Biomedical Engineering Reference
In-Depth Information
The response of skin to two extreme types of injury, namely, a mild injury (blis-
tering) and a very severe injury (full thickness skin excision), has been described
extensively. A blister can be inflicted by a brasion or by a very mild burn. Shear
forces or thermal injury cause failure at the interface between epidermis and dermis
(dermal-epidermal junction), followed by exudation of lymph fluid into the injured
space (Asmussen and Sollner 1993). A similar model wound can be generated by
repeated stripping of the epidermis with a tape (Nanney and King 1996). The blister
typically separates the dermis and the epidermis at the level of the basement mem-
brane; if the experiment is conducted carefully enough, the basement membrane re-
mains mostly intact. The underlying dermis reddens, swells, and often forms a small
amount of exudate but remains, otherwise, relatively intact. Since, the injury does
not extend deep into the dermis, blood vessels are not injured and there is no bleed-
ing. Soon, the necrotic epidermis forming the blister is sloughed off, leaving behind
an epidermis-free surface. Keratinocytes migrate from the injured edges and reat-
tach themselves onto the inner layer (lamina densa) of the relatively intact basement
membrane (Krawczyk and Wilgram 1973; Beerens et al. 1975). Keratinocyte mi-
gration also originates in the appendages of skin (hair follicles, sweat glands, seba-
ceous glands) that are located in the dermis. Migration of keratinocytes finally leads
to formation of a continuous cell layer (confluence) over the basement membrane
and the migration stops; the cells undergo mitosis and eventually form a maturation
gradient by differentiation to a multilayered and keratinizing epidermis (Fig.
2.1
).
No sign of the blister can be detected on the regenerated epidermis, indicating that
the ruptured dermo-epidermal junction has been restored (Briggaman et al. 1971;
Marks et al. 1975; Konig and Bruckner-Tuderman 1991; Stenn and Malhotra 1992).
A much more severe injury is excision of the epidermis and of the entire layer of
dermis to generate a full-thickness excisional skin wound (referred to often below
as a dermis-free defect). In a useful example, involving a clinical trial of human
volunteers, a dermis-free defect in the forearm was studied and a richly vascularized
connective tissue (granulation tissue) soon formed inside the defect. Two different
processes of defect closure, contraction of the dermal edges and epithelialization,
were monitored. After the 17th day, contraction of the dermal edges had led to
closure of somewhat less than half of the original defect area (Fig.
2.2
). The bal-
ance of defect closure, somewhat over 50 % of the original area, was contributed by
epithelialization (Ramirez et al. 1969). A simple analysis of the data in this study
shows that the keratinocytes from the edges migrated and proliferated over dis-
tances at least as long as 15 mm and covered an area totaling more than 5 cm
2
.
The two familiar examples of skin wound healing described above span the
range from complete recovery of physiological skin structure after careful blister-
ing, all the way to formation of scar without recovery of physiological structure
after excision of the dermis through its full thickness. The outcomes of these two
healing models are as different as they can be and will be used below as paradigms
of the two basic outcomes of a healing process (regeneration vs. repair). Neverthe-
less, in both cases, keratinocytes migrated and proliferated extensively from their
original location at the edge of the injured tissue, eventually forming a regenerated
epidermis over a large area. The evidence clearly shows that extensive epithelializa-
