WO2011026323A1 - 静电纺丝制备的人工神经移植物及其制备方法和专用装置 - Google Patents

静电纺丝制备的人工神经移植物及其制备方法和专用装置 Download PDF

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WO2011026323A1
WO2011026323A1 PCT/CN2010/071471 CN2010071471W WO2011026323A1 WO 2011026323 A1 WO2011026323 A1 WO 2011026323A1 CN 2010071471 W CN2010071471 W CN 2010071471W WO 2011026323 A1 WO2011026323 A1 WO 2011026323A1
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Prior art keywords
solution
electrospinning
acid
nerve graft
artificial nerve
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PCT/CN2010/071471
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English (en)
French (fr)
Inventor
杨宇民
顾晓松
丁斐
徐山青
严晓莉
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南通大学
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Application filed by 南通大学 filed Critical 南通大学
Priority to BRPI1005526A priority Critical patent/BRPI1005526A2/pt
Priority to GB1111699.3A priority patent/GB2485252A/en
Priority to JP2012527181A priority patent/JP2013503661A/ja
Priority to US12/998,651 priority patent/US20110270411A1/en
Publication of WO2011026323A1 publication Critical patent/WO2011026323A1/zh

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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
    • A61L27/56—Porous materials, e.g. foams or sponges
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02—Prostheses implantable into the body
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14—Macromolecular materials
    • A61L27/18—Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14—Macromolecular materials
    • A61L27/22—Polypeptides or derivatives thereof, e.g. degradation products
    • A61L27/222—Gelatin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14—Macromolecular materials
    • A61L27/22—Polypeptides or derivatives thereof, e.g. degradation products
    • A61L27/227—Other specific proteins or polypeptides not covered by A61L27/222, A61L27/225 or A61L27/24
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14—Macromolecular materials
    • A61L27/22—Polypeptides or derivatives thereof, e.g. degradation products
    • A61L27/24—Collagen
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/58—Materials at least partially resorbable by the body
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
    • C08L5/00—Compositions of polysaccharides or of their derivatives not provided for in groups C08L1/00 or C08L3/00
    • C08L5/08—Chitin; Chondroitin sulfate; Hyaluronic acid; Derivatives thereof
    • 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
    • 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
    • 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
    • D01F—CHEMICAL FEATURES IN THE MANUFACTURE OF ARTIFICIAL FILAMENTS, THREADS, FIBRES, BRISTLES OR RIBBONS; APPARATUS SPECIALLY ADAPTED FOR THE MANUFACTURE OF CARBON FILAMENTS
    • D01F4/00—Monocomponent artificial filaments or the like of proteins; Manufacture thereof
    • D01F4/02—Monocomponent artificial filaments or the like of proteins; Manufacture thereof from fibroin
    • D—TEXTILES; PAPER
    • D01—NATURAL OR MAN-MADE THREADS OR FIBRES; SPINNING
    • D01F—CHEMICAL FEATURES IN THE MANUFACTURE OF ARTIFICIAL FILAMENTS, THREADS, FIBRES, BRISTLES OR RIBBONS; APPARATUS SPECIALLY ADAPTED FOR THE MANUFACTURE OF CARBON FILAMENTS
    • D01F6/00—Monocomponent artificial filaments or the like of synthetic polymers; Manufacture thereof
    • D01F6/58—Monocomponent artificial filaments or the like of synthetic polymers; Manufacture thereof from homopolycondensation products
    • D01F6/62—Monocomponent artificial filaments or the like of synthetic polymers; Manufacture thereof from homopolycondensation products from polyesters
    • D01F6/625—Monocomponent artificial filaments or the like of synthetic polymers; Manufacture thereof from homopolycondensation products from polyesters derived from hydroxy-carboxylic acids, e.g. lactones
    • D—TEXTILES; PAPER
    • D01—NATURAL OR MAN-MADE THREADS OR FIBRES; SPINNING
    • D01F—CHEMICAL FEATURES IN THE MANUFACTURE OF ARTIFICIAL FILAMENTS, THREADS, FIBRES, BRISTLES OR RIBBONS; APPARATUS SPECIALLY ADAPTED FOR THE MANUFACTURE OF CARBON FILAMENTS
    • D01F9/00—Artificial filaments or the like of other substances; Manufacture thereof; Apparatus specially adapted for the manufacture of carbon filaments
    • 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
    • A61L2400/00—Materials characterised by their function or physical properties
    • A61L2400/12—Nanosized materials, e.g. nanofibres, nanoparticles, nanowires, nanotubes; Nanostructured surfaces
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2430/00—Materials or treatment for tissue regeneration
    • A61L2430/32—Materials or treatment for tissue regeneration for nerve reconstruction

Definitions

  • the present invention relates to an artificial nerve graft for bridging a damaged peripheral nerve and promoting its regeneration and repair, and a preparation method thereof.
  • Electrostatic spinning is one of the most important methods for preparing nanofibers.
  • the core of this technology is that under the action of high-voltage static electricity of several thousand to several tens of thousands of volts of polymer solution, the electric field force overcomes the surface tension of the polymer solution, and under the action of electric field force, a stable jet of jet is formed, and finally the solvent evaporates and is charged.
  • the fluid is collected by a collecting device under the action of an electric field force, and the product is a nonwoven fabric-like fibrous web or film composed of nano-sized fibers.
  • Electrospinning products have a large specific surface area; and there are many pore gaps of different sizes.
  • the network structure of nano-scale fibers is similar to that of extracellular matrix structure, which is beneficial to cell adhesion and thus promotes tissue regeneration.
  • An object of the present invention is to provide an electrospinning artificial nerve graft which is advantageous for cell adhesion and capable of promoting regeneration of tissues, a preparation method thereof and a special device.
  • An artificial nerve graft prepared by electrospinning characterized by: a ductal nerve graft composed of nanofibers prepared by a polymer by an electrospinning method.
  • the polymer is one or more of silk fibroin, chitosan, polyglycolic acid, polycaprolactone, collagen, polylactic acid, and gelatin.
  • the invention discloses a preparation method of an artificial nerve graft prepared by electrospinning, characterized in that: the polymer is dissolved in a solvent to prepare a spinning dope, and then the spinning is performed by an electrospinning solution injector by an electrospinning process.
  • the solution is sprayed on a collecting roller for rotation and reciprocating movement to form nanofibers, and a tube is formed on the collecting roller, and the tube is removed for post-treatment to obtain a duct-like artificial nerve graft.
  • a special device for preparing an artificial nerve graft prepared by electrospinning characterized in that: a micro metering pump is included, a micro metering pump is connected with a spinning solution injector, and a spinning solution injector is arranged to rotate simultaneously in a spinning direction And a reciprocating moving roller, a computer control device controls the operation of the micro-metering pump, the spinning solution injector and the collecting roller, and the high-voltage electrostatic generator provides high-voltage static electricity to the device.
  • therapeutic cytokines such as nerve growth factor (NGF), neurotrophin-3 (NT-3), and brain-derived neurotrophic factor (BDNF) may also be added.
  • NGF nerve growth factor
  • NT-3 neurotrophin-3
  • BDNF brain-derived neurotrophic factor
  • glial cell-derived neurotrophic factor medullary F which can be used alone or in combination.
  • Seed cells containing therapeutic effects may also be added to the prepared artificial nerve graft, and the types of seed cells may be bone marrow stromal stem cells, neural stem cells, Schwann cells, olfactory ensheathing cells, embryonic stem cells, etc., which can be used for individual cell types. , can also be used in combination with several cells.
  • the materials used in the products of the invention are all degradable materials and have good biocompatibility with the human body.
  • the obtained product does not contain exogenous toxic or side-effect substances brought in by the preparation process.
  • the wall of the catheter tube has a micro-porous three-dimensional structure, which provides a necessary route for the transportation of nutrients required for the growth process of nerve cells, and has a good effect. It provides the necessary induction and necessary growth space for the growth of nerve cells.
  • the product has good histocompatibility.
  • This product is used in rats to repair the 1 cm distance defect of the sciatic nerve, indicating that the product can be beneficial to nerve regeneration, resulting in recovery of nerve function recovery, and the product has good biocompatibility.
  • the electrospinning product has a large specific surface area; and has many pore gaps of different sizes, the network structure composed of nano-scale fibers is similar to the structure of the extracellular matrix, which is beneficial to cell adhesion and thus can promote tissue. Regeneration, the resulting artificial nerve graft not only has good biocompatibility and biodegradability, but also has good mechanical properties. At the same time, the artificial nerve graft can be combined with a therapeutic cytokine, drug or seed cell.
  • FIG. 1 is a view showing the structure of a special device for preparing an artificial nerve graft of the present invention. Detailed ways
  • a special device for preparing an artificial nerve graft prepared by electrospinning comprising a micro-metering pump 1, a micro-metering pump connected with a spinning solution injector 2, and a spinning solution injector arranged in the spinning direction to simultaneously rotate and reciprocate
  • the moving collecting roller 3 a computer control unit 4 controls the operation of the micro-metering pump, the spinning solution injector and the collecting roller, and the high-voltage electrostatic generator 5 supplies high-voltage static electricity to the device.
  • the silk is heat treated in a weak alkaline solution (0.1 to 10% sodium carbonate or 0.1 to 10% potassium carbonate) at 50 to 100 ° C, and then the treated fiber is washed with distilled water to obtain a silk fibroin fiber.
  • the dissolved mixed solution was placed in a cellulose film bag and dialyzed against distilled water.
  • the dialyzed silk fibroin solution is injected into a flat plate mold, and after drying, a silk fibroin film is obtained, and the obtained silk fibroin film is dissolved into a spinning dope with formic acid at a solution concentration of 13% (mass concentration), and then electrospinning is employed.
  • the process is processed by the special device for preparing the artificial nerve graft prepared by electrospinning, and the spinning dope is metered into the solution injector by the micro metering pump, and the spinning solution is sprayed on the collecting roller for rotation and reciprocating movement.
  • the high voltage electrostatic generator voltage is 20 KV during the forming process
  • the solution spraying speed is 0.3 ml/h
  • the distance between the end of the solution injector and the collecting roller is 7-11 cm. 5 ⁇
  • the collecting roller translation speed of 1. 5m / hour, the speed of 150 rev / min.
  • the initially formed silk fibroin catheter is placed in an ethanol solution for post-treatment, and then washed successively with distilled water to obtain a nanofiber silk fibroin artificial nerve graft.
  • Example 2 Example 2:
  • Chitosan is dissolved with weak acid, the weak acid is acetic acid (or phosphoric acid, citric acid, lactic acid), the concentration is 2 ⁇ 15% (example 2%, 8%, 15%), adding a certain concentration of collagen solution (example 5%, 25%, 50%) to prepare a spinning dope having a concentration (mass concentration) of 10%, and then using an electrospinning process to form a special apparatus for preparing an artificial nerve graft prepared by electrospinning, by a micrometer metering pump After the metering, the spinning dope enters the solution ejector, and the spinning solution is sprayed on the collecting roller for rotation and reciprocating movement to form nanofibers, and a tube is formed on the collecting roller, and the high voltage electrostatic generator voltage is 25 KV during the forming process.
  • the weak acid is acetic acid (or phosphoric acid, citric acid, lactic acid)
  • the concentration is 2 ⁇ 15% (example 2%, 8%, 15%)
  • the solution spray rate was 0.2 ml/h
  • the distance between the end of the solution injector and the collecting roller was 8-11 cm
  • the transfer speed of the collecting roller was 2 m/hr
  • the rotational speed was 90 rpm.
  • the initially formed catheter was washed successively with sodium hydroxide (1 mol/L) solution, 50 mmol/L phosphate buffer solution and distilled water to obtain a nanofiber chitosan/collagen composite artificial nerve graft.
  • Polyglycolic acid (PGA), polylactic acid (PLA), or glycolic acid lactic acid copolymer (PLGA, 50/50) is dissolved in chloroform to form a spinning solution at a solution concentration of 10-20% (mass concentration), followed by electrospinning
  • the silk process is formed by using the above-mentioned special device for preparing an artificial nerve graft prepared by electrospinning, and the spinning dope is metered by a micro metering pump into a solution injector, and the spinning solution is sprayed on a collecting roller for rotation and reciprocating movement.
  • the high voltage electrostatic generator voltage is 20-30 KV
  • the solution spraying speed is 0.2 ml/h
  • the distance between the end of the solution injector and the collecting roller is 7_11.
  • Cm collecting roller translation speed 2m / hour
  • the speed is 70-130 rev / min.
  • the post-treatment of the initially formed catheter into the ethanol solution is followed by washing with distilled water to obtain artificial nerve grafts of nanofiber polyglycolic acid, polylactic acid, or glycolic acid lactic acid copolymer, respectively.

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Description

静电纺丝制备的人工神经移植物及其制备方法和专用装置 技术领域
本发明涉及一种用于桥接损伤周围神经并促进其再生修复的人工神经移植物 及其制备方法。 背景技术
随着社会现代化进程和人们生活节奏的加快， 不可避免的会出现更多的交 通事故、 工伤事故、 运动意外等事件， 同时频繁的局部战争和暴力事件及地震 等自然灾害， 均会造成周围神经损伤， 临床上但当中长距离的神经缺损不能依 靠端对端的缝合来弥补神经缺失时， 就不得不依靠移植物来桥接修复。 寻找和 研制较为合适的移植物问题虽然已有一百多年的历史了， 但除了自体神经成为 首选的神经缺损桥接移植物外， 至今在人类仍在寻找理想的， 能够在临床上广 泛应用的神经移植替代物。就自体神经移植中， 因为供移植用的神经来源有限、 组织结构和尺寸难以匹配、 移植供区长期失神经支配等原因， 也未能在临床上 广泛使用。
随着组织工程学的出现和发展， 为构建自体神经移植替代品提供了一条新的 出路。 已有的人工神经移植物的制备主要有两条途径， 一是利用原有的管道， 如 化学去细胞同种异体神经， 就是利用原来神经的管道， 将异体细胞去掉。 二是利 用适当的模具， 采用溶液浇注法来制备， 如我们先前制备的壳聚糖和丝素蛋白医 用人工神经移植物。
静电纺丝 （electrostatic spinning) 是目前制备纳米纤维最重要的方法之 一。 这一技术的核心是聚合物溶液在几千到几万伏高压静电作用下， 电场力克服 聚合物溶液的表面张力， 在电场力作用下喷射形成一股稳定的喷射流体， 最后溶 剂挥发， 带电流体在电场力作用下被收集装置收集， 产物是由纳米级纤维组成的 类似无纺布状的纤维网、 膜。
静电纺丝产物拥有很大的比表面积； 且拥有很多尺度不等的孔间隙， 其纳米 级的纤维构成的网状结构与细胞外基质结构比较相似， 利于细胞的黏附， 因而能 够促进组织的再生。 发明内容
本发明的目的在于提供一种利于细胞的黏附， 能够促进组织的再生的静电纺 丝制备的人工神经移植物及其制备方法和专用装置。
本发明的技术解决方案是：
一种静电纺丝制备的人工神经移植物， 其特征是： 由聚合物经静电纺丝方法 制备的纳米纤维组成的导管状神经移植物。
聚合物是丝素蛋白、 壳聚糖、 聚乙醇酸、 聚己内酯、 胶原、 聚乳酸和明胶等 中的一种或几种。
一种静电纺丝制备的人工神经移植物的制备方法， 其特征是： 将聚合物溶解 在溶剂中， 制成纺丝原液， 然后采用静电纺丝工艺， 经静电纺丝溶液喷射器将纺 丝溶液喷射在作旋转和往返移动的收集辊上， 形成纳米纤维， 并在收集辊上形成 管子， 将管子取下进行后处理， 得导管状人工神经移植物。
一种制备静电纺丝制备的人工神经移植物的专用装置， 其特征是： 包括微量 计量泵， 微量计量泵与纺丝溶液喷射器连接， 纺丝溶液喷射器的喷丝方向上设置 同时作旋转和往返移动的收集辊， 一个计算机控制装置控制微量计量泵、 纺丝溶 液喷射器及收集辊的工作， 高压静电发生器为装置提供高压静电。
在制备上述人工神经移植物中或者制备后，还可加入有治疗作用的细胞因子， 如神经生长因子（NGF)、神经营养因子 -3 (NT-3 )、脑源性神经营养因子（BDNF)、 胶质细胞源性神经营养因子 髓 F) , 它们可单独种类使用， 也可联合使用。
制备好的人工神经移植物内还可添加含有治疗作用的种子细胞， 种子细胞的 类型可以是骨髓基质干细胞、 神经干细胞、 雪旺氏细胞、 嗅鞘细胞、 胚胎干细胞 等， 它们可单独细胞种类使用， 也可几种细胞联合使用。
本发明的产品所用材料均为可降解性材料， 与人体有着良好的生物相容性。 制得的产品不含有由于制备工艺带入的外源性毒、 副作用物质。 导管管壁具有丰 富微孔的三唯结构， 为神经细胞生长过程所需的营养物质的输送提供了必须的途 径， 使用效果好。 为神经细胞的生长提供了必要的诱导作用和必须的生长空间。
我们将以上制得的产品在体外与神经组织细胞联合培养， 经形态观察、 酶代 谢活力测定、 神经生长因子的表达测定， 显示该产品具有良好的组织相容性。 大 鼠动物体内使用该产品修复坐骨神经 1厘米距离缺损， 标明该产品能有利于神经 再生， 导致恢复损伤神经功能的恢复， 同时该产品具有很好的生物相容性。 由于静电纺丝产物拥有很大的比表面积； 且拥有很多尺度不等的孔间隙， 其 纳米级的纤维构成的网状结构与细胞外基质结构比较相似， 利于细胞的黏附， 因 而能够促进组织的再生， 因此构成的人工神经移植物不仅具有良好生物相容性和 生物可降解性， 还具有良好的力学性能。 同时该人工神经移植物可结合治疗用的 细胞因子、 药物或者种子细胞。 附图说明
图 1是本发明制备人工神经移植物的专用装置结构示图。 具体实施方式
下面结合附图和实施例对本发明作进一步说明。
一种制备静电纺丝制备的人工神经移植物的专用装置， 包括微量计量泵 1， 微量计量泵与纺丝溶液喷射器 2连接， 纺丝溶液喷射器的喷丝方向上设置同时作 旋转和往返移动的收集辊 3， 一个计算机控制装置 4控制微量计量泵、 纺丝溶液 喷射器及收集辊的工作， 高压静电发生器 5为装置提供高压静电。
实施例 1 :
将蚕丝在弱碱溶液 （0. 1〜10 %碳酸钠或 0. 1〜10 %碳酸钾） 中 50〜100°C加 热处理， 然后将处理后的纤维用蒸馏水清洗得到丝素蛋白纤维， 将上述制备的部 分蚕丝丝素蛋白纤维于 25-8CTC (例 25°C、 50°C、 80 °C ) 下， 溶解在氯化钙、 乙 醇和水的三元体系中（摩尔比是氯化钙： 乙醇： 水 = 1 : 2： 8 )， 溶解时间为 0. 5〜 6小时 （例 0. 5、 3、 6小时）将溶解的混合溶液装入纤维素膜袋， 用蒸馏水透析。 然后将透析后的丝素溶液注入平板模具， 经干燥后得丝素蛋白膜， 将得到的丝素 膜用甲酸进行溶解成纺丝原液， 溶液浓度 13% (质量浓度） ， 然后采用静电纺丝 工艺用上述制备静电纺丝制备的人工神经移植物的专用装置进行成型加工， 由微 量计量泵计量后纺丝原液进入溶液喷射器， 将纺丝溶液喷射在作旋转和往返移动 的收集辊上， 形成纳米纤维， 并在收集辊上形成管子， 上述成型加工时高压静电 发生器电压 20 KV, 溶液喷射速度 0. 3 ml/h, 溶液喷射器端部与收集辊之间的距 离 7-11 cm， 收集辊平移速度 1. 5m/小时， 转速为 150转 /分钟。 再将初步成型的 丝素蛋白导管放入的乙醇溶液进行后处理后， 然后先后用蒸馏水清洗， 得到纳米 纤维蚕丝丝素蛋白人工神经移植物。 实施例 2:
将壳聚糖用弱酸溶解， 弱酸是醋酸 （或磷酸、 柠檬酸、 乳酸） ， 浓度为 2〜 15 % (例 2 %、 8 %、 15 % ) ， 加入一定浓度的胶原溶液（例 5%、 25%、 50%)制备 成浓度 （质量浓度） 为 10%的纺丝原液， 然后采用静电纺丝工艺用上述制备静电 纺丝制备的人工神经移植物的专用装置进行成型加工， 由微量计量泵计量后纺丝 原液进入溶液喷射器， 将纺丝溶液喷射在作旋转和往返移动的收集辊上， 形成纳 米纤维， 并在收集辊上形成管子， 上述成型加工时高压静电发生器电压 25 KV, 溶液喷射速度 0. 2 ml/h, 溶液喷射器端部与收集辊之间的距离 8-11 cm, 收集辊 平移速度 2m/小时， 转速为 90转 /分钟。 再将初步成型的导管先后用氢氧化钠 （1 mol/L)溶液、 50mmol/L磷酸盐缓冲液及蒸馏水清洗， 得到纳米纤维壳聚糖 /胶原 复合人工神经移植物。
实施例 3:
将聚乙醇酸 (PGA)、 聚乳酸 （PLA)、 或乙醇酸乳酸共聚物 (PLGA， 50/50)用氯仿溶 解成纺丝溶液， 溶液浓度 10-20% (质量浓度） ， 然后采用静电纺丝工艺用上述制 备静电纺丝制备的人工神经移植物的专用装置进行成型加工， 由微量计量泵计量 后纺丝原液进入溶液喷射器， 将纺丝溶液喷射在作旋转和往返移动的收集辊上， 形成纳米纤维， 并在收集辊上形成管子， 上述成型加工时高压静电发生器电压 20-30 KV,溶液喷射速度 0. 2 ml/h,溶液喷射器端部与收集辊之间的距离 7_11 cm, 收集辊平移速度 2m/小时， 转速为 70-130转 /分钟。 再将初步成型的导管放入的 乙醇溶液进行后处理后， 然后先后用蒸馏水清洗， 分别得到纳米纤维聚乙醇酸、 聚乳酸， 或乙醇酸乳酸共聚物的人工神经移植物。

Claims

权 利 要 求
1、一种静电纺丝制备的人工神经移植物， 其特征是： 由聚合物经静电纺丝方 法制备的纳米纤维组成的导管状神经移植物。
2、根据权利要求 1所述的静电纺丝制备的人工神经移植物， 其特征是： 聚合 物是丝素蛋白、 壳聚糖、 聚乙醇酸、 聚己内酯、 胶原、 聚乳酸和明胶等中的一种 或几种。
3、一种静电纺丝制备的人工神经移植物的制备方法， 其特征是： 将聚合物溶 解在溶剂中， 制成纺丝原液， 然后采用静电纺丝工艺， 经静电纺丝溶液喷射器将 纺丝溶液喷射在作旋转和往返移动的收集辊上， 形成纳米纤维， 并在收集辊上形 成管子， 将管子取下进行后处理， 得导管状人工神经移植物。
4、根据权利要求 3所述的静电纺丝制备的人工神经移植物的制备方法，其特 征是： 将蚕丝在 0. 1〜10 %碳酸钠或 0. 1〜10 %碳酸钾中 50〜100°C加热处理， 然 后将处理后的纤维用蒸馏水清洗得到丝素蛋白纤维， 将蚕丝丝素蛋白纤维于 25-80 °C下， 溶解在氯化钙、 乙醇和水的三元体系中， 该三元体系的摩尔比是氯化 钙： 乙醇： 水 = 1 : 2： 8， 溶解时间为 0. 5〜6小时， 将溶解的混合溶液装入纤维 素膜袋， 用蒸馏水透析， 然后将透析后的丝素溶液注入平板模具， 经干燥后得丝 素蛋白膜， 将得到的丝素膜用甲酸进行溶解成纺丝液， 然后用静电纺丝工艺进行 成型加工， 溶液浓度 13%， 电压 20 KV, 溶液流速 0. 3 ml/h, 针尖与收集屏之间 的距离 7-11 cm， 收集辊平移速度 1. 5m/小时， 转速为 150转 /分钟， 再将初步成 型的丝素蛋白导管放入乙醇溶液进行后处理， 然后用蒸馏水清洗， 得到导管状纳 米纤维蚕丝丝素蛋白人工神经移植物。
5、根据权利要求 3所述的静电纺丝制备的人工神经移植物的制备方法，其特 征是： 将壳聚糖用弱酸溶解， 弱酸是醋酸、 磷酸、 柠檬酸、 或乳酸， 浓度为 2〜 15 % , 加入浓度为 5^25%的胶原溶液制备成纺丝液， 然后用静电纺丝工艺进行成 型加工， 溶液浓度 10%， 电压 25 KV， 溶液流速 0. 2 ml/h， 针尖与收集屏之间的 距离 8-11 cm, 收集辊平移速度 2m/小时， 转速为 90转 /分钟， 再将初步成型的 导管先后用 l mol/L氢氧化钠溶液、 50mmol/L磷酸盐缓冲液及蒸馏水清洗， 得到 导管状纳米纤维壳聚糖 /胶原复合人工神经移植物。
6、根据权利要求 3所述的静电纺丝制备的人工神经移植物的制备方法，其特 征是： 将聚乙醇酸、 聚乳酸或乙醇酸乳酸共聚物用氯仿溶解成纺丝溶液， 然后用 静电纺丝工艺进行成型加工，溶液浓度 10-20%，电压 20-30 KV，溶液流速 0. 2 ml/h, 针尖与收集屏之间的距离 7-11 cm， 收集辊平移速度 2m/小时， 转速为 70_130转 /分钟，再将初步成型的导管放入的乙醇溶液进行后处理后，然后先后用蒸馏水清 洗， 分别得到导管状纳米纤维聚乙醇酸、 聚乳酸或乙醇酸乳酸共聚物的人工神经 移植物。
7、 一种制备权利要求 1所述的静电纺丝制备的人工神经移植物的专用装置， 其特征是： 包括微量计量泵， 微量计量泵与纺丝溶液喷射器连接， 纺丝溶液喷射 器的喷丝方向上设置同时作旋转和往返移动的收集辊， 一个计算机控制装置控制 微量计量泵、 纺丝溶液喷射器及收集辊的工作， 高压静电发生器为装置提供高压 静电。
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Cited By (3)

* Cited by examiner, † Cited by third party
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CN102871772A (zh) * 2011-07-13 2013-01-16 冯淑芹 一种多孔可降解血管及其制备方法
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US10328032B2 (en) 2005-03-04 2019-06-25 Biosurfaces, Inc. Nanofibrous materials as drug, protein, or genetic release vehicles
CN101664346A (zh) * 2009-09-02 2010-03-10 南通大学 静电纺丝制备的人工神经移植物及其制备方法和专用装置
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WO2015187555A1 (en) * 2014-06-02 2015-12-10 Biosurfaces, Inc. Nanofibrous materials as drug, protein, or genetic release vehicles
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CN113875878A (zh) * 2021-08-31 2022-01-04 深圳市星期零食品科技有限公司 一种植物蛋白肉仿生纤维的加工方法

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1844509A (zh) * 2006-04-18 2006-10-11 北京理工大学 一种丝素蛋白多孔结构材料的制备方法
CN1944724A (zh) * 2006-10-11 2007-04-11 东华大学 胶原蛋白和壳聚糖复合纳米纤维及膜静电纺丝的制备方法
JP2007303015A (ja) * 2006-05-10 2007-11-22 Univ Of Shiga Prefecture 静電紡糸装置
WO2009102792A2 (en) * 2008-02-12 2009-08-20 Osteotech, Inc. Collagen products and methods for producing collagen products
CN101664346A (zh) * 2009-09-02 2010-03-10 南通大学 静电纺丝制备的人工神经移植物及其制备方法和专用装置

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP4496360B2 (ja) * 2003-04-24 2010-07-07 国立大学法人九州大学 医療用高分子ナノ・マイクロファイバー
JP2007167366A (ja) * 2005-12-22 2007-07-05 Teijin Ltd 神経再生材料
US20070269481A1 (en) * 2006-01-27 2007-11-22 The Regents Of The University Of California Biomimetic Scaffolds
JP4982887B2 (ja) * 2007-02-20 2012-07-25 北海道曹達株式会社 神経再生チューブ及びその製造方法

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1844509A (zh) * 2006-04-18 2006-10-11 北京理工大学 一种丝素蛋白多孔结构材料的制备方法
JP2007303015A (ja) * 2006-05-10 2007-11-22 Univ Of Shiga Prefecture 静電紡糸装置
CN1944724A (zh) * 2006-10-11 2007-04-11 东华大学 胶原蛋白和壳聚糖复合纳米纤维及膜静电纺丝的制备方法
WO2009102792A2 (en) * 2008-02-12 2009-08-20 Osteotech, Inc. Collagen products and methods for producing collagen products
CN101664346A (zh) * 2009-09-02 2010-03-10 南通大学 静电纺丝制备的人工神经移植物及其制备方法和专用装置

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
WANG SHUDONG ET AL: "Structure and Biomechanical Properties of Electrospun PLA", MATERIALS ENGINEERING, vol. 10, October 2008 (2008-10-01), pages 316 - 320 *
WANG SHUDONG ET AL: "Structure and Properties of Electro-spun Silk Fibroin-Gelatin Tubular Scaffold", SILK, no. 7, July 2009 (2009-07-01), pages 18 - 21, XP055159306 *
WU JIALIN ET AL: "Research and Developments of Composite Nanofibers Prepared By Electrospinning", SYNTHETIC FIBRE, no. 2, February 2009 (2009-02-01), pages 9 - 12 *

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102813562A (zh) * 2011-06-10 2012-12-12 冯淑芹 三维大孔径纳米级纤维支架与制备方法
CN102871772A (zh) * 2011-07-13 2013-01-16 冯淑芹 一种多孔可降解血管及其制备方法
CN115591016A (zh) * 2022-11-08 2023-01-13 南通大学（Cn） 一种具有取向微通道的神经移植物及其制备方法
CN115591016B (zh) * 2022-11-08 2023-12-19 南通大学 一种具有取向微通道的神经移植物及其制备方法

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