Biomedical Engineering Reference
In-Depth Information
correlated with structural features of regenerates, they cannot replace morphologi-
cal information. Other functional tests, such as permeability using protein tracers,
can be used to detect the presence or absence of a physiological perineurium or
endoneurium in the regenerated trunk (Azzam et al. 1991).
Electrophysiological data for several tubulated configurations are presented in
Table 6.2 . The data show that, in several studies, the fidelity of regeneration (fraction
of property observed divided by the normal value) reached values close to or even
equal to 1, corresponding to fidelity of regeneration values of 100 %, indicative of
normal behavior. Unfortunately, the data cannot be compared internally because
of the uncontrolled variation of basic experimental parameters (species, length
of study, gap length) that are known to affect the values of electrophysiological
properties. In the majority of studies electrophysiological values were significantly
lower than normal. However, the observation that the regenerated nerve conducted
an electric signal shows without doubt that, in each case, nerve fibers had been
synthesized along the entire length of the nerve trunk. Other data have shown that
substantial numbers of large-diameter fibers (i.e., axons larger than 6 μm known
to be responsible for values of conduction velocity) were present in the tibial and
peroneal branches of the rat sciatic nerve when a 10-mm gap was bridged with a
collagen tube filled with NRT (Chamberlain et al. 2000b).
6.5
Summary of Regenerative Activity of Various Tubulated
Configurations
The criteria for an anatomically well-defined defect in a peripheral nerve have been
satisfied by selecting transection of tissue over crushing; by extending the scale of
injury beyond the scale of the nerve fiber to that of the fascicle; avoiding generation
of a hemisection and transecting instead across the entire diameter of the fascicle
or nerve trunk, all the way to the perineurial tissue (single fascicle) or epineurium
(multifasciculated trunk) surrounding it; and inserting the stumps in a tube in or-
der to contain loss of exudate and invasion of extraneous tissues from neighboring
organs. This tubulated configuration has been extensively used by several indepen-
dent investigators.
Although a very useful experimental configuration for the study of induced re-
generation, the tubulated nerve gap cannot be considered a spontaneously healing
defect because the nonzero regenerative activity of almost any tube induces mea-
surable nerve regeneration. Instead, the spontaneously healing defect is the untu-
bulated gap, healing of which leads to synthesis of neuroma provided that the gap
separating the stumps is sufficiently long.
Two assays were used in this chapter to evaluate the synthesis of nerves in vivo.
The frequency of reinnervation across a tubulated gap, %N , used by several investi-
gators, was the basis of a short-term assay (< 20 weeks) for regenerative activity of
an experimental configuration. %N data from independent investigators, obtained
at various levels of the gap length using two animal species (rat and mouse), were
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