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.

Effects of a bone-like mineral film on phenotype of adult human mesenchymal stem cells in vitro.

Multipotent cell types are rapidly becoming key components in a variety of tissue engineering schemes, and mesenchymal stem cells (MSCs) are emerging as an important tool in bone tissue regeneration. Although several soluble signals influencing osteogenic differentiation of MSCs in vitro are well-characterized, relatively little is known about the influence of substrate signals. This study was aimed at elucidating the effects of a bone-like mineral (BLM), which is vital in the process of bone bonding to orthopedic implant materials, on the osteogenic differentiation of human MSCs in vitro. Growth of a BLM film (carbonate apatite, Ca/P = 1.55) on poly(lactide-co-glycolide) (PLG) substrates was achieved via surface hydrolysis and subsequent incubation in a modified simulated body fluid. The BLM film demonstrated significantly increased adsorption of fibronectin, and supported enhanced proliferation of human mesenchymal stem cells (hMSCs) relative to PLG substrates. In the absence of osteogenic supplements hMSCs did not display a high expression of osteogenic markers on BLM or PLG. In the presence of osteogenic supplements hMSCs exhibited greater expression of osteogenic markers on PLG substrates than on BLM substrates, as measured by alkaline phosphatase activity and osteocalcin production. Taken together, these data support the concept that substrate signals significantly influence MSC growth and differentiation, highlighting the importance of carrier material composition in stem cell-based tissue engineering schemes.