自固化载硒纳米微球/磷酸钙复合骨修复材料的制备及性能
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摘要
研究制备具有促修复、抗肿瘤的可注射缓释硒纳米微球复合磷酸钙骨水泥材料.采用乳化交联法制备Na_2SeO_3/CS缓释硒纳米微球,将微球与磷酸钙骨水泥(CPC)复合,制备Na_2SeO_3/CS/CPC骨修复系统,对该系统的固化时间、力学强度、缓释硒及降解性能、形貌、晶相构成进行测定和表征分析,并对其体外细胞活性进行研究.结果表明:相对于纯的CPC,当掺入Na_2SeO_3/CS纳米微球的量为4%时,复合CPC的注射性良好,固化时间5.75～11.5 min,固化强度提高,微观结构显示CPC均匀地包裹在壳聚糖微球表面并形成了针片状HA晶体,微球的添加对复合CPC材料的晶相组分无显著影响,缓释硒效应良好,有效缓释达22 d,降解性优于纯CPC,形成了蜂窝状完善的网状三维立体多孔结构,利于组织细胞和血管及神经的黏附长入.体外细胞实验表明,复合CPC对人乳腺癌细胞MCF-7及MG-63人骨肉瘤细胞增生的抑制作用显著,且对两株细胞增生的抑制性差异不显著.本研究为非承骨微创、缺陷修复及骨肿瘤的术后恢复、防止复发和转移的预防和治疗提供一种新思路,同时为拓展功能元素硒的合理应用奠定实验基础.
The study was to prepare composite calcium phosphate cement with improved repair and anti-tumor injectable sustained-release selenium nanoparticle. Na_2SeO_3/CS sustained release selenium nanospheres were prepared by emulsification and crosslinking method. The microspheres were combined with calcium phosphate cement(CPC) to prepare the Na_2SeO_3/CS/CPC bone repair system. The curing time, mechanical strength, sustained release selenium and degradation properties, morphology and phase composition of the system were measured and characterized, and the activity of the cells in vitro was studied. The results showed that compared with pure CPC, when the amount of Na_2SeO_3/CS nano microspheres was 4 %,the injection of composite CPC was good, the curing time was 5.75-11.5 minutes and the curing strength was improved. The microstructure showed that CPC was evenly wrapped on the surface of chitosan microspheres and formed a needle like HA crystal. The addition of the microspheres to the crystalline phase of the composite CPC material had no significant effect in the components. The sustained release selenium effect was good, the effective release was 22 d, and the degradation was better than the pure CPC. The honeycomb like three-dimensional porous structure of the network was formed, which was beneficial to the adhesion of tissue cells and blood vessels and nerves. In vitro cell test showed that the inhibitory effect of compound CPC on the proliferations of MCF-7 and MG-63 human osteosarcoma cells in human breast cancer cells was significant, and the inhibitory difference between the two cell proliferations was not significant. This study provided a new idea for non-bone bearing minimally invasive, defect repair and postoperative recovery of bone tumors, prevention and treatment of recurrence and metastasis, and provided an experimental basis for the rational application of functional element selenium.
The study was to prepare composite calcium phosphate cement with improved repair and anti-tumor injectable sustained-release selenium nanoparticle. Na_2SeO_3/CS sustained release selenium nanospheres were prepared by emulsification and crosslinking method. The microspheres were combined with calcium phosphate cement(CPC) to prepare the Na_2SeO_3/CS/CPC bone repair system. The curing time, mechanical strength, sustained release selenium and degradation properties, morphology and phase composition of the system were measured and characterized, and the activity of the cells in vitro was studied. The results showed that compared with pure CPC, when the amount of Na_2SeO_3/CS nano microspheres was 4 %,the injection of composite CPC was good, the curing time was 5.75-11.5 minutes and the curing strength was improved. The microstructure showed that CPC was evenly wrapped on the surface of chitosan microspheres and formed a needle like HA crystal. The addition of the microspheres to the crystalline phase of the composite CPC material had no significant effect in the components. The sustained release selenium effect was good, the effective release was 22 d, and the degradation was better than the pure CPC. The honeycomb like three-dimensional porous structure of the network was formed, which was beneficial to the adhesion of tissue cells and blood vessels and nerves. In vitro cell test showed that the inhibitory effect of compound CPC on the proliferations of MCF-7 and MG-63 human osteosarcoma cells in human breast cancer cells was significant, and the inhibitory difference between the two cell proliferations was not significant. This study provided a new idea for non-bone bearing minimally invasive, defect repair and postoperative recovery of bone tumors, prevention and treatment of recurrence and metastasis, and provided an experimental basis for the rational application of functional element selenium.
引文
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[10] Zhou Y, Jia X, Tan L, et al. Magnetically enhanced cytotoxicity of paramagnetic selenium-ferroferric oxide nanocomposites on human osteoblast-like MG-63 cells [J]. Biosens Bioelectron, 2010, 25: 1116.
[11] Wang Y H, Lv P, Ma Z, et al. Enhanced healing of rat calvarial critical size defect with selenium-doped lamellar biocomposites [J]. Biol Trace Elem Res, 2013, 155: 72.
[12] Rodríguez-Valencia C, Lopez-álvarez M, Cochón-Cores B, et al. Novel selenium-doped hydroxyapatite coatings for biomedical applications [J]. J Biomed Mater Res A, 2013, 101: 853.
[13] Tran P A, Taylor E, Sarin L, et al. Novel anti-cancer, anti-bacterial coatings for biomaterial applications: Selenium nanoclusters [J]. Mater Res Soc Symp Proc, 2010, 1209: 205.
[14] Tran P A, Webster T J. Antimicrobial selenium nanoparticle coatings on polymeric medical devices [J]. Nanotechnology, 2013, 24: 155.
[15] Wang Q, Webster T J. Nanostructured selenium for preventing biofilm formation on medical devices [J]. Mater Res Soc Symp Proc, 2012, 1415: 105.
[16] Tran P A, Sarin L, Hurt R H, et al. Transforming orthopedic biomaterials into bone cancer inhibiting implants:The role of selenium nanoclusters [J]. Mater Res Soc Symp Proc, 2008, 1136: 122.
[17] Wang Y, Chen J, Zhang D, et al. Tumoricidal effects of a selenium (Se)-polysaccharide from Ziyang green tea on human osteosarcoma U-2OS cells [J]. Carbohyd Polym, 2013, 98: 1186.
[18] Tran P A, Taylor E, Sarin L, et al. Novel anti-cancer, anti-bacterial coatings for biomaterial applications: selenium nanoclusters [J]. Mater Res Soc Symp Proc, 2010, 1209: 205.
[19] Wang Q, Webster Thomas J. Nanostructured selenium for preventing biofilm formation on medical devices [J]. Mater Res Soc Symp Proc, 2012, 1415: 105.
[20] Zwolak I, Zaporowska H. Selenium interactions and toxicity: a review [J]. Cell Biol Toxicol, 2012, 28: 31
[21] Brozmanova J, Mániková D, Vl. Selenium: a double-edged sword for defense and offence in cancer [J]. Arch Toxicol, 2010, 84: 919.
[22] 冉青, 商龙臣, 吴少尉, 等. SeMet/CS纳米复合微球的制备、缓释性能及抑制肿瘤活性 [J]. 四川大学学报: 自然科学版, 2018, 55: 1058.
[23] 邓育红, 崔旭, 彭松林. SrHA/PMMA复合骨水泥的制备、理化性能及细胞相容性研究 [J]. 生物骨科材抖与临床研究, 2016, 13: 1.
[24] 张涛. 不同钙磷摩尔比/多重孔隙磷酸钙骨水泥的研究 [D]. 西南交通大学, 2007: 11.
[25] Zhang H X, He Q Y. Optimization study on the detection of tumor cell proliferation with CCK-8 method [J]. J Pharm Res, 2016, 35: 63.
[26] Takagi S, Chow L C, Hirayama S, et al. Properties of elastomeric calcium phosphate cement-chitosan composites [J]. Dent Mater, 2003: 19: 797.
[2] 黄顺勇. 磷酸钙骨水泥的临床应用与研究进展[J]. 中外医学研究. 2015, 13: 1719.
[3] 张海燕, 邬伟魁, 宋伟, 等. 磷酸钙骨水泥载药研究[J]. 中国实验方剂学杂, 2012, 18: 224.
[4] 殷力, 胡明鑫, 王海涛, 等. 载阿仑膦酸钠/磷酸钙骨水泥复合体系微观结构的研究[J]. 中华实验外科杂志, 2017, 34: 94.
[5] 商龙臣, 李娇, 倪书萍, 等. (HgmSen)(m=1, 2, 3, n=1, 2)分子离子团簇结构和光谱性质[J] . 四川大学学报: 自然科学版, 2016, 53: 138.
[6] 陈红霞. Cr掺杂ZnSe团簇稳定性和磁性质[J].原子与分子物理学报, 2018, 35: 429.
[7] 袁丽君, 袁林喜, 尹雪斌. 硒的生理功能、摄入现状与对策研究进展[J]. 生物技术进展, 2017, 7: 506.
[8] 陈红霞, 杜思洁. ZnSe小团簇结构稳定性和电子性质研究[J]. 原子与分子物理学报, 2018, 35: 789.
[9] Vekariya K K, Kaur J, Tikoo K. Alleviating anastrozole induced bone toxicity by selenium nanoparticles in SD rats [J]. Toxicol Appl Pharm, 2013, 268: 212.
[10] Zhou Y, Jia X, Tan L, et al. Magnetically enhanced cytotoxicity of paramagnetic selenium-ferroferric oxide nanocomposites on human osteoblast-like MG-63 cells [J]. Biosens Bioelectron, 2010, 25: 1116.
[11] Wang Y H, Lv P, Ma Z, et al. Enhanced healing of rat calvarial critical size defect with selenium-doped lamellar biocomposites [J]. Biol Trace Elem Res, 2013, 155: 72.
[12] Rodríguez-Valencia C, Lopez-álvarez M, Cochón-Cores B, et al. Novel selenium-doped hydroxyapatite coatings for biomedical applications [J]. J Biomed Mater Res A, 2013, 101: 853.
[13] Tran P A, Taylor E, Sarin L, et al. Novel anti-cancer, anti-bacterial coatings for biomaterial applications: Selenium nanoclusters [J]. Mater Res Soc Symp Proc, 2010, 1209: 205.
[14] Tran P A, Webster T J. Antimicrobial selenium nanoparticle coatings on polymeric medical devices [J]. Nanotechnology, 2013, 24: 155.
[15] Wang Q, Webster T J. Nanostructured selenium for preventing biofilm formation on medical devices [J]. Mater Res Soc Symp Proc, 2012, 1415: 105.
[16] Tran P A, Sarin L, Hurt R H, et al. Transforming orthopedic biomaterials into bone cancer inhibiting implants:The role of selenium nanoclusters [J]. Mater Res Soc Symp Proc, 2008, 1136: 122.
[17] Wang Y, Chen J, Zhang D, et al. Tumoricidal effects of a selenium (Se)-polysaccharide from Ziyang green tea on human osteosarcoma U-2OS cells [J]. Carbohyd Polym, 2013, 98: 1186.
[18] Tran P A, Taylor E, Sarin L, et al. Novel anti-cancer, anti-bacterial coatings for biomaterial applications: selenium nanoclusters [J]. Mater Res Soc Symp Proc, 2010, 1209: 205.
[19] Wang Q, Webster Thomas J. Nanostructured selenium for preventing biofilm formation on medical devices [J]. Mater Res Soc Symp Proc, 2012, 1415: 105.
[20] Zwolak I, Zaporowska H. Selenium interactions and toxicity: a review [J]. Cell Biol Toxicol, 2012, 28: 31
[21] Brozmanova J, Mániková D, Vl. Selenium: a double-edged sword for defense and offence in cancer [J]. Arch Toxicol, 2010, 84: 919.
[22] 冉青, 商龙臣, 吴少尉, 等. SeMet/CS纳米复合微球的制备、缓释性能及抑制肿瘤活性 [J]. 四川大学学报: 自然科学版, 2018, 55: 1058.
[23] 邓育红, 崔旭, 彭松林. SrHA/PMMA复合骨水泥的制备、理化性能及细胞相容性研究 [J]. 生物骨科材抖与临床研究, 2016, 13: 1.
[24] 张涛. 不同钙磷摩尔比/多重孔隙磷酸钙骨水泥的研究 [D]. 西南交通大学, 2007: 11.
[25] Zhang H X, He Q Y. Optimization study on the detection of tumor cell proliferation with CCK-8 method [J]. J Pharm Res, 2016, 35: 63.
[26] Takagi S, Chow L C, Hirayama S, et al. Properties of elastomeric calcium phosphate cement-chitosan composites [J]. Dent Mater, 2003: 19: 797.