Biomedical Engineering Reference
In-Depth Information
and lethality. Additionally, instillation of MWNTs also lead to a nonspecific
interstitial pneumonia-like reaction, and instillation of SWNTs lead to a
decreased bacterial clearance and a loss of pulmonary function.
83,85,156-159
A
study by Lam et al.
160
proved these pathologic reactions to be independent of
metal impurities. In contrast, an earlier study by Huczko et al.
157
reported no
evidence of inflammatory reactions, or perturbation of lung function, after
instillation of MWNTs in guinea pigs. However, this study is also disputed
due to the absence of lung pathology examination.
Since intratracheal instillation is not a correct representation of the natural
entrance of materials into the lungs, Li et al.
161
compared instillation of SWNTs
in the lungs with systemic inhalation, and showed less severe effects from inha-
lation of the material. This is probably due to an altered aggregation size and
distribution in the lungs. This theory is further supported by other studies, in
which administration of agglomerated nanotubes led to the mechanical block-
age of airways.
156,159
On the other hand, pharyngeal aspirated SWNTs caused
severe granulomatous inflammations and accumulation of oxidative stress
markers.
162
In addition to the administration route of CNTs, physico-chemical
and environmental factors, such as the particle size, the free particle life, and
the residence time in the lungs, were also found to determine toxicity to a great
extent.
13,135,163
One of the studies investigating the effects of the particle size
on toxicity was performed by Muller et al.
151
who instilled grinded and non-
grinded MWNTs intratracheally in rats. The nongrinded MWNTs remained
longest in the airways and resulted in granulomas in the bronchi, while the
grinded MWNTs were better dispersed in the lung tissue and showed a higher
degree of pulmonary inflammation with fibrotic granulomas in the alveolar
space. Since there are many other administration routes besides instillation
and inhalation, toxicity studies were performed for these routes as well. It is
very likely that CNTs will be in contact with the bloodstream, after degradation
or remodeling of a bone tissue-engineered construct. When entered into the
bloodstream, CNTs were found to induce thrombosis by platelet aggregation
and to provoke vascular effects related to mitochondrial oxidative modification
and accelerated artheroma formation.
164
However, implantation of degradable
PPF scaffolds with incorporated ultrashort SWNTs in a rabbit model showed no
toxic effects of the released ultrashort SWNTs, as compared with animals that
received pure PPF scaffolds. In contrast, a drastic favorable increase in bone
ingrowth was reported.
165
While toxicity is being investigated elaborately, there is almost no knowl-
edge on the distribution of CNTs in the body after release from scaffold
materials. Part of the problem is that the small size of the particles makes it
impossible to visualize them microscopically unless they are agglomerated.
Oberdorster et al.
135
reported that nanoparticles located in the lung translocate
into the pulmonary interstitium, which indicates that the particles might also
damage other tissues in the body. Also, translocation of nanosized TiO
2
and
iridium-192-labeled particles from the lung into the bloodstream and to sec-
ondary organs was reported.
166,167
To gain insight into the CNT distribution,
