Efficient Single-Dose Induction of Osteogenic Differentiation of Stem Cells Using Multi-Bioactive Hybrid Nanocarriers

abstract

Bone regeneration requires the presence of specific factors to induce the differentiation of stem cells into osteoblasts. These factors induce osteogenesis by stimulating the expression of bone-related proteins, bone cell proliferation and differentiation. Herein, bioactive mesoporous silica nanoparticles are doped with calcium and phosphate ions while the porous network is loaded with dexamethasone (MSN-CaPDex). The bioactive MSN-CaPDex nanocarriers are prepared without affecting the narrow size distribution, pore structure, and morphology of the MSNs, while incorporating multi-stimuli, complementary ionic/biochemical bioactive mediators. The bioactive nanocarriers induce osteogenic differentiation of human bone marrow mesenchymal stem cells (hBM-MSCs) after a single-dose administration, and without the need for further soluble osteogenic factors, in contrast to the standard continuous stimulation provided by osteogenic medium. The hBM-MSCs exhibit several biomarkers of osteogenic differentiation, including alkaline phosphatase peaking at early time points, secretion of osteopontin and osteocalcin, and deposition of a calcium-rich matrix. Overall, by inducing the osteogenic differentiation of stem cells with a single-dose administration and without requiring repeated osteogenic supplementation, the newly synthesized multi-bioactive hybrid nanocarrier shows great potential for bone tissue engineering applications.

keywords

MESOPOROUS SILICA NANOPARTICLES; CARBOXYMETHYLCHITOSAN/POLY(AMIDOAMINE) DENDRIMER NANOPARTICLES; CALCIUM-PHOSPHATE; STROMAL CELLS; BONE-MARROW; DEXAMETHASONE; DELIVERY; PARTICLES; SCAFFOLDS; GLASSES

subject category

Materials Science

authors

Tavares, MT; Oliveira, MB; Gaspar, VM; Mano, JF; Farinha, JPS; Baleizao, C

our authors

acknowledgements

This work was supported by Fundos Europeus Estruturais e de Investimento (FEEI), Programa Operacional Regional de Lisboa-FEDER (02/SAICT/2017), and national funds from FundacAo para a Ciencia e a Tecnologia (FCT-Portugal) and COMPETE (FEDER) within projects UIDB/50011/2020 (CICECO-Aveiro Institute of Materials), UIDB/00100/2020 (CQE), PTDC/CTM-POL/3698/2014 and PTDC/CTM-CTM/32444/2017 (02/SAICT/2017/032444). M.T. also thanks FCT for a Ph.D. grant (FCT-PD/BD/114019/2015). Image acquisition was performed in the LiM facility of iBiMED, a node of PPBI (Portuguese Platform of BioImaging): POCI-01-0145-FEDER-022122.

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