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made of the same material (
Aebischer Valentini, Dario, Domenici, &
Galletti., 1987
).
Another way to induce an electrical field along the nerve bridge is to
insert a cathode electrode at the midpoint of a silicone tube and the anode
electrode distal to it creating a constant negative electric field in distal direc-
tion. Using the described technique, two independent studies were per-
formed which provided the electrical stimulation over 21 days in a 5-mm
nerve gap and demonstrated opposing results. The first study described a tre-
mendous increase of the number of regenerated axons proximal to the cath-
ode (
Roman, Strahlendorf, Coates, & Rowley, 1987
) and the other
deleterious effects on the axonal regeneration distal to the cathode
(
Hanson & McGinnis, 1994
). It had to be concluded that this way to apply
electrical stimulation to a regenerating nerve is difficult to control.
Current developments to apply electrical stimuli via conductive nerve
guidances channels and scaffolds have been recently discussed in a compre-
hensive review (
Ghasemi-Mobarakeh et al., 2011
). This field of bioengi-
neering is still evolving, and further investigations are needed to design
the optimal scaffold combining intrinsic electrical stimulation paradigms
for optimal support of regeneration and axonal guidance.
Very recently, however, it has been described that copper loop-
electrodes secured at the proximal and distal end of a conductive micro-
channel scaffold could be used for brief (1 h), low-frequency (20 Hz)
electrical stimulation to induce an electrical field along a 15-mm rat sciatic
nerve gap (
Huang et al., 2012
). Repeated electrical stimulation (every second
day at eight times) together with nerve reconstruction bymeans of themicro-
structured conductive nerve guide demonstrated high efficacy to promote
axonal and functional recovery of large nerve defects (
Huang et al., 2012
).
The bioengineering field provides diverse possibilities to combine
regeneration-supportive strategies in an optimized nerve reconstruction
treatment, and further developments are needed. However, electrical stim-
ulation has already been combined to other treatments
that
showed
regeneration-promoting activities as well.
2.4. Electrical stimulation combined with other treatments
We performed a study in which we combined the brief, low-frequency
direct stimulation protocol with the transplantation of silicone tubes con-
taining na¨ve Schwann cells or Schwann cells genetically modified to over-
express fibroblast growth factor-2 (
Haastert-Talini et al., 2011
). The latter
