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Glasby, Gschmeissner, Hitchcock, & Huang, 1986 ). Finally, a com-
bined conduit by enriching vein segments with fresh skeletal muscle
fibers (muscle-in-vein conduit) is used to improve effectiveness of
tubulization nerve repair ( Battiston, Tos, Cushway, & Geuna, 2000;
Battiston, Tos, Geuna, Giacobini-Robecchi, & Guglielmone, 2000;
Brunelli, Battiston, Vigasio, Brunelli, & Marocolo, 1993; Fornaro,
Tos, Geuna, Giacobini-Robecchi, & Battiston, 2001; Tos, Battiston,
Ciclamini, Geuna, & Artiaco, 2012 ).
Non-biological grafts . The use of non-biological materials for nerve
reconstruction has a lengthy history started at the beginning of the
twentieth century, and many attempts to use various nonbiological
materials, such as metals, permeable cellulose esters, gelatine tubes, rub-
ber, plastics, etc., were carried out ( Fields, Le Beau, Longo, & Ellisman,
1989 ). The past 30 years saw an impressive increase of experimental
studies aimed at testing new biomaterials for nerve regeneration, such
as decalcified silicone tube, bone tube, nylon fiber tube, polyurethanes,
etc. ( Battiston et al., 2005; Pfister, Papaloizos, Merkle, &Gander, 2007;
Schmidt & Leach, 2003 ). The results have been in general very success-
ful, and their effectiveness is similar and sometimes even superior to tra-
ditional nerve autografts ( Navarro et al., 1996; Yannas & Hill, 2004;
Young, Wiberg, & Terenghi, 2002 ).
Moreover, direct neurotization of denervated muscles is used in situations
where the motor nerve has been avulsed and direct nerve suture or grafting
is not possible ( Brunelli, 2005 ). It has been demonstrated that an axon that is
in contact with a denervated muscular fiber can form a new neuromuscular
junction (NMJ). A prerequisite for this procedure is that there is some resid-
ual trophism of the muscle. Generally, however, neurotization procedures
have poor functional outcome.
Finally, end-to-side neurorrhaphy is based on the assumption that an
intact nerve can “donate” axons to the distal end of an injured nerve
( Papalia et al., 2003 ). This technique has received particular interest when
the nerve gap is large or when the lesion is proximal, both of which severely
limit nerve regeneration.
iii.
3. CHANGES OCCURRING DISTALLY TO THE DAMAGED
NERVE: FOCUS ON SKELETAL MUSCLE
Target organ atrophy might represent a limiting factor in functional
recovery after nerve repair and regeneration. Among the different sensory
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