resumo
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.
palavras-chave
MESOPOROUS SILICA NANOPARTICLES; CARBOXYMETHYLCHITOSAN/POLY(AMIDOAMINE) DENDRIMER NANOPARTICLES; CALCIUM-PHOSPHATE; STROMAL CELLS; BONE-MARROW; DEXAMETHASONE; DELIVERY; PARTICLES; SCAFFOLDS; GLASSES
categoria
Materials Science
autores
Tavares, MT; Oliveira, MB; Gaspar, VM; Mano, JF; Farinha, JPS; Baleizao, C
nossos autores
João Mano
Vice-Diretoragradecimentos
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.