Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Dec 9:8:610232.
doi: 10.3389/fchem.2020.610232. eCollection 2020.

Bifunctional, Copper-Doped, Mesoporous Silica Nanosphere-Modified, Bioceramic Scaffolds for Bone Tumor Therapy

Hongshi Ma  1 , Zhenjiang Ma  1 , Qufei Chen  1 , Wentao Li  1 , Xiangfei Liu  2 , Xiaojun Ma  3 , Yuanqing Mao  1 , Han Yang  1 , Hui Ma  1 , Jinwu Wang  1
Affiliations

Bifunctional, Copper-Doped, Mesoporous Silica Nanosphere-Modified, Bioceramic Scaffolds for Bone Tumor Therapy

Hongshi Ma et al. Front Chem. .

Abstract

In the traditional surgical intervention procedure, residual tumor cells may potentially cause tumor recurrence. In addition, large bone defects caused by surgery are difficult to self-repair. Thus, it is necessary to design a bioactive scaffold that can not only kill residual tumor cells but also promote bone defect regeneration simultaneously. Here, we successfully developed Cu-containing mesoporous silica nanosphere-modified β-tricalcium phosphate (Cu-MSN-TCP) scaffolds, with uniform and dense nanolayers with spherical morphology via 3D printing and spin coating. The scaffolds exhibited coating time- and laser power density-dependent photothermal performance, which favored the effective killing of tumor cells under near-infrared laser irradiation. Furthermore, the prepared scaffolds favored the proliferation and attachment of rabbit bone marrow-derived mesenchymal stem cells and stimulated the gene expression of osteogenic markers. Overall, Cu-MSN-TCP scaffolds can be considered for complete eradication of residual bone tumor cells and simultaneous healing of large bone defects, which may provide a novel and effective strategy for bone tumor therapy. In the future, such Cu-MSN-TCP scaffolds may function as carriers of anti-cancer drugs or immune checkpoint inhibitors in chemo-/photothermal or immune-/photothermal therapy of bone tumors, favoring for effective treatment.

Keywords: 3D printing; Cu-containing mesoporous silica nanospheres; bifunctional scaffolds; photothermal tumor therapy; tissue regeneration.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Schematic illustration of prepared Cu-containing mesoporous silica nanospheres modified β-TCP scaffolds by combining 3D printing and spin coating method, and potential application of prepared scaffolds in photothermal tumor therapy and simultaneous osteogenesis promotion.
Figure 2
Figure 2
Transmission electron microscope images of Cu-containing mesoporous silica nanospheres (Cu-MSN) in bright field (BF) model (a) and high-angle annular dark field (HAAD) model (b). Energy-dispersive spectrometry element mapping images of all (c), Si (d), O (e), and Cu (f) elements distributed in Cu-MSN. Energy-dispersive spectroscopy analysis (g,h) of Cu-MSN.
Figure 3
Figure 3
Scanning electron microscope images of β-tricalcium phosphate (β-TCP) (a1,a2), 2Cu-MSN-TCP (b1,b2), 4Cu-MSN-TCP (c1,c2), 6Cu-MSN-TCP (d1,d2), and 8Cu-MSN-TCP (e1,e2) scaffolds. The concentration of released Ca (f), Si (g), and Cu (h) ions from β-TCP and 8Cu-MSN-TCP scaffolds in phosphate-buffered saline (PBS) on days 1, 4, and 7.
Figure 4
Figure 4
Cu-containing mesoporous silica nanospheres modified β-tricalcium phosphate (Cu-MSN-TCP) scaffolds exhibited a coating time-dependent (a) and laser power density-dependent (b) photothermal performance. The photothermal heating and cooling curve of 8Cu-MSN-TCP scaffolds under irradiation at 0.9 W/cm2 (c). Visual thermal images and temperature change of β-TCP (d) and 8Cu-MSN-TCP (e) scaffolds can be recorded and obtained using an infrared (IR) thermal camera.
Figure 5
Figure 5
The viability of MG-63 tumor cells, treated with 8Cu-MSN-TCP scaffolds after being irradiated once (a) and twice (b) (n = 3). Confocal laser scanning microscope images of MG 63 tumor cells treated with β-TCP without irradiation (c), β-TCP scaffold with irradiation (d), 8Cu-MSN-TCP without irradiation (e), and 8Cu-MSN-TCP with irradiation (f). MG 63 tumor cells were stained with calcein AM (green fluorescence, live cells) and ethidium homodimer-1 (red fluorescence, dead cells). Hyperthermia induced by 8Cu-MSs-TCP scaffolds had sufficient killing effect on tumor cells.
Figure 6
Figure 6
The viability of rabbit bone marrow-derived mesenchymal stem cells in β-TCP and 8Cu-MSN-TCP scaffolds for 1, 3, and 5 days (a) (n = 3). Scanning electron microscopy (b,c) and confocal microscopy images of nucleus (d1,e1), cytoskeleton (d2,e2) and merged mode (d3,e3) of rBMSCs of rBMSCs in β-TCP (b,d) and 8Cu-MSN-TCP scaffolds (c,e), suggesting that 8Cu-MSN-TCP scaffolds had satisfactory biocompatibility.
Figure 7
Figure 7
The osteogenic differentiation of rabbit bone marrow-derived mesenchymal stem cells was assessed by RT-qPCR. The gene expression of OPN (a), Runx2 (b), BSP (c), VEGF (d), BMP 2 (e) in the blank group, β-TCP, and 8Cu-MSN-TCP scaffolds (n = 3). 8Cu-MSN-TCP scaffolds can recognize the promotion of osteogenesis.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Chen W., Ouyang J., Liu H., Chen M., Zeng K., Sheng J. P., et al. . (2017). Black phosphorus nanosheet-based drug delivery system for synergistic photodynamic/photothermal/chemotherapy of cancer. Adv. Mat. 29:1603864. 10.1002/adma.201603864 - DOI - PubMed
    1. Chu K. F., Dupuy D. E. (2014). Thermal ablation of tumours: biological mechanisms and advances in therapy. Nat. Rev. Cancer 14, 199–208. 10.1038/nrc3672 - DOI - PubMed
    1. Figueroa L. A., Alvarez O. M., Cruz J. S., Contreras R. G., Hernández F. J., Arrocena M. C. A. (2017). Nanomaterials made of non-toxic metallic sulfides: a systematic review of their potential biomedical applications. Mater. Sci. Eng. C 76, 1305–1315. 10.1016/j.msec.2017.02.120 - DOI - PubMed
    1. Hassan M. N., Yassin M. A., Suliman S., Lie S. A., Gjengedal H., Mustafa K. (2019). The bone regeneration capacity of 3D-printed templates in calvarial defect models: a systematic review and meta-analysis. Acta Biomater. 91, 1–23. 10.1016/j.actbio.2019.04.017 - DOI - PubMed
    1. Kaplan B., Merdler U., Szklanny A. A., Redenski I., Guo S., Bar-Mucha Z., et al. . (2020). Rapid prototyping fabrication of soft and oriented polyester scaffolds for axonal guidance. Biomaterials 251:120062. 10.1016/j.biomaterials.2020.120062 - DOI - PubMed