WO2018090925A1 - 一种皮肤烧伤修复材料及其制备方法 - Google Patents

一种皮肤烧伤修复材料及其制备方法 Download PDF

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WO2018090925A1
WO2018090925A1 PCT/CN2017/111057 CN2017111057W WO2018090925A1 WO 2018090925 A1 WO2018090925 A1 WO 2018090925A1 CN 2017111057 W CN2017111057 W CN 2017111057W WO 2018090925 A1 WO2018090925 A1 WO 2018090925A1
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spinning
coaxial
fiber
spinning solution
skin burn
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French (fr)
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王林格
李卫昌
朱玥
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South China University of Technology SCUT
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South China University of Technology SCUT
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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
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/60—Materials for use in artificial skin
    • 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
    • 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
    • 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
    • D01—NATURAL OR MAN-MADE THREADS OR FIBRES; SPINNING
    • D01D—MECHANICAL METHODS OR APPARATUS IN THE MANUFACTURE OF ARTIFICIAL FILAMENTS, THREADS, FIBRES, BRISTLES OR RIBBONS
    • D01D5/00—Formation of filaments, threads, or the like
    • D01D5/0007—Electro-spinning
    • D01D5/0015—Electro-spinning characterised by the initial state of the material
    • D01D5/003—Electro-spinning characterised by the initial state of the material the material being a polymer solution or dispersion
    • D01D5/0038—Electro-spinning characterised by the initial state of the material the material being a polymer solution or dispersion the fibre formed by solvent evaporation, i.e. dry electro-spinning
    • D—TEXTILES; PAPER
    • D01—NATURAL OR MAN-MADE THREADS OR FIBRES; SPINNING
    • D01D—MECHANICAL METHODS OR APPARATUS IN THE MANUFACTURE OF ARTIFICIAL FILAMENTS, THREADS, FIBRES, BRISTLES OR RIBBONS
    • D01D5/00—Formation of filaments, threads, or the like
    • D01D5/0007—Electro-spinning
    • D01D5/0061—Electro-spinning characterised by the electro-spinning apparatus
    • D01D5/0069—Electro-spinning characterised by the electro-spinning apparatus characterised by the spinning section, e.g. capillary tube, protrusion or pin
    • D—TEXTILES; PAPER
    • D01—NATURAL OR MAN-MADE THREADS OR FIBRES; SPINNING
    • D01D—MECHANICAL METHODS OR APPARATUS IN THE MANUFACTURE OF ARTIFICIAL FILAMENTS, THREADS, FIBRES, BRISTLES OR RIBBONS
    • D01D5/00—Formation of filaments, threads, or the like
    • D01D5/0007—Electro-spinning
    • D01D5/0061—Electro-spinning characterised by the electro-spinning apparatus
    • D01D5/0076—Electro-spinning characterised by the electro-spinning apparatus characterised by the collecting device, e.g. drum, wheel, endless belt, plate or grid
    • D—TEXTILES; PAPER
    • D01—NATURAL OR MAN-MADE THREADS OR FIBRES; SPINNING
    • D01D—MECHANICAL METHODS OR APPARATUS IN THE MANUFACTURE OF ARTIFICIAL FILAMENTS, THREADS, FIBRES, BRISTLES OR RIBBONS
    • D01D5/00—Formation of filaments, threads, or the like
    • D01D5/0007—Electro-spinning
    • D01D5/0061—Electro-spinning characterised by the electro-spinning apparatus
    • D01D5/0092—Electro-spinning characterised by the electro-spinning apparatus characterised by the electrical field, e.g. combined with a magnetic fields, using biased or alternating fields
    • 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
    • A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/404—Biocides, antimicrobial agents, antiseptic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/412—Tissue-regenerating or healing or proliferative agents
    • 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

Definitions

  • the invention belongs to the field of biomedicine, and particularly relates to a skin burn repairing material and a preparation method thereof.
  • the skin is the largest organ in the human body and plays a key role in regulating body temperature, preventing microbes and maintaining moisture.
  • Normal healthy skin is a complex and metabolically active human organ.
  • the skin consists of three parts: the epidermis layer, the dermis layer and the subcutaneous tissue.
  • burns are a common cause of skin defects and abnormalities, which bring inconvenience to life and tremendous psychological stress.
  • Skin burn repair is a complex biological process that traditionally divides burn repair into three phases, namely the inflammatory response phase, the tissue formation phase, and the matrix reconstruction phase; these three phases overlap in time.
  • the healing process is not only related to the patient's physical condition, but also based on the characteristics of burn wounds. It is the key to give targeted repair at different stages of repair.
  • anti-inflammatory drugs are needed to avoid or control wound infection during the inflammatory reaction period.
  • the matrix reconstruction period needs to promote repair drugs to improve wound healing efficiency.
  • Electrospinning is a technology for continuously preparing ultrafine fibers and fiber membranes. The principle and preparation process is that the charged spinning solution overcomes the surface tension of the solution by the driving of the electrostatic field and is continuously stretched and volatilized with the solvent. Finally, it is solidified on the collecting device to form ultrafine fibers and fiber membranes.
  • the fibers (membranes) prepared by electrospinning have the characteristics of large fiber length-to-diameter ratio, high specific surface area, good pore diameter regulation and permeability, and the composition of electrospun fibers.
  • the composition has the advantages of wide splice selectivity, and can be a single polymer, a polymer mixture, a polymer/inorganic mixture; in addition, the electrospinning method has the advantages of simple device, easy expansion of production, and low energy consumption. Therefore, fiber and fiber membranes with different diameters, morphologies and topologies can be obtained by screening spinning raw materials and controlling electrospinning parameters; skin repair materials with different characteristics and functions can be prepared according to the clinical requirements of skin burn treatment.
  • the present invention provides a skin burn repairing material and
  • the preparation method comprises the steps of: adding a load in the process of preparing the fiber by electrospinning, so that the prepared electrospun coaxial fiber has certain functionality, and optimizing the application effect of the micro-nano structure on the surface of the material.
  • the invention separately prepares the functional load in the spinning solution to be uniformly blended, is prepared by the coaxial electrospinning process, and affects the adhesion effect of the microorganisms and bacteria by regulating the surface micro-nano structure on the material.
  • the present invention is achieved by the following technical solutions.
  • a method for preparing a skin burn repairing material comprising the following steps:
  • step 2) Electrospinning to prepare fiber material: the spinning solution obtained in step 1) is separately loaded into a coaxial injection device with a spinning needle for coaxial electrospinning, and the spinning needle is connected to the static positive pressure Above, the flow rate of the spinning solution is controlled by a syringe pump, and the fiber is collected by a wire collecting device, and the coaxial fiber containing the drug is obtained after the solvent is evaporated and dried;
  • the spinning solution obtained in the step 3) is loaded into the injection device with the spinneret, and the upper surface layer of the coaxial fiber obtained in the step 2) is used as the receiving device. Electrospinning is carried out to construct a micro-nano structure on the surface of the coaxial fiber to obtain a skin burn repairing material.
  • the spinning solution of step 1) it may be a one-component polymer or a multi-component polymer.
  • the polymer material is one or more of a natural polymer material, a derivative thereof, and a synthetic polymer;
  • the carrier is one or more of a drug, a protein, and a growth factor.
  • the natural polymer material and its derivative are at least one of chitosan, collagen, cellulose, gelatin, silk fibroin and transparent fatty acid;
  • the synthetic polymer is polycaprolactone, Polylactide, polylactic acid, polyglycolide, poly- ⁇ -hydroxybutyl ester, polyglycolic acid, polyanhydride, polyethylene glycol, polyphosphate, carrageenan, polyvinylpyrrolidone, polystyrene, polyvinyl alcohol More than one of polyphosphazene and hydrogenated styrene-butadiene block copolymerization.
  • the drug is dexamethasone, nimodipine, total saponins of Panax notoginseng, Leng Ningkang, demolin, oxime, lidocaine, mupirocin, tetracycline hydrochloride, polyhexamethylene More than one of hydrazine, moxifloxacin hydrochloride, nanosilver, lysozyme, vancomycin, berberine, antibacterial polypeptide, crude extract of lobular vine, eucalyptus oil, desert teak extract and curcumin;
  • the factors are one of epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), kinein, platelet-derived growth factor (PDGF), and growth hormone release inhibitor (SRIH).
  • the protein is one or more of fibrin, globulin, keratin, and hemoglobin.
  • the organic solvent is chloroform (CHCl3), tetrahydrofuran (THF), hexafluoroisopropanol (HFIP), acetone (Acetone), methyl acetate (methyl) Acetate), N,N-dimethylformamide (DMF), methyl isobutyl ketone (MIBK), N,N-dimethylacetamide (DMAC), dimethyl sulfoxide (DMSO), dichloromethane One or more of (DCM), acetonitrile, and ethanol (Ethanol).
  • CHCl3 chloroform
  • THFIP hexafluoroisopropanol
  • acetone Acetone
  • methyl acetate methyl Acetate
  • DMF N,N-dimethylformamide
  • MIBK methyl isobutyl ketone
  • DMAC dimethyl sulfoxide
  • Ethanol dichloromethane One or more of (DCM), acetonitrile, and
  • the concentration of the polymer in the spinning solution in step 1) is 1 to 35.
  • the mass ratio of the polymer material/load in the spinning solution is 1000: (1 to 100); the stirring speed is 100 to 800 r/min, and the stirring time is 2 to 48 hours.
  • the spinning needle of step 2) is a coaxial needle composed of a plurality of concentric needles or a plurality of non-concentric needles wrapped by one needle.
  • the electrostatic positive pressure of the electrospinning in step 2) and step 4) is 8 to 40 kV; the distance between the wire and the wire receiving device is 10 to 60 cm. More preferably, it is 10 to 35 cm; the injection rate is 0.5 to 10
  • the injection rate of the coaxial spinning may be the same or different in mL/h; the ambient temperature of the electrospinning is 10 to 55 ° C, and the relative humidity is 10% to 90%.
  • the wire collecting device of the step 2) is a flat wire receiving device, a drum wire collecting device or a spot electrode-inducing wire collecting device;
  • the flat wire receiving device is composed of a flat plate or a flat plate connected to a negative high voltage;
  • the wire receiving device is composed of a roller or a motor connected to the ground or connected to a negative high voltage, and the rotation speed of the drum is 50 to 3,500.
  • the spot electrode induced wire collecting device is 2 to 6 after the flat plate or the drum wire collecting device
  • the cm is placed with a metal material point electrode grounded or connected to a negative high voltage, and the negative high voltage is -30 to -1 kV.
  • a skin burn repairing material prepared by the above-mentioned preparation method which may be a blended fiber of a carrier and a polymer or a coaxial fiber having a core-shell structure.
  • Two different kinds of supports in the core-shell structure fiber may be contained in the corresponding core shell layer or the core layer and the shell layer, respectively.
  • the invention selects a good biocompatible polymer material and a functional load, and according to the characteristics of different stages of skin burn repair, a core-shell structure microfiber is prepared by coaxial electrospinning, and functionalities are respectively added in the core shell.
  • the load which then regulates the surface micro-nano structure of the fiber material, is effective against external microbial invasion and bacterial growth.
  • the present invention has the following advantages and technical effects:
  • the base material used in the invention has good biocompatibility, avoids the secondary injury of the traditional medical gauze to the wounded area during dressing change, and can effectively resist re-infection caused by external factors.
  • the invention adopts the electrospinning method to prepare a skin burn repairing material, and the device has the advantages of simple process, good repeatability and large-scale mass production.
  • Figure 1 a is a scanning electron microscope image of the surface layer of the skin burn repair material prepared in Example 1;
  • Figure 1 b is a scanning electron microscope image of the inner surface of the skin burn repair material prepared in Example 1;
  • Figure 2a is a scanning microscope image of the coaxial fiber prepared in Example 2;
  • Example 2b is a transmission electron microscope image of the coaxial fiber prepared in Example 2;
  • Figure 3a is a contact angle test chart of the inner surface of the skin burn repair material prepared in Example 3;
  • Figure 3b is a test view of the contact angle of the surface layer of the skin burn repair material prepared in Example 3;
  • Figure 4 is a graph showing the release of the load contained in the coaxial fiber prepared in Example 4.
  • Figure 5a is a scanning electron microscope image of a single-oriented skin burn repair material prepared in Example 5;
  • Figure 5b is a scanning electron microscope image of the multi-oriented skin burn repair material prepared in Example 5;
  • Figure 6 is a graph showing the results of CCK8 cytotoxicity test of the repair materials of Example 5, Example 7, and Example 8 co-cultured with skin fibroblasts.
  • HFIP hexafluoroisopropanol
  • the coaxial electrospinning device is used, and the spinning solution is used as the shell layer, and the spinning solution is used as the core layer for coaxial electrospinning, and the relative humidity is 99. %, the ambient temperature is 55 ° C, the spinning positive voltage is 20 kV, using a flat wire receiving device, and a grounding needle (dot electrode) is placed 2 cm behind the wire receiving plate, between the wire needle and the wire receiving plate The distance is 15 Cm, the injection flow rate of the two mixed spinning solutions is 6 mL / h, and the coaxial fiber is reserved after the solvent is volatilized.
  • a hydrogenated styrene-butadiene block copolymer to DMF to prepare a mixed solution of 1% by mass, 200 Mechanical stirring at r/min for 18 h, mixing and forming a mixed spinning solution and electrospinning, the relative humidity is 50%, the ambient temperature is 25 °C, and the spinning positive voltage is 40. kV, the collected coaxial fiber is grounded as the wire receiving device, the distance between the needle and the wire receiving plate is 30 cm, and the injection flow rate is 1 mL/h, to obtain a skin burn repair material with micro-nano structure surface, through the scanning electron microscope to the upper surface layer (Fig. 1 a) and the inner surface (Fig. 1) b) Observation of the microscopic morphology. Compared with the two, it can be found that the upper surface layer is regulated and has obvious micro-nano structure. By co-cultivation with E. coli, the fiber with micro-nano structure can inhibit the adhesion and growth of bacteria.
  • Polylactic acid and panax notoginseng saponin (mass ratio of 10:1) were added to DMF to prepare a blending solution with a mass fraction of 35%. The mixture was mechanically stirred at r/min for 48 h, and uniformly mixed to form a mixed spinning solution.
  • Polycaprolactone and polyethylene glycol (5:1 by mass) were blended into THF to make a mass fraction of 10%.
  • FGF fibroblast growth factor
  • the coaxial electrospinning device is used for the coaxial electrospinning with the spinning mixed solution as the shell layer and the spinning mixed solution as the core layer, the relative humidity is 15%, the ambient temperature is 15 ° C, and the spinning positive voltage is 40 kV, using a flat wire receiving device, a grounding point electrode is placed 2 cm behind the wire receiving device, the distance between the needle and the wire receiving plate is 20 cm, and the flow rate of the spinning mixed solution is 1
  • the flow rate of the two injections of mL/h and the spinning mixed solution was 0.5 mL/h, and the coaxial fiber was reserved after the solvent was volatilized.
  • the unregulated surface micro-morphology was observed by scanning electron microscopy and transmission electron microscopy respectively.
  • the core-shell structure can be clearly seen.
  • the FGF can be sustained by the nuclear layer to achieve sustained release effect. Continuous administration during the process can effectively promote wound healing.
  • DMAC N,N-dimethylacetamide
  • CHCl3 mass fraction of 8%
  • the coaxial electrospinning device is used, and the spinning solution is used as the shell layer, and the spinning solution is used as the core layer for coaxial electrospinning, and the relative humidity is 80. %, ambient temperature is 35 ° C, spinning voltage is 20 kV, using a flat wire receiving device, a grounding point electrode is placed 3 cm behind the wire receiving device, the distance between the needle and the wire receiving plate is 12 cm, two Solution injection flow rate is 2 mL/h; the coaxial fiber is reserved after the solvent is volatilized.
  • the hydrogenated styrene-butadiene block copolymer was added to DMF to prepare a mixed solution with a mass fraction of 2%, and mechanically stirred at 200 r/min. h, mixing and forming a mixed spinning solution three and electrospinning, the relative humidity is 65%, the ambient temperature is 22.5 °C, and the spinning positive voltage is 35 kV, using the collected coaxial fiber receiving wire device, placed -30 kV point electrode 3 cm behind the wire receiving device, the distance between the needle and the wire receiving plate is 60 cm, the injection flow rate is 1.5 In the case of mL/h, a skin burn repair material having a micro-nano structure surface is obtained.
  • the hydrophilicity of the material can be effectively regulated, and the inner surface (Fig. 3a) and the upper surface layer are tested by contact angle (Fig. 3).
  • Hydrophilic; the surface micro-nano structure of the fiber has a strong hydrophobicity, which is effective in limiting the adhesion of bacteria and microorganisms.
  • Coaxial electrospinning was carried out by using a coaxial electrospinning device with a mixed spinning solution as a shell layer and a mixed spinning solution as a core layer, and the relative humidity was 75. %, the ambient temperature is 30 ° C, the spinning voltage is 20 kV, the flat wire receiving device is used, and the -1 kV spot electrode is placed 3 cm behind the wire receiving device, and the distance between the needle and the wire receiving plate is 15 Cm, the injection flow rate of the two mixed spinning solutions is 5 mL / h; after the solvent is volatilized, the coaxial fiber is reserved.
  • the drug loading shell layer and the nuclear layer have different release rates (as shown in Fig. 4), so that the drug loaded on the shell layer has a burst release effect in the early stage of wound healing.
  • the corresponding drug-assisted antibacterial and anti-inflammatory drugs are provided, and the nuclear layer drug has a sustained release effect, and provides a continuous drug supply during the matrix reconstruction period in the late stage of wound healing, thereby promoting wound repair.
  • Polycaprolactone and polyethylene glycol were blended into CHCl3 to make a mass fraction of 15%.
  • the coaxial electrospinning device is used, and the mixed spinning solution is used as the shell layer, and the mixed spinning solution is used as the core layer for coaxial electrospinning, and the relative humidity is 60. %, the ambient temperature is 30 °C, the spinning positive voltage is 25 kV, the roller grounding wire receiving device (roller speed is 3500 r/min), the distance between the needle and the wire receiving plate is 20 Cm, both solutions have a flow rate of 2 mL/h; the collected coaxial fibers are removed from the drum and rotated clockwise 90 after every 0.5 h. o Re-attach to the drum to continue spinning, so that the single-oriented and multi-oriented fibers are obtained repeatedly.
  • the antibacterial polypeptide-loaded repair material, the surface micro-nanostructure-regulated fiber and the unloaded drug-used fiber of the present embodiment were respectively cultured together with Staphylococcus aureus, and the fiber loaded with the antibacterial polypeptide was found to have an obvious antibacterial effect.
  • the fiber with micro-nano structure has a significant antibacterial effect, while the ordinary fiber does not have antibacterial and antibacterial effects.
  • the coaxial electrospinning device is used, and the mixed spinning solution is used as the shell layer, and the mixed spinning solution is used as the core layer for coaxial electrospinning, and the relative humidity is 65. %, the ambient temperature is 35 °C, the spinning positive voltage is 20 kV, and the roller-connected -1 kV negative pressure wire-receiving device (roller speed is 1750 r/min), the distance between the needle and the wire receiving plate is 15 Cm, both solutions have a flow rate of 3 mL/h; the collected coaxial fibers are removed from the drum and rotated clockwise after every 0.3 h. o Re-attach to the drum to continue spinning, so that the single-oriented and multi-oriented fibers are obtained repeatedly.
  • Chitosan and vancomycin (mass ratio: 150:1) were added to HFIP to prepare a blending solution with a mass fraction of 18%, mechanically stirred at 400 r/min for 48 h, and mixed to form a mixed spinning solution. .
  • the polymer comprises polylactide and polyethylene glycol), mechanically stirred at 200 r/min for 6 h, mixed uniformly to form a mixed spinning solution 2, and a coaxial electrospinning device is used to mix the spinning solution
  • the mixed spinning solution is the core layer for coaxial electrospinning
  • the relative humidity is 55 %
  • the ambient temperature is 30 ° C
  • the spinning positive voltage is 30 kV
  • the flat plate is connected to the -15 kV negative high pressure as the collecting device
  • the needle The distance from the wire receiving plate is 35 cm
  • the injection flow rate of the mixed spinning solution is 5 mL/h
  • the injection flow rate of the mixed spinning solution is 3 mL/h.
  • the ambient temperature is the same as the coaxial spinning condition.
  • the positive spinning voltage is 15 kV.
  • the collected coaxial fiber is grounded as the wire-receiving device.
  • the distance between the needle and the wire receiving plate is 10 cm.
  • the injection flow rate is 1 mL/h, a skin burn repair material having a micro-nano structure surface was obtained, and the prepared repair material was immersed in a medium to prepare an extract and cultured, as shown in Fig. 6, which was found to have good biocompatibility.

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  • Life Sciences & Earth Sciences (AREA)
  • Textile Engineering (AREA)
  • Medicinal Chemistry (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
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  • Mechanical Engineering (AREA)
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  • Biomedical Technology (AREA)
  • Molecular Biology (AREA)
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Abstract

一种皮肤烧伤修复材料的制备方法，包括如下步骤：1)纺丝溶液的配制：将高分子材料与负载物溶于有机溶剂中，充分搅拌溶解，得到两种含有负载物的纺丝溶液；2)静电纺丝制备纤维材料：将步骤1)中得到的纺丝溶液分别装入带有喷丝针头的同轴注射装置中，进行同轴静电纺丝，喷丝针头连接在静电正高压之上，由注射泵控制纺丝溶液的流速，并采用收丝装置收集纤维，待溶剂挥发干燥即得含有负载药物的同轴纤维；3)纺丝溶液的配制：将高分子材料溶于有机溶剂中，充分搅拌溶解，得到纺丝溶液；4)纤维膜上表层微纳结构的制备：将步骤3)中得到的纺丝溶液装入带有喷丝针头的注射装置中，采用步骤2)中得到的同轴纤维的上表层为接收装置，进行静电纺丝，在同轴纤维表面构建微纳结构，得一种皮肤烧伤修复材料。

Description

一种皮肤烧伤修复材料及其制备方法
技术领域
本发明属于生物医学领域，具体涉及一种皮肤烧伤修复材料及其制备方法。
背景技术
皮肤是人体最大的器官，在调节体温、在微生物防御及保持水分等方面具有关键性的作用。正常的健康皮肤是一个结构复杂且新陈代谢活跃的人体器官，皮肤由表皮层、真皮层和皮下组织三个部分构成。在日常生活中，烧伤是造成皮肤缺损与异常的常见因素，给患者带来了生活上的不便及巨大的心理压力。皮肤的烧伤修复是一个复杂的生物学过程，传统上将烧伤修复分为三个阶段，即炎症反应期、组织形成期和基质重建期；这三个阶段在时间上相互重叠。愈合过程不仅与患者本身的体质有关，而且以烧伤创面特性为基础，在不同的修复阶段给予有针对性的修复是关键，如在炎症反应期需要抗菌消炎药物避免或控制伤口感染，组织形成期和基质重建期需要促修复药物来提高创面愈合效率。随着医学水平的不断发展以及人们对敷料要求的不断提高，传统的修复材料已不能满足临床要求。
人工皮肤修复材料作为一种烧伤皮肤修复材料和替代品，在自体皮有限以及供体紧缺的情况下，可以使皮肤大面积受损的烧伤患者得到修复治疗并使之恢复相关的生理功能。理想的皮肤修复材料具有减轻创面疼痛感、吸收渗出液、良好的透气性、减少疤痕与收缩、抗菌防感染和促愈合等功能。静电纺丝是一种可连续制备超细纤维及纤维膜的技术，其原理和制备过程是通过静电场的驱动使带电纺丝溶液克服溶液表面张力并不断地被拉伸并随着溶剂挥发，最终在收集装置上固化形成超细纤维及纤维膜。与传统无纺布、脱脂棉类的敷料相比，静电纺丝制备的纤维（膜）具有纤维长径比大、比表面积高，孔径可调控和通透性好等特点；另外静电纺纤维的组成成分具有可纺选择性宽的优点，可以是单一高分子、高分子混合物、高分子/无机混合物；此外，静电纺丝法还具有装置简单、易于扩大生产、能耗低的优点。因此，通过对筛选纺丝原料、调控静电纺参数来获得不同直径、形貌及拓扑结构的纤维及纤维膜；可根据皮肤烧伤治疗的临床需求制备具有不同特性和功能的皮肤修复材料。
发明内容
为了改善现有人工皮肤修复材料在减轻创面疼痛感、吸收渗出液、良好透气性、减少疤痕与收缩、抗菌防感染和促愈合等方面的功能，本发明提供了一种皮肤烧伤修复材料及其制备方法，在静电纺丝制备纤维的过程中加入负载物，使所制备的电纺同轴纤维具有一定的功能性，并对材料表面微纳结构调控优化其应用效果。
本发明是分别将功能性负载物置于纺丝溶液中共混均匀，通过同轴静电纺丝工艺制备的，并通过调控材料上表层微纳结构进而影响微生物及细菌的粘附效果。
本发明通过以下技术方案实现。
一种皮肤烧伤修复材料的制备方法，包括如下步骤：
1）纺丝溶液的配制：将高分子材料与负载物溶于有机溶剂中，充分搅拌溶解，得到两种含有负载物的纺丝溶液；
2）静电纺丝制备纤维材料：将步骤1）中得到的纺丝溶液分别装入带有喷丝针头的同轴注射装置中，进行同轴静电纺丝，喷丝针头连接在静电正高压之上，由注射泵控制纺丝溶液的流速，并采用收丝装置收集纤维，待溶剂挥发干燥即得含有负载药物的同轴纤维；
3）纺丝溶液的配制：将高分子材料溶于有机溶剂中，充分搅拌溶解，得到纺丝溶液；
4）纤维膜上表层微纳结构的制备：将步骤3）中得到的纺丝溶液装入带有喷丝针头的注射装置中，采用步骤2）中得到的同轴纤维的上表层为接收装置，进行静电纺丝，在同轴纤维表面构建微纳结构，得一种皮肤烧伤修复材料。
优选的，步骤1）所述纺丝溶液中，可以是单组分高分子也可以是多组分高分子。
优选的，所述高分子材料为天然高分子材料及其衍生物和合成高分子中的一种以上；所述负载物为药物、蛋白和生长因子中的一种以上。
进一步优选的，所述天然高分子材料及其衍生物为壳聚糖、胶原、纤维素、明胶、丝素蛋白和透明脂酸中的一种以上；所述合成高分子为聚己内酯、聚丙交酯、聚乳酸、聚乙交酯、聚β-羟丁酯、聚羟基乙酸、聚酸酐、聚乙二醇、聚磷酸酯、角叉胶、聚乙烯吡咯烷酮、聚苯乙烯、聚乙烯醇、聚膦腈类和氢化苯乙烯-丁二烯嵌段共聚中的一种以上。
进一步优选的，所述药物为地塞米松、尼莫地平、三七总皂苷、冷宁康、德莫林、慷舒灵、利多卡因、莫匹罗星、盐酸四环素、聚六亚甲基胍、盐酸莫西沙星、纳米银、溶菌酶、万古霉素、黄连素、抗菌多肽、小叶藤黄粗提物、鸸鹋油、沙漠柚木提取物和姜黄素中的一种以上；所述生长因子为表皮生长因子（EGF）、血管内皮生长因子（VEGF）、成纤细胞生长因子（FGF）、金因肽、血小板来源增殖因子（PDGF）以及生长激素释放抑制因子（SRIH）中的一种以上；所述蛋白为纤维蛋白、球蛋白、角蛋白和血红蛋白中的一种以上。
优选的，所述有机溶剂为氯仿（CHCl3）、四氢呋喃（THF）、六氟异丙醇（HFIP）、丙酮（Acetone）、醋酸甲酯（methyl acetate）、N,N-二甲基甲酰胺（DMF）、甲基异丁酮（MIBK）、N,N-二甲基乙酰胺（DMAC）、二甲基亚砜（DMSO）、二氯甲烷（DCM）、甲基氰（Acetonitrile）和乙醇（Ethanol）中的一种以上。
优选的，步骤1）所述纺丝溶液中高分子的浓度为1～35 wt%；所述纺丝溶液中高分子材料/负载物的质量比为1000：（1～100）；所述搅拌的转速为100～800 r/min，搅拌的时间为2～48 h。
优选的，步骤2）所述喷丝针头为同轴针头，该同轴针头由若干根同心针头组成或由一个针头内包裹若干根非同心针头组成。
优选的，步骤2）与步骤4）中静电纺丝的静电正高压为8～40 kV；出丝与收丝装置间距为10～60 cm ，更优选为10～35 cm；注射速率为0.5～10 mL/h，同轴纺丝注射速率可以相同也可以不同；所述静电纺丝的环境温度为10～55℃，相对湿度为10%～90%。
优选的，步骤2）所述收丝装置为平板收丝装置、滚筒收丝装置或点电极诱导收丝装置；所述平板收丝装置由一块接地或与负高压相连的平板构成；所述滚筒收丝装置由接地或与负高压相连的滚筒与电机组成，滚筒的转速为50～3500 r/min；当滚筒收丝时，每纺一层将收集得到的纤维旋转0～90°并重新贴附于滚筒表面继续纺丝，最终可形成多层及多方向取向的三维结构；所述点电极诱导收丝装置为在平板或滚筒收丝装置后2～6 cm放置一个接地或与负高压相连的金属材质点电极，所述的负高压为-30～-1 kV。
由以上所述的制备方法制得的一种皮肤烧伤修复材料，该修复材料可以是负载物与高分子共混纤维或是具有核壳结构的同轴纤维。所述核壳结构纤维中两种不同种类负载物可以分别在对应的核壳层或核层和壳层中都含有。
本发明选用良好生物相容性高分子材料及功能性负载物，根据皮肤烧伤修复不同阶段的特性，利用同轴静电纺丝制备具有核壳结构超细纤维，并分别在核壳内加入功能性负载物，随后调控该纤维材料上表层微纳结构，可有效抵御外部微生物入侵以及细菌的滋生。
与现有技术相比，本发明具有如下优点与技术效果：
1、本发明所采用的基体材料具有良好的生物相容性，避免了传统的医用纱布在换药时对创伤区域产生的二次伤害，并可有效抵御外部因素引起的再次感染。
2、本发明采用静电纺丝法制备皮肤烧伤修复材料，设备工艺简单、重复性好、可进行大规模量产。
附图说明
图1 a为实施例1制备的皮肤烧伤修复材料上表层的扫描电镜图像；
图1 b为实施例1制备的皮肤烧伤修复材料内表面的扫描电镜图像；
图2 a为实施例2制备的同轴纤维的扫描显微镜图像；
图2 b为实施例2制备的同轴纤维的透射电子显微镜图像；
图3 a为实施例3制备的皮肤烧伤修复材料内表面的接触角测试图；
图3 b为实施例3制备的皮肤烧伤修复材料上表层的接触角测试图；
图4为实施例4制备的同轴纤维中所含负载物的释放曲线图；
图5 a为实施例5制备的单取向的皮肤烧伤修复材料的扫描电镜图像；
图5 b为实施例5制备的多取向的皮肤烧伤修复材料的扫描电镜图像；
图6为实施例5、实施例7和实施例8的修复材料与皮肤成纤维细胞共培养的CCK8细胞毒性测试结果对比图。
具体实施方式
以下结合附图和实例对本发明的具体实施作进一步说明，但本发明的实施和保护不限于此。
实施例1
将聚乳酸和聚乙烯吡咯烷酮（质量比为7:1）共混加入到DCM和THF混合溶剂中（质量比DCM /THF = 2:1）配制成质量分数为10 %的共混溶液，并加入纳米银（质量比为高分子/纳米银 = 200:1，所述高分子包括聚乳酸和聚乙烯吡咯烷酮），400 r/min转速下机械搅拌6 h，混合均匀形成混合纺丝溶液一；将明胶和地塞米松（质量比为300:1）加入到HFIP（六氟异丙醇）中配制成质量分数为9 %的共混溶液，300 r/min转速下机械搅拌24 h，混合均匀形成混合纺丝溶液二。采用同轴静电纺丝装置，以纺丝溶液一为壳层、纺丝溶液二为核层进行同轴静电纺丝，相对湿度为99 %、环境温度为55℃，纺丝正电压为20 kV，采用平板收丝装置，另外在收丝板后2 cm处设置一个接地针头（点电极），出丝针头与收丝板之间的距离为15 cm，两种混合纺丝溶液进样流速都是6 mL/h，待溶剂挥发后得同轴纤维备用。将氢化苯乙烯-丁二烯嵌段共聚物加入到DMF中配制质量分数为1 %的混合溶液，200 r/min转速下机械搅拌18 h，混合均匀形成混合纺丝溶液三并进行静电纺丝，相对湿度为50 %、环境温度为25℃，纺丝正电压为40 kV，采用所收集到的同轴纤维接地为收丝装置，针头与收丝板之间的距离为30 cm，进样流速为1 mL/h，得到具有微纳结构表面的皮肤烧伤修复材料，通过扫描电子显微镜对其上表层（如图1 a）和内表面（如图1 b）微观形貌进行观察，两者相比可发现上表层经过调控有明显的微纳结构存在，通过与大肠杆菌共培养，具有微纳结构的纤维可抑制细菌的粘附与生长。
实施例2
将聚乳酸和盐酸三七总皂苷（质量比为10:1）一并加入到DMF中配制成质量分数为35%的共混溶液，100 r/min转速下机械搅拌48 h，混合均匀形成混合纺丝溶液一。将聚己内酯和聚乙二醇（质量比为5:1）共混加入到THF中配制成质量分数为10 % 的共混溶液，并加入成纤细胞生长因子（FGF）（质量比为高分子/FGF=1000:1，所述高分子包括聚乳酸、聚己内酯和聚乙二醇），800 r/min转速下机械搅拌2 h，混合均匀形成混合纺丝溶液二。采用同轴静电纺丝装置，以纺丝混合溶液一为壳层、纺丝混合溶液二为核层进行同轴静电纺丝，相对湿度为15%、环境温度为15℃，纺丝正电压为40 kV，采用平板收丝装置，在收丝装置后2 cm处放一接地点电极，针头与收丝板之间的距离为20 cm，纺丝混合溶液一进样流速1 mL/h，纺丝混合溶液二进样流速0.5 mL/h，待溶剂挥发后得同轴纤维备用。将聚乙交酯加入到THF中配制质量分数为3 %的混合溶液，220 r/min转速下机械搅拌12 h，混合均匀形成混合纺丝溶液三并进行静电纺丝，相对湿度为15%、环境温度为15℃，纺丝正电压为40 kV，采用所收集到的同轴纤维为收丝装置，在收丝装置后6 cm处放一接地点电极，针头与收丝装置之间的距离为20 cm，进样流速为5 mL/h，得到具有微纳结构表面的皮肤烧伤修复材料。分别通过扫描电子显微镜和透射电镜对其未经调控表面微观形貌进行观察，如图2a、图2b，可以明显看到核壳结构；通过核层负载的FGF可达到缓释效果，在伤口修复的过程中持续给药，可有效促进伤口的愈合。
实施例3
将胶原和壳聚糖（质量比4:1）共混加入到六氟异丙醇中配制成质量分数为11 % 的共混溶液，并加入小叶藤黄粗提物（质量比为高分子/小叶藤黄粗提物= 400:1，所述高分子包括胶原和壳聚糖），350 r/min转速下机械搅拌48 h，混合均匀形成混合纺丝溶液一；将聚乙二醇加入到DMAC（N,N-二甲基乙酰胺）和CHCl3混合溶剂中（质量比DMAC / CHCl3 = 1:4）中配制成质量分数为8 %的共混溶液，300 r/min转速下机械搅拌18 h，混合均匀形成混合纺丝溶液二。采用同轴静电纺丝装置，以纺丝溶液一为壳层、纺丝溶液二为核层进行同轴静电纺丝，相对湿度为80 %、环境温度为35℃，纺丝电压为20 kV，采用平板收丝装置，在收丝装置后3 cm处放一接地点电极，针头与收丝板之间的距离为12 cm，两种溶液进样流速都是2 mL/h；待溶剂挥发后得同轴纤维备用。将氢化苯乙烯-丁二烯嵌段共聚物加入到DMF中配制质量分数为2 %的混合溶液，200 r/min转速下机械搅拌18 h，混合均匀形成混合纺丝溶液三并进行静电纺丝，相对湿度为65 %、环境温度为22.5 ℃，纺丝正电压为35 kV，采用所收集到的同轴纤维接收丝装置，在收丝装置后3 cm处放置接-30 kV点电极，针头与收丝板之间的距离为60 cm，进样流速为1.5 mL/h，得到具有微纳结构表面的皮肤烧伤修复材料。通过微纳结构的构建可有效调控该材料的亲疏水性，采用接触角测试其内表面（如图3 a）和上表层（如图3 b）亲水性；表面微纳结构的纤维具有很强的疏水性，该性能可有效限制细菌以及微生物的粘附。
实施例4
将聚丙交酯加入到DMAC中配制成质量分数为15 % 的共混溶液，并加入万古霉素（质量比为聚丙交酯/万古霉素= 200:1），400 r/min转速下机械搅拌15 h，混合均匀形成混合纺丝溶液一；将聚乙烯醇和金因肽（质量比为350:1）加入到DMSO溶剂中配制成质量分数为13 %的共混溶液，600 r/min转速下机械搅拌10 h，混合均匀形成混合纺丝溶液二。采用同轴静电纺丝装置，以混合纺丝溶液一为壳层、混合纺丝溶液二为核层进行同轴静电纺丝，相对湿度为75 %、环境温度为30℃，纺丝电压为20 kV，采用平板收丝装置，在收丝装置后3 cm处放置接-1 kV点电极，针头与收丝板之间的距离为15 cm，两种混合纺丝溶液进样流速都是5 mL/h；待溶剂挥发后得同轴纤维备用。将聚苯乙烯加入到DMF中配制质量分数为3 %的混合溶液，500 r/min转速下机械搅拌8 h，混合均匀形成混合纺丝溶液三并进行静电纺丝，相对湿度为45 %、环境温度为20℃，纺丝正电压为10 kV，采用所收集到的同轴纤维为收丝装置，在收丝装置后3 cm处放置接-15 kV点电极，针头与收丝板之间的距离为8 cm，进样流速为4 mL/h，得到具有微纳结构表面的皮肤烧伤修复材料。通过药物释放测试可明显观察到药物负载壳层和核层具有不同的释放速率（如图4所示），由此可见负载于壳层的药物具有突释效果可在伤口愈合初期的炎症反应期给予相应的药物辅助抗菌消炎，核层药物具有缓释效果，在伤口愈合后期的基质重建期提供持续性的药物供给，促进伤口的修复。
实施例5
将聚己内酯和聚乙二醇（质量比为10:1）共混加入到CHCl3中配制成质量分数为15 % 的共混溶液，并加入聚六亚甲基胍（质量比为高分子/聚六亚甲基胍= 200:1，所述高分子包括聚己内酯和聚乙二醇），350 r/min转速下机械搅拌8 h，混合均匀形成混合纺丝溶液一，将聚乳酸和聚六亚甲基胍（质量比为200:1）加入到DCM中配制成质量分数为10 %的共混溶液，200 r/min转速下机械搅拌18 h，混合均匀形成混合纺丝溶液二。采用同轴静电纺丝装置，以混合纺丝溶液一为壳层、混合纺丝溶液二为核层进行同轴静电纺丝，相对湿度为60 %、环境温度为30℃，纺丝正电压为25 kV，采用滚筒接地收丝装置（滚筒转速为3500 r/min），针头与收丝板之间的距离为20 cm，两种溶液进样流速都是2 mL/h；每隔0.5 h后将所收集的同轴纤维从滚筒取下并顺时针旋转90 o重新贴附于滚筒上继续纺丝，如此反复可得到单取向和多取向纤维。将聚乙烯醇加入到THF中配制质量分数为3 %的混合溶液，150 r/min转速下机械搅拌12 h，混合均匀形成混合纺丝溶液三并进行静电纺丝，相对湿度为40 %、环境温度为30℃，纺丝正电压为20 kV，采用所收集到的取向纤维接地为收丝装置，针头与收丝板之间的距离为15 cm，进样流速是1 mL/h，得到具有微纳结构表面的皮肤烧伤修复材料。通过扫描电子显微镜可观察到纤维的取向微观结构（图5 a为单取向，图5 b为多取向），将制备的修复材料浸泡于培养基中制备浸提液并细胞培养，发现其具有良好的生物相容性（如图6）。
实施例6
将胶原和抗菌多肽（质量比100:1）加入到HFIP中配制成质量分数为10 %的共混溶液，300 r/min转速下机械搅拌16 h，混合均匀形成混合纺丝溶液一。将聚丙交酯和聚乙烯吡咯烷酮（质量比为7:3）共混加入到THF中配制成质量分数为12 % 的共混溶液，并加入姜黄素（质量比为高分子/姜黄素= 150:1，所述高分子包括聚丙交酯和聚乙烯吡咯烷酮），250 r/min转速下机械搅拌12 h，混合均匀形成混合纺丝溶液二，采用同轴静电纺丝装置，以混合纺丝溶液一为壳层、混合纺丝溶液二为核层进行同轴静电纺丝，相对湿度55 %、环境温度为28℃，纺丝正电压为20 kV，采用滚筒接地收丝装置（滚筒转速为50 r/min），针头与收丝板之间的距离为15 cm，两种溶液进样流速都是1 mL/h；每隔1 h后将所收集的同轴纤维从滚筒取下并顺时针旋转0o重新贴附于滚筒上继续纺丝，如此反复可得到单取向致密纤维备用。将聚乳酸加入到DCM中配制质量分数为5 %的混合溶液，相同条件下机械搅拌，混合均匀形成混合纺丝溶液三并进行静电纺丝，相对湿度为和环境温度同同轴纺丝条件，纺丝正电压为15 kV，采用所收集到的同轴纤维接地为收丝装置，针头与收丝板之间的距离为15 cm，进样流速是2 mL/h，得到具有微纳结构表面的皮肤烧伤修复材料。分别将本实施例所得负载抗菌多肽的修复材料、表面微纳结构调控的纤维和无负载药物的普通纤维与金黄色葡萄球菌一起培养后观察，可发现其负载抗菌多肽的纤维具有明显的抗菌效果，具有微纳结构的纤维抑菌效果显著，而普通纤维不具有抑菌抗菌效果。
实施例7
将聚乙交酯加入到CHCl3中配制成质量分数为10 % 的溶液，并加入聚六亚甲基胍（质量比为聚乙交酯/聚六亚甲基胍= 100:1），300 r/min转速下机械搅拌10 h，混合均匀形成混合纺丝溶液一，将聚乙二醇和聚六亚甲基胍（质量比为100:1）加入到THF中配制成质量分数为9 %的共混溶液，200 r/min转速下机械搅拌12 h，混合均匀形成混合纺丝溶液二。采用同轴静电纺丝装置，以混合纺丝溶液一为壳层、混合纺丝溶液二为核层进行同轴静电纺丝，相对湿度为65 %、环境温度为35℃，纺丝正电压为20 kV，采用滚筒接-1 kV负压收丝装置（滚筒转速为1750 r/min），针头与收丝板之间的距离为15 cm，两种溶液进样流速都是3 mL/h；每隔0.3 h后将所收集的同轴纤维从滚筒取下并顺时针旋转45 o重新贴附于滚筒上继续纺丝，如此反复可得到单取向和多取向纤维。将聚乳酸加入到DMF中配制质量分数为1 %的混合溶液，100 r/min转速下机械搅拌12 h，混合均匀形成混合纺丝溶液三并进行静电纺丝，相对湿度为65 %、环境温度为30℃，纺丝正电压为20 kV，采用所收集到的取向纤维接-30 kV为收丝装置，针头与收丝板之间的距离为25 cm，进样流速是1 mL/h，得到具有微纳结构表面的皮肤烧伤修复材料，将制备的修复材料浸泡于培养基中制备浸提液并细胞培养，如图6，发现其具有良好的生物相容性。
实施例8
将壳聚糖和万古霉素（质量比150:1）加入到HFIP中配制成质量分数为18 %的共混溶液，400 r/min转速下机械搅拌48 h，混合均匀形成混合纺丝溶液一。将聚丙交酯和聚乙二醇（质量比为6:4）共混加入到THF中配制成质量分数为10% 的共混溶液，并加入FGF（质量比为高分子/ FGF= 300:1，所述高分子包括聚丙交酯和聚乙二醇），200 r/min转速下机械搅拌6 h，混合均匀形成混合纺丝溶液二，采用同轴静电纺丝装置，以混合纺丝溶液一为壳层、混合纺丝溶液二为核层进行同轴静电纺丝，相对湿度55 %、环境温度为30℃，纺丝正电压为30 kV，平板接 -15 kV负高压为收集装置，针头与收丝板之间的距离为35 cm，混合纺丝溶液一进样流速是5 mL/h，混合纺丝溶液一进样流速是3 mL/h。将聚己内酯加入到THF中配制质量分数为6 %的混合溶液，与混合纺丝溶液一相同条件下机械搅拌，混合均匀形成混合纺丝溶液三，并进行静电纺丝，相对湿度为和环境温度与同轴纺丝条件相同，纺丝正电压为15 kV，采用所收集到的同轴纤维接地为收丝装置，针头与收丝板之间的距离为10 cm，进样流速是1 mL/h，得到具有微纳结构表面的皮肤烧伤修复材料，将制备的修复材料浸泡于培养基中制备浸提液并细胞培养，如图6，发现其具有良好的生物相容性。

Claims (10)

  1. 一种皮肤烧伤修复材料的制备方法，其特征在于，包括如下步骤：
    1）纺丝溶液的配制：将高分子材料与负载物溶于有机溶剂中，充分搅拌溶解，得到两种含有负载物的纺丝溶液；
    2）静电纺丝制备纤维材料：将步骤1）中得到的纺丝溶液分别装入带有喷丝针头的同轴注射装置中，进行同轴静电纺丝，喷丝针头连接在静电正高压之上，由注射泵控制纺丝溶液的流速，并采用收丝装置收集纤维，待溶剂挥发干燥即得含有负载药物的同轴纤维；
    3）纺丝溶液的配制：将高分子材料溶于有机溶剂中，充分搅拌溶解，得到纺丝溶液；
    4）纤维膜上表层微纳结构的制备：将步骤3）中得到的纺丝溶液装入带有喷丝针头的注射装置中，采用步骤2）中得到的同轴纤维的上表层为接收装置，进行静电纺丝，在同轴纤维表面构建微纳结构，得一种皮肤烧伤修复材料。
  2. 根据权利要求1所述的一种皮肤烧伤修复材料的制备方法，其特征在于，所述高分子材料为天然高分子材料及其衍生物和合成高分子中的一种以上；所述负载物为药物、蛋白和生长因子中的一种以上。
  3. 根据权利要求2所述的一种皮肤烧伤修复材料的制备方法，其特征在于，所述天然高分子材料及其衍生物为壳聚糖、胶原、纤维素、明胶、丝素蛋白和透明脂酸中的一种以上；所述合成高分子为聚己内酯、聚丙交酯、聚乳酸、聚乙交酯、聚β-羟丁酯、聚羟基乙酸、聚酸酐、聚乙二醇、聚磷酸酯、角叉胶、聚乙烯吡咯烷酮、聚苯乙烯、聚乙烯醇、聚膦腈类和氢化苯乙烯-丁二烯嵌段共聚中的一种以上。
  4. 根据权利要求2所述的一种皮肤烧伤修复材料的制备方法，其特征在于，所述药物为地塞米松、尼莫地平、三七总皂苷、冷宁康、德莫林、慷舒灵、利多卡因、莫匹罗星、盐酸四环素、聚六亚甲基胍、盐酸莫西沙星、纳米银、溶菌酶、万古霉素、黄连素、抗菌多肽、小叶藤黄粗提物、鸸鹋油、沙漠柚木提取物和姜黄素中的一种以上；所述生长因子为表皮生长因子、血管内皮生长因子、成纤细胞生长因子、金因肽、血小板来源增殖因子和生长激素释放抑制因子中的一种以上；所述蛋白为纤维蛋白、球蛋白、角蛋白和血红蛋白中的一种以上。
  5. 根据权利要求1所述的一种皮肤烧伤修复材料的制备方法，其特征在于，所述有机溶剂为氯仿、四氢呋喃、六氟异丙醇、丙酮、醋酸甲酯、N,N-二甲基甲酰胺、甲基异丁酮、N,N-二甲基乙酰胺、二甲基亚砜、二氯甲烷、甲基氰和乙醇中的一种以上。
  6. 根据权利要求1所述的一种皮肤烧伤修复材料的制备方法，其特征在于，步骤1）所述纺丝溶液中高分子的浓度为1～35 wt%；所述纺丝溶液中高分子材料/负载物的质量比为1000：（1～100）；所述搅拌的转速为100～800 r/min，搅拌的时间为2～48 h。
  7. 根据权利要求1所述的一种皮肤烧伤修复材料的制备方法，其特征在于，步骤2）所述喷丝针头为同轴针头，该同轴针头由若干根同心针头组成或由一个针头内包裹若干根非同心针头组成。
  8. 根据权利要求1所述的一种皮肤烧伤修复材料的制备方法，其特征在于，步骤2）与步骤4）中静电纺丝的静电正高压为8～40 kV，出丝与收丝装置间距为10～60 cm，注射速率为0.5～10 mL/h，同轴纺丝注射速率可以相同也可以不同；所述静电纺丝的环境温度为10～55℃，相对湿度为10%～90%。
  9. 根据权利要求1所述的一种皮肤烧伤修复材料的制备方法，其特征在于，步骤2）所述收丝装置为平板收丝装置、滚筒收丝装置或点电极诱导收丝装置；所述平板收丝装置由一块接地或与负高压相连的平板构成；所述滚筒收丝装置由接地或与负高压相连的滚筒与电机组成，滚筒的转速为50～3500 r/min；当滚筒收丝时，每纺一层将收集得到的纤维旋转0～90°并重新贴附于滚筒表面继续纺丝，最终可形成多层及多方向取向的三维结构；所述点电极诱导收丝装置为在平板或滚筒收丝装置后2～6 cm放置一个接地或与负高压相连的金属材质点电极，所述的负高压为-30～-1 kV。
  10. 由权利要求1-9任一项所述的制备方法制得的一种皮肤烧伤修复材料。
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