Biomedical Engineering Reference
In-Depth Information
of nonfunctionalized, hydrophobic CNTs is linked to their high potential to
penetrate and aggregate within the hydrophobic cell membrane, leading to
rupture and cell death. Zanello et al.
148
stated that neutrally charged CNTs
resulted in optimal osteoblast proliferation and bone matrix-forming func-
tions, compared with sidewall functionalization that introduced a positive
or negative net charge. Besides the type of sidewall groups, the amount of
sidewall groups also influences the cytotoxicity, for there is an inverse rela-
tion between the toxic potential and the degree of sidewall functionaliza-
tion.
78,85,149
Another important parameter related to toxicity appeared to be
the mass of the CNTs. Short MWNTs showed higher cytototoxicity than
long ones. Also, short SWNTs displayed a higher toxic behavior than short
MWNTs.
150,151
Finally, even though toxicity decreases with an increase in
purification and sidewall functionalization, the toxic behavior of CNTs is
still concentration, dose, and time dependent, as shown in a study by Cui et
al. Here, cell proliferation of human embryo kidney cells was inhibited, and
cell adhesive ability decreased, in a dose- and time-dependent manner after
addition of suspended SWNTs.
85,137,140
However, we should stress that the literature is not consistent, and frequently
contradictory results are described. Ingestion of MWNTs and SWNTs by macro-
phages, for instance, leads to necrosis and degeneration, as described in a study
by the group of Jia et al.
150
while it does not lead to any signs of toxicity in a study
by the group of Cherukuri et al.
152
Also, the addition of three types of SWNTs,
namely purified SWNTs, SWNTs functionalized with 4-
tert
-butylphenylene,
and ultrashort SWNTs, to a fibroblast culture did not result in any cytotoxic-
ity in a study by Shi et al.
153
Another noticeable report is the favorable positive
cellular interaction, as well as the sustained cell viability, of macrophages and
leukemia cells, after the addition of functionalized SWNTs in suspension.
152,154
Finally, Bottini et al.
155
found an increase in toxicity to be correlated to a decrease
in hydrohobicity of CNTs, thus contradicting the earlier reported opposite
correlation.
4.4.3.2
In Vivo
Studies on Carbon Nanotubes
The large surface area of nanoparticles allows easy entrance to the body,
and makes them more biologically active than their larger counterparts.
135
Potential routes for CNTs to enter the body are by inhalation, through the
skin, by ingestion, or by injection/infusion. Although we mainly focused
on nanomaterials incorporated into bone constructs in our
in vivo
experi-
ment sections, for a full overview of the pathological effects of CNTs, it is
necessary to mention data on inhalation toxicity, which is the most studied
administration route.
In vivo
studies with MWNTs, as well as with SWNTs, show pulmonary
responses after inhalation to be of immediate concern. Intratracheal instil-
lation of MWNTs and SWNTs in mice, guinea pigs, and rats lead to a dose-
dependent formation of granulomas, fibrosis or necrosis, inflammation,
