Biomedical Engineering Reference
In-Depth Information
orthophosphates inside cells, so the existing forms of these particles
during the biological processes could be understood. Further, a
critical step will be the investigation of possible changes of gene or
protein expression in the absence and presence of various nano-
sized calcium orthophosphates, which may directly be related to cell
proliferation and differentiation [13].
An understanding of the interactions between nano-sized
particles and living cells is still a great challenge [663]. Future studies
will focus on (1) the detailed interfacial structure of nanodimensional
calcium orthophosphates and the specific adsorption of proteins or
other matrices; (2) an uptake processes of the nano-sized particles
by cells; (3) metabolism of nano-sized calcium orthophosphates
inside the cells and its possible interference with physiological
reactions. Another important topic is a biological security of nano-
sized particles in general [119, 120, 665, 666] and those of calcium
orthophosphates particularly [667]. For example, toxicity of nano-
sized HA was found to vary considerably, which was related to their
physico-chemical properties. Furthermore, cell death correlate
strongly with the load of nano-sized particles. Namely, the biological
effects of rod-shaped apatite, 50-80 nm in length, were investigated on
human monocyte-derived macrophages [152]. High concentrations
of apatite (200 nano-sized particles per cell) were incubated for 24
h with the macrophages in both serum and serum-free conditions.
This induced high levels of lactate dehydrogenase release, which is
an indicator of cellular damage. However, lower concentrations (20
and 2 nano-sized particles per cell) of the rod-shaped apatite did
not affect the cell viability similarly to the control group that did not
contain nano-sized apatite [152]. Similarly, intracellular dissolution
of nano-sized HA as a function of time suggests that increased
cytoplasmic calcium load is likely to be the cause of cell death [667].
Furthermore, nano-sized calcium orthophosphates were found to
interfere with cell cycle of cultured human ovarian granulosa cells
thus increasing cell apoptosis [668]. That pilot study suggested
that effects of nano-sized particles on ovarian function should
be extensively investigated. Additional examples of cytotoxicity
experiments of nanodimensional calcium orthophosphates are well
described in a recent review [605].
To finalize this topic, one should stress that,
evaluation of
nano-sized particles includes the particle's activity, biodistribution,
and pharmacokinetic properties. Ultimately, all these properties are
in vivo
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