WO2022193599A1 - 一种脊髓再生修复材料的制备方法 - Google Patents

一种脊髓再生修复材料的制备方法 Download PDF

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WO2022193599A1
WO2022193599A1 PCT/CN2021/120015 CN2021120015W WO2022193599A1 WO 2022193599 A1 WO2022193599 A1 WO 2022193599A1 CN 2021120015 W CN2021120015 W CN 2021120015W WO 2022193599 A1 WO2022193599 A1 WO 2022193599A1
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spinal cord
repair material
mold
cord regeneration
preparing
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PCT/CN2021/120015
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English (en)
French (fr)
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宋天喜
李洪景
刘洋
崔孟龙
仇志烨
朱艳泽
胡艳丽
何志敏
崔云
李良才
朱金亮
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潍坊奥精医学研究有限公司
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Publication of WO2022193599A1 publication Critical patent/WO2022193599A1/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
    • A61L27/14—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
    • A61L27/14—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
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/54—Biologically active materials, e.g. therapeutic substances
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/56—Porous materials, e.g. foams or sponges
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • 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 relates to a preparation method of a spinal cord regeneration and repair material.
  • Spinal cord injury is a common clinical disease. Spinal cord injury is caused by a variety of reasons, tumor, inflammation, trauma, etc. can lead to spinal cord injury. Spinal cord injury has a great impact on patients, the most common is the loss of neurological function below the spinal cord injury surface, and the more serious can cause functional defects of the cardiovascular system, respiratory system, and digestive system. These functional deficits will affect the patient's normal life.
  • the best method for spinal cord regeneration and repair is to construct a degradable tissue engineering scaffold at the spinal cord injury, and use the tissue engineering scaffold as a carrier of transplanted cells or as a carrier of active factors that can protect neurons and promote axon regeneration.
  • tissue engineering scaffold as a carrier of transplanted cells or as a carrier of active factors that can protect neurons and promote axon regeneration.
  • the shortcomings of the existing spinal cord regeneration and repair materials are: 1. It cannot form a precise three-dimensional structure and cannot adapt to the shape of the spinal cord injury. 2. The micropores formed by the engineering scaffold are small, which is not conducive to the reproduction and growth of cells.
  • the purpose of the present invention is to provide a preparation method of a spinal cord regeneration and repair material suitable for cell reproduction and growth, which can be adapted to the shape of the spinal cord injury and is suitable for cell reproduction and growth.
  • the preparation method of the spinal cord regeneration repair material includes the following steps: step 1) making a mold according to the shape of the bone marrow, and the mold is a cylinder that is connected up and down; step 2) Place a plurality of filaments running through both ends in the mold; step 3) seal the lower end of the mold; step 4) inject biological slurry into the mold, put it into a freeze dryer, and thermally induce phase separation to remove the biological slurry. solvent to obtain a solid with a large number of micropores; step 5) taking the solid material out of the cylinder and extracting the filaments to obtain a solid scaffold with a large number of micropores and multiple axial channels.
  • the step 1) includes the following specific steps: step 1.1) designing a three-dimensional model of the spinal cord with computer-aided design software; step 1.2) making a mold according to the three-dimensional model of the spinal cord.
  • the filaments in the step 2) are stainless steel wires.
  • the biological slurry in the step 4) is a mixture of collagen and chitosan.
  • the collagen is type I, III or IV collagen.
  • the preparation method of the biological slurry includes the following steps: Step 4.1) Dissolve collagen and chitosan in a mass ratio of 2:1-1:1 in a 0.05 mol/L acetic acid solution, and in a constant temperature environment of 4 degrees Celsius, with Stir at 800 rpm for 60 minutes.
  • the preparation method of the spinal cord regeneration and repair material further includes: step 6) putting the solid scaffold obtained in step 5 into a biological cross-linking agent for cross-linking and then freeze-drying.
  • the biological cross-linking agent is genipin solution.
  • the preparation method of the spinal cord regeneration and repair material further includes: step 7) immersing the micropores in the solid support with cell growth factors.
  • the preparation method of the spinal cord regeneration and repair material further includes: step 8) injecting seed cells into the axial channel in the solid support.
  • the beneficial effects of the invention are as follows: the three-dimensional model of the spinal cord produced by three-dimensional modeling can better match the shape of the spinal cord injury; Both sex and mechanical properties can reach a high level; the axial channel is consistent with the direction of nerve conduction, which is beneficial to guide the proliferation and differentiation of seed cells, and establish new synaptic connections. Propagation and growth of seed cells in the channel.
  • Step 1) Make a mold according to the shape of the bone marrow, and the mold is a cylinder that penetrates up and down.
  • the step 1) includes the following specific steps: step 1.1) designing a three-dimensional model of the spinal cord with computer-aided design software; step 1.2) making a mold according to the three-dimensional model of the spinal cord.
  • Step 2) A plurality of filaments running through both ends are placed in the mold, and the filaments are preferably stainless steel wires.
  • Step 3 Close the lower end of the mold.
  • Step 4) inject the biological slurry into the mold, put it into the freeze dryer, and thermally induce phase separation to remove the solvent in the biological slurry to obtain a solid substance with a large number of micropores;
  • the preparation method of the biological slurry includes the following steps: 4.1) Dissolve type I collagen and chitosan with a mass ratio of 2:1 in 0.05 mol/L acetic acid solution, and stir at 800 rpm for 60 minutes in a constant temperature environment of 4 degrees Celsius.
  • Step 5 Take the solid material out of the cylinder and extract the filaments to obtain a solid scaffold with a large number of micropores and multiple axial channels.
  • Step 6) The solid scaffold obtained in step 5 is placed in a biological cross-linking agent for cross-linking and then freeze-dried.
  • the biological cross-linking agent in this example is a genipin solution, and the cross-linking process includes: immersing the solid scaffold in a genipin solution with a concentration of 10 g/L for 48 hours, then lyophilizing it at -40 degrees Celsius for 24 hours .
  • Step 7) Immerse the micropores in the solid scaffold with cell growth factors.
  • Step 8) Inject seed cells into the axial channels in the solid scaffold.
  • Step 1) Make a mold according to the shape of the bone marrow, and the mold is a cylinder that penetrates up and down.
  • the step 1) includes the following specific steps: step 1.1) designing a three-dimensional model of the spinal cord with computer-aided design software; step 1.2) making a mold according to the three-dimensional model of the spinal cord.
  • Step 2) A plurality of filaments running through both ends are placed in the mold, and the filaments are preferably stainless steel wires.
  • Step 3 Close the lower end of the mold.
  • Step 4) inject the biological slurry into the mold, put it into the freeze dryer, and thermally induce phase separation to remove the solvent in the biological slurry to obtain a solid substance with a large number of micropores;
  • the preparation method of the biological slurry includes the following steps: 4.1) Dissolve type III collagen and chitosan with a mass ratio of 3:2 in 0.05 mol/L acetic acid solution, and stir at 800 rpm for 60 minutes in a constant temperature environment of 4 degrees Celsius.
  • Step 5 Take the solid material out of the cylinder and extract the filaments to obtain a solid scaffold with a large number of micropores and multiple axial channels.
  • Step 6) The solid scaffold obtained in step 5 is placed in a biological cross-linking agent for cross-linking and then freeze-dried.
  • the biological cross-linking agent in this example is a genipin solution, and the cross-linking process includes: immersing the solid scaffold in a genipin solution with a concentration of 10 g/L for 48 hours, then lyophilizing it at -40 degrees Celsius for 24 hours .
  • Step 7) Immerse the micropores in the solid scaffold with cell growth factors.
  • Step 8) Inject seed cells into the axial channels in the solid scaffold.
  • Step 1) Make a mold according to the shape of the bone marrow, and the mold is a cylinder that penetrates up and down.
  • the step 1) includes the following specific steps: step 1.1) designing a three-dimensional model of the spinal cord with computer-aided design software; step 1.2) making a mold according to the three-dimensional model of the spinal cord.
  • Step 2) A plurality of filaments running through both ends are placed in the mold, and the filaments are preferably stainless steel wires.
  • Step 3 Close the lower end of the mold.
  • Step 4) inject the biological slurry into the mold, put it into the freeze dryer, and thermally induce phase separation to remove the solvent in the biological slurry to obtain a solid substance with a large number of micropores;
  • the preparation method of the biological slurry includes the following steps: 4.1) Dissolve collagen IV and chitosan with a mass ratio of 1:1 in 0.05 mol/L acetic acid solution, and stir at 800 rpm for 60 minutes in a constant temperature environment of 4 degrees Celsius.
  • Step 5 Take the solid material out of the cylinder and extract the filaments to obtain a solid scaffold with a large number of micropores and multiple axial channels.
  • Step 6) The solid scaffold obtained in step 5 is placed in a biological cross-linking agent for cross-linking and then freeze-dried.
  • the biological cross-linking agent in this example is a genipin solution, and the cross-linking process includes: immersing the solid scaffold in a genipin solution with a concentration of 10 g/L for 48 hours, then lyophilizing it at -40 degrees Celsius for 24 hours .
  • Step 7) Immerse the micropores in the solid scaffold with cell growth factors.
  • Step 8) Inject seed cells into the axial channels in the solid scaffold.

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Abstract

本发明公开了一种脊髓再生修复材料的制备方法，包括如下步骤：步骤1）根据骨髓的形状制作模具，模具为上下贯通的筒体；步骤2）模具内放置多条贯穿两端的细丝；步骤3）将模具的下端封闭；步骤4）向模具中注入生物浆料，放入冻干机中，热致相分离去除生物浆料中的溶剂，得到具有大量微孔的固体物；步骤5）将固体物从筒体中取出并将细丝抽取出来得到具有大量微孔和多条轴向通道的固体支架。通过三维建模制作出的脊髓三维模型可以跟脊髓损伤处的形状更好的吻合；轴向通道与神经传导方向相一致，有利于引导种子细胞增殖、分化，建立新的突触联络，微孔用于存留细胞生长因子，促进轴向通道内种子细胞的繁殖、生长。

Description

一种脊髓再生修复材料的制备方法 技术领域
本发明涉及一种脊髓再生修复材料的制备方法。
 背景技术
脊髓损伤是临床上常见的疾病。脊髓损伤由多种原因引起，肿瘤、炎症、外伤等都会导致脊髓损伤。脊髓损伤对患者影响较大，最常见的是脊髓损伤面以下的神经功能缺失，较为严重的还会造成心血管系统、呼吸系统、消化系统等的功能缺陷。这些功能缺陷都会影响患者的正常生活。
脊髓损伤不仅破坏力大，而且很难恢复，这是因为在脊髓损伤之后很难通过自身神经元在全横断处形成突触来修复神经传导通路。所以直到现在，脊髓再生修复仍是临床医学的重要课题。
目前，脊髓再生修复最好的方法是通过在脊髓损伤处构建一种可降解的组织工程支架，利用组织工程支架作为移植细胞或作为具有保护神经元和促进轴突再生作用的活性因子的载体，通过移植成体干细胞、诱导性多潜能干细胞和胚胎干细胞等方式在脊髓损伤处形成新的神经元，由此建立突触联系，形成有效的突触连接。
现有脊髓再生修复材料的缺点在于：1、不能形成精确的三维结构，不能与脊髓损伤处的形状相适应。2、工程支架所形成的微孔较小，不利于细胞的繁殖生长。
 技术问题
本发明的目的是针对以上问题提供一种能够与脊髓损伤处的形状相适应的、适宜于细胞繁殖生长的脊髓再生修复材料的制备方法。
 技术解决方案
为达到上述目的，本发明公开了一种脊髓再生修复材料的制备方法，该脊髓再生修复材料的制备方法包括如下步骤：步骤1）根据骨髓的形状制作模具，模具为上下贯通的筒体；步骤2）模具内放置多条贯穿两端的细丝；步骤3）将模具的下端封闭；步骤4）向模具中注入生物浆料，放入冻干机中，热致相分离去除生物浆料中的溶剂，得到具有大量微孔的固体物；步骤5）将固体物从筒体中取出并将细丝抽取出来得到具有大量微孔和多条轴向通道的固体支架。
所述步骤1）包括如下具体的步骤：步骤1.1）用计算机辅助设计软件设计脊髓三维模型；步骤1.2）根据脊髓三维模型制作模具。
所述步骤2）中的细丝为不锈钢丝。
所述步骤4）中的生物浆料为胶原与壳聚糖的混合物。
所述胶原为I、III或IV型胶原。
所述生物浆料的制作方法包括如下步骤：步骤4.1）取质量比为2:1-1:1的胶原蛋白和壳聚糖溶于0.05摩尔/升醋酸溶液，在4摄氏度恒温环境中，以800转/分搅拌60分钟。
该脊髓再生修复材料的制备方法还包括：步骤6）将步骤5中得到的固体支架放入生物交联剂中进行交联后冻干。
所述生物交联剂为京尼平溶液。
所述该脊髓再生修复材料的制备方法还包括：步骤7）使固体支架中的微孔中浸入细胞生长因子。
所述该脊髓再生修复材料的制备方法还包括：步骤8）向固体支架中的轴向通道中注入种子细胞。
 有益效果
本发明的有益效果在于：通过三维建模制作出的脊髓三维模型可以跟脊髓损伤处的形状更好的吻合；胶原蛋白和壳聚糖制成的固体支架经过交联之后，无论是生物相容性、还是力学性能都能达到较高的水平；轴向通道与神经传导方向相一致，有利于引导种子细胞增殖、分化，建立新的突触联络，微孔用于存留细胞生长因子，促进轴向通道内种子细胞的繁殖、生长。
 本发明的最佳实施方式
实施例1。
步骤1）根据骨髓的形状制作模具，模具为上下贯通的筒体。所述步骤1）包括如下具体的步骤：步骤1.1）用计算机辅助设计软件设计脊髓三维模型；步骤1.2）根据脊髓三维模型制作模具。
步骤2）模具内放置多条贯穿两端的细丝，细丝优选不锈钢丝。
步骤3）将模具的下端封闭。
步骤4）向模具中注入生物浆料，放入冻干机中，热致相分离去除生物浆料中的溶剂，得到具有大量微孔的固体物；生物浆料的制作方法包括如下步骤：步骤4.1）取质量比为2:1的I型胶原蛋白和壳聚糖溶于0.05摩尔/升醋酸溶液，在4摄氏度恒温环境中，以800转/分搅拌60分钟。
步骤5）将固体物从筒体中取出并将细丝抽取出来得到具有大量微孔和多条轴向通道的固体支架。
步骤6）将步骤5中得到的固体支架放入生物交联剂中进行交联后冻干。本实施例中的生物交联剂为京尼平溶液，交联过程包括：将固体支架浸入浓度为10克/升京尼平溶液中交联48小时后，在-40摄氏度下冻干24小时。
步骤7）使固体支架中的微孔中浸入细胞生长因子。
步骤8）向固体支架中的轴向通道中注入种子细胞。
 本发明的实施方式
实施例2。
步骤1）根据骨髓的形状制作模具，模具为上下贯通的筒体。所述步骤1）包括如下具体的步骤：步骤1.1）用计算机辅助设计软件设计脊髓三维模型；步骤1.2）根据脊髓三维模型制作模具。
步骤2）模具内放置多条贯穿两端的细丝，细丝优选不锈钢丝。
步骤3）将模具的下端封闭。
步骤4）向模具中注入生物浆料，放入冻干机中，热致相分离去除生物浆料中的溶剂，得到具有大量微孔的固体物；生物浆料的制作方法包括如下步骤：步骤4.1）取质量比为3:2的III型胶原蛋白和壳聚糖溶于0.05摩尔/升醋酸溶液，在4摄氏度恒温环境中，以800转/分搅拌60分钟。
步骤5）将固体物从筒体中取出并将细丝抽取出来得到具有大量微孔和多条轴向通道的固体支架。
步骤6）将步骤5中得到的固体支架放入生物交联剂中进行交联后冻干。本实施例中的生物交联剂为京尼平溶液，交联过程包括：将固体支架浸入浓度为10克/升京尼平溶液中交联48小时后，在-40摄氏度下冻干24小时。
步骤7）使固体支架中的微孔中浸入细胞生长因子。
步骤8）向固体支架中的轴向通道中注入种子细胞。
实施例3。
步骤1）根据骨髓的形状制作模具，模具为上下贯通的筒体。所述步骤1）包括如下具体的步骤：步骤1.1）用计算机辅助设计软件设计脊髓三维模型；步骤1.2）根据脊髓三维模型制作模具。
步骤2）模具内放置多条贯穿两端的细丝，细丝优选不锈钢丝。
步骤3）将模具的下端封闭。
步骤4）向模具中注入生物浆料，放入冻干机中，热致相分离去除生物浆料中的溶剂，得到具有大量微孔的固体物；生物浆料的制作方法包括如下步骤：步骤4.1）取质量比为1:1的IV型胶原蛋白和壳聚糖溶于0.05摩尔/升醋酸溶液，在4摄氏度恒温环境中，以800转/分搅拌60分钟。
步骤5）将固体物从筒体中取出并将细丝抽取出来得到具有大量微孔和多条轴向通道的固体支架。
步骤6）将步骤5中得到的固体支架放入生物交联剂中进行交联后冻干。本实施例中的生物交联剂为京尼平溶液，交联过程包括：将固体支架浸入浓度为10克/升京尼平溶液中交联48小时后，在-40摄氏度下冻干24小时。
步骤7）使固体支架中的微孔中浸入细胞生长因子。
步骤8）向固体支架中的轴向通道中注入种子细胞。
以上所述仅是本发明的优选实施方式，应当指出，对于本技术领域的普通技术人员来说，在不脱离本发明技术原理的前提下，还可以做出若干改进和替换，这些改进和替换也应视为本发明的保护范围。
以上所述仅是本发明的优选实施方式，应当指出，对于本技术领域的普通技术人员来说，在不脱离本发明技术原理的前提下，还可以做出若干改进和替换，这些改进和替换也应视为本发明的保护范围。

Claims (10)

  1. 一种脊髓再生修复材料的制备方法，其特征在于,该脊髓再生修复材料的制备方法包括如下步骤：
    步骤1）根据骨髓的形状制作模具，模具为上下贯通的筒体；
    步骤2）模具内放置多条贯穿两端的细丝；
    步骤3）将模具的下端封闭；
    步骤4）向模具中注入生物浆料，放入冻干机中，热致相分离去除生物浆料中的溶剂，得到具有大量微孔的固体物；
    步骤5）将固体物从筒体中取出并将细丝抽取出来得到具有大量微孔和多条轴向通道的固体支架。
  2. 如权利要求1所述的脊髓再生修复材料的制备方法，其特征在于，所述步骤1）包括如下具体的步骤：
    步骤1.1）用计算机辅助设计软件设计脊髓三维模型；
    步骤1.2）根据脊髓三维模型制作模具。
  3. 如权利要求1所述的脊髓再生修复材料的制备方法，其特征在于，所述步骤2）中的细丝为不锈钢丝。
  4. 如权利要求1所述的脊髓再生修复材料的制备方法，其特征在于，所述步骤4）中的生物浆料为胶原与壳聚糖的混合物。
  5. 如权利要求4所述的脊髓再生修复材料的制备方法，其特征在于，所述胶原为I、III或IV型胶原。
  6. 如权利要求4所述的脊髓再生修复材料的制备方法，其特征在于，所述生物浆料的制作方法包括如下步骤：步骤4.1）取质量比为2:1-1:1的胶原蛋白和壳聚糖溶于0.05摩尔/升醋酸溶液，在4摄氏度恒温环境中，以800转/分搅拌60分钟。
  7. 如权利要求1所述的脊髓再生修复材料的制备方法，其特征在于，该脊髓再生修复材料的制备方法还包括：步骤6）将步骤5中得到的固体支架放入生物交联剂中进行交联后冻干。
  8. 如权利要求7所述的脊髓再生修复材料的制备方法，其特征在于，所述生物交联剂为京尼平溶液。
  9. 如权利要求7所述的脊髓再生修复材料的制备方法，其特征在于，所述该脊髓再生修复材料的制备方法还包括：步骤7）使固体支架中的微孔中浸入细胞生长因子。
  10. 如权利要求7所述的脊髓再生修复材料的制备方法，其特征在于，所述该脊髓再生修复材料的制备方法还包括：步骤8）向固体支架中的轴向通道中注入种子细胞。
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CN112891624A (zh) * 2021-03-19 2021-06-04 潍坊奥精医学研究有限公司 一种脊髓再生修复材料的制备方法

Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1593354A (zh) * 2004-06-25 2005-03-16 清华大学 一种神经组织工程管状支架及其制备方法
CN101766836A (zh) * 2009-01-21 2010-07-07 丁坦 纳米银脊髓、周围神经修复材料的制备方法
US20110276066A1 (en) * 2010-04-15 2011-11-10 National University Of Ireland, Galway Multichannel collagen nerve conduit for nerve repair
CN102512266A (zh) * 2012-01-16 2012-06-27 杭州电子科技大学 脊髓损伤修复组织工程支架的制备方法
CN102671237A (zh) * 2009-01-16 2012-09-19 中国人民解放军第四军医大学 一种高仿真组织工程神经修复材料及其制备方法
CN102688110A (zh) * 2012-06-13 2012-09-26 北京天新福医疗器材有限公司 一种多孔径神经修复管，其制备方法与应用
CN103263308A (zh) * 2013-05-17 2013-08-28 中国人民解放军第四军医大学 多微孔可降解胶原-壳聚糖神经导管及其制备方法
US20190290283A1 (en) * 2018-03-26 2019-09-26 Wichita State University Composite neural conduit
CN112891624A (zh) * 2021-03-19 2021-06-04 潍坊奥精医学研究有限公司 一种脊髓再生修复材料的制备方法

Patent Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1593354A (zh) * 2004-06-25 2005-03-16 清华大学 一种神经组织工程管状支架及其制备方法
CN102671237A (zh) * 2009-01-16 2012-09-19 中国人民解放军第四军医大学 一种高仿真组织工程神经修复材料及其制备方法
CN101766836A (zh) * 2009-01-21 2010-07-07 丁坦 纳米银脊髓、周围神经修复材料的制备方法
US20110276066A1 (en) * 2010-04-15 2011-11-10 National University Of Ireland, Galway Multichannel collagen nerve conduit for nerve repair
CN102512266A (zh) * 2012-01-16 2012-06-27 杭州电子科技大学 脊髓损伤修复组织工程支架的制备方法
CN102688110A (zh) * 2012-06-13 2012-09-26 北京天新福医疗器材有限公司 一种多孔径神经修复管，其制备方法与应用
CN103263308A (zh) * 2013-05-17 2013-08-28 中国人民解放军第四军医大学 多微孔可降解胶原-壳聚糖神经导管及其制备方法
US20190290283A1 (en) * 2018-03-26 2019-09-26 Wichita State University Composite neural conduit
CN112891624A (zh) * 2021-03-19 2021-06-04 潍坊奥精医学研究有限公司 一种脊髓再生修复材料的制备方法

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