Biomedical Engineering Reference
In-Depth Information
Fig. 4.6 Formation of in vitro capillaries by HDMEC embedded in fibrin/collagen type I gel
polymerised on top of PS ( a-c ) or Ti6Al4V alloy ( d-f ) untreated ( a , d ) or treated with 0.25 ( b , e )
or 0.5 mM H 2 O 2 ( c , f ) 4 h after gel polymerisation. The cells were stained with calcein AM for
fluorescent microscopy (scale bar: 300 m m )
angiogenic potential of endothelial cells [ 98 ]. In contrast, in another study treatment
of microvascular endothelial cells with much higher H 2 O 2 concentrations (0.1-
0.5 mM for 15 min) induced tubular morphogenesis in type I collagen gel [ 78 ] . The
differences between the reports could possibly be explained by different cell types
and cell culture media and in vitro conditions.
The situation in vivo might be even more complicated, since other cell types can
modulate angiogenesis in response to oxidative stress. Thus, in in vitro studies exog-
enous H 2 O 2 has been shown to induce VEGF expression in vascular smooth muscle
cells [ 72 ] , keratinocytes [ 5 ] as well as endothelial cells [ 26 ]. This was also observed
for metal ions. Co 2+ has been shown to induce VEGF mRNA expression in osteo-
blasts [ 81 ] and VEGF release by fi broblasts [ 86 ]. Metal ions can also be involved in
the regulation of other growth factors with angiogenic activity. Thus, macrophages
exposed to CoCl 2 secrete bFGF and PDGF [ 42 ]. Metal ions have the ability to modu-
late angiogenesis directly in vitro. In the same in vitro system as in this study CoCl 2
significantly reduced angiogenic potential of endothelial cells [ 67 ] .
Altogether, it is unclear if oxidative stress on Ti6Al4V alloy has an influence on
angiogenesis. Studies on the effect of cathodically polarised Ti6Al4V on the forma-
tion of in vitro capillaries by HDMEC could provide an answer to this question.
In conclusion, a permanent state of oxidative stress appears to exist in endothe-
lial cells grown in direct contact with Ti6Al4V surfaces. Although the nature of the
stressor is unknown, it is possible that corrosion might take place at the interface of
titanium alloy, since ROS formation is expected to occur as a result of the cathodic
partial reaction of corrosion.
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