Biomedical Engineering Reference
In-Depth Information
Synthesis of the entire tissue triad (i.e., practically the entire organ) requires con-
ditions that are clearly more complex than those for synthesis of tissue components
(Table
7.3
). For example, to synthesize skin, minus appendages, it is required to
exogenously supply both keratinocytes and the appropriate nondiffusible regula-
tor. Put differently, synthesis of the entire skin organ requires supply of the two
reactants that must be supplied to separately synthesize each of the two major tissue
components of the organ, that is, keratinocytes to synthesize the epidermis with its
BM and the nondiffusible regulator to synthesize the dermis. The entire skin organ,
without appendages, can be synthesized in practice using a protocol generated sim-
ply by adding the reaction diagrams for synthesis of its two major tissue compo-
nents. This is a remarkably simple protocol for synthesis of an organ.
Does this simple rule also describe the protocol for synthesis of an entire pe-
ripheral nerve? Synthesis of a conducting nerve trunk requires exogenous supply
of a nondiffusible regulator in the form of an appropriate tube, preferably with a
tube filling of high regenerative activity. No other reactant need be exogenously
supplied; in particular, an exogenous supply of Schwann cells, the analog of an
exogenous supply of keratinocytes necessary for inducing synthesis of skin, is not
required to synthesize a conducting nerve trunk comprising thousands of myelin-
ated nerve fibers. It has been concluded above that the stumps of the defect are a
supplier of Schwann cells, fibroblasts, and endothelial cells. The endogenous cell
supply suffices to induce regeneration of nerve fibers; an exogenous cell supply
appears, therefore, unnecessary for this task. Unlike the synthesis of skin, requiring
the exogenous supply both of keratinocytes and a nondiffusible regulator, in exist-
ing protocols for synthesis of a conducting nerve trunk, the exogenous nondiffus-
ible regulator is required but the Schwann cells are not. Do these findings suggest a
fundamental difference in the reactants required for these two organs?
The nerve trunks regenerated so far have closely resembled intact nerves closely
only rarely and under narrowly defined conditions, for example, relatively short
gaps (Table 6.3). Schwann cells have been exogenously supplied in the gap between
the tubulated nerve stumps in a number of cases with very good results, as discussed
in Chap. 6 (Guénard et al. 1992; Kim et al. 1994; Son and Thompson 1995; Ans-
selin et al. 1997). Even in these cases, however, neither the tube type was selected
to take advantage of its role as a nondiffusible regulator nor was a nondiffusible
tube filling with regenerative activity employed. Each of these forms of nondiffus-
ible regulation is separately known to profoundly affect regeneration (Chamberlain
et al. 1998b, 2000a, b). Clearly, there is need for additional study to identify the
tube type as well as the type of active tube filling that can lift the role of nondiffus-
ible regulation of organ regeneration to a sufficiently higher level (Yannas 2000).
However, in these studies where an effort was made to increase the regenerative
activity of the nondiffusible regulators, no use was made of an exogenous Schwann
cell supply. Clearly, the success achieved with synthesis of skin suggests that an
improved peripheral nerve may result from combined use of Schwann cells together
with appropriate nondiffusible regulators.
