WO2022120902A1 - 骨修复支架及其制备方法 - Google Patents

骨修复支架及其制备方法 Download PDF

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WO2022120902A1
WO2022120902A1 PCT/CN2020/136555 CN2020136555W WO2022120902A1 WO 2022120902 A1 WO2022120902 A1 WO 2022120902A1 CN 2020136555 W CN2020136555 W CN 2020136555W WO 2022120902 A1 WO2022120902 A1 WO 2022120902A1
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bone repair
repair scaffold
shape memory
scaffold according
memory polyurethane
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French (fr)
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赖毓霄
张原驰
张卫
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Shenzhen Institute of Advanced Technology of CAS
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    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
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    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
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Definitions

  • the invention belongs to the technical field of biomedicine, and particularly relates to a bone repair support and a preparation method thereof.
  • Bone repair scaffolds as an important means of internal fixation of bone defects caused by fractures and osteoporosis, have always received a lot of attention.
  • Traditional scaffold materials are three-dimensional scaffolds with certain stability, such as rectangles, cubes, cylinders, etc., so as to form a relatively stable growth space for new tissue after implantation, but many clinical bone defects are irregular defects. , it is difficult for a material with a fixed shape to completely repair the defective space.
  • shape memory polymer can deform and compress the material to a smaller size as required, and can restore its original shape in a specific environment when implanted in the human body.
  • This special function provides a more convenient and stable direction for the realization of minimally invasive surgery and the fixation and support of bone defects, especially the shape memory material regulated by near-infrared light, which can realize the remote regulation of implanted materials in vivo.
  • How to improve the mechanical properties of shape memory polymer bone repair scaffolds is a problem that needs to be solved in the industry.
  • the present invention provides a bone repair scaffold and a preparation method thereof, so as to solve the problem of poor mechanical properties of the existing shape memory polymer bone repair scaffold.
  • one aspect of the present invention is to provide a bone repair scaffold, the material of the bone repair scaffold includes shape memory polyurethane and metal magnesium, and the mass ratio of the shape memory polyurethane to the metal magnesium is 100. : (1 to 10).
  • the mass ratio of the shape memory polyurethane to the metal magnesium is 100:(3-5).
  • the particle size of the metallic magnesium is 40 ⁇ m ⁇ 100 ⁇ m.
  • the particle size of the metallic magnesium is 50 ⁇ m ⁇ 80 ⁇ m.
  • the shape memory polyurethane is formed by the reaction of the following raw material components: 23.0%-25.0% diphenylmethane diisocyanate, 7.0%-8.0% chain extension agent and 67.0% to 70.0% of polycaprolactone diol.
  • the ratio of the isocyanate groups contained in the diphenylmethane diisocyanate to the hydroxyl groups of all the raw materials participating in the reaction is (1.0-1.2):1.
  • the chain extender is selected from any one of 1,4-butanediol, 1,6-hexanediol and ethylene glycol.
  • the number average molecular weight of the polycaprolactone diol is 3000-8000.
  • Another aspect of the present invention is to provide a preparation method of the above-mentioned bone repair scaffold, comprising:
  • the scaffold embryo body is freeze-dried to obtain the bone repair scaffold.
  • the printing speed is 0.1mm/s ⁇ 1.5mm/s
  • the temperature of the printing nozzle is 10°C ⁇ 20°C
  • the temperature of the freeze drying is -80°C ⁇ -70°C
  • the time is 48h ⁇ 72h.
  • the material of the bone repair scaffold provided by the embodiment of the present invention includes shape memory polyurethane (SMPU) and metal magnesium (Mg).
  • SMPU shape memory polyurethane
  • Mg metal magnesium
  • Magnesium ions can stimulate the sensory nerve terminals in the natural periosteum to release more neurotransmitters, further promote the osteogenic differentiation of stem cells in the periosteum, so that the bone repair scaffold has good bone regeneration performance; (3) ), magnesium has a photothermal effect, under the irradiation of near-infrared light, the magnesium in the composite material converts light energy into heat energy, activates the thermal response mechanism of SMPU, realizes shape recovery in vivo, and provides long-range stimulation-response for bone repair scaffolds Feasibility of regulation.
  • a bone repair scaffold is rapidly formed under low temperature conditions through a 3D printing process, and its morphology and structure can be controlled in a variety of ways, and a porous scaffold with controllable and uniform pore size can be prepared. , which has the advantages of simple process flow, easy industrialization implementation, and wide applicability.
  • Fig. 1 is the test curve diagram of the photothermal effect of the bone repair scaffold in the embodiment of the present invention
  • Fig. 2 is the test curve diagram of the stress-strain of the bone repair scaffold in the embodiment of the present invention.
  • Fig. 3 is the test curve diagram of the shape memory performance of the bone repair scaffold in the embodiment of the present invention.
  • FIG. 4 is a cell live and dead staining diagram of the bone repair scaffold in the embodiment of the present invention.
  • the embodiment of the present invention first provides a bone repair scaffold, the material of the bone repair scaffold includes shape memory polyurethane (SMPU) and metal magnesium (Mg), and the mass ratio of the shape memory polyurethane to the metal magnesium is 100: (1 to 10).
  • SMPU shape memory polyurethane
  • Mg metal magnesium
  • magnesium ions can stimulate the sensory nerve endings in the natural periosteum to release more neurotransmitters. It further promotes the osteogenic differentiation of stem cells in the periosteum, so that the bone repair scaffold has a good performance of promoting bone regeneration; thirdly, magnesium has a photothermal effect. Under the irradiation of near-infrared light, the magnesium in the composite material converts light energy into heat energy, Activating the thermal response mechanism of SMPU to achieve shape recovery in vivo provides the feasibility of remote stimulus-response regulation for bone repair scaffolds.
  • the mass ratio of the shape memory polyurethane to the metal magnesium is 100:(3-5). More preferably, the mass ratio of the two is selected to be 100:4.
  • the particle size of the metal magnesium is 40 ⁇ m ⁇ 100 ⁇ m. In a more preferred solution, the particle size of the metal magnesium is 50 ⁇ m to 80 ⁇ m, the metal magnesium with a larger particle size range is easier to disperse in the shape memory polyurethane, and the formed bone repair scaffold has higher mechanical strength.
  • the shape memory polyurethane is formed by the reaction of the following raw material components: 23.0%-25.0% of diphenylmethane diisocyanate, 7.0%-8.0% % of chain extender and 67.0% to 70.0% of polycaprolactone diol.
  • the ratio of the isocyanate groups contained in the diphenylmethane diisocyanate to the hydroxyl groups of all the raw materials participating in the reaction is (1.0-1.2):1, preferably 1:1.
  • the chain extender is selected from any one of 1,4-butanediol, 1,6-hexanediol and ethylene glycol, and 1,4-butanediol is preferably used.
  • the number average molecular weight of the polycaprolactone diol is 3000-8000, preferably 5000.
  • the embodiment of the present invention also provides a preparation method of the above-mentioned bone repair scaffold, and the preparation method includes the following steps:
  • Step 1 Dissolving the shape memory polyurethane in an organic solvent, adding metal magnesium, stirring and mixing to obtain a printing precursor liquid.
  • the shape memory polyurethane is prepared by the following process:
  • the reaction mixture pours into a polytetrafluoroethylene mold quickly after stirring, put it into an oven to solidify, and obtain the SMPU solid.
  • the temperature of the oven can be set to 85°C, and the curing time can be 16h.
  • the ratio of the isocyanate group contained in diphenylmethane diisocyanate (MDI) to the hydroxyl group of all the raw materials participating in the reaction is 1:1, and the chain extender (BDO) is selected as 1,4 -Butanediol, polycaprolactone diol (PCL-diol) has a number average molecular weight of 5000.
  • PCL-diol constitutes the soft segment of the SMPU
  • BDO and MDI constitute the hard segment of the SMPU.
  • the reaction formula is as follows:
  • the organic solvent is preferably a mixed solvent of 1,4-dioxane and dimethyl sulfoxide, and the volume ratio of 1,4-dioxane and dimethyl sulfoxide is preferably 5: 1.
  • the metal magnesium is added, and the quality of the added metal magnesium is controlled so that the mass ratio of the shape memory polyurethane to the metal magnesium is 100:(1 ⁇ 10), preferably 100:(3 ⁇ 5), most preferably 100:4.
  • Step 2 using the printing precursor solution to obtain a scaffold embryo body through a 3D printing process.
  • the printing device is preferably a low temperature rapid prototyping (LT-RP) printer
  • the printing speed can be set to 0.1mm/s ⁇ 1.5mm/s
  • the temperature of the printing nozzle can be set to 10°C ⁇ 20°C.
  • the printing speed is 0.2 mm/s
  • the temperature of the printing nozzle is 12°C.
  • Step 3 freeze-drying the scaffold embryo to obtain the bone repair scaffold.
  • the temperature of the freeze-drying is -80°C ⁇ -70°C, and the time is 48h ⁇ 72h.
  • the preparation method of the bone repair scaffold provided in the above embodiment can be rapidly formed into a bone repair scaffold through a 3D printing process under low temperature conditions. It has the advantages of simple process flow and easy industrialization implementation, and has wide applicability.
  • the filling speed of the nozzle is 0.2 mm/s, and the temperature of the nozzle is 12°C.
  • Example 1 The difference between this example and Example 1 is that the metal Mg added in step (4) of Example 1 makes the mass percentage of Mg relative to SMPU to be 4%, that is, the mass ratio of SMPU to Mg is 100:4, The rest of the process is the same as that of Example 1.
  • the bone repair scaffold sample S-2 was prepared and obtained.
  • Example 1 The difference between this example and Example 1 is that the metal Mg added in step (4) of Example 1 makes the mass percentage of Mg relative to SMPU to be 6%, that is, the mass ratio of SMPU to Mg is 100:6, The rest of the process is the same as that of Example 1.
  • the bone repair scaffold sample S-3 was prepared and obtained.
  • Example 1 The difference between this example and Example 1 is that the metal Mg added in step (4) of Example 1 makes the mass percentage of Mg relative to SMPU to be 8%, that is, the mass ratio of SMPU to Mg is 100:8, The rest of the process is the same as that of Example 1.
  • the bone repair scaffold sample S-4 was prepared.
  • the photothermal effect test of the bone repair scaffolds obtained in Examples 1-4 and Comparative Examples is shown in FIG. 1 .
  • the wavelength of the irradiated near-infrared light was 808 nm, and the power density was 1 w/cm 2 .
  • the sample of the comparative example has basically no temperature rise.
  • the temperature of the samples of Examples 1-4 increases with the increase of the irradiation time.
  • the temperature of the sample of Example 4 rises relatively fastest, and the rise is also the largest, and the photothermal effect is the best. .
  • Example 4 The stress-strain tests of the bone repair scaffolds obtained in Examples 1-4 and Comparative Examples are shown in FIG. 2 . Among them, the compressive strength of the sample of Example 4 is the highest, and the compressive strength of the sample of Example 2 and Example 3 is not much different.
  • the shape memory properties of the bone repair scaffolds obtained in Examples 1-4 and Comparative Example under the irradiation of near-infrared light are shown in FIG. 3 .
  • the comparative example had a higher fixation rate, but almost no response.
  • the shape fixation rate of the samples increases, but the recovery rate decreases.
  • the cytocompatibility comparison of the bone repair scaffolds obtained in Examples 1-4 and the comparative example is shown in FIG. 4 .
  • the cells in Examples 1-4 have a more obvious number of live cells, and the higher the number of live cells, the better the compatibility of the sample cells, and The number of dead cells (middle column of images) in Comparative Examples and Examples was also very low, indicating that the samples of Examples 1-4 had better cytocompatibility.
  • Example 2 Based on the above test results, the sample in Example 2 has the most balanced photothermal effect, mechanical strength, shape memory performance and biocompatibility. Therefore, in the composite bone repair scaffold provided in the embodiment of the present invention, SMPU and Mg The mass ratio is preferably 100:(3 to 5), and most preferably 100:4.
  • the bone repair scaffold provided by the present invention improves the mechanical strength of the bone repair scaffold by adding metal magnesium and has a good performance of promoting bone regeneration, and can utilize the photothermal effect of magnesium to provide the bone repair scaffold with remote stimulation-response regulation and control. Feasibility; the preparation method of the bone repair scaffold of the present invention has the advantages of simple process flow, easy industrialization and wide applicability.

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Abstract

一种骨修复支架，所述骨修复支架的材料包括形状记忆聚氨酯和金属镁，所述形状记忆聚氨酯与所述金属镁的质量比为100:(1～10)。所述骨修复支架的制备方法包括：将形状记忆聚氨酯溶解于有机溶剂中，再加入金属镁，搅拌混合获得打印前驱液；将所述打印前驱液通过3D打印工艺获得支架胚体；将所述支架胚体进行冷冻干燥，获得所述骨修复支架。所述的骨修复支架，通过添加金属镁提高了骨修复支架的机械强度且具有良好的促骨再生的性能；所述的骨修复支架的制备方法具有工艺流程简单、易于产业化实施的优点，具有广泛的适用性。

Description

骨修复支架及其制备方法 技术领域
本发明属于生物医学技术领域，具体涉及一种骨修复支架及其制备方法。
背景技术
由骨折、创伤等引起的大范围骨缺损修复一直以来都是公共卫生领域最受关注的问题之一。为解决自体骨移植的局限性，骨组织工程在近年来被不断发展。骨修复支架作为骨折、骨质疏松等造成的骨缺损内固定的重要手段，一直以来都被给予很多关注，当骨产生缺损时，骨骼质量降低直接影响到固定物的稳定性和把持力。传统的支架材料是具有一定稳定性的三维支架，例如长方形、立方体、圆柱体等，以便于植入体内后形成一个较稳定的新生组织生长空间，但临床上很多骨缺损均为非规则性缺损，形状固定的材料难以完整修复缺损的空间。另外，目前临床上有很多手术方案都追求微创治疗，传统的支架材料难以实施。
近年来，随着医疗技术和材料科技的快速发展，更多的高分子材料被应用于骨修复以及制作骨修复支架，并取得了较好的固定修复效果。与金属内固定物相比，其最具有临床吸引力的是高分子材料具有优秀的生物相容性从而不会引发二次感染等。但是，对于一般的聚合物材料制作的骨缺损内固定物来说，机械性能较弱限制了其被广泛应用。根据Rezwan,Kurosh等人在2006年发表的文章(Biomaterials 27.18(2006):3413-3431)中报道，在体内可降解的高分子聚合物的骨支架产品中，存在机械性能不足的问题。
形状记忆聚合物作为一种既具有生物相容性又具有形状记忆功能的智能医用材料，可以按照需求将材料变形压缩到较小的尺寸，在植入人体就可以在特定环境中恢复原始形状，这种特殊功能为实现微创手术以及骨缺损固定支撑提供了更便利更稳定的方向，尤其是近红外光调控的形状记忆材料，可以实现体内植入材料的远程调控。如何提升形状记忆聚合物骨修复支架的机械性能是业内需要解决的问题。
发明内容
鉴于现有技术存在的不足，本发明提供一种骨修复支架及其制备方法，以解决现有的形状记忆聚合物骨修复支架的机械性能较差的问题。
为实现上述发明目的，本发明的一方面是提供了一种骨修复支架，所述骨修复支架的材料包括形状记忆聚氨酯和金属镁，所述形状记忆聚氨酯与所述金属镁的质量比为100:(1～10)。
其中，所述形状记忆聚氨酯与所述金属镁的质量比为100:(3～5)。
其中，所述金属镁的粒径为40μm～100μm。
其中，所述金属镁的粒径为50μm～80μm。
其中，以所述形状记忆聚氨酯的质量为100％计，所述形状记忆聚氨酯由如下的原料组分反应形成：23.0％～25.0％的二苯基甲烷二异氰酸酯、7.0％～8.0％的扩链剂以及67.0％～70.0％的聚己内酯二醇。
其中，所述二苯基甲烷二异氰酸酯中所含有的异氰酸酯基团与参加反应的所有所述原料的羟基的比值为(1.0～1.2):1。
其中，所述扩链剂选自1,4-丁二醇、1,6-己二醇和乙二醇中的任意一种。
其中，所述聚己内酯二醇的数均分子量为3000～8000。
本发明的另一方面是提供一种如上所述的骨修复支架的制备方法，其包括：
将形状记忆聚氨酯溶解于有机溶剂中，再加入金属镁，搅拌混合获得打印前驱液；
将所述打印前驱液通过3D打印工艺获得支架胚体；
将所述支架胚体进行冷冻干燥，获得所述骨修复支架。
其中，所述3D打印工艺中打印速度为0.1mm/s～1.5mm/s，打印喷头的温度为10℃～20℃；所述冷冻干燥的温度为-80℃～-70℃，时间为48h～72h。
本发明实施例提供的骨修复支架，其材料包括形状记忆聚氨酯(SMPU)和金属镁(Mg)，通过添加金属镁，其具有如下的有益效果：(1)、提高了骨修复支架的机械强度；(2)、镁离子可以刺激天然骨膜中的感觉神经末端从而释放更多的神经递质，进一步促进骨膜内干细胞的成骨分化，使得骨修复支架具有良 好的促骨再生的性能；(3)、镁具有光热效应，在近红外光的照射下，复合材料中的镁将光能转化成热能，激活SMPU的热响应机制，在体内实现形状回复，为骨修复支架提供实现远程刺激-响应调控的可行性。
本发明实施例提供的骨修复支架的制备方法，通过3D打印工艺在低温条件下快速成型为骨修复支架，其形貌结构可进行多样化控制，可制备形成为孔径可控且均匀的多孔支架，其具有工艺流程简单、易产业化实施的优点，具有广泛的适用性。
附图说明
图1是本发明实施例中的骨修复支架的光热效应的测试曲线图；
图2是本发明实施例中的骨修复支架的应力应变的测试曲线图；
图3是本发明实施例中的骨修复支架的形状记忆性能的测试曲线图；
图4是本发明实施例中的骨修复支架的细胞活死染色图。
具体实施方式
为使本发明的目的、技术方案和优点更加清楚，下面结合附图对本发明的具体实施方式进行详细说明。这些优选实施方式的示例在附图中进行了例示。附图中所示和根据附图描述的本发明的实施方式仅仅是示例性的，并且本发明并不限于这些实施方式。
在此，还需要说明的是，为了避免因不必要的细节而模糊了本发明，在附图中仅仅示出了与根据本发明的方案密切相关的结构和/或处理步骤，而省略了与本发明关系不大的其他细节。
本发明实施例首先提供了一种骨修复支架，所述骨修复支架的材料包括形状记忆聚氨酯(SMPU)和金属镁(Mg)，所述形状记忆聚氨酯与所述金属镁的质量比为100:(1～10)。
通过在形状记忆聚氨酯中添加金属镁形成为骨修复支架的材料，首先是提高了骨修复支架的机械强度；其次，镁离子可以刺激天然骨膜中的感觉神经末端从而释放更多的神经递质，进一步促进骨膜内干细胞的成骨分化，使得骨修复支架具有良好的促骨再生的性能；再次，镁具有光热效应，在近红外光的照射下，复合材料中的镁将光能转化成热能，激活SMPU的热响应机制，在体内 实现形状回复，为骨修复支架提供实现远程刺激-响应调控的可行性。
在优选的方案中，所述形状记忆聚氨酯与所述金属镁的质量比为100:(3～5)。更为优选的是两者的质量比选择为100:4。
在优选的方案中，所述金属镁的粒径为40μm～100μm。更为优选的方案中，所述金属镁的粒径为50μm～80μm，更粒径范围的金属镁更易分散于形状记忆聚氨酯中，且成型后的骨修复支架具备更高的机械强度。
在优选的方案中，以所述形状记忆聚氨酯的质量为100％计，所述形状记忆聚氨酯由如下的原料组分反应形成：23.0％～25.0％的二苯基甲烷二异氰酸酯、7.0％～8.0％的扩链剂以及67.0％～70.0％的聚己内酯二醇。
其中，所述二苯基甲烷二异氰酸酯中所含有的异氰酸酯基团与参加反应的所有所述原料的羟基的比值为(1.0～1.2):1，优选为1:1。
其中，所述扩链剂选自1,4-丁二醇、1,6-己二醇和乙二醇中的任意一种，优选使用1,4-丁二醇。
其中，所述聚己内酯二醇的数均分子量为3000～8000，优选为5000。
本发明实施例还提供了如上所述的骨修复支架的制备方法，所述制备方法包括以下步骤：
步骤一、将形状记忆聚氨酯溶解于有机溶剂中，再加入金属镁，搅拌混合获得打印前驱液。
在优选的方案中，所述形状记忆聚氨酯由以下工艺制备获得：
(1)、将二苯基甲烷二异氰酸酯、扩链剂以及聚己内酯二醇分别置于真空干燥箱中干燥一定的时间以彻底除去水分。具体的干燥工艺条件例如是：在105℃的温度下在真空环境中干燥2h以上。
(2)、将干燥完成后的二苯基甲烷二异氰酸酯、扩链剂以及聚己内酯二醇按预定比例混合搅拌，升温至反应温度并持续搅拌。具体的干燥工艺条件例如是：升温至85℃并保持反应温度为85℃，设定搅拌速度为150rmp/min，搅拌时间为5min。
(3)、搅拌完成后迅速将反应混合物倒入聚四氟乙烯模具中，放入烘箱固化，得到SMPU固体。具体的，烘箱的温度可以设定为85℃，固化时间为16h。
在更优选的方案中，二苯基甲烷二异氰酸酯(MDI)所含有的异氰酸酯基团与参加反应的所有所述原料的羟基的比值为1:1，扩链剂(BDO)选择为1,4-丁二醇，聚己内酯二醇(PCL-diol)的数均分子量为5000。其中，PCL-diol构成SMPU的软段，BDO和MDI则构成SMPU的硬段。反应式如下：
Figure PCTCN2020136555-appb-000001
其中
Figure PCTCN2020136555-appb-000002
具体为
Figure PCTCN2020136555-appb-000003
在优选的方案中，所述有机溶剂优选为1,4-二氧六环与二甲基亚砜混合溶剂，1,4-二氧六环与二甲基亚砜的体积比优选为5:1，待形状记忆聚氨酯完全溶解于混合溶剂之后再加入金属镁，加入的金属镁质量控制为使得形状记忆聚氨酯与金属镁的质量比为100:(1～10)，优选是100:(3～5)，最为优选的是100:4。
步骤二、将所述打印前驱液通过3D打印工艺获得支架胚体。
具体地，打印设备优选为低温快速成型(LT-RP)打印机，打印速度可以设定为0.1mm/s～1.5mm/s，打印喷头的温度可以设定为10℃～20℃。优选的方案中，打印速度为0.2mm/s，打印喷头的温度12℃。
步骤三、将所述支架胚体进行冷冻干燥，获得所述骨修复支架。
其中，所述冷冻干燥的温度为-80℃～-70℃，时间为48h～72h。
如上实施例提供的骨修复支架的制备方法，通过3D打印工艺在低温条件下 快速成型为骨修复支架，其形貌结构可进行多样化控制，可制备形成为孔径可控且均匀的多孔支架，具有工艺流程简单、易产业化实施的有限，具有广泛的适用性。
本发明实施例提供的骨修复支架在使用时，在55℃～65℃条件下进行变形压缩处理，并于室温下静置冷却塑形，再通过手术植入骨缺损部位，然后在近红外光的照射下(波长为808nm，功率密度范围为P＝0.5w/cm 2～2w/cm 2，功率密度优选为1w/cm 2)，骨修复支架逐渐恢复到自然状态，并进一步固定支撑骨缺损部位和促进骨组织的生长和愈合。
实施例1
(1)、将PCL-diol，MDI和BDO于真空干燥箱中以105℃的真空环境中干燥2小时以上彻底除去水分。
(2)、干燥完成后将PCL-diol，MDI和BDO按比例混合搅拌，反应温度保持在85℃，搅拌速度为150rmp/min，搅拌时间5min。
(3)、搅拌完成后迅速将混合物倒入聚四氟乙烯模具中，放入烘箱固化16h，温度保持在85℃，即得到SMPU固体。
(4)、将制备的SMPU用1，4-二氧六环与二甲基亚砜混合液(体积比为5:1)进行搅拌溶解，待SMPU完全溶解后加入金属Mg，混合均匀后制成打印液。本实施例加入的金属Mg使得Mg相对于SMPU的质量百分比为2％，即，SMPU与Mg的质量比为100:2。
(5)、将上述步骤(4)的打印液使用LT-RP打印机进行3D打印，喷头填充速度为0.2mm/s，喷头温度为12℃。
(6)、打印完成后，在-80℃冷冻干燥2天即得到具有形状记忆功能的SMPU复合骨修复支架样品S-1。
实施例2
本实施例与实施例1的区别在于，将实施例1的步骤(4)中加入的金属Mg使得Mg相对于SMPU的质量百分比为4％，即，SMPU与Mg的质量比为100:4，其余工艺与实施例1的相同。本实施例制备获得骨修复支架样品S-2。
实施例3
本实施例与实施例1的区别在于，将实施例1的步骤(4)中加入的金属Mg使得Mg相对于SMPU的质量百分比为6％，即，SMPU与Mg的质量比为100:6，其余工艺与实施例1的相同。本实施例制备获得骨修复支架样品S-3。
实施例4
本实施例与实施例1的区别在于，将实施例1的步骤(4)中加入的金属Mg使得Mg相对于SMPU的质量百分比为8％，即，SMPU与Mg的质量比为100:8，其余工艺与实施例1的相同。本实施例制备获得骨修复支架样品S-4。
对比例
对比例与实施例1-4的区别在于，步骤(4)中不加入Mg，即Mg含量为0％，其余工艺与实施例1-4的相同。对比例制备获得骨修复支架样品S-0。
对比例和实施例1-4所使用的原料及其用量见下表：
Figure PCTCN2020136555-appb-000004
实施例1-4与对比例获得的骨修复支架的光热效应测试参见图1。其中，照射的近红外光的波长为808nm，功率密度为1w/cm 2。对比例的样品基本没有温度上升，实施例1-4的样品的温度均随着照射时间的增加而增大，实施例4的样品的温度上升相对最快，上升幅度也最大，光热效应最好。
实施例1-4与对比例获得的骨修复支架的应力-应变测试参见图2。其中，实施例4的样品抗压强度最大，而实施例2与实施例3的样品抗压强度相差不大。
实施例1-4与对比例获得的骨修复支架的在近红外光(波长为808nm，功率密度为1w/cm 2)照射下的形状记忆性能参见图3。对比例的固定率较高，但是几乎没有回复。实施例1-4的样品中，随着Mg含量的增加，样品的形状固定率在增加，但是回复率在降低。
实施例1-4与对比例获得的骨修复支架的细胞相容性对比参见图4。相比于 空白组细胞(无样品)以及对比例的活死染色情况，实施例1-4中的细胞具有更明显的活细胞数量，活细胞数量越多代表着样品细胞相容越好，并且对比例和实施例中的死细胞数量(中间一列图像)也非常少，表明实施例1-4的样品具有较好的细胞相容性。
综合以上的测试结果，实施例2中样品具有性能最平衡的光热效应、机械强度、形状记忆性能以及生物相容性，因此，在本发明实施例提供的复合骨修复支架中，SMPU与Mg的质量比优选为100:(3～5)，最为优选的是100:4。
本发明提供的骨修复支架，通过添加金属镁提高了骨修复支架的机械强度且具有良好的促骨再生的性能，并且可以利用镁具有的光热效应为骨修复支架提供实现远程刺激-响应调控的可行性；本发明的骨修复支架的制备方法具有工艺流程简单、易于产业化实施的优点，具有广泛的适用性。
以上所述仅是本申请的具体实施方式，应当指出，对于本技术领域的普通技术人员来说，在不脱离本申请原理的前提下，还可以做出若干改进和润饰，这些改进和润饰也应视为本申请的保护范围。

Claims (20)

  1. 一种骨修复支架，其中，所述骨修复支架的材料包括形状记忆聚氨酯和金属镁，所述形状记忆聚氨酯与所述金属镁的质量比为100:(1～10)。
  2. 根据权利要求1所述的骨修复支架，其中，所述形状记忆聚氨酯与所述金属镁的质量比为100:(3～5)。
  3. 根据权利要求2所述的骨修复支架，其中，所述形状记忆聚氨酯与所述金属镁的质量比为100:4。
  4. 根据权利要求1所述的骨修复支架，其中，所述金属镁的粒径为40μm～100μm。
  5. 根据权利要求4所述的骨修复支架，其中，所述金属镁的粒径为50μm～80μm。
  6. 根据权利要求1所述的骨修复支架，其中，以所述形状记忆聚氨酯的质量为100％计，所述形状记忆聚氨酯由如下的原料组分反应形成：23.0％～25.0％的二苯基甲烷二异氰酸酯、7.0％～8.0％的扩链剂以及67.0％～70.0％的聚己内酯二醇。
  7. 根据权利要求6所述的骨修复支架，其中，所述二苯基甲烷二异氰酸酯中所含有的异氰酸酯基团与参加反应的所有所述原料的羟基的比值为(1.0～1.2):1。
  8. 根据权利要求7所述的骨修复支架，其中，所述二苯基甲烷二异氰酸酯中所含有的异氰酸酯基团与参加反应的所有所述原料的羟基的比值为1:1。
  9. 根据权利要求6所述的骨修复支架，其中，所述扩链剂选自1,4-丁二醇、1,6-己二醇和乙二醇中的任意一种。
  10. 根据权利要求6所述的骨修复支架，其中，所述聚己内酯二醇的数均分子量为3000～8000。
  11. 一种骨修复支架的制备方法，其中，包括：
    将形状记忆聚氨酯溶解于有机溶剂中，再加入金属镁，搅拌混合获得打印前驱液；
    将所述打印前驱液通过3D打印工艺获得支架胚体；
    将所述支架胚体进行冷冻干燥，获得所述骨修复支架。
  12. 根据权利要求11所述的骨修复支架的制备方法，其中，所述3D打印工艺中打印速度为0.1mm/s～1.5mm/s，打印喷头的温度为10℃～20℃；所述冷冻干燥的温度为-80℃～-70℃，时间为48h～72h。
  13. 根据权利要求11所述的骨修复支架的制备方法，其中，所述形状记忆聚氨酯与所述金属镁的质量比为100:(1～10)。
  14. 根据权利要求11所述的骨修复支架的制备方法，其中，所述形状记忆聚氨酯与所述金属镁的质量比为100:(3～5)。
  15. 根据权利要求11所述的骨修复支架的制备方法，其中，所述金属镁的粒径为40μm～100μm。
  16. 根据权利要求15所述的骨修复支架的制备方法，其中，所述金属镁的粒径为50μm～80μm。
  17. 根据权利要求11所述的骨修复支架的制备方法，其中，以所述形状记忆聚氨酯的质量为100％计，所述形状记忆聚氨酯由如下的原料组分反应形成：23.0％～25.0％的二苯基甲烷二异氰酸酯、7.0％～8.0％的扩链剂以及67.0％～70.0％的聚己内酯二醇。
  18. 根据权利要求17所述的骨修复支架的制备方法，其中，所述二苯基甲烷二异氰酸酯中所含有的异氰酸酯基团与参加反应的所有所述原料的羟基的比值为(1.0～1.2):1。
  19. 根据权利要求17所述的骨修复支架的制备方法，其中，所述扩链剂选自1,4-丁二醇、1,6-己二醇和乙二醇中的任意一种。
  20. 根据权利要求17所述的骨修复支架的制备方法，其中，所述聚己内酯二醇的数均分子量为3000～8000。
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