Biomedical Engineering Reference
In-Depth Information
membrane also led to significant injury to the stroma. The persistent observation
of scar formation in organs in which the basement membrane had been penetrated
(Vracko 1974) can, therefore, alternatively be explained entirely by reference to the
injury inflicted to the stroma.
The collective evidence strongly suggests that the basement membrane is the
limiting boundary that separates regenerative from nonregenerative tissues in sev-
eral organs.
2.3
Are Basement Membranes Regenerative?
Independent data of high structural resolution have shown that healing processes
inside the basement membrane can be separated from those in the tissues imme-
diately over and underneath it. Improved experimental approaches have provided
intriguing information on the limiting surface inside the basement membrane that
separates regenerative tissues from nonregenerative ones.
In studies of epidermolysis bullosa (EB), an inheritable disease that leads to
compromised defect healing in skin, formation of suction blisters was used as the
method for generating defects (Uitto et al. 1996). The blister pulled and separated
the epidermis away from the dermis, splitting the dermo-epidermal junction at the
mechanically weakest tissue layer. In skin, hemidesmosomes line the interior of
the basal cell membrane (the interface between epithelia and basement membrane)
and the basement membrane comprises three specialized structures: lamina lucida,
lamina densa, and the fibroreticular layer; the latter is closest to the stroma. The
location of the plane of tissue separation was identified in this study by transmission
electron microscopy, and the extent of scarring resulting at the end of the healing
process was recorded separately.
Although as many as ten different forms of EB have been tabulated (Lever and
Schaumburg-Lever 1990), the results of this study (Uitto et al. 1996) were grouped
according to three major categories of inherited defects. In the first (EB simplex),
blister formation occurred through the epidermis and healing proceeded without
significant scarring. In the second type of defect (junctional EB), tissue separation
occurred through the basement membrane, specifically within the lamina lucida,
while the lamina densa remained intact; in this case also, no scarring was observed
(Haber et al. 1985). Finally, in the third type of defect (dystrophic EB), tissue sepa-
ration occurred below the basement membrane, within the papillary dermis, at the
level of anchoring fibrils; here, healing resulted in extensive scarring (Uitto et al.
1996). The data clearly suggest that the skin basement membrane itself is regenera-
tive (Fig.
2.6
).
Epidermolysis bullosa (
EB
) is a cluster of genetic diseases characterized by fragility and easy
blistering of specific layers of skin. In
EB
simplex, the separation occurs at the level of basal kera-
tinocytes of the epidermis; healing occurs without scarring. In junctional forms of
EB
, the
blister
forms at the level of lamina lucida of the basement membrane and also leads to healing without
scarring. However, in dystrophic forms of
EB
, cleavage occurs within the subepidermal region of
