Biomedical Engineering Reference
In-Depth Information
the two tubes differed in both chemical composition and protein permeability, it is
not possible to assign the observed advantage in regenerative activity unambigu-
ously to either property of the collagen tube. Filling the collagen tube with nerve
regeneration template (a scaffold very similar to the dermis regeneration template,
DRT) led to a significant increase in electrophysiological properties (conduction
velocity and amplitude) of the regenerate over the PBS-filled collagen tube control
after 60 weeks (Chamberlain et al. 1998b). A direct comparison of collagen tubes
and silicone tubes in the mouse sciatic nerve model gave a significant advantage,
corresponding to a
ΔL
value of 1.8 mm, in favor of the collagen tube (Navarro et al.
1996).
The effect of filling of collagen tubes with nerve regeneration template (NRT)
could not be expressed in terms of a length shift,
ΔL,
as both the group treated with
the NRT-filled collagen tube as well as the group treated with the unfilled collagen
tube were reported to lead to a frequency of reinnervation of 100 %. The results
suggested that the 10-mm gap length used in the study (Chamberlain et al. 1998b)
was not long enough to confirm the significant advantage in the electrophysiologi-
cal performance of the regenerate that formed in the NRT-filled collagen tube over
that which formed in the unfilled collagen tube (see above). However, morphologi-
cal data clearly showed an increase in average axon diameter from 30 to 60 weeks,
providing evidence for continuing remodelling processes after long periods of re-
generation (Chamberlain et al. 1998b).
A longer gap was provided for study of the NRT-filled collagen tube by selecting
a surgical procedure that had been described earlier (Lundborg et al. 1982a). In the
so-called cross-anastomosis (CA) procedure, both contralateral sciatic nerves of the
rat are transected; the right sciatic nerve is transected proximally at the sciatic notch,
allowing the right distal segment to be placed near the left proximal stump inside
the opposite ends of the experimental tube. Unlike the more common procedure that
is limited to the femoral site segment of a single sciatic nerve, the CA procedure
allows study of gap lengths over 20 mm. There is some evidence that values of the
critical axon elongation measured by the CA procedure lead to consistently lower
values of critical axon elongation than at the commonly used femoral site, where
both stumps have originated from the same nerve; for example, time-independent
values of
L
c
for PBS-filled silicone tubes were 11.7 ± 0.5 mm for the femoral site
but only 7.7 ± 0.04 mm for the CA site (Spilker 2000). A very large value of the shift
length,
ΔL
> 25 mm, was estimated for an NRT-filled collagen tube that had been
implanted by the CA procedure in the rat. The data included
%N
= 100 at 16 mm
(6 out of 6 animals),18 mm (5/5),20 mm (5/5), and 22 mm (4/4), one of the longest
gaps studied in the rat sciatic nerve (Spilker 2000). The lack of sufficient indepen-
dent data at the CA site makes it difficult to compare the performance of this con-
figuration with those studied at the commonly used single-leg site.
A library of almost identical collagen scaffolds, differing only in scaffold deg-
radation rate, showed that maximum quality of regeneration across a 15-mm gap
in the rat sciatic nerve was obtained when the degradation rate had been optimized
(using crosslinking) to 2-3 weeks (Harley et al. 2004). This finding is critical to
a description of the molecular mechanism of regeneration induced by an active
