Biomedical Engineering Reference
In-Depth Information
6.6
Summary
In this section we summarize the conditions under which synthesis of tissue compo-
nents of a peripheral nerve, and the entire nerve itself, was achieved.
Synthesis of a
myelin sheath
around axons elongating from neurons in culture
was observed to occur when SCs were present but not in their absence. The pres-
ence of ECM, including a BM, was not required for the myelination process pro-
vided that SCs and neurons were both present.
Encasement of myelinated axons by
BM
required the presence not only of the
neuron but also of laminin, one of the macromolecular components of BM. Al-
though fibroblasts synthesized BM in the presence of SCs, they were not required.
Nor was the presence of neurons required in vivo; in other studies, the presence of
laminin in the culture medium with SCs sufficed to lead to synthesis of BM. How-
ever, BM was not synthesized when SCs were present in culture in the absence of
both neurons and components of the BM.
Synthesis of a physiological
endoneurium
was not observed in vitro. However,
synthesis of very thin collagen fibrils, reminiscent of those comprising the endo-
neurium, took place in the presence of neurons and SCs in culture, outside newly
synthesized BM, suggesting the possibility that elements of the endoneurium had
been also synthesized adjacent to the myelinated fibers. There was no evidence that
a physiological endoneurium had been synthesized in vivo. Although endoneurial
vessels were synthesized inside minifascicles of the nerve trunk regenerated across
a gap bridged by a silicone tube, the vessels did not form tight intercellular junc-
tions and were, therefore, deficient in their ability to provide a permeability barrier
to conducting fibers of the intrafascicular space.
A mature
perineurium
was not synthesized in vitro; instead, elongated cells were
observed to encircle SCs and axons in culture provided that fibroblasts were also
present but not in their absence. A physiological perineurium was, however, synthe-
sized in vivo using a variety of configurations for tubulation of the transected nerve
gap. The nerve trunk that was synthesized following tubulation of the transected
gap in the rat sciatic nerve with a silicone tube comprised minifascicles surrounded
by a mature perineurium. This newly synthesized perineurial sheath functioned as a
physiological permeability barrier.
There was no evidence that a physiological
epineurium
was synthesized either
in vitro or in vivo.
There was extensive evidence that a
nerve trunk
, innervated along its entire
length of several mm and capable of substantial conduction of electric signals was
synthesized using various kinds of tubes. In certain instances, and provided that
the synthesized length generally did not exceed a few mm, the properties of the
regenerated nerve trunk matched those of the normal nerve. The tubulated con-
figurations that had the highest regenerative activity were those in which the tube
wall comprised collagen with optimized degradation half-life rather than a synthetic
polymer; and had a cell-permeable rather than an impermeable wall. In addition, the
following tube fillings showed very high regenerative activity: suspensions of SCs;
a solution either of aFGF or bFGF; crosslinked ECM networks rather than solutions
