掺钕介孔硼硅酸盐生物活性玻璃陶瓷骨水泥的制备与性能表征

doi:10.15541/jim20220114

无机材料学报 ›› 2022, Vol. 37 ›› Issue (11): 1245-1258.DOI: 10.15541/jim20220114

所属专题：【生物材料】肿瘤治疗；【生物材料】骨骼与齿类组织修复

• 研究快报 • 上一篇

掺钕介孔硼硅酸盐生物活性玻璃陶瓷骨水泥的制备与性能表征

陈铖¹(), 丁晶鑫¹, 王会²(), 王德平¹()

1.同济大学材料科学与工程学院, 上海 201804
2.上海中医药大学康复科学学院, 康复医学研究所, 中医药智能康复教育部工程研究中心, 上海 201203

收稿日期:2022-03-02 修回日期:2022-04-03 出版日期:2022-05-07 网络出版日期:2022-05-07
通讯作者: 王会, 副研究员. E-mail: WHIL86@shutcm.edu.cn;
王德平, 教授. E-mail: wdpshk@tongji.edu.cn
作者简介:陈铖(1997-), 男, 硕士研究生. E-mail: 1930642@tongji.edu.cn

Nd-doped Mesoporous Borosilicate Bioactive Glass-ceramic Bone Cement

CHEN Cheng¹(), DING Jingxin¹, WANG Hui²(), WANG Deping¹()

1. School of Materials Science and Engineering, Tongji University, Shanghai 201804, China
2. Engineering Research Center of Traditional Chinese Medicine Intelligent Rehabilitation, Ministry of Education, Institute of Rehabilitation Medicine, School of Rehabilitation Science, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China

Received:2022-03-02 Revised:2022-04-03 Published:2022-05-07 Online:2022-05-07
Contact: WANG Hui, associate professor. E-mail: WHIL86@shutcm.edu.cn;
WANG Deping, professor. E-mail: wdpshk@tongji.edu.cn
About author:CHEN Cheng (1997-), male, Master candidate. E-mail: 1930642@tongji.edu.cn
Supported by:
National Natural Science Foundation of China(52172286);National Natural Science Foundation of China(51772210);National Key R&D Program of China(2018YFC1106302)

摘要/Abstract

摘要：

骨肉瘤是一种常见的恶性骨肿瘤, 常通过手术切除进行治疗。但术后造成的骨缺损难以自愈, 残余肿瘤细胞还会增加复发可能性。本研究开发了一种用于修复骨缺损和协同治疗骨肉瘤的掺钕介孔硼硅酸盐生物活性玻璃陶瓷骨水泥。首先通过溶胶-凝胶法结合固态反应制备了可作为光热剂和药物载体的掺钕介孔硼硅酸盐生物活性玻璃陶瓷微球(MBGC-xNd), 然后将微球与海藻酸钠(SA)溶液混合制备了可同时进行光热治疗和化学治疗的可注射骨水泥(MBGC-xNd/SA)。结果表明掺Nd³⁺赋予微球可控的光热性能, 负载阿霉素(DOX)的微球显示出持续的药物释放行为。此外, 载药骨水泥的药物释放量随着温度的升高而显著增加, 说明光热疗法产生的热量可促进DOX释放。体外细胞实验结果表明, MBGC-xNd/SA具有良好的促成骨活性, 并且光热-化学联合疗法对MG-63骨肉瘤细胞起到了更显著的杀伤作用, 表现出协同效应。因此，MBGC-xNd/SA作为一种新颖的多功能骨修复材料, 在骨肉瘤的术后治疗方面具有良好的应用前景。

关键词: 掺钕介孔硼硅酸盐生物活性玻璃陶瓷, 骨水泥, 骨缺损修复, 光热-化学联合疗法

Abstract:

As a common malignant bone tumor, osteosarcoma is usually treated by surgical resection. However, the bone defects caused by surgery are difficult to heal, and the possibility of osteosarcoma recurrence can also be increased by the residual tumor cells. Therefore, a Nd-doped mesoporous borosilicate bioactive glass-ceramic bone cement was developed for repair of bone defects and synergistic therapy of osteosarcoma. Firstly, as photothermal agent and drug carrier, Nd-doped mesoporous borosilicate bioactive glass-ceramic (MBGC-xNd) microspheres were prepared through Sol-Gel method and solid-state reaction. Then MBGC-xNd microspheres were mixed with sodium alginate (SA) solution to prepare injectable bone cement (MBGC-xNd/SA). The results showed that Nd³⁺ endows microspheres with controllable photothermal properties, and microspheres loaded with doxorubicin (DOX) showed sustained drug release behavior. In addition, the drug release from drug-loaded bone cement was significantly accelerated with the increase of temperature, indicating that the heat generated by photothermal therapy had the possibility of promoting the release of DOX. In vitro cell experiment results showed that MBGC-xNd/SA had good osteogenic activity. Simultaneously, photothermal-chemical combination therapy had a more significant killing effect on MG-63 osteosarcoma cells, indicating a synergistic effect. Therefore, MBGC-xNd/SA, as a novel multifunctional bone repair material, exhibits a potential application in the postoperative treatment of osteosarcoma.

Key words: Nd-doped mesoporous borsilicate bioactive glass-ceramic, bone cement, bone defect repair, photo-thermal-chemical combination therapy

中图分类号:

R318

陈铖, 丁晶鑫, 王会, 王德平. 掺钕介孔硼硅酸盐生物活性玻璃陶瓷骨水泥的制备与性能表征[J]. 无机材料学报, 2022, 37(11): 1245-1258.

CHEN Cheng, DING Jingxin, WANG Hui, WANG Deping. Nd-doped Mesoporous Borosilicate Bioactive Glass-ceramic Bone Cement[J]. Journal of Inorganic Materials, 2022, 37(11): 1245-1258.

图/表 11

Scheme 1 Schematic diagram of preparation and properties of MBGC-xNd microspheres and MBGC-xNd/SA bone cement The color figure can be obtained from online edition

Table 1 Composition in molar percent of MBGC-xNd microspheres

Sample	SiO₂	B₂O₃	P₂O₅	CaO	NdO_3/2
MBGC-0Nd	50	10	4	36	0
MBGC-1Nd	50	10	4	35	1
MBGC-3Nd	50	10	4	33	3
MBGC-5Nd	50	10	4	31	5

Fig. 1 Characterization of MBGC-xNd microspheres (a-e) TEM images of (a) MBN, (b) MBGC-0Nd microspheres, (c) MBGC-1Nd microspheres, (d) MBGC-3Nd microspheres, and (e) MBGC-5Nd microspheres; (f) High-resolution TEM image of MBGC-3Nd microspheres with insert showing the interplanar crystal spacing at about 0.334 nm; (g) XRD patterns of MBN and MBGC-xNd microspheres; (h) N2 adsorption-desorption isotherm and (i) pore size distribution curve of MBGC-xNd microsphere The color figures can be obtained from online edition

Table 2 Pore structure of MBN and MBGC-xNd microspheres

Sample	Specific surface area/(m²·g^-1)	Pore size /nm	Pore volume /(cm³·g^-1)
MBN	329.261	12.506	0.4498
MBGC-0Nd	42.092	6.024	0.0634
MBGC-1Nd	36.065	4.776	0.0431
MBGC-3Nd	34.424	4.496	0.0387
MBGC-5Nd	28.818	3.710	0.0268

Fig. 2 Changes of (A) Ca and (B) Si concentrations with MBGC-xNd microspheres in SBF The color figures can be obtained from online edition

Fig. 3 Cumulative release curves of DOX from (A) MBGC-xNd@DOX microspheres in PBS at pH 4.7 and (B) MBGC-3Nd/SA@DOX in PBS at pH 4.7 under different ambient temperatures The color figures can be obtained from online edition

Fig. 4 Photothermal properties of MBGC-xNd microspheres (A) Heating curves of MBGC-xNd microspheres under 808 nm laser irradiation (3.2 W/cm2); (B) Heating curves of MBGC-3Nd microspheres under 808 nm laser irradiation at different power densities; (C) Heating curves of MBGC-3Nd/SA immersed in SBF under 808 nm laser irradiation (2.4 W/cm2); (D) Energy level diagram of Nd3+ The color figures can be obtained from online edition

Fig. 5 Characterization of MBGC-3Nd/SA bone cement (A) Photo of extruded bone cement; (B) SEM image of MBGC-3Nd/SA; (C) Schematic illustration of the setting process of MBGC-3Nd/SA The color figures can be obtained from online edition

Fig. 6 Setting properties of MBGC-xNd/SA (A) Setting time; (B) Injectability; (C) Compressive strength; (D) Anti-washout property. *: p<0.05 (n=5) The color figures can be obtained from online edition

Fig. 7 (A) Proliferation results and (B) alkaline phosphate activity of rBMSCs cultured in the bone cement extract *: p < 0.05; **: p < 0.01. (n = 5). The color figure can be obtained from online edition

Fig. 8 Relative survival of MG-63 cells co-cultured with (A) bone cement under 808 nm laser irradiation at a power density of 2.4 W/cm2 for 5 min and (B) MBGC-3Nd/SA under PTT, CHT or combination therapy. *: p<0.05; **: p<0.01, ***: p<0.001 (n=5) The color figures can be obtained from online edition

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掺钕介孔硼硅酸盐生物活性玻璃陶瓷骨水泥的制备与性能表征

Nd-doped Mesoporous Borosilicate Bioactive Glass-ceramic Bone Cement

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