Biomedical Engineering Reference
In-Depth Information
corrected for these variations in experimental protocol by use of the critical axon
elongation,
L
c,
a measure of the regenerated length beyond which axon elongation
drops to zero. The silicone tube configuration was assigned the status of a standard
and the critical axon elongation of different configurations were compared with that
of the standard, yielding a parameter, the length shift,
ΔL
, that was used to compare
a large number of configurations described in the literature on a self-consistent ba-
sis (Table
6.1
). Electrophysiological observations, obtained in the long term (> 20
weeks), were used to obtain values for the fidelity of regeneration, the fraction of
the normal value for a functional property that was recovered following a lengthy
regeneration process (Table
6.2
).
Comparison of several tubulated configurations in terms of the corresponding
value of the length shift, elicited from the data in the literature, showed several
significant trends in regenerative activity that are summarized below. The analysis
is primarily based on data in Table
6.1
.
Tubulation of nerve stumps had very significant regenerative activity relative
to stumps in a nontubulated gap. Insertion of the distal stump inside the tube also
had very significant regenerative activity compared with leaving the distal stump
outside or to simple ligation of the distal tube end. Tubes constructed from two
synthetic polymers (plasticized poly(lactic acid) and a copolymer of LA and
ε-caprolactone) showed significantly more regenerative activity than a tube based
on an ethylene-vinyl acetate copolymer. A cell-permeable tube wall showed very
significant regenerative activity compared with the impermeable tube; however,
a protein-permeable tube did not show such an advantage. Tubes fabricated from
the highly porous nerve regeneration template, a collagen scaffold with optimized
degradation half-life, showed very high regenerative activity.
Tube fillings showed widely varying activity. SC suspensions had very signifi-
cant regenerative activity. Incorporation of bFGF and aFGF, but not NGF, solutions
showed significant to very significant regenerative activity. Solutions or gels based
on ECM macromolecules such as collagen, fibronectin, and laminin did not have
significant regenerative activity. Insoluble substrates that showed very significant
regenerative activity when used as tube fillings were either highly oriented fibrin
fibers, polyamide filaments that were axially oriented and did not fill the entire
lumen, or highly porous ECM analogs, including the nerve regeneration template
(NRT), with oriented pore channel axes, high specific surface, and a sufficiently
optimized degradation rate.
On the basis of the evidence form critical axon elongation data it has been pos-
sible to review theories of peripheral nerve regeneration for their ability to account
for the data. These theories include the neurotrophic theory, the contact guidance
theory, the pressure cuff theory and the BM microtube theory. The reader is referred
to the literature for a review of this analysis (Yannas et al. 2007). Other approaches
for selection of nerve conduits have also been presented (di Summa et al. 2011,
2014; Pabari et al. 2014).
