膜状结构，从铝箔上撕下，制得静电纺丝膜A。
称取0.5g羧甲基纤维素钠，加入水中溶解，调节pH＝6，配制成带阴离子基团的B溶液,在B溶液中加入0.5g盐酸二甲双胍溶解；将上述静电纺丝膜浸泡在B溶液中静电组装，干燥成膜，用注射用水冲洗，冷冻干燥，产品经过辐照灭菌。
实施例10
准备一直径12cm的培养皿(经洗涤、灭菌及除热原处理)，干燥，作为静电纺丝接收器；称取1gPLGA，加入10m丙酮溶解，配制可降解高分子材料PLGA的静电纺丝A溶液；将上述溶液加入静电纺装置的注射器中，调节微量注射泵的推注速率0.1-0.3mm/min，调节正电压15V，负电压2V，调节接收装置的接收距离为15厘米，并将纤维接收为膜状结构，制得静电纺丝膜A。
称取0.5g羧甲基葡聚糖，加入水中溶解，调节pH＝6，配制成带阴离子基团的B溶液；将上述溶液倒入制得静电纺丝膜A的培养皿，浸泡，干燥成膜，在静电纺丝膜A上组装一层羧甲基葡聚糖膜B。
称取0.5g胶原，加入醋酸水溶液溶液溶解，配制成带阳离子基团的C溶液；将上述溶液 倒入培养皿，浸泡，干燥成膜，在膜B上静电组装一层胶原。B液C液交替叠加20次后进行静电纺丝叠加A；不断交替重复5次，用注射用水冲洗，冷冻干燥，产品经过环氧乙烷灭菌。
实施例11
称取1g PLGA，加入10m丙酮溶解，配制可降解高分子材料PLGA的3D打印A溶液；将上述溶液加入3D打印装置中，电脑导入脑膜组织相关数据，进行3D打印成A膜，打印速率0.1mm/min，打印温度10℃。
称取0.1g透明质酸，加入水中溶解，调节pH＝6，配制成带阴离子基团的B溶液；将上述3D打印膜片A放入溶液中浸泡，干燥成膜，在3D打印膜A上组装一层羧甲基葡聚糖膜B。
称取0.1g胶原，加入醋酸水溶液溶液溶解，配制成带阳离子基团的C溶液；将上述3D打印膜片放入溶液C浸泡，干燥成膜，在膜B上静电组装一层胶原。B液C液交替叠加20；用注射用水冲洗，冷冻干燥，产品经过辐照灭菌。
实施例12
按实施例所制备样品，对其亲水性、力学性能评价、浸泡收缩性以及扫描电子显微镜进行试验，本实施例中所使用的PLGA静电纺丝膜的制备方法参照实施例10中静电纺丝膜A的制备方法。
1、亲水性，通过接触角来评价样品的亲水性，接触角测量参考技术标准：GB/T 30447-2013，结果如表1所示：
表1
Figure PCTCN2018123280-appb-000001
Figure PCTCN2018123280-appb-000002
试验结果显示，通过该技术制得所有实施例的复合支架材料接触角均小于90°，较单一的PLGA静电纺丝膜接触角140°，从高疏水性支架材料转变为亲水性支架材料。
2、力学性能，参照技术标准：GB/T 1014.1-2006，试验结果如表2所示：
表2
Figure PCTCN2018123280-appb-000003
3、浸泡实验，将供试品放入生理盐水中，放入恒温培养箱，于10min、20min、30min、 2h、24h测量其表面积变化率，试验结果如表3所示：
表3
Figure PCTCN2018123280-appb-000004
4、扫描电子显微镜试验，参照技术标准：GB/T 16594-2008，实施例10制备所得材料的扫描电子显微镜试验结果，
综上所述，本发明有效克服了现有技术中的种种缺点而具高度产业利用价值。
上述实施例仅例示性说明本发明的原理及其功效，而非用于限制本发明。任何熟悉此技术的人士皆可在不违背本发明的精神及范畴下，对上述实施例进行修饰或改变。因此，举凡所属技术领域中具有通常知识者在未脱离本发明所揭示的精神与技术思想下所完成的一切等效修饰或改变，仍应由本发明的权利要求所涵盖。

Claims (10)

  1. 一种复合支架材料，包括带有电荷的纤维骨架材料，所述纤维骨架材料上通过静电引力包覆有交替叠加的正电荷生物相容性材料和负电荷生物相容性材料。
  2. 如权利要求1所述的复合支架材料，其特征在于，还包括如下技术特征中的一个或多个：
    A1)所述复合支架材料和/或纤维骨架材料为层体和/或球体和/或管体；
    A2)所述纤维骨架材料由纤维构成；
    A3)所述纤维的直径为3nm-60000nm；
    A4)所述纤维占纤维骨架材料的体积百分数为20％-90％。
  3. 如权利要求2所述的复合支架材料，其特征在于，还包括如下技术特征中的一个或多个：
    B1)所述纤维由静电纺丝和/或3D打印制备获得；
    B2)构成所述纤维骨架材料的纤维带有电荷；
    B3)构成所述纤维骨架材料的纤维为通过电荷改性处理所得的纤维；
    B4)构成所述纤维骨架材料的纤维携带有正电荷基团和/或负电荷基团，所述正电荷基团选自氨基、季铵基中的一种或多种的组合，所述负电荷基团选自巯基、羧基、磺酸基、磷酸基中的一种或多种的组合；
    B5)所述纤维为生物相容性材料，所述纤维为高分子材料；
    B6)所述纤维为高分子生物相容性材料，所述高分子生物相容性材料为有机合成高分子材料和/或天然生物高分子材料；
    B7)所述纤维中掺杂有带电荷的掺入材料，所述掺入材料选自天然生物高分子材料。
  4. 如权利要求3所述的复合支架材料，其特征在于，所述天然生物高分子材料选自聚赖氨酸、聚谷氨酸、胶原蛋白、丝素蛋白、大豆蛋白、弹性蛋白、透明质酸、壳聚糖、羧甲基壳聚糖、羧甲基葡聚糖、羧甲基葡萄糖、肝素、海藻酸、硫酸软骨素、羧甲基淀粉、羧甲基纤维素；所述有机合成高分子材料选自聚乳酸、聚羟基乙酸、聚己内酯、聚乳酸乙醇酸共聚物、聚乳酸己内酯共聚物聚对氧环己酮、三亚甲基碳酸酯、聚乙烯、聚丙烯、聚四氟乙烯、聚氨酯、聚乙二醇、聚乙烯吡咯烷酮中的一种或多种的组合。
  5. 如权利要求1所述的复合支架材料，其特征在于，还包括如下技术特征中的一个或多个：
    C1)纤维骨架材料中添加有功能因子和/或功能多肽，纤维骨架材料中的功能因子的添加量为不大于50wt％，纤维骨架材料中的功能多肽的添加量为不大于50wt％；
    C2)所述骨架材料上通过静电自组装包覆有交替叠加的正电荷生物相容性材料和负电荷生物相容性材料；
    C3)所述正电荷生物相容性材料选自聚赖氨酸、胶原蛋白、丝素蛋白、纤连蛋白、层 粘连蛋白、纤维蛋白原、壳聚糖中的一种或多种的组合，所述负电荷生物相容性材料选自聚谷氨酸、胶原蛋白、丝素蛋白、纤连蛋白、层粘连蛋白、纤维蛋白原、透明质酸、羧甲基壳聚糖、羧甲基葡聚糖、羧甲基葡萄糖、肝素、海藻酸、硫酸软骨素、羧甲基淀粉、羧甲基纤维素中的一种或多种的组合；
    C4)所述正电荷生物相容性材料和/或负电荷生物相容性材料中添加有功能因子和/或功能多肽，正电荷生物相容性材料和/或负电荷生物相容性材料中的功能因子的添加量不大于50wt％，正电荷生物相容性材料和/或负电荷生物相容性材料中的功能多肽的添加量不大于50wt％。
  6. 如权利要求5所述的复合支架材料，其特征在于，所述功能因子选自纤连蛋白、层粘连蛋白、血管内皮生长因子、纤维蛋白原、神经生长因子、表皮生长因子、成纤维细胞生长因子、转化生长因子、骨形态发生蛋白、类胰岛素生长因子、血小板衍生生长因子、羟基磷灰石、氯化锶、凝血酶的一种或多种组合，所述功能多肽选自RGD多肽、含-精氨酸-甘氨酸-天冬氨酸-的多肽、含-缬氨酸-甘氨酸-缬氨酸-丙氨酸-脯氨酸-甘氨酸-的多肽或含-异亮氨酸-赖氨酸-缬氨酸-丙氨酸-缬氨酸-的多肽中的一种或多种的组合。
  7. 如权利要求1所述的复合支架材料，其特征在于，所述纤维骨架材料占复合支架材料总质量的5-95wt％，所述正电荷生物相容性材料和负电荷生物相容性材料占复合支架材料总质量的5-95wt％。
  8. 如权利要求1-7任一权利要求所述的复合支架材料的制备方法，包括：将高分子生物相容性材料通过静电纺丝和/或3D打印形成纤维骨架材料，通过静电自组装交替包覆正电荷生物相容性材料和负电荷生物相容性材料。
  9. 如权利要求8所述的制备方法，其特征在于，还包括如下技术特征中的一个或多个：
    D1)静电纺丝中推注速度为0.001-90mm/min，高压发生器的正电压为0.1-40kv，高压发生器的负电压为0.1-10kv，纺丝注射器与接收装置的距离为3-30cm，3D打印的速度为0.001mm-100mm/min，打印温度为-20℃-400℃，静电自组装采用喷涂和/或浸泡的方法；
    D2)自组装后还包括干燥、灭菌；
    D3)静电纺丝和/或3D打印在溶剂存在的条件下进行，所述溶剂选自甲酸、乙酸、乙醇、丙酮、二甲基甲酰胺、二甲基乙酰胺、四氢呋喃、二甲基亚砜、六氟异丙醇、三氟乙醇、二氯甲烷、三氯甲烷、甲醇、氯仿、二噁烷、三氟乙烷、三氟乙酸、水、生理盐水、缓冲溶液中的一种或多种的组合。
  10. 如权利要求1-7任一权利要求所述的复合支架材料在制备生物相容性材料中的用途， 优选为在制备组织黏贴膜、组织修复再生补片、药物载体材料和/或组织工程支架材料中的用途。
PCT/CN2018/123280 2018-01-23 2018-12-25 一种复合支架材料及其制备方法和用途 WO2019144741A1 (zh)

Priority Applications (1)

Application Number Priority Date Filing Date Title
US16/964,198 US20230191003A1 (en) 2018-01-23 2018-12-25 Composite scaffold material, preparation method therefor and use thereof

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN201810063541.7 2018-01-23
CN201810063541.7A CN110064074A (zh) 2018-01-23 2018-01-23 一种复合支架材料及其制备方法和用途

Publications (1)

Publication Number Publication Date
WO2019144741A1 true WO2019144741A1 (zh) 2019-08-01

Family

ID=67365082

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2018/123280 WO2019144741A1 (zh) 2018-01-23 2018-12-25 一种复合支架材料及其制备方法和用途

Country Status (3)

Country Link
US (1) US20230191003A1 (zh)
CN (1) CN110064074A (zh)
WO (1) WO2019144741A1 (zh)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN116617468A (zh) * 2023-05-10 2023-08-22 万瑞飞鸿(北京)医疗器材有限公司 一种心脏支架及其制备方法和应用

Families Citing this family (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110507842B (zh) * 2019-09-06 2021-11-09 东华大学 一种细菌纤维素/透明质酸/ε-聚赖氨酸功能型敷料及其制备方法
CN110917409B (zh) * 2019-12-06 2022-06-03 重庆医科大学附属口腔医院 二甲双胍缓释tHA/PCL引导组织再生膜及其制备方法
CN113440652A (zh) * 2020-03-26 2021-09-28 中国科学院深圳先进技术研究院 人工血管及其制备方法
CN111793899B (zh) * 2020-04-30 2021-06-18 杭州医学院 仿生纳米纤维材料及其制备方法与应用
CN111544653A (zh) * 2020-05-04 2020-08-18 湖北省百纳慧喻生物科技有限公司 一种适应多维临床需求的仿生叠层组织工程皮肤及其制备方法
CN115120562A (zh) * 2021-03-24 2022-09-30 苏州博创同康生物工程有限公司 一种载药纳米纤维支架微粒及其制备方法和应用
CN115227872A (zh) * 2021-04-25 2022-10-25 上海大学 基于胶原蛋白纤维的药物缓释体系及其构建方法与应用
CN113403846A (zh) * 2021-07-30 2021-09-17 南昌大学附属口腔医院(江西省口腔医院) 一种具有仿生矿化和抗菌功能的聚乳酸纳米纤维复合膜及其制备方法和应用
CN113750294B (zh) * 2021-08-31 2022-08-16 四川大学 负载多种基因载体微球的神经修复支架及制备方法

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1456716A (zh) * 2003-06-10 2003-11-19 清华大学 利用电纺丝制备组织工程支架材料的方法及装置
WO2006099315A2 (en) * 2005-03-11 2006-09-21 Wake Forest University Health Sciences Electrospun cell matrices
US20070244569A1 (en) * 2006-04-12 2007-10-18 Jan Weber Endoprosthesis having a fiber meshwork disposed thereon
CN101849850A (zh) * 2010-04-12 2010-10-06 苏州博创同康生物工程有限公司 一种仿生原位再生修复纳米补片、制备方法及用途
CN103751847A (zh) * 2013-11-25 2014-04-30 同济大学 促组织再生控释多重生长因子自组装涂层的制备方法
CN107296979A (zh) * 2017-07-02 2017-10-27 东华大学 一种组织工程纳米纤维血管支架及其制备方法
CN107510862A (zh) * 2016-06-15 2017-12-26 中国科学院苏州纳米技术与纳米仿生研究所 担载梯度浓度生物活性分子的有序纤维支架、制法及应用

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101791431B (zh) * 2010-02-04 2012-11-07 同济大学 一种生物可降解促牙周组织再生膜片的制备方法

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1456716A (zh) * 2003-06-10 2003-11-19 清华大学 利用电纺丝制备组织工程支架材料的方法及装置
WO2006099315A2 (en) * 2005-03-11 2006-09-21 Wake Forest University Health Sciences Electrospun cell matrices
US20070244569A1 (en) * 2006-04-12 2007-10-18 Jan Weber Endoprosthesis having a fiber meshwork disposed thereon
CN101849850A (zh) * 2010-04-12 2010-10-06 苏州博创同康生物工程有限公司 一种仿生原位再生修复纳米补片、制备方法及用途
CN103751847A (zh) * 2013-11-25 2014-04-30 同济大学 促组织再生控释多重生长因子自组装涂层的制备方法
CN107510862A (zh) * 2016-06-15 2017-12-26 中国科学院苏州纳米技术与纳米仿生研究所 担载梯度浓度生物活性分子的有序纤维支架、制法及应用
CN107296979A (zh) * 2017-07-02 2017-10-27 东华大学 一种组织工程纳米纤维血管支架及其制备方法

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN116617468A (zh) * 2023-05-10 2023-08-22 万瑞飞鸿(北京)医疗器材有限公司 一种心脏支架及其制备方法和应用
CN116617468B (zh) * 2023-05-10 2024-05-28 万瑞飞鸿(北京)医疗器材有限公司 一种心脏支架及其制备方法和应用

Also Published As

Publication number Publication date
CN110064074A (zh) 2019-07-30
US20230191003A1 (en) 2023-06-22

Similar Documents

Publication Publication Date Title
WO2019144741A1 (zh) 一种复合支架材料及其制备方法和用途
Biswas et al. Recent advancement of biopolymers and their potential biomedical applications
Rnjak-Kovacina et al. Electrospun synthetic human elastin: collagen composite scaffolds for dermal tissue engineering
Hong et al. Generating elastic, biodegradable polyurethane/poly (lactide-co-glycolide) fibrous sheets with controlled antibiotic release via two-stream electrospinning
JP4619789B2 (ja) 皮膚およびその他の組織のためのシーラント
JP4496360B2 (ja) 医療用高分子ナノ・マイクロファイバー
Lukanina et al. Multi-hierarchical tissue-engineering ECM-like scaffolds based on cellulose acetate with collagen and chitosan fillers
Vandghanooni et al. Natural polypeptides-based electrically conductive biomaterials for tissue engineering
JP2006506110A (ja) 硫酸化多糖及び線維状タンパク質の凝集性共沈殿物及びその使用
Chopra et al. Biopolymer-based scaffolds for tissue engineering applications
CN101703796A (zh) 纳米纤维人工血管修饰内层及制备方法
WO2009149181A2 (en) Methods and compositions for manipulating electroprocessed scaffold material properties using cross-linking and fiber tertiary structure
Oliveira et al. Promising biomolecules
Wu et al. Advances in large gap peripheral nerve injury repair and regeneration with bridging nerve guidance conduits
CN105879121A (zh) 植入式医疗器械的生物相容性表面涂层及其涂覆方法
Arca et al. Chitosan based systems for tissue engineering part II: soft tissues
Balusamy et al. Electrospun nanofibers for wound dressing and tissue engineering applications
JP5374496B2 (ja) 医療用組成物
Poshina et al. Electrospinning of Polysaccharides for Tissue Engineering Applications
Chircov et al. Natural, synthetic, and hybrid and composite biomaterials for neural tissue engineering
CN114099781A (zh) 一种人源性生物组织材料及培养细胞刺激方法和装置
Bacakova et al. Nanofibrous scaffolds as promising cell carriers for tissue engineering
Sen et al. Conducting Polymers as Efficient Materials for Tissue Engineering
Punjabi et al. Conducting polymers: Biodegradable tissue engineering
Cheng et al. The fabrication of conductive material-decorated hydrogels for tissue 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: 18902199

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 18902199

Country of ref document: EP

Kind code of ref document: A1