CN111908798A - Sr/Mg/Zn/Cu doped silicon-based sol-gel bioactive glass powder and preparation method and application thereof - Google Patents

Sr/Mg/Zn/Cu doped silicon-based sol-gel bioactive glass powder and preparation method and application thereof Download PDF

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CN111908798A
CN111908798A CN202010837825.4A CN202010837825A CN111908798A CN 111908798 A CN111908798 A CN 111908798A CN 202010837825 A CN202010837825 A CN 202010837825A CN 111908798 A CN111908798 A CN 111908798A
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陈晓峰
欧阳鹿
王刚
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Foshan Jinlan Biotechnology Co ltd
South China University of Technology SCUT
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Abstract

The invention discloses Sr/Mg/Zn/Cu doped silicon-based sol-gel bioactive glass powderAnd a preparation method and application thereof. The preparation method comprises the following steps: (1) mixing the catalyst with water, adding ethyl orthosilicate, triethyl phosphate, calcium nitrate tetrahydrate and Sr2+、Mg2+、Zn2+And Cu2+Stirring and hydrolyzing one or more ionic salts to obtain ion-doped silicon-based bioactive glass sol; (2) standing, aging and drying the obtained ion-doped silicon-based bioactive glass sol to obtain an ion-doped silicon-based sol-gel bioactive glass xerogel precursor; (3) and carrying out heat treatment on the obtained bioactive glass xerogel precursor to obtain bioactive glass powder. The bioactive glass powder can meet different clinical special repair effects, and has wide application prospects in bone tissue repair, oral repair, skin repair and body immune regulation.

Description

一种掺杂Sr/Mg/Zn/Cu的硅基溶胶-凝胶生物活性玻璃粉体及 其制备方法与应用A silicon-based sol-gel bioactive glass powder doped with Sr/Mg/Zn/Cu and Its preparation method and application

技术领域technical field

本发明属于生物活性玻璃领域,具体涉及一种掺杂Sr/Mg/Zn/Cu的硅基溶胶-凝胶生物活性玻璃粉体及其制备方法与应用。The invention belongs to the field of bioactive glass, and in particular relates to a silicon-based sol-gel bioactive glass powder doped with Sr/Mg/Zn/Cu and a preparation method and application thereof.

背景技术Background technique

生物活性玻璃(Bioactive Glass,BG)是1969年由美国科学家Larry Hench课题组首次研发,它具有良好的生物相容性和促进成骨细胞增殖分化能力以及基因激活作用,被认为是一种具有优异组织修复性能的生物材料。而近期的研究表明,生物活性玻璃不仅能够促进骨、牙齿等硬组织的修复,也与软组织能够很好地结合,促进皮肤等软组织的再生修复。Bioactive Glass (BG) was first developed by the American scientist Larry Hench's research group in 1969. It has good biocompatibility, the ability to promote osteoblast proliferation and differentiation, and gene activation. Biomaterials with tissue repair properties. Recent studies have shown that bioactive glass can not only promote the repair of hard tissues such as bones and teeth, but also integrate well with soft tissues to promote the regeneration and repair of soft tissues such as skin.

溶胶-凝胶法是一种制备纳米材料的常用技术。溶胶-凝胶技术制备生物活性玻璃的反应是在室温下完成,煅烧温度较低,制备条件易于达到且可精细均匀调控其成分变化,对其进行分子层级上的调整,以控制降解速率,达到生物活性与细胞活性的统一。溶胶-凝胶法制备生物活性玻璃具有微纳米多孔结构及较大的比表面积,以利于材料的离子溶出,使材料与外界环境发生离子交换、达到材料的可控降解,实现快速生物矿化,有利于促进组织的再生修复。植入体内后,材料凭借自身的表面积和介孔孔隙,在表面形成碳酸羟基磷灰石,与骨组织产生化学结合,并吸附相关的蛋白质合成胶原纤维,促进骨祖细胞的粘附、分化和骨细胞的细胞外基质的代谢。另一方面,随材料降解过程,来自生物活性玻璃中的硅、钙、磷等离子溶解产物离子激活成骨相关基因的表达,激活成骨相关的信号通路,调控成骨相关细胞的黏附、增殖和分化,在分子水平调控骨缺损修复过程,促进骨组织的再生。相比于小分子药物负载、RNA接枝等改性方法比较,在玻璃网络中引入具有特定修复效果的微量离子,只需在合成制备中加入微量离子复合物,简化制备工艺,同时离子在玻璃网络结构中较稳定,受温湿度等影响较小,引入的离子离子能随着生物活性玻璃的降解而缓慢释放,被人体吸收利用,参与新组织的形成,发挥其生物学作用。The sol-gel method is a common technique for preparing nanomaterials. The reaction of sol-gel technology to prepare bioactive glass is completed at room temperature, the calcination temperature is low, the preparation conditions are easy to achieve, and its composition changes can be finely and uniformly regulated, and it can be adjusted at the molecular level to control the degradation rate. The unity of biological activity and cellular activity. The bioactive glass prepared by the sol-gel method has a micro-nano porous structure and a large specific surface area, which is conducive to the ion dissolution of the material, enables the material to exchange ions with the external environment, achieves controllable degradation of the material, and achieves rapid biomineralization. Helps to promote tissue regeneration and repair. After being implanted into the body, the material forms hydroxycarbonated apatite on the surface by virtue of its own surface area and mesoporous pores, which chemically binds with bone tissue, and adsorbs related proteins to synthesize collagen fibers, which promotes the adhesion, differentiation and development of osteoprogenitor cells. Metabolism of the extracellular matrix of osteocytes. On the other hand, along with the material degradation process, ions from the bioactive glass such as silicon, calcium, phosphorus and other ionized lysates activate the expression of osteogenesis-related genes, activate osteogenesis-related signaling pathways, and regulate the adhesion, proliferation and proliferation of osteogenesis-related cells. Differentiation, regulate the process of bone defect repair at the molecular level, and promote the regeneration of bone tissue. Compared with the modification methods such as small molecule drug loading and RNA grafting, the introduction of trace ions with specific repair effects into the glass network requires only trace ion complexes to be added in the synthesis preparation, which simplifies the preparation process. The network structure is relatively stable and is less affected by temperature and humidity. The introduced ions can be slowly released as the bioactive glass degrades, absorbed and utilized by the human body, participating in the formation of new tissues and exerting its biological effects.

锶(strontium,Sr)是人体必需的微量元素,在体内参与维持正常机能,具有防龋和增强骨强度的作用。低剂量的Sr能够有效地治疗骨质疏松症,目前药物雷尼酸锶在治疗骨质疏松症上起到良好的效果。研究发现,一定量的Sr能够促进成骨细胞增殖、分化,同时通过抑制破骨细胞形成防止骨组织再吸收,从而促进新骨的长成。Strontium (Strontium, Sr) is an essential trace element for the human body, which is involved in maintaining normal functions in the body, and has the effect of preventing caries and enhancing bone strength. Low-dose Sr can effectively treat osteoporosis, and the current drug strontium ranelate has a good effect on the treatment of osteoporosis. Studies have found that a certain amount of Sr can promote the proliferation and differentiation of osteoblasts, and at the same time prevent the resorption of bone tissue by inhibiting the formation of osteoclasts, thereby promoting the growth of new bone.

镁(magnesium,Mg)元素是骨代谢过程的重要元素,影响成骨细胞和破骨细胞细胞活性以及骨骼生长,特别是在成骨的早期阶段中刺激成骨细胞分化。Mg缺乏会影响整个骨代谢过程,导致骨生长受限、成骨细胞活性降低、骨质疏松和脆骨病等。Magnesium (Mg) is an important element in bone metabolism, affecting osteoblast and osteoclast cell activity and bone growth, especially stimulating osteoblast differentiation in the early stages of osteogenesis. Mg deficiency affects the entire process of bone metabolism, resulting in restricted bone growth, decreased osteoblast activity, osteoporosis, and brittle bone disease.

锌(zinc,Zn)元素对维持人体各种功能具有重要作用,它参与DNA及蛋白的合成,并通过蛋白合成刺激骨形成,能够刺激成骨类细胞释放碱性磷酸酶,增强成骨相关基因的表达以及胶原合成达到协同成骨的作用。Zn对骨骼发育有直接影响,胎儿及幼儿期缺Zn可引起骨骼发育异常。研究显示,Zn能促进骨形成,加速骨蛋白合成,提高骨中Ca的浓度及碱性磷酸酶的含量,增加骨组织中的胶原量,适量的Zn还能促进成骨细胞的增殖和分化,并有效地抑制破骨细胞的骨吸收作用。Zinc (Zn) element plays an important role in maintaining various functions of the human body. It participates in the synthesis of DNA and protein, and stimulates bone formation through protein synthesis. It can stimulate osteoblasts to release alkaline phosphatase and enhance osteogenesis-related genes. expression and collagen synthesis to achieve synergistic osteogenesis. Zn has a direct effect on skeletal development, and Zn deficiency in fetuses and early childhood can cause abnormal skeletal development. Studies have shown that Zn can promote bone formation, accelerate bone protein synthesis, increase the concentration of Ca in bone and the content of alkaline phosphatase, and increase the amount of collagen in bone tissue. An appropriate amount of Zn can also promote the proliferation and differentiation of osteoblasts. And effectively inhibit the bone resorption of osteoclasts.

铜(copper,Cu)元素能够诱导人骨髓间充质细胞释放缺氧诱导因子和上调血管内皮生长因子,有助于骨缺损区域再血管化,而新血管生成有利于骨组织的修复和再生。研究表明低浓度的铜和硅能够协同刺激再血管化,新血管生成有利于骨组织的修复和再生。Copper (Cu) element can induce human bone marrow mesenchymal cells to release hypoxia-inducible factor and up-regulate vascular endothelial growth factor, which contributes to the revascularization of bone defect areas, and the formation of new blood vessels is conducive to the repair and regeneration of bone tissue. Studies have shown that low concentrations of copper and silicon can synergistically stimulate revascularization, and the formation of new blood vessels is beneficial to the repair and regeneration of bone tissue.

因此本发明将组分的多元性、离子的特殊临床修复效果性与溶胶-凝胶生物活性玻璃有机结合,解决离子掺杂生物活性玻璃组分不均,矿化效果较差,体外羟基磷灰石形成能力不理想的问题,得到具有不同治疗效果的掺杂Sr/Mg/Zn/Cu组分的硅基溶胶-凝胶生物活性玻璃粉体。Therefore, the present invention organically combines the diversity of components and the special clinical repairing effect of ions with the sol-gel bioactive glass, so as to solve the problem of uneven components of the ion-doped bioactive glass, poor mineralization effect, and in vitro hydroxyapatite Due to the problem of unsatisfactory stone formation ability, silicon-based sol-gel bioactive glass powders doped with Sr/Mg/Zn/Cu components with different therapeutic effects were obtained.

发明内容SUMMARY OF THE INVENTION

本发明的目的在于针对现有技术的不足,提供一种掺杂Sr/Mg/Zn/Cu的硅基溶胶-凝胶生物活性玻璃粉体及其制备方法与应用,该制备方法可得到组分均匀、具有纳米孔隙及高比表面积、优异羟基磷灰石形成能力、含有特定治疗离子的生物活性组织修复材料,且制备方法简单方便且转化效率高,对于溶胶-凝胶法生物活性玻璃相关产品开发具有重要意义。The purpose of the present invention is to provide a silicon-based sol-gel bioactive glass powder doped with Sr/Mg/Zn/Cu and its preparation method and application in view of the deficiencies of the prior art, and the preparation method can obtain components Uniform, nano-porous and high specific surface area, excellent hydroxyapatite forming ability, bioactive tissue repair material containing specific therapeutic ions, and simple and convenient preparation method and high conversion efficiency, for sol-gel method bioactive glass related products Development is important.

为达到上述目的,本发明的技术方案如下。In order to achieve the above objects, the technical solutions of the present invention are as follows.

一种掺杂Sr/Mg/Zn/Cu的硅基溶胶-凝胶生物活性玻璃粉体的制备方法,包括以下步骤:A preparation method of silicon-based sol-gel bioactive glass powder doped with Sr/Mg/Zn/Cu, comprising the following steps:

(1)将催化剂与水配制成混合溶液,搅拌至完全溶解,得到催化剂溶液,然后依次加入正硅酸乙酯、磷酸三乙酯、四水硝酸钙以及离子盐,充分搅拌水解得到离子掺杂的硅基生物活性玻璃溶胶;所述离子盐为含有Sr2+、Mg2+、Zn2+和Cu2+中的一种或多种的无机盐或相关醇盐;(1) The catalyst and water are prepared into a mixed solution, stirred until completely dissolved to obtain a catalyst solution, and then ethyl orthosilicate, triethyl phosphate, calcium nitrate tetrahydrate and ionic salt are added successively, and the ionic doping is obtained by fully stirring and hydrolyzing The silicon-based bioactive glass sol; the ionic salt is an inorganic salt or related alkoxide containing one or more of Sr 2+ , Mg 2+ , Zn 2+ and Cu 2+ ;

(2)将步骤(1)所得离子掺杂的硅基生物活性玻璃溶胶静置陈化,使水解缩聚反应充分进行,形成湿凝胶,后置于干燥箱中梯度干燥,得到离子掺杂的硅基溶胶-凝胶生物活性玻璃干凝胶前驱体;(2) The ion-doped silicon-based bioactive glass sol obtained in step (1) is allowed to stand and age, so that the hydrolysis and polycondensation reaction can be fully carried out to form a wet gel, which is then placed in a drying oven for gradient drying to obtain the ion-doped glass sol. Silica-based sol-gel bioactive glass xerogel precursor;

(3)将步骤(2)所得生物活性玻璃干凝胶前驱体置于程序控制高温电阻炉中进行热处理,经湿法研磨、筛分得到具有纳米孔隙的掺杂Sr/Mg/Zn/Cu的硅基溶胶-凝胶生物活性玻璃粉体。(3) placing the bioactive glass xerogel precursor obtained in step (2) in a program-controlled high-temperature resistance furnace for heat treatment, wet grinding and sieving to obtain a doped Sr/Mg/Zn/Cu with nanopores Silica-based sol-gel bioactive glass powder.

优选的,步骤(1)中所述催化剂:水:正硅酸乙酯的摩尔比为(2~8):1000:(70~140)。Preferably, the molar ratio of catalyst: water: ethyl orthosilicate in step (1) is (2-8): 1000: (70-140).

优选的,步骤(1)所述催化剂为盐酸或者氨水。Preferably, the catalyst in step (1) is hydrochloric acid or ammonia water.

优选的,步骤(1)中所述正硅酸乙酯、磷酸三乙酯、四水硝酸钙、离子盐的摩尔比为正硅酸乙酯:磷酸三乙酯;四水硝酸钙:离子盐=(50~80):(14~4):(5~40):(0~15),按照所述正硅酸乙酯、磷酸三乙酯、四水硝酸钙、离子无机盐摩尔比,最终得到的具有纳米孔隙的掺杂Sr/Mg/Zn/Cu的硅基溶胶-凝胶生物活性玻璃粉体中二氧化硅、五氧化二磷、氧化钙及无机盐的摩尔比=(40~70):(36~16):(1~8):(0~15)。Preferably, the molar ratio of ethyl orthosilicate, triethyl phosphate, calcium nitrate tetrahydrate and ionic salt in step (1) is ethyl orthosilicate: triethyl phosphate; calcium nitrate tetrahydrate: ionic salt =(50~80):(14~4):(5~40):(0~15), according to the molar ratio of ethyl orthosilicate, triethyl phosphate, calcium nitrate tetrahydrate and ionic inorganic salt, The molar ratio of silica, phosphorus pentoxide, calcium oxide and inorganic salt in the finally obtained silicon-based sol-gel bioactive glass powder doped with Sr/Mg/Zn/Cu with nanopores=(40~ 70): (36-16): (1-8): (0-15).

优选的,步骤(1)中所述离子无机盐为氯化盐类及其水合物或硝酸盐类及其水合物或及其相关醇盐,可选自硝酸锌、氯化铜、硝酸镁、硝酸银、硝酸锶、硝酸钻、硝酸铁、硝酸铜、氯化锶、甲醇镁、醋酸锌等,包括但不限于所述物质。Preferably, the ionic inorganic salts in step (1) are chloride salts and their hydrates or nitrates and their hydrates or their related alkoxides, which can be selected from zinc nitrate, copper chloride, magnesium nitrate, Silver nitrate, strontium nitrate, cobalt nitrate, ferric nitrate, copper nitrate, strontium chloride, magnesium methoxide, zinc acetate, etc., including but not limited to the aforementioned substances.

优选的,步骤(1)所述水解搅拌时间为2~8小时。Preferably, the hydrolysis and stirring time in step (1) is 2 to 8 hours.

优选的,步骤(2)所述的陈化温度为15-35℃,陈化时间为2~5天,溶胶静置陈化发生水解缩聚反应得到湿凝胶。Preferably, the aging temperature in step (2) is 15-35° C., the aging time is 2-5 days, and the sol is left to stand for aging to undergo hydrolysis and polycondensation reaction to obtain wet gel.

优选的,步骤(2)所述的设定干燥箱梯度温度为50~75℃及100~140℃,干燥时间2~9 天,得到均匀的大颗粒状干凝胶前驱体。Preferably, in step (2), the gradient temperature of the drying oven is set to be 50-75°C and 100-140°C, and the drying time is 2-9 days to obtain a uniform large granular xerogel precursor.

优选的,步骤(3)所述的高温烧结温度为550~850℃,烧结的保温时间为1-4小时。Preferably, the high-temperature sintering temperature in step (3) is 550-850° C., and the sintering holding time is 1-4 hours.

优选的,步骤(3)所述的湿法球磨,球磨罐为聚四氟乙烯材质,球磨时间为3~10小时,球磨介质为无水乙醇,研磨体为石英圆球,球磨物料的质量比为生物活性玻璃粉体:研磨体:球磨介质=(1~5):(2~10):(1~2);球磨过后干燥去除球磨介质、筛分得到颗粒均匀、具有纳米孔隙的掺杂Sr/Mg/Zn/Cu的硅基溶胶-凝胶生物活性玻璃粉体。Preferably, in the wet ball milling described in step (3), the ball milling tank is made of polytetrafluoroethylene, the ball milling time is 3 to 10 hours, the ball milling medium is anhydrous ethanol, the grinding body is a quartz ball, and the mass ratio of the ball milling material is It is a bioactive glass powder: grinding body: ball milling medium = (1~5): (2~10): (1~2); after ball milling, the ball milling medium is removed by drying and sieving to obtain a dopant with uniform particles and nano pores Silica-based sol-gel bioactive glass powders of Sr/Mg/Zn/Cu.

由以上所述的制备方法得到的一种掺杂Sr/Mg/Zn/Cu的硅基溶胶-凝胶生物活性玻璃粉体,该掺杂Sr/Mg/Zn/Cu的硅基溶胶-凝胶生物活性玻璃粉体颗粒粒径分布为10~900μm、比表面积在100~300m2/g。A silicon-based sol-gel bioactive glass powder doped with Sr/Mg/Zn/Cu obtained by the above-mentioned preparation method, the silicon-based sol-gel doped with Sr/Mg/Zn/Cu The particle size distribution of the bioactive glass powder is 10-900 μm, and the specific surface area is 100-300 m 2 /g.

以上所述的掺杂Sr/Mg/Zn/Cu的硅基溶胶-凝胶生物活性玻璃粉体能稳定释放生物活性玻璃本体的硅、钙、磷等离子溶解产物和其掺杂的Sr2+和或Mg2+和或Zn2+和或Cu2+等离子,良好的体外羟基磷灰石形成能力并促进细胞生长,离子满足不同临床特殊修复效果,在骨组织修复、口腔修复、皮肤修复及机体免疫调控方面具有广阔的应用前景。The silicon-based sol-gel bioactive glass powder doped with Sr/Mg/Zn/Cu described above can stably release the silicon, calcium, phosphorus plasma dissolved products of the bioactive glass body and its doped Sr 2+ and Or Mg 2+ and or Zn 2+ and or Cu 2+ plasma, good in vitro hydroxyapatite formation ability and promote cell growth, ions meet different clinical special repair effects, in bone tissue repair, oral repair, skin repair and body repair It has broad application prospects in immune regulation.

本发明采用新一代溶胶-凝胶法制备掺杂Sr/Mg/Zn/Cu的硅基溶胶-凝胶生物活性玻璃粉体,在生物活性玻璃的制备过程中引入特定治疗元素锶/镁/锌/铜,实现优异的组织修复效果;掺杂Sr/Mg/Zn/Cu后不改变生物活性玻璃的微观结构及生物相容性。The invention adopts a new generation sol-gel method to prepare silicon-based sol-gel bioactive glass powder doped with Sr/Mg/Zn/Cu, and introduces specific therapeutic elements strontium/magnesium/zinc in the preparation process of the bioactive glass /Cu, to achieve excellent tissue repair effect; the microstructure and biocompatibility of bioactive glass are not changed after doping with Sr/Mg/Zn/Cu.

与现有技术相比,本发明具有以下优势:Compared with the prior art, the present invention has the following advantages:

本发明选取生物活性玻璃和治疗性元素锶/镁/锌/铜两种材料进行复合,离子以无机盐的形式加入生物活性玻璃的合成中。掺杂Sr/Mg/Zn/Cu的硅基溶胶-凝胶生物活性玻璃粉体组分均匀、体外羟基磷灰石形成能力优异、稳定释放离子用于特定组织修复效果;元素适量掺杂,体外矿化效果好,并不改变材料的生物活性;合成材料来源广泛,价格低廉;制备方法简单方便且转化效率高,对于溶胶-凝胶法生物活性玻璃相关产品开发具有重要意义。In the present invention, two materials of bioactive glass and therapeutic elements strontium/magnesium/zinc/copper are selected for compounding, and ions are added to the synthesis of bioactive glass in the form of inorganic salts. The silicon-based sol-gel bioactive glass powder doped with Sr/Mg/Zn/Cu has uniform composition, excellent hydroxyapatite formation ability in vitro, and stable release of ions for specific tissue repair effects; appropriate amount of element doping, in vitro The mineralization effect is good, and the biological activity of the material is not changed; the synthetic material has a wide range of sources and low price; the preparation method is simple and convenient, and the conversion efficiency is high, which is of great significance for the development of sol-gel bioactive glass related products.

附图说明Description of drawings

图1为本发明掺杂Sr/Mg/Zn/Cu的硅基溶胶-凝胶生物活性玻璃粉体的制备工艺流程图。FIG. 1 is a flow chart of the preparation process of the silicon-based sol-gel bioactive glass powder doped with Sr/Mg/Zn/Cu according to the present invention.

图2为实施例1制得的掺杂Sr/Mg/Zn/Cu的硅基溶胶-凝胶生物活性玻璃粉体放大倍数为 101倍的扫描电镜图。2 is a scanning electron microscope image of the silicon-based sol-gel bioactive glass powder doped with Sr/Mg/Zn/Cu prepared in Example 1 at a magnification of 101 times.

图3为实施例1制得的掺杂Sr/Mg/Zn/Cu的硅基溶胶-凝胶生物活性玻璃粉体放大倍数为 10万倍的扫描电镜图。3 is a scanning electron microscope image of the silicon-based sol-gel bioactive glass powder doped with Sr/Mg/Zn/Cu prepared in Example 1 at a magnification of 100,000 times.

图4为实施例2制得的掺杂Zn/Cu的硅基溶胶-凝胶生物活性玻璃粉体的体外矿化性能图。4 is a graph showing the in vitro mineralization properties of the Zn/Cu-doped silicon-based sol-gel bioactive glass powder prepared in Example 2.

图5为实施例3制得的掺杂Mg/Zn/Cu的硅基溶胶-凝胶生物活性玻璃粉体的表面孔结构分析图。5 is an analysis diagram of the surface pore structure of the silicon-based sol-gel bioactive glass powder doped with Mg/Zn/Cu prepared in Example 3. FIG.

图6为实施例4制得的掺杂Sr的硅基溶胶-凝胶生物活性玻璃粉体的X射线能谱分析 (EDS)图。6 is an X-ray energy dispersive spectroscopy (EDS) image of the Sr-doped silicon-based sol-gel bioactive glass powder prepared in Example 4.

图7为实施例4制得的掺杂Sr的硅基溶胶-凝胶生物活性玻璃粉体的X射线光电子能谱分析(XPS)图。FIG. 7 is an X-ray photoelectron spectroscopy (XPS) image of the Sr-doped silicon-based sol-gel bioactive glass powder prepared in Example 4. FIG.

图8为实施例4制得的掺杂Sr的硅基溶胶-凝胶生物活性玻璃粉体的细胞增殖活力分析结果。FIG. 8 is the analysis result of cell proliferation activity of the Sr-doped silicon-based sol-gel bioactive glass powder prepared in Example 4. FIG.

具体实施方式Detailed ways

下面结合实施例及附图对本发明作进一步详细的描述,但本发明的实施方式不限于此。The present invention will be described in further detail below with reference to the embodiments and the accompanying drawings, but the embodiments of the present invention are not limited thereto.

以下各实施例的掺杂Sr/Mg/Zn/Cu的硅基溶胶-凝胶生物活性玻璃粉体的制备工艺流程图如图1所示。The flow chart of the preparation process of the silicon-based sol-gel bioactive glass powder doped with Sr/Mg/Zn/Cu in the following embodiments is shown in FIG. 1 .

实施例1Example 1

一种掺杂Sr/Mg/Zn/Cu的硅基溶胶-凝胶生物活性玻璃粉体,其制备方法如下:A silicon-based sol-gel bioactive glass powder doped with Sr/Mg/Zn/Cu, the preparation method thereof is as follows:

(1)含Sr/Mg/Zn/Cu的生物活性玻璃溶胶的制备步骤:(1) Preparation steps of bioactive glass sol containing Sr/Mg/Zn/Cu:

将26ml浓度为2mol/L的盐酸与78mL去离子水配制成混合溶液,搅拌10min至完全溶解,得到催化剂溶液,后依次加入110.1g正硅酸乙酯、10.9g磷酸三乙酯、58.6g四水硝酸钙和5.2g硝酸锶、3g硝酸镁、4.4g硝酸铜、4.4g硝酸锌,充分搅拌4h水解得到透明均一的含3Sr-1Mg-1Zn-1Cu(mol%)的生物活性玻璃溶胶;26ml of hydrochloric acid with a concentration of 2mol/L and 78ml of deionized water were prepared into a mixed solution, stirred for 10min until completely dissolved, to obtain a catalyst solution, and then 110.1g of ethyl orthosilicate, 10.9g of triethyl phosphate, 58.6g of tetraethyl phosphate were added in sequence. Water calcium nitrate, 5.2g strontium nitrate, 3g magnesium nitrate, 4.4g copper nitrate, 4.4g zinc nitrate, fully stirred for 4h and hydrolyzed to obtain a transparent and uniform bioactive glass sol containing 3Sr-1Mg-1Zn-1Cu (mol%);

(2)含Sr/Mg/Zn/Cu的生物活性玻璃干凝胶前驱体的制备步骤:(2) Preparation steps of bioactive glass xerogel precursor containing Sr/Mg/Zn/Cu:

将步骤(1)所得生物活性玻璃溶胶静置在35℃陈化2天,使水解缩聚反应充分进行,形成湿凝胶,后置于干燥箱中梯度干燥,50℃干燥4天和135℃干燥3天,得到掺Sr/Mg/Zn/Cu 生物活性玻璃干凝胶前驱体;The bioactive glass sol obtained in step (1) was allowed to stand at 35°C for 2 days, so that the hydrolysis and polycondensation reaction was fully carried out to form a wet gel, which was then placed in a drying oven for gradient drying, dried at 50°C for 4 days and dried at 135°C. After 3 days, the precursor of Sr/Mg/Zn/Cu bioactive glass xerogel was obtained;

(3)将掺Sr/Mg/Zn/Cu的生物活性玻璃干凝胶前驱体进行烧结处理:(3) Sintering the Sr/Mg/Zn/Cu-doped bioactive glass xerogel precursor:

将步骤(2)所得生物活性玻璃干凝胶前驱体置于高温电阻炉中进行600℃热处理烧结4h,经湿法研磨3h、筛分得到所述具有纳米孔隙结构的掺杂Sr/Mg/Zn/Cu的硅基溶胶-凝胶生物活性玻璃粉体。The bioactive glass xerogel precursor obtained in step (2) is placed in a high-temperature resistance furnace for heat treatment and sintering at 600° C. for 4 hours, followed by wet grinding for 3 hours and sieving to obtain the doped Sr/Mg/Zn with nano-pore structure. /Cu silica-based sol-gel bioactive glass powder.

本实施例的掺杂Sr/Mg/Zn/Cu的硅基溶胶-凝胶生物活性玻璃粉体的制备方法工艺流程示意图如图1所示,图2和图3为本实施例制得的掺杂Sr/Mg/Zn/Cu的硅基溶胶-凝胶生物活性玻璃粉体放大倍数为101倍和10万倍的扫描电镜图,由图2和图3可见本实施例制备的掺杂 Sr/Mg/Zn/Cu的硅基溶胶-凝胶生物活性玻璃粉体由大量均一纳米级微球组成,颗粒间存在微小纳米孔隙,掺杂离子不改变生物活性玻璃表面形貌结构。根据激光粒度仪及BET多点法计算出本实施例的掺杂Sr/Mg/Zn/Cu的硅基溶胶-凝胶生物活性玻璃粉体粒径分布为10~810μm、比表面积为204.9m2/g。The process flow diagram of the preparation method of the Sr/Mg/Zn/Cu doped silicon-based sol-gel bioactive glass powder in this embodiment is shown in FIG. 1 , and FIG. 2 and FIG. 3 The SEM images of the doped Sr/Mg/Zn/Cu silicon-based sol-gel bioactive glass powder with magnifications of 101 times and 100,000 times can be seen from Figures 2 and 3 that the doped Sr/ The silicon-based sol-gel bioactive glass powder of Mg/Zn/Cu is composed of a large number of uniform nano-scale microspheres, and there are tiny nano-pores between the particles. Doping ions does not change the surface morphology of the bioactive glass. According to the laser particle size analyzer and BET multi-point method, the particle size distribution of the silicon-based sol-gel bioactive glass powder doped with Sr/Mg/Zn/Cu in this embodiment is 10-810 μm, and the specific surface area is 204.9 m 2 /g.

实施例2Example 2

一种掺杂Zn/Cu的硅基溶胶-凝胶生物活性玻璃粉体,其制备方法如下:A silicon-based sol-gel bioactive glass powder doped with Zn/Cu, the preparation method thereof is as follows:

(1)含Zn/Cu的生物活性玻璃溶胶的制备步骤:(1) Preparation steps of bioactive glass sol containing Zn/Cu:

将26ml浓度为2mol/L的盐酸与78mL去离子水配制成混合溶液,搅拌10min至完全溶解,得到催化剂溶液,后依次加入110.1g正硅酸乙酯、10.9g磷酸三乙酯、58.6g四水硝酸钙和13.2g硝酸铜、13.2g硝酸锌,充分搅拌4h水解得到透明均一的含3Zn-3Cu(mol%) 的生物活性玻璃溶胶;26ml of hydrochloric acid with a concentration of 2mol/L and 78ml of deionized water were prepared into a mixed solution, stirred for 10min until completely dissolved, to obtain a catalyst solution, and then 110.1g of ethyl orthosilicate, 10.9g of triethyl phosphate, 58.6g of tetraethyl phosphate were added in sequence. Water calcium nitrate, 13.2g copper nitrate, 13.2g zinc nitrate, fully stirred for 4h and hydrolyzed to obtain a transparent and uniform bioactive glass sol containing 3Zn-3Cu (mol%);

(2)含Zn/Cu的生物活性玻璃干凝胶前驱体的制备步骤:(2) Preparation steps of Zn/Cu-containing bioactive glass xerogel precursor:

将步骤(1)所得生物活性玻璃溶胶静置在25℃陈化3天,使水解缩聚反应充分进行,形成湿凝胶,后置于干燥箱中梯度干燥,60℃干燥3天和140℃干燥2天,得到掺Zn-Cu生物活性玻璃干凝胶前驱体;The bioactive glass sol obtained in step (1) was left to age at 25°C for 3 days, so that the hydrolysis and polycondensation reaction was fully carried out to form a wet gel, which was then placed in a drying oven for gradient drying, dried at 60°C for 3 days and dried at 140°C. After 2 days, the Zn-Cu bioactive glass xerogel precursor was obtained;

(3)将掺Zn/Cu的生物活性玻璃干凝胶前驱体进行烧结处理:(3) Sintering the Zn/Cu-doped bioactive glass xerogel precursor:

将步骤(2)所得生物活性玻璃干凝胶前驱体置于高温电阻炉中进行600℃热处理烧结4h,经湿法研磨3h、筛分得到所述具有纳米孔隙结构的掺杂Zn/Cu的硅基溶胶-凝胶生物活性玻璃粉体。The bioactive glass xerogel precursor obtained in step (2) is placed in a high-temperature resistance furnace for heat treatment and sintering at 600° C. for 4 hours, wet grinding for 3 hours, and sieved to obtain the Zn/Cu doped silicon with nano-pore structure. Based sol-gel bioactive glass powder.

对本实施例制备的掺杂Zn/Cu的硅基溶胶-凝胶生物活性玻璃粉体根据标准ISO/FDIS 23317:2007(E)在模拟体液中浸泡5天后以表征其体外矿化性能,扫描电镜图(如图4)结果显示材料在短时间即可生成结晶性良好的针片状羟基磷灰石,说明本实施例制备的掺杂 Zn/Cu的硅基溶胶-凝胶生物活性玻璃粉体具有良好的羟基磷灰石形成能力及优异矿化效果。根据激光粒度仪及BET多点法计算出本实施例的掺杂Zn/Cu的硅基溶胶-凝胶生物活性玻璃粉体粒径分布为15~850μm、比表面积为125.5m2/g。The Zn/Cu-doped silicon-based sol-gel bioactive glass powders prepared in this example were soaked in simulated body fluids for 5 days according to the standard ISO/FDIS 23317:2007(E) to characterize their in vitro mineralization properties. Scanning electron microscopy The results of the figure (as shown in Figure 4) show that the material can generate needle-like hydroxyapatite with good crystallinity in a short time, indicating that the silicon-based sol-gel bioactive glass powder doped with Zn/Cu prepared in this example It has good hydroxyapatite forming ability and excellent mineralization effect. According to the laser particle size analyzer and the BET multi-point method, the particle size distribution of the Zn/Cu-doped silicon-based sol-gel bioactive glass powder in this embodiment is calculated to be 15-850 μm, and the specific surface area is 125.5 m 2 /g.

实施例3Example 3

一种掺杂Mg/Zn/Cu的硅基溶胶-凝胶生物活性玻璃粉体,其制备方法如下:A silicon-based sol-gel bioactive glass powder doped with Mg/Zn/Cu, the preparation method thereof is as follows:

(1)含Mg/Zn/Cu的生物活性玻璃溶胶的制备步骤:(1) Preparation steps of bioactive glass sol containing Mg/Zn/Cu:

将26ml浓度为2mol/L的盐酸与78mL去离子水配制成混合溶液,搅拌10min至完全溶解,得到催化剂溶液,后依次加入110.1g正硅酸乙酯、10.9g磷酸三乙酯、58.6g四水硝酸钙和6g硝酸镁、8.8g硝酸铜、8.8g硝酸锌,充分搅拌4h水解得到透明均一的含 2Mg-2Zn-2Cu(mol%)的生物活性玻璃溶胶;26ml of hydrochloric acid with a concentration of 2mol/L and 78ml of deionized water were prepared into a mixed solution, stirred for 10min until completely dissolved, to obtain a catalyst solution, and then 110.1g of ethyl orthosilicate, 10.9g of triethyl phosphate, 58.6g of tetraethyl phosphate were added in sequence. Water calcium nitrate, 6g magnesium nitrate, 8.8g copper nitrate, 8.8g zinc nitrate, fully stirred for 4h and hydrolyzed to obtain a transparent and uniform bioactive glass sol containing 2Mg-2Zn-2Cu (mol%);

(2)含Mg/Zn/Cu的生物活性玻璃干凝胶前驱体的制备步骤:(2) Preparation steps of bioactive glass xerogel precursor containing Mg/Zn/Cu:

将步骤(1)所得生物活性玻璃溶胶静置在35℃陈化2天,使水解缩聚反应充分进行,形成湿凝胶,后置于干燥箱中梯度干燥,50℃干燥4天和135℃干燥3天,得到掺Mg/Zn/Cu生物活性玻璃干凝胶前驱体;The bioactive glass sol obtained in step (1) was allowed to stand at 35°C for 2 days, so that the hydrolysis and polycondensation reaction was fully carried out to form a wet gel, which was then placed in a drying oven for gradient drying, dried at 50°C for 4 days and dried at 135°C. After 3 days, the Mg/Zn/Cu bioactive glass xerogel precursor was obtained;

(3)将掺Mg/Zn/Cu的生物活性玻璃干凝胶前驱体进行烧结处理:(3) Sintering the Mg/Zn/Cu-doped bioactive glass xerogel precursor:

将步骤(2)所得生物活性玻璃干凝胶前驱体置于高温电阻炉中进行600℃热处理烧结4h,经湿法研磨3h、筛分得到所述具有纳米孔隙结构的掺杂Mg/Zn/Cu的硅基溶胶-凝胶生物活性玻璃粉体。The bioactive glass xerogel precursor obtained in step (2) is placed in a high-temperature resistance furnace for heat treatment and sintering at 600° C. for 4 hours, wet-grinding for 3 hours, and sieved to obtain the doped Mg/Zn/Cu with nano-pore structure. Silica-based sol-gel bioactive glass powder.

使用比表面与孔径分析仪及激光粒度仪,对本实施例制备的掺杂Mg/Zn/Cu的硅基溶胶- 凝胶生物活性玻璃粉体进行比表面积和颗粒粒径的测试,材料的比表面积和介孔孔径按照 GB/T 19587-2004和GB/T 21650.2-2008的规定进行检测,结果如图5,可见所得掺杂Mg/Zn/Cu 的硅基溶胶-凝胶生物活性玻璃粉体富含大量由纳米颗粒堆积形成的狭缝孔介孔,粒径分布为10~740μm,孔径为6.546nm,比表面积为161.6m2/g,比表面积较高。The specific surface area and particle size of the silicon-based sol-gel bioactive glass powder doped with Mg/Zn/Cu prepared in this example were tested by using a specific surface and pore size analyzer and a laser particle size analyzer. The specific surface area of the material and mesoporous pore size were tested according to the regulations of GB/T 19587-2004 and GB/T 21650.2-2008. The results are shown in Figure 5. It can be seen that the obtained silicon-based sol-gel bioactive glass powder doped with Mg/Zn/Cu is rich in It contains a large number of slit mesopores formed by the accumulation of nanoparticles, the particle size distribution is 10-740μm, the pore size is 6.546nm, and the specific surface area is 161.6m 2 /g, which is relatively high.

实施例4Example 4

一种掺杂Sr的硅基溶胶-凝胶生物活性玻璃粉体,其制备方法如下:A silicon-based sol-gel bioactive glass powder doped with Sr, its preparation method is as follows:

(1)含Sr的生物活性玻璃溶胶的制备步骤:(1) Preparation steps of Sr-containing bioactive glass sol:

将26ml浓度为2mol/L的盐酸与78mL去离子水配制成混合溶液,搅拌10min至完全溶解,得到催化剂溶液,后依次加入110.1g正硅酸乙酯、10.9g磷酸三乙酯、58.6g四水硝酸钙和10.4g硝酸锶,充分搅拌4h水解得到透明均一的含6Sr(mol%)的生物活性玻璃溶胶;26ml of hydrochloric acid with a concentration of 2mol/L and 78ml of deionized water were prepared into a mixed solution, stirred for 10min until completely dissolved, to obtain a catalyst solution, and then 110.1g of ethyl orthosilicate, 10.9g of triethyl phosphate, 58.6g of tetraethyl phosphate were added in sequence. Water calcium nitrate and 10.4g strontium nitrate, fully stirred for 4h and hydrolyzed to obtain a transparent and uniform bioactive glass sol containing 6Sr (mol%);

(2)含Sr的生物活性玻璃干凝胶前驱体的制备步骤:(2) Preparation steps of Sr-containing bioactive glass xerogel precursor:

将步骤(1)所得生物活性玻璃溶胶静置在35℃陈化2天,使水解缩聚反应充分进行,形成湿凝胶,后置于干燥箱中梯度干燥,50℃干燥4天和135℃干燥3天,得到掺Sr生物活性玻璃干凝胶前驱体;The bioactive glass sol obtained in step (1) was allowed to stand at 35°C for 2 days, so that the hydrolysis and polycondensation reaction was fully carried out to form a wet gel, which was then placed in a drying oven for gradient drying, dried at 50°C for 4 days and dried at 135°C. After 3 days, the Sr-doped bioactive glass xerogel precursor was obtained;

(3)将掺Sr的生物活性玻璃干凝胶前驱体进行烧结处理:(3) sintering the Sr-doped bioactive glass xerogel precursor:

将步骤(2)所得生物活性玻璃干凝胶前驱体置于高温电阻炉中进行700℃热处理烧结4h,经湿法研磨3h、筛分得到所述具有纳米孔隙结构的掺杂Sr的硅基溶胶-凝胶生物活性玻璃粉体。The bioactive glass xerogel precursor obtained in step (2) is placed in a high temperature resistance furnace for heat treatment and sintering at 700 ° C for 4 hours, wet grinding for 3 hours, and sieving to obtain the Sr-doped silicon-based sol with nano-pore structure. -Gel bioactive glass powder.

对本实施例制备的掺杂Sr的硅基溶胶-凝胶生物活性玻璃粉体进行以下表征:X射线能谱分析(EDS)图(见图6)、X射线光电子能谱分析(XPS)图(见图7)、生物相容性分析结果图(见图8)。由图6可知,本实施例所得的掺杂Sr的硅基溶胶-凝胶生物活性玻璃粉体可观察到明显的Si、O、P、Ca、Sr对应的特征峰,根据计算可得所述掺杂Sr的硅基溶胶- 凝胶生物活性玻璃粉体中各元素对应摩尔比大致为二氧化硅、五氧化二磷、氧化钙及氧化锶的摩尔比=53.9:36.7:3.6:5.9;由图7可知,本实施例所得的掺杂Sr的硅基溶胶-凝胶生物活性玻璃粉体锶元素已成功掺入;根据激光粒度仪及BET多点法计算出本实施例的掺杂Sr的硅基溶胶-凝胶生物活性玻璃粉体粒径分布为10~750μm、比表面积为125.5m2/g。由图8可知,本实施例所得的可见所述掺杂Sr的硅基溶胶-凝胶生物活性玻璃粉体与小鼠骨髓间充质干细胞(BMSC)共培养不同天数(1、3、5天)后的CCK-8细胞增殖结果柱状图,从左至右为所述掺杂Sr的硅基溶胶-凝胶生物活性玻璃粉体的不同浓度细胞培养液,依次为1000 μg/mL、500μg/mL、200μg/mL、20μg/mL、及空白组(只有细胞),横坐标为材料与细胞培养时间,纵坐标为细胞活力值。相比于空白组,掺杂Sr的硅基溶胶-凝胶生物活性玻璃粉体对细胞增殖有促进作用,说明该材料具有良好的生物相容性能,促进细胞的黏附和增殖。The Sr-doped silicon-based sol-gel bioactive glass powder prepared in this example was characterized as follows: X-ray energy spectroscopy (EDS) diagram (see Figure 6), X-ray photoelectron spectroscopy (XPS) diagram ( See Figure 7), and the results of biocompatibility analysis (see Figure 8). It can be seen from FIG. 6 that the Sr-doped silicon-based sol-gel bioactive glass powder obtained in this example can observe obvious characteristic peaks corresponding to Si, O, P, Ca, and Sr. The corresponding molar ratio of each element in the Sr-doped silicon-based sol-gel bioactive glass powder is roughly the molar ratio of silicon dioxide, phosphorus pentoxide, calcium oxide and strontium oxide=53.9:36.7:3.6:5.9; Fig. 7 shows that the Sr-doped silicon-based sol-gel bioactive glass powder obtained in this example has been successfully doped with strontium element; The particle size distribution of the silica-based sol-gel bioactive glass powder is 10-750 μm, and the specific surface area is 125.5 m 2 /g. It can be seen from FIG. 8 that the Sr-doped silica-based sol-gel bioactive glass powder obtained in this example was co-cultured with mouse bone marrow mesenchymal stem cells (BMSC) for different days (1, 3, 5 days). ) histogram of CCK-8 cell proliferation results, from left to right are the cell culture solutions of the Sr-doped silica-based sol-gel bioactive glass powder with different concentrations, 1000 μg/mL, 500 μg/mL mL, 200 μg/mL, 20 μg/mL, and blank group (only cells), the abscissa is the material and cell culture time, and the ordinate is the cell viability value. Compared with the blank group, the silicon-based sol-gel bioactive glass powder doped with Sr can promote cell proliferation, indicating that the material has good biocompatibility and promotes cell adhesion and proliferation.

上述实施例为本发明较佳的实施方式,但本发明的实施方式并不受上述实施例的限制,其他任何在未背离本发明的精神实质与原理下所作的改变、修饰、替代、组合、简化,均应为等效的置换方式,都包含在本发明的保护范围之内。The above-mentioned embodiments are preferred embodiments of the present invention, but the embodiments of the present invention are not limited by the above-mentioned embodiments, and any other changes, modifications, substitutions, combinations, The simplification should be equivalent replacement manners, which are all included in the protection scope of the present invention.

Claims (10)

1. A preparation method of Sr/Mg/Zn/Cu doped silicon-based sol-gel bioactive glass powder is characterized by comprising the following steps:
(1) preparing a mixed solution of a catalyst and water, stirring until the mixed solution is completely dissolved to obtain a catalyst solution, then sequentially adding tetraethoxysilane, triethyl phosphate, calcium nitrate tetrahydrate and an ionic salt, and fully stirring and hydrolyzing to obtain ion-doped silicon-based bioactive glass sol; the ionic salt contains Sr2+、Mg2+、Zn2+And Cu2+Inorganic salts or related alkoxides of one or more of (a);
(2) standing and aging the ion-doped silicon-based bioactive glass sol obtained in the step (1) to fully perform a hydrolysis polycondensation reaction to form wet gel, and then placing the wet gel in a drying box for gradient drying to obtain an ion-doped silicon-based sol-gel bioactive glass xerogel precursor;
(3) and (3) placing the bioactive glass xerogel precursor obtained in the step (2) into a program-controlled high-temperature resistance furnace for heat treatment, and obtaining the Sr/Mg/Zn/Cu-doped silicon-based sol-gel bioactive glass powder with nano pores through wet grinding and screening.
2. The method of claim 1, wherein: the catalyst in the step (1): water: the molar ratio of the ethyl orthosilicate is (2-8): (800-1000): (70-140); the catalyst is hydrochloric acid or ammonia water; the stirring hydrolysis time is 2-8 hours.
3. The method of claim 1, wherein: in the step (1), the molar ratio of the ethyl orthosilicate, the triethyl phosphate, the calcium nitrate tetrahydrate and the ionic salt is that the ethyl orthosilicate is as follows: triethyl phosphate; calcium nitrate tetrahydrate: an ionic salt (50-80): (14-4): (5-40): (0-15).
4. The method of claim 1, wherein: the ionic salt in the step (1) is selected from one or more of zinc nitrate, copper chloride, magnesium nitrate, silver nitrate, strontium nitrate, cobalt nitrate, ferric nitrate, copper nitrate, strontium chloride, magnesium methoxide and zinc acetate.
5. The method of claim 1, wherein: the aging temperature in the step (2) is 15-35 ℃, and the aging time is 2-5 days.
6. The method of claim 1, wherein: and (2) gradient drying, namely setting the gradient temperature of a drying box to be 50-75 ℃ and 100-140 ℃, and drying for 2-9 days.
7. The method of claim 1, wherein: the temperature of the heat treatment in the step (3) is 550-850 ℃, and the heat preservation time of the heat treatment is 1-4 hours.
8. The method of claim 1, wherein: and (3) carrying out wet grinding, wherein a ball milling tank is made of polytetrafluoroethylene, the ball milling time is 3-10 hours, and a ball milling medium is absolute ethyl alcohol.
9. The Sr/Mg/Zn/Cu doped silicon-based sol-gel bioactive glass powder prepared by the preparation method of any one of claims 1 to 8 is characterized in that the Sr/Mg/Zn/Cu doped silicon-based sol-gel bioactive glass powder has the particle size distribution of 10 to 900 microns and the specific surface area of 100 to 300m2/g。
10. The use of the Sr/Mg/Zn/Cu doped silica-based sol-gel bioactive glass powder of claim 9 in bone tissue repair, oral repair, skin repair and immune regulation of the body.
CN202010837825.4A 2020-04-30 2020-08-19 Sr/Mg/Zn/Cu doped silicon-based sol-gel bioactive glass powder and preparation method and application thereof Pending CN111908798A (en)

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