Biomedical Engineering Reference
In-Depth Information
active centre. Upon interaction with H 2 O 2 cysteine sulfenic acid (Cys-SOH) is
formed in the active site of one subunit, which subsequently forms a disulphide
bond with an additional cysteine residue of another subunit. The disulphide bond is
then reduced by Trx, a protein that has two cysteine groups that form disulphide
bonds upon oxidation. Trx, in turn, is reduced by the NADPH-dependent enzyme
thioredoxin reductase [ 22, 32, 71 ] .
Physiological concentrations of ROS are involved in cell signalling. Among oth-
ers, insulin, VEGF, PDGF and TNF-a-induced signalling is ROS dependent [ 21,
71 ]. Protein tyrosine phosphatases (PTP) have been shown to be one of the specific
targets of ROS in cell signalling. Their activity is reduced upon ROS oxidation of
cysteine residues essential for PTP catalysis and can be restored by cellular thiols.
PTP activity regulates, in turn, the signalling cascades induced by receptor tyrosine
kinases [ 22, 45 ] .
ROS play an important role in endothelial cell functions. Vascular NADPH oxi-
dase and endothelial NO-synthase (eNOS) are the important sources of ROS in
endothelial cells. ROS can regulate among others inflammatory and angiogenic
responses of endothelial cells, thus contributing to wound healing [ 52, 90 ] . Oxidative
stress has also been shown to be involved in the pathogenesis of cardiovascular dis-
eases, such as atherosclerosis, hypertension and ischemia-reperfusion injury [ 15 ] .
4.5
Ti6Al4V-Induced Oxidative Stress
Titanium and titanium alloys are materials of choice for many medical applications.
Apart from their excellent mechanical properties, widely accepted titanium corro-
sion resistance and good biocompatibility are the main reasons for wide use of tita-
nium-based biomaterials. The surface of Ti6Al4V, the titanium alloy used in this
study, as well as other titanium-based materials, is normally covered with a 3-5 nm
thick air-formed TiO 2 layer that is thought to be responsible for their biocompatibil-
ity [ 94 ]. However, several facts point to the reactivity of titanium surfaces. Bikondoa
et al. [ 2 ] showed that defects such as oxygen vacancies in a model oxide surface,
rutile TiO 2 (110), mediate the dissociation of water. Another indication for titanium
alloy reactivity is an elevated concentration of titanium in the serum of patients after
implantation. Dramatic increase in titanium serum concentration was demonstrated
in patients with failed knee implants [ 29, 35 ]. Titanium release is a result of the
anodic corrosion process, which takes place at the sites of defects in the TiO 2 layer.
Wear particles formed at the interface bone/implant or implant/cement (used for the
fixation of the implant) can disrupt the protective TiO 2 film, thus further inducing
corrosion and leading to the synergistic fretting-wear process. Metal ions are
released from the metal implants as well as from their wear debris and can reach
significant concentrations in peri-implant tissues and blood. Ti-ion concentrations
in tissues surrounding hip prosthesis can reach 0.6 mM [ 3 ]. It is important to note
that normally only Ti ion elevation is detected in patients with implants made of
titanium alloys. Hence, the concentration of Al showed no differences between
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