The Role of Oxidative Stress in the Response of Endothelial Cells to Metals - Biologically Responsive Biomaterials for Tissue Engineering - page 66

Interaction of RANK-positive monocytes with RANKL-positive fibroblasts or
osteoblasts is known to lead to multi-nuclear giant-cell formation and osteoclast
differentiation from progenitor macrophages [ 41 ]. RANKL interaction with its
receptor is inhibited by osteoprotegerin (OPG). Endothelial cells are the main pro-
ducers of OPG, although in the case of synovial membrane formation they are
located remotely from bone resorption sites, further pointing to the important role
of endothelial cells in aseptic loosening [ 55 ] . TNF- a and IL-1b are believed to regu-
late the RANKL system, although the direct influence of metal degradation prod-
ucts on osteoclastogenesis has also been reported. Thus, macrophages that
phagocytosed metal and polymer particles were shown to differentiate into osteo-
clasts capable of bone resorption [ 73 ]. Furthermore, metals undergo electrochemi-
cal corrosion, which can lead to release of metal ions [ 33 ]. Metal particles are also
a source of metal ions, therefore amplifying tissue responses to metal degradation
products. This response can include local and remote toxicity, induction of chronic
inflammation, bone resorption and loosening and failure of implants [ 1, 53, 82 ] .
Although considerable information has been collected since the onset of metal
implant use, the cellular reactions induced by implant degradation products that
may finally lead to implant failure are not yet well studied.
Metal corrosion is an electrochemical process occurring at the interface between
metal and its environment. It consists of anodic and cathodic half-reactions [ 101 ] .
The two half-reactions can be separated spatially. Metal oxidation takes place in the
anodic region, and the electrons released in this process flow to the cathodic region,
where they take part in the oxygen reduction in aqueous solutions with neutral pH.
In acidic pH cathodic half-reaction leads to hydrogen development. While anodic
half-reaction usually takes place at the sites of metal structure irregularities or
mechanical damage, the cathodic half-reaction can occur almost anywhere due to
the conductor properties of metals and the electrolyte-containing body liquids.
As a result of anodic half-reaction, metal ions are released into solution ( 4.1 ).
This process also occurs in vivo and is manifested as increased concentration of
metal ions in the serum of patients with metal implants [ 29 ] . Furthermore, an oxide
layer is formed on the surface of the metal as a result of this process ( 4.2 ).

Anodic Reaction

z + −

(4.1)

Metal dissolution : Me →+ Me z e ,

3

z + +

Oxide formation : Me + z H O →+ MeO z H O . (4.2)

2 z / 2 3

2

In contrast, cathodic partial reaction and the effects of its products on biological
processes are rarely taken into consideration in experimental studies. Importantly,
however, cathodic oxygen reduction ( 4.3 and 4.4 ) proceeds through several partial