Biomedical Engineering Reference
In-Depth Information
nerve, as nondiffusible regulators. Although it may appear somewhat strange to ap-
ply this term to a tube, there is strong evidence, presented in Chap. 6, that tubulation
itself induces significant regeneration of transected peripheral nerves across a small
gap. There is also evidence that the tube suppresses the formation of a sheath of
contractile cells around a healing nerve stump (Soller et al. 2013); such suppression
is related to the extent of regeneration obtained as described in later chapters and
appears also to sensitively depend on the physicochemical properties of the tube
wall, including surface chemistry and cell permeability (Chamberlain et al. 2000a).
The reaction diagrams in Table
7.2
provide certain clear guidelines. Considering
the series Dgs. N1-N5, we notice that synthesis of a myelin sheath (myelination)
around a neuron (myelinated axon. MAX) did not require the presence of fibro-
blasts; nor did it require the presence of ECM in the form either of a type I collagen
substrate, COFL (Dg. N1), a reconstructed BM, RBM (Dg. N3), or laminin (LA)
(Dg. N5). According to Dg. N2, axons did not self-myelinate in culture. An in vivo
environment was not required for myelination. Synthesis of a myelin sheath was not
obtained simply in the presence of Schwann cells in culture; the presence of axons
was required (Dg. N4).
Synthesis of a BM encasing Schwann cells was achieved in culture, in the pres-
ence of axons and Schwann cells (Dg. N7). An in vivo environment was not re-
quired for BM synthesis. The resulting nerve fiber, MAX
ยท
BM, is the elementary
unit of conduction in the nerve trunk. Neither isolated axons (Dg. N6) nor isolated
Schwann cells (Dg. N8) yielded a BM. Although axons and Schwann cells syn-
thesized a BM in the presence of laminin (Dg. N9), the presence of laminin was
not required, as shown by Dg. N7. Interestingly, a BM could be synthesized in the
absence of axons (i.e., in the absence of myelination), both in vitro and in vivo.
For example, BM was synthesized in culture in the presence of Schwann cells and
laminin (Dg. N12) or Schwann cells and fibroblasts (Dg. N11). BM was also syn-
thesized around Schwann cells inside a silicone chamber that bridged a 10-mm gap
in the rat sciatic nerve. The chamber was filled with a collagen matrix seeded with
exogenously supplied Schwann cells; however, the tube was closed at both ends
by a Millipore filter that excluded axons although allowing entry of exudate from
the stumps (Dg. N10). The BM normally encases Schwann cells in physiological
tissues, rather than existing separately from them; for this reason, we will select
Dg. N7 as the irreducible reaction diagram for synthesis of a BM encasing Schwann
cells that have formed a myelin sheath around axons in culture; we will also select
Dg. N12 as an irreducible diagram for synthesis of a BM in culture in the absence
of a myelin sheath.
A physiologically functioning endoneurium was not synthesized when neurons
were cultured with Schwann cells (Dg. N13). Evidence that the vasculature of the
endoneurium was not physiological was observed in a study of the transected and
tubulated nerve (Dg. N14), even when synthesis of a physiological perineurium had
been demonstrated in the same nerve trunk (Azzam et al. 1991).
A perineurium was not synthesized in culture in the presence of neurons and
Schwann cells (Dg. N15) or in the presence of neurons and fibroblasts (Dg. N16).
In the presence of all three cell types in culture (i.e., neurons, Schwann cells, and
