Biomedical Engineering Reference
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analysis of induced regeneration of peripheral nerves and leads instead to consider-
ation of the endoneurial stroma as an indicator of at least equal importance.
2.1.3
Spontaneously Regenerative Tissues
Let us summarize the results of the four well-documented experiments described
above with models of skin and peripheral nerve injury. The combined evidence
showed that an increase in the severity of injury did not suppress the incidence
of spontaneous proliferation and migration of keratinocytes in skin; nor was the
spontaneous elongation of axons and the myelinating activity of Schwann cells sup-
pressed in nerves. We conclude that keratinocytes and axons, as well as Schwann
cells, are intrinsically capable of restoration of the original specialized functional
tissues (epidermis and myelinated axons, respectively) and that they exhibit this
property after two very distinct injuries. Even when the injured organ as a whole
does not recover its structure, these individual tissue components show a remark-
able ability to migrate and proliferate (skin), or elongate and become myelinated
(nerve).
2.2
Other Tissues Are Nonregenerative
A reactant does not have regenerative activity unless it leads to synthesis of a tissue
that does not regenerate spontaneously. Preparation of an experimental defect for
the study of induced regeneration should, therefore, be based on thorough exci-
sion of nonregenerative tissues prior to the experimental study of a reactant with
unknown activity and critical assays of induced regeneration should be focused on
the identification of these nonregenerative tissues at the completion of the study. In
this section we will identify these tissues.
2.2.1
The Dermis Is Nonregenerative
The structure of the physiological dermis was described briefly above; a more de-
tailed description appears in Chap. 4.
The adult mammalian dermis does not regenerate spontaneously. This can be ob-
served most clearly in the response to a severe injury, such as the excision of the epi-
dermis and of the dermis down to its full thickness (dermis-free defect). The resulting
defect closes spontaneously by contraction of edges and synthesis of epithelialized
scar (Fig. 2.2 ). The epidermis of scar is thinner than that in physiologic skin and
there are few, if any, undulations (rete ridges) in its dermal-epidermal junction; in the
subepidermal region of scar, skin appendages are typically absent. The connective tis-
sue layer of scar (dermal scar) is largely avascular, rarely has nerve endings, and the
collagen fibers are packed tightly with their axes oriented largely in the plane of the
epidermis rather than packed almost randomly, as in physiological dermis. When only
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