Biomedical Engineering Reference
In-Depth Information
combination of ultrasonication and centrifugation using organic solvents
[201]
. During the purifica-
tion by strong acids, chemical oxidation occurs at the end cap of CNTs and at the wall-defect sites
resulting in the introduction of functional oxygenated groups
[193]
. Purified SWNTs have the most
adverse effect on cellular behavior because of its larger surface area when compared to MWNT,
carbon graphite, active carbon, and carbon black
[188]
. Purified SWNTs are more cytotoxic than
unmodified SWNTs, due to the functional group (carboxyl and hydroxyl) density on SWNT surface
generated by acid treatment
[191,202,203]
. Other studies have indicated that higher degree of side-
wall functionalization leads to reduced cytotoxicity
[204]
. Functionalized CNTs can cross the cell
membrane and accumulate in the cytoplasm without being toxic to cells
[205]
. Furthermore, these
functional groups also allow CNTs to conjugate with other biomolecules such as nucleic acids and
proteins enhancing biocompatibility
[206]
. Surface chemistry also affects aggregation of nanotubes
resulting from van der Waals interactions between the tubes. Unmodified CNTs cannot disperse in
water due to their hydrophobic nature and accumulate into cells, tissues, and organs leading to
toxicity
[207]
. Cytotoxic effects of well-dispersed SWNT were compared with the toxicity of
agglomerated SWNTs with asbestos as a reference. Rope-like agglomerated nanotubes were
reported to be the most toxic.
MWNTs with diameter of 20
40 nm and average lengths of 220 and 825 nm induce similar
activities and slight toxicities
[208]
. SWNTs with length shorter than
189 nm are more easily
consumed and induce greater toxicity
[209]
. Larger lengths of CNT (in micron range) are unable to
cross the cell membranes. Methods used to disperse CNTs affect cytotoxicity
[210,211]
. The type
of CNT (single wall versus multiple walls) could also affect toxicity since the surface area per unit
mass of SWNT is greater than that of MWNT. It is difficult to compare the results between toxicity
induced by SWNT versus MWNT as it is unclear whether results should be compared to same
mass concentration of CNT or the same total surface area.
In vivo toxicity studies have been conducted using CNTs. Pulmonary toxicity was attributed to
mechanical blockage of the airways in both rat
[182,212]
and mice
[213
B
215]
models. Warheit
et al.
[182]
suggested that granuloma formation within the lungs of rats occurred due to the pres-
ence of SWNT aggregates. Other studies have reported that intravenously administered low doses
of functionalized CNTs showed no toxicity even after persisting in the body for 4 months
[216]
.
Even at high concentrations, modified MWNT showed only low acute toxicity
[211]
. In vivo
studies for applications in bone
tissue engineering have also yielded promising results. Usui et al.
[217]
reported that MWNT implanted into mouse skull induced minimal local inflammation and
showed high bone
tissue compatibility by permitting bone repair. In one study
[218]
, a threefold
increase in bone
tissue growth was observed in defects repaired with scaffolds containing nano-
tube composite over polymer scaffolds. CNT composites also permitted bone formation and bone
repair without signs of rejection and inflammation when implanted in critical-sized rat calvaria
[219]
. Composites of MWNT/polycarbosilane implanted in the subcutaneous tissue and femur of
rats showed little inflammatory response and supported newly formed bone
[220]
. Nanotube-filled
nanocomposite-derived microcatheters exhibited highly reduced thrombus formation compared to
pure nylon-derived microcatheters when implanted in adult beagle dogs
[221]
.
It is more relevant to evaluate the toxicity of scaffolds that are assembled for tissue engineering.
Here substrates are developed with the aim of directing and controlling cellular behavior on these
scaffolds capable of replacing or regenerating tissues
[222
225]
. The scaffolds are 3D structures
that act as substrates for cell adhesion and proliferation. Recently scaffolds based on CNTs have
