Biomedical Engineering Reference
In-Depth Information
primarily bundles of very fine unmyelinated fibers (axons) meandering through ap-
parently disorganized fibrous tissue (Wall and Gutnick 1974).
These results are insufficient to decide the issue of uniformity in scars from dif-
ferent organs. The available data show, however, that, although the tissue products
of repair in skin, tendon, and peripheral nerve comprised mostly collagen fibers,
they appeared to be distinguished by significant morphological differences. The
few available data do not support the hypothesis that there is a tissue with unique
morphology (e.g., architecture of collagen fibers) that could hypothetically be con-
sidered as the universal product of repair processes in different organs.
1.11
Theoretical Views of Adult Failure to Regenerate
Vertebrate limb regeneration has been often interpreted by use of the lucidly pre-
sented paradigm of the highly dedifferentiated cluster of cells, the
blastema
(Hay
1966), that leads spectacularly to limb regeneration once given the chance to form
at the apex of an amputated limb. The blastema paradigm has been used to explain
adult response to healing, mostly by invoking the absence of blastema formation in
cases of failed regeneration. These views were summarized in the form of recom-
mendations for an improved effort to accomplish the goal of limb regeneration in
the adult: The detailed steps consisted of upregulating cell dedifferentiation, stimu-
lating cell division, and delaying redifferentiation (Wallace 1981). A similar hy-
pothesis was presented in an effort to explain the lack of regeneration in amputated
limbs of vertebrates. It was postulated that scar formation at the limb tips of such
vertebrates is the result of a “nonfunctional” defect epidermis that does not maintain
dedifferentiated and undifferentiated cells in the cell cycle over a sufficiently long
period; instead, differentiation occurs early, producing scar and preventing blastema
formation (Tassava and Olsen 1982).
The blastema paradigm has been used to explain observations of certain sponta-
neous regenerative phenomena with mammals. Lack of blastema formation due to
interference from synthesis of scar was invoked to explain the difference between
regenerative and nonregenerative ears in various species (Goss and Grimes 1975).
The basic paradigm was the full-thickness hole in the rabbit ear, a hole known to
regenerate fully, including formation of hair follicles and sebaceous glands. In this
model of dermis-free defect, contraction is not observed and the hole fills up en-
tirely by the synthesis of new physiological tissues (Joseph and Dyson 1966). While
holes in the ears of lagomorphs, including rabbits, hares, and pikas, are thought to
regenerate fully with blastema formation, similar holes in sheep and dogs form scar
tissue (Goss and Grimes 1972, 1975). Comparison of morphological features of
regenerating and nonregenerating ear holes highlighted transient epidermal down-
growths located between the original intact dermis of the skin and the tissues that
gave rise to the blastema (Goss and Grimes 1975; Goss 1980, 1992). In the rabbit,
but not in the sheep or dog, these transient epidermal tissues were presumptive-
ly involved in interaction with the underlying cartilage (epidermal-chondrogenic
interaction) that hypothetically inhibited scar formation.These epidermal tissues
