Uptake of calcium phosphate nanoshells by osteoblasts and their effect on growth and differentiation

Abstract

The influence of calcium phosphate nanoshell materials on the uptake, viability, and mineralization of human fetal osteoblast cultures was evaluated. Proliferation rates and alkaline phosphatase activity of the cultures were unaffected by the addition of nanoshells to the growth media, but mineralization levels were enhanced by nearly 40%, in contrast to media prepared without nanoshells, or with other calcium phosphate nanomaterials. Nanoshells were internalized by macropinocytosis, and migrated toward the cell nucleus at a rate of 0.34 microm hr(-1). Dye-loaded nanoshells maintained high light emission intensity for over five days while inside the cells, where they could be used as intracellular markers for in vitro microscopic imaging. From these results, it appears that the CaP nanoshells could be developed into a safe sensor and delivery vehicle for osteoblast cell culture studies, whereas the carrier itself has intrinsic bioactivity and may itself upregulate the formation of new bone.

Nanoparticles and their potential for application in bone

“…The expression of alkaline phosphatase, a marker for osteoblast differentiation, 118 was found to be reduced by the addition of titanium and silver nanoparticles, 109,119 whereas alkaline phosphatase activity and collagen type I synthesis, as well as calcium deposition and mineralization, were increased in the presence of calcium phosphate nanoshells, hydroxyapatite-coated iron oxide particles, strontium-doped hydroxyapatite nanocrystal surfaces, and nanostructured zinc oxide and titania in a different experimental series. 111,[120][121][122] These collected findings imply the involvement of complex mechanisms in the internalization of differently composed nanoparticles and in the evocation of variable osteoblast responses.…”

“…Similar to MSCs, osteoblasts were demonstrated to internalize a variety of nanoparticles, such as wear debris, 109 quantum dot/hydroxyapatite composites, 110 calcium phosphate nanoshells, 111 and polymeric particles. 112 Again, various factors influenced nanoparticle uptake and potential cellular effects.…”

Investigation into the role of NaOH and calcium ions in the synthesis of calcium phosphate nanoshells

“…CaP nanoshells were prepared using a base titration method that is a modified version of the method reported by Schmidt et al (2008). First, the hydrated DOPA solution was stirred at 1000 rpm for 1 h and sonicated in an ultrasonic bath for 15 min to reduce the size and improve the size distribution of the DOPA template (Schmidt, 2006).…”

“…Liposomes, however, are non-toxic, biodegradable and non-immunogenic (Lasic, 1995) and thus are safe to be used in the human body. Based on the studies by Schmidt et al (2008), 1,2-dioleoyl-sn-glycero-3-phosphate sodium salt (DOPA) liposomes can be used as templates to form CaP nanoshells. The negatively charged head group of DOPA liposomes assists in the localisation of ions around the spherical surface of the nanoshells (Schmidt et al, 2004).…”

“…A hollow spherical morphology of CaP nanoshells with an average particle size of 152 ± 48 nm was obtained. Meanwhile, the thickness of the CaP nanoshells depends on the quantity of the base solution (Schmidt et al, 2008). Therefore, the template is not the only controlling factor of the shape of the CaP nanoshells because some discrepancies arise in the synthesis when using templates (Pileni, 2003).…”