Biomedical Engineering Reference
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as DRT. One protocol that approximates these conditions in vitro is Dg. S26; how-
ever, no dermis was synthesized under these conditions. Diffusible regulators (i.e.,
soluble chemical messengers for cell communication) such as cytokines and growth
factors are present in the exudate that flows very early into the defect; they are also
secreted by degranulating platelets and are synthesized by cells migrating into the
defect. The cytokine field produced in this manner comprises the time-dependent
concentrations of several cytokines known to be simultaneously present in the de-
fect during spontaneous healing; these concentrations are probably changing in re-
sponse to signals from adjacent cells or tissues (paracrine signals). Several of these
diffusible regulators have been identified and their individual role outlined (Clark
1996b). However, the dynamics of the cell-cell signaling processes during sponta-
neous healing in the presence of multiple cytokines have not been elucidated; con-
sequently, it is not clear just what the complex cytokine field contributes to tissue
synthesis in the dermis-free defect. Clearly, however, the cytokine field is missing
in studies conducted in vitro.
In conclusion, the available evidence strongly suggests that the defect is a re-
quired supplier both of fibroblasts and endothelial cells, as well as of the time-
dependent cytokine field, during the synthesis of a dermis. It is well known that
these two cell types are involved in cell-cell signalling (the signals being the cyto-
kines), especially during fibroplasia and angiogenesis, the major pathways respon-
sible for the synthesis of granulation tissue and dermal scar (McPherson and Piez
1988; Eckes et al. 1996; Madri et al. 1996). Clearly, fibroblasts, endothelial cells
and the cytokine field are intimately related and their function cannot be considered
separately. We conclude that it is not the separate requirement for the cytokine field
or for fibroblast or endothelial cell presence, but the specific regulation of fibroblast
and endothelial cell function by the cytokine field, that must be primarily respon-
sible for the uniqueness of the in vivo environment in the synthesis of certain skin
components.
7.4
Conditions for Synthesis of Peripheral Nerves
We now examine the reaction diagrams for synthesis of tissue components of pe-
ripheral nerves, presented in Table 7.2 .
Introduction of a neuron in a reaction medium will not be regarded as indicat-
ing the supply of a reactant. Certainly, axons are indispensable components of a
physiologically conducting nerve fiber and axon elongation is indispensable during
regeneration across a tubulated gap. Nevertheless, in the context of a chapter de-
voted to synthesis of tissues, the axon will be viewed here simply as the substrate on
the surface of which a highly specialized tissue, the myelin sheath, is synthesized.
Although axons will be explicitly shown in the reaction diagrams below, their pres-
ence will be regarded as being equivalent to the presence of a constant background
in the protocols.
In the symbolic language of this chapter, we will classify the silicone tube, as
well as several other tube types used in tubulation of the stumps of a transected
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