Nd-doped Mesoporous Borosilicate Bioactive Glass-ceramic Bone Cement

doi:10.15541/jim20220114

Abstract

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

CLC Number:

R318

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.

Figures/Tables 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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