Minimum Reactants Required for Synthesis of Skin and Peripheral Nerves; Extension to Tissues of Other Organs - Tissue and Organ Regeneration in Adults - page 181

symbolically represented as E · BM · RR · D · AP. When only appendages are miss-
ing, the representation of skin changes to E · BM · RR · D, also referred to below as
partial skin (PS). Occasionally, rete ridges in a partial organ product are missing,
and the symbolic representation becomes E · BM · D.
The simplified view of an organ as a “linear assembly” of tissues is occasionally
partly supported by experimental evidence. An illustration is the synthesis of an
epidermis attached to a physiological BM (E · BM) in a dermis-free defect (Carver
et al. 1993b); even though the dermis is missing in this tissue product, the epider-
mis-BM bilayer, E · BM, survives for days, a sufficiently long experimental period
to allow the investigators to make several useful observations about its structure.
Another example is the preparation of a BM on a dermis in the absence of an epi-
dermis (BM · D) (Guo and Grinnell 1989); here, the epidermis is missing but the
BM-dermis bilayer persists over a period of time.
Nevertheless, there are often serious problems with this approximation. A tissue
that has been synthesized outside its anatomical context eventually shows evidence
of its instability. Such a tissue may often be tentatively connected physically to the
rest of the organ; and it may be unvascularized or unsupported metabolically by the
organ. For example, there is strong evidence, presented in Chap. 5, that an epider-
mis, synthesized in vitro without a BM or a dermis attached to it, fails to attach itself
on the muscle surface of a dermis-free defect surface (Billingham and Reynolds
1952; Billingham and Russell 1956; Eldad et al. 1987; Latarjet et al. 1987; Carver
et al. 1993b; Cooper et al. 1993; Kangesu et al. 1993b; Orgill et al. 1998). On
the other hand, an epidermis, originally synthesized in vitro in an immature state,
undergoes rapid maturation after it has been placed on a dermal substrate in vivo
(Prunieras 1975; Faure et al. 1987). The evidence clearly shows that the individual
tissue of an organ can be considered as a discrete, stable entity only as a rough first
approximation, e.g., in the context of an experimental protocol where the question
posed is whether the tissue in question can be synthesized at all, even in a state that
is only temporarily stable. We recall that chemists frequently find it very valuable
to include in equations symbolic representation for free radicals, most of which are
very unstable species.
With few exceptions for data obtained with skin defects (see Breuing et al. 1992;
Levine et al. 1993) or nerve defects (Fu and Gordon 1997), data on concentration
levels of diffusible regulators in defects have rarely been reported; extensive data
are a rarity. The uniform cytokine field hypothesis is expected to apply only under
the initial conditions for the process, i.e., immediately after the injury and just be-
fore the addition of any reactant(s). The postulated uniformity is expected to fail
soon after addition of a reactant to the defect. The exudate in the defect typically
responds to addition of a reactant by a modification of its contents, the direction or
extent of which strongly depends on the nature of the reactant.
Finally, the degree of relevance of an irreducible reaction diagram to the process-
es of remodeling in an adult or to developmental processes in a growing organism
is unclear. The conditions in a healing defect, in which an inflammatory exudate is