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

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.

Bioactive silica nanoparticles with calcium and phosphate for single dose osteogenic differentiation.

The differentiation of adult stem cells is usually performed in vitro, by exposing them to specific factors. Alternatively, one can use nanocarriers containing such factors, to be internalized by the cells. In this work we have reduce the size of those carriers to the nanoscale, developing bioactive silica nanoparticles with diameters under 100 nm, containing calcium and phosphate ions (SiNPs-CaP). These ions, once released inside adult stem cells, induce bone cell proliferation and differentiation, and stimulate the expression of bone-related proteins in a single dose administration. The SiNPs-CaP nanomaterials were prepared through a sol-gel approach, and the ions added with a post-synthesis functionalization method. The synthesized SiNPs-CaP have narrow size distribution, good colloidal stability, and show high levels of ion incorporation. Furthermore, the SiNPs-CaP have good cytocompatibility and promote the osteogenic differentiation of human bone marrow mesenchymal stem cells (hBMSC), with alkaline phosphatase, osteopontin and osteocalcin production levels comparable to the ones obtained in standard osteogenic medium. The novel bioactive SiNPs-CaP are synthesized in a simple and fast manner and show the ability to promote osteogenic differentiation after a single dose administration, independently from external osteogenic inducers, showing great potential as carriers in bone tissue engineering applications.