WO2023179422A1 - 弹性多孔支架及其制备方法和应用 - Google Patents
弹性多孔支架及其制备方法和应用 Download PDFInfo
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Classifications
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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
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/14—Macromolecular materials
- A61L27/22—Polypeptides or derivatives thereof, e.g. degradation products
- A61L27/227—Other specific proteins or polypeptides not covered by A61L27/222, A61L27/225 or A61L27/24
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/14—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
- 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
- A61L2430/02—Materials or treatment for tissue regeneration for reconstruction of bones; weight-bearing implants
Definitions
- the purpose of the present invention is to provide an elastic porous scaffold and its preparation method and application.
- the scaffold has high porosity and large pore size, can mimic the structure of natural extracellular matrix, and can be widely used in bone tissue engineering and regenerative medicine.
- the present invention provides a method for preparing an elastic porous scaffold, which includes the following steps:
- the electrospinning process is as follows: add the spinning solution to the syringe, install it on the propulsion pump, connect the high voltage, set the spinning machine voltage to 1-12KV, and the propulsion rate to 0.5-4mL /h, the distance from the aluminum foil receiver is 8-20cm, and electrospinning is performed.
- the mass concentration of the short fiber homogenate is 1-50%.
- the pore diameter of the elastic porous scaffold is 1-50 ⁇ m, and the porosity is 20-90%.
- the present invention provides an application of the above-mentioned elastic porous scaffold in bone tissue engineering and regenerative medicine.
- Figure 2 is an FT-IR analysis chart of the elastic porous scaffold before and after cross-linking in Example 2 of the present invention.
- Figure 3 is a compressive stress-strain curve of the elastic porous scaffold in Example 2 of the present invention.
- the invention provides an elastic porous scaffold and its preparation method and application.
- the invention mainly uses polymers as raw materials, prepares nanofiber membranes through electrospinning, and then uses a homogenizer to prepare short fiber homogenate solution, which is mixed with the polymer solution to perform external casting processing and freeze-drying to prepare a three-dimensional scaffold with a porous structure. , and finally obtained an elastic porous scaffold material with good elasticity and internal interconnected pore structure, which is conducive to cell proliferation and adhesion, and can be widely used in bone tissue engineering and regenerative medicine.
- the obtained three-dimensional scaffold was soaked in genipin/PVA solution for cross-linking for 24 hours, frozen at -20°C for 1 hour, then washed three times with ice-cold deionized water, transferred to the required mold, and freeze-dried to obtain an elastic porous scaffold.
- Figure 1 shows the micromorphology of the elastic scaffold.
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Transplantation (AREA)
- Epidemiology (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Dermatology (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Dispersion Chemistry (AREA)
- Biophysics (AREA)
- Materials For Medical Uses (AREA)
- Manufacture Of Porous Articles, And Recovery And Treatment Of Waste Products (AREA)
Abstract
一种弹性多孔支架及其制备方法和应用，制备方法包括：将高分子聚合物溶于溶剂中通过静电纺丝，得到纳米纤维膜；在脆断液溶剂中脆断，形成短纤维匀浆液；并与高分子溶液混合形成混合液，然后将混合液浇注进模具中冷冻干燥，得到三维支架；浸入具有交联剂的高分子溶液中，低温冷冻，冷冻干燥；通过将静电纺丝技术与冷冻干燥技术相结合，制备的支架具有纳米纤维结构，内部联通的孔道利于细胞增殖、黏附；外浇注处理后的支架在湿态下应变达到80％时能够恢复原状，具有良好的弹性性能、高孔隙率和高吸水性能，能够在骨组织工程和再生医学方面具有较广泛的应用。
Description
本发明属于生物材料骨组织工程和再生医学领域，具体涉及一种弹性多孔支架及其制备方法和应用。
自体骨或异体骨材料在体内移植一直是人们用来修复大面积骨损伤的方法，然而这些材料自身就存在着不可忽视的缺陷。自体骨移植虽易被患者接受，但是会给患者造成新的创伤和痛苦，异体骨材料虽然取材方便，但是存在疾病传播和免疫排斥的风险，从生物安全上很难达到令人满意的修复效果。骨组织工程与再生医学在这种背景下应运而生，带给骨修复新的期盼。
传统三维支架的制备方法很多，如热压成型法、溶剂浇铸法、快速成型法等均可制备组织工程支架，但上述这些方法无法完美地仿生天然的细胞外基质结构。随着现代社会对于骨组织工程材料的需求日益增加，对组织工程支架功能的要求越来越高，静电纺丝、自组装和相分离技术应运而生。静电纺丝技术所制备的是一种由多层纤维堆积而成的纤维膜，其力学性能较差，不能很好的应用于骨缺损。自组装技术所制备的膜或支架，其稳定性或有不足，结构有可能被破坏。相分离技术可以控制支架孔的形状、孔度分布和大小，但支架的力学性能较差。因此，选择一种适合的方法，制备一种具有弹性性能、内部联通多孔结构的支架尤为重要。
聚乳酸(PLA)、聚羟基乙酸(PGA)、聚己内酯(PCL)、聚乙二醇等可降解的合成高分子化合物，具有优良生物相容性、无毒、良好的成囊和成膜性能以及良好的骨诱导潜能等优点，常用于微球、纳米粒子及组织工程支架的制备，并被广泛应用于骨组织工程领域。
发明内容
针对现有技术中的不足，本发明的目的是提供一种弹性多孔支架及其制备方法和应用。该支架具有较高孔隙率和大孔径，可以仿生天然细胞外基质的结构，能够在骨组织工程和再生医学方面具有较广泛的应用。
为达到上述目的，本发明的解决方案是：
第一方面，本发明提供了一种弹性多孔支架的制备方法，其包括如下步骤：
(1)、将高分子材料溶于溶剂中，搅拌，得到纺丝溶液，通过静电纺丝，得到纳米纤维膜；
(2)、将纳米纤维膜在脆断液溶剂中进行脆断，形成短纤维匀浆液；
(3)、将短纤维匀浆液与高分子溶液充分混合形成混合液，然后将混合液浇注进模具中冷冻干燥，得到三维支架；
(4)、将三维支架浸入具有交联剂的高分子溶液中，将交联后的支架低温冷冻，浸泡冲洗，冷冻干燥，得到弹性多孔支架。
优选地，步骤(1)中，高分子材料自合成高分子和天然高分子中的一种以上。
优选地，合成高分子选自聚乳酸(PLA)、聚羟基乙酸(PGA)、聚己内酯(PCL)、聚乙二醇中的一种以上。
优选地，天然高分子选自胶原、透明质酸、壳聚糖、丝素蛋白和海藻酸钠中的一种以上。
优选地，步骤(1)中，溶剂选自六氟异丙醇、三氟乙酸、二氯甲烷、三氯甲烷、四氢呋喃、二甲基亚砜和乙酸乙酯中的一种以上。
优选地，步骤(1)中，静电纺丝的工艺为：将纺丝溶液加入到注射器中，安装在推进泵上，连接高压，设置纺丝机电压为1-12KV，推进速率为0.5-4mL/h，距离铝箔接收器距离为8-20cm，进行静电纺丝。
优选地，步骤(2)中，脆断液溶剂选自乙醇、聚丙烯酰胺及叔丁醇与水的一种或多种混合溶液。
优选地，步骤(2)中，短纤维匀浆液的质量浓度为1-50％。
优选地，步骤(3)中，高分子溶液的质量浓度为1-50％，短纤维匀浆液与高分子溶液的体积比为1:100-100:1，混合液的质量浓度为0.1-40％。
优选地，步骤(3)中，三维支架的孔径为1-50μm，孔隙率为20-90％。
优选地，步骤(4)中，交联剂为天然提取的绿色交联剂，交联剂选自京尼平和没食子酸中的一种以上。
优选地，步骤(4)中，三维支架的交联时间为1-48h。
优选地，步骤(4)中，交联剂的高分子溶液中交联剂与高分子溶液的质量比为1:100-100:1，低温冷冻的温度为(-100)-0℃，低温冷冻的时间为0.5-24h。
优选地，步骤(3)和步骤(4)中，高分子溶液中的高分子物质选自聚乙烯醇(PVA)、十二烷基苯磺酸钠(SDBS)、聚氨酯、聚乳酸-羟基乙酸共聚物(PLGA)、丝素蛋白、聚乙二醇、胶原和明胶中的一种以上。
优选地，步骤(3)和步骤(4)中，高分子溶液中的溶剂选自去离子水、二甲基亚砜、四氢呋喃和1,4-二氧六环中的一种以上。
步骤(3)中，高分子溶液中高分子物质的溶解温度为20-110℃。
优选地，步骤(4)中，弹性多孔支架的孔径为1-50μm，孔隙率为20-90％。
第二方面，本发明提供了一种弹性多孔支架，其由上述的制备方法得到。
第三方面，本发明提供了一种上述的弹性多孔支架的应用，弹性多孔支架在骨组织工程和再生医学方面中的应用。
由于采用上述方案，本发明的有益效果是：
本发明通过将静电纺丝技术与冷冻干燥技术相结合，制备的支架具有纳米纤维结构，内部联通的孔道利于细胞增殖、黏附；外浇注处理后的支架在湿态下应变达到80％时能够恢复原状，具有良好的弹性性能、高孔隙率和高吸水性能，能够在骨组织工程和再生医学方面具有较广泛的应用。
图1为本发明实施例1的弹性多孔支架的扫描电镜图。
图2为本发明实施例2的交联前后弹性多孔支架的FT-IR分析图谱。
图3为本发明实施例2的弹性多孔支架的压缩应力-应变曲线图。
图4为本发明实施例2的弹性多孔支架的吸水率曲线图。
本发明提供了一种弹性多孔支架及其制备方法和应用。
本发明主要以高分子为原料，通过静电纺丝制备纳米纤维膜，再使用匀浆机制备短纤维匀浆液，与高分子溶液混合，从而进行外浇注处理，冷冻干燥制备具有多孔结构的三维支架，最后得到具有良好弹性，内部存在联通孔道结构的弹性多孔支架材料，利于细胞的增殖、黏附，能够在骨组织工程和再生医学反面具有较广泛的应用。
以下通过附图和实施例对本发明作进一步的说明。
实施例1：
称取1g的聚羟基乙酸和丝素蛋白，溶于10mL的六氟异丙醇中，搅拌均匀进行静电纺丝，得到分布均匀的纳米纤维膜。将制备的纳米纤维膜剪碎，称重。使用匀浆机将纳米纤维膜在聚丙烯酰胺中脆断成为短纤维匀浆液。90℃条件下将聚乙烯醇(PVA)溶于水中(PVA质量浓度为2.5％)，再与上述短纤维匀浆液混合均匀，超声，将超声后的混合液浇注到模具里，置于-80℃冰箱进行预冻1h，然后冷冻干燥得到三维支架。将所得三维支架浸泡在京尼平/PVA溶液中进行交联24h，-20℃冷冻1h，然后用冰去离子水清洗3次，并转移至所需的模具中，通过冷冻干燥即得弹性多孔支架。图1显示了弹性支架的微观形貌。
实施例2：
称取质量比为2：1的羟基乙酸共聚物和胶原，溶于六氟异丙醇中配制得质量浓度12％的
溶液，搅拌均匀，进行静电纺丝，得到分布均匀的纳米纤维膜。将制备的纳米纤维膜剪碎，称重。使用匀浆机将纳米纤维膜在叔丁醇中脆断成为质量浓度5％的短纤维匀浆液。将甘油配制成质量浓度10％的甘油/水溶液，再与上述短纤维匀浆液混合均匀，超声，将超声后的溶液浇注到模具里，置于-80℃冰箱进行预冻2h，然后冷冻干燥得到三维支架。将所得三维支架浸泡于没食子酸/PVA溶液中进行交联24h，-20℃冷冻1h，然后用冰去离子水清洗3次，并转移至所需的模具中，通过冷冻干燥即得弹性多孔支架。该支架在水中的吸水率能够达到1200％，并且在湿态下压缩应变达到80％时能够恢复原状具有良好的弹性性能(如图3所示，横坐标为应变，纵坐标为应力，压缩结束后应力和应变均回到起点，证明支架完全回弹，具有良好弹性)，而普通大孔支架在压缩之后孔坍塌，不会回到原来形貌，如原来1cm的厚度，压缩结束后只有0.3cm。而本发明制备的支架可以在压缩之后回到原位，因此具有良好弹性性能、孔隙率和高吸水性能(如图2至图4所示)。
上述对实施例的描述是为了便于该技术领域的普通技术人员能理解和使用本发明。熟悉本领域技术人员显然可以容易的对这些实施例做出各种修改，并把在此说明的一般原理应用到其他实施例中，而不必经过创造性的劳动。因此，本发明不限于上述实施例。本领域技术人员根据本发明的原理，不脱离本发明的范畴所做出的改进和修改都应该在本发明的保护范围之内。
Claims (10)
- 一种弹性多孔支架的制备方法，其特征在于：其包括如下步骤：(1)、将高分子材料溶于溶剂中，搅拌，得到纺丝溶液，通过静电纺丝，得到纳米纤维膜；(2)、将所述纳米纤维膜在脆断液溶剂中进行脆断，形成短纤维匀浆液；(3)、将所述短纤维匀浆液与高分子溶液充分混合形成混合液，然后将混合液浇注进模具中冷冻干燥，得到三维支架；(4)、将所述三维支架浸入具有交联剂的高分子溶液中，将交联后的支架低温冷冻，浸泡冲洗，冷冻干燥，得到弹性多孔支架。
- 根据权利要求1所述的弹性多孔支架的制备方法，其特征在于：步骤(1)中，所述高分子材料自合成高分子和天然高分子中的一种以上；优选地，所述合成高分子选自聚乳酸、聚羟基乙酸、聚己内酯、聚乙二醇中的一种以上；优选地，所述天然高分子选自胶原、透明质酸、壳聚糖、丝素蛋白和海藻酸钠中的一种以上。
- 根据权利要求1所述的弹性多孔支架的制备方法，其特征在于：步骤(1)中，所述溶剂选自六氟异丙醇、三氟乙酸、二氯甲烷、三氯甲烷、四氢呋喃、二甲基亚砜和乙酸乙酯中的一种以上；和/或，步骤(1)中，所述静电纺丝的参数为：纺丝机电压为1-12KV，推进速率为0.5-4mL/h，接收器距离为8-20cm。
- 根据权利要求1所述的弹性多孔支架的制备方法，其特征在于：步骤(2)中，所述脆断液溶剂选自乙醇、聚丙烯酰胺及叔丁醇与水的一种或多种混合溶液；和/或，步骤(2)中，所述短纤维匀浆液的质量浓度为1-50％。
- 根据权利要求1所述的弹性多孔支架的制备方法，其特征在于：步骤(3)中，所述高分子溶液的质量浓度为1-50％，所述短纤维匀浆液与高分子溶液的体积比为1:100-100:1，所述混合液的质量浓度为0.1-40％；和/或，步骤(3)中，所述三维支架的孔径为1-50μm，孔隙率为20-90％。
- 根据权利要求1所述的弹性多孔支架的制备方法，其特征在于：步骤(4)中，所述交联剂选自京尼平和没食子酸中的一种以上；和/或，步骤(4)中，所述三维支架的交联时间为1-48h；和/或，步骤(4)中，所述交联剂的高分子溶液中交联剂与高分子溶液的质量比为1:100-100:1；所述低温冷冻的温度为(-100)-0℃，所述低温冷冻的时间为0.5-24h。
- 根据权利要求1所述的弹性多孔支架的制备方法，其特征在于：步骤(3)和步骤(4)中，所述高分子溶液中的高分子物质选自聚乙烯醇、十二烷基苯磺酸钠、聚氨酯、聚乳酸-羟基乙酸共聚物、丝素蛋白、聚乙二醇、胶原和明胶中的一种以上；和/或，步骤(3)和步骤(4)中，所述高分子溶液中的溶剂选自去离子水、二甲基亚砜、四氢呋喃和1,4-二氧六环中的一种以上。
- 根据权利要求1所述的弹性多孔支架的制备方法，其特征在于：步骤(4)中，所述弹性多孔支架的孔径为1-50μm，孔隙率为20-90％。
- 一种弹性多孔支架，其特征在于：其由权利要求1-8任一项所述的制备方法得到。
- 一种如权利要求9所述的弹性多孔支架的应用，所述弹性多孔支架在骨组织工程和再生医学方面中的应用。
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