Biology Reference
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implanted in an intact nerve but to have the nerve grow through them. The
first andmost investigated design of a regenerative electrode was the sieve elec-
trode ( Fig. 2.1 F), composed of an array of via holes with electrodes built around
them and placed in the gap between stumps of a transected nerve. Thus,
the axons regenerate through the holes, and the electrodes can interface the
small bunch of axons of every single hole reaching a high level of selectivity.
The most ambitious utilization of sieve electrodes is the implantation in
the sectioned nerves of an amputee so as to interface the axons that formerly
innervated the severed limb for a bidirectional interface with the prosthetic
limb. However, it cannot be discarded the even more challenging use of
controlling signal rerouted from the regenerated nerve to the adequate distal
target after simple nerve transection ( Rosen, Grosser, &Hentz, 1990 ). Sieve
electrodes have not been implanted in humans yet, but several studies have
verified nerve regeneration through these electrodes with successful inter-
facing of the regenerated fibers in frogs ( Kovacs et al., 1994 ), fish
( Mensinger et al., 2000 ), rats ( Navarro et al., 1996, 1998 ), rabbits
( Kawada et al., 2004 ), and cats ( Panetsos, Avenda˜o, Negredo, Castro, &
Bonacasa, 2008 ). Regenerative electrodes not only grant selective stimula-
tion of small groups of regenerated fibers ( Lago, Udina, et al., 2007 ) but also
allow providing receptive signals from different sensory areas to the interface
( Navarro et al., 1998 ). Despite full nerve regeneration is not achieved due to
the obstacle of the sieve for growing axons, sieve electrodes have shown
promising results after 30 months implant in cats, as only minor electrical
changes were found in regenerated nerves and sound levels of functionality
were reached ( Panetsos et al., 2008 ). However, extensive research done with
these electrodes has raised some questions that still need to be solved. Sieve
electrodes are thought to make the axons grow through small holes limiting
the possibility to use these electrodes in acute experiments ( Navarro et al.,
2005 ). Long-term studies have shown signs of axonopathy in some
regenerated fibers due to compression after 6 months in rats ( Lago,
Ceballos, Rodr´guez, Stieglitz, & Navarro, 2005 ). In addition, axons do
not grow following the same fascicle topography than in the intact nerve
and this disorganization can difficult optimal interfacing of distinct fascicles.
Moreover, small unmyelinated axons have a higher growing capacity in
comparison with larger myelinated axons through the sieves; this favors
the smaller axons to grow through the center of the electrode submitting
larger axons to the periphery or even outside the interface thus preventing
their possibility to be properly contacted ( Castro, Negredo, & Avenda˜o,
2008; Lago, Udina, et al., 2007 ).
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