Biomedical Engineering Reference
In-Depth Information
times to the mouse tail, almost all of the stratum corneum and a few layers of the
stratum granulosum were removed; however, the basal and spinous layers remained
intact. Three days later, the epidermis had become three times thicker (hyperplasia)
and the stratum corneum began to reappear; by day 7, the epidermis returned to
its preinjury thickness and was apparently also restored (Stoschek et al. 1992). In
contrast, an increase in the depth of injury to include the underlying dermis led to ir-
reversible injury (Billingham and Medawar 1955; Ross and Benditt 1961; Luccioli
et al. 1964; Dunphy and Van Winkle 1968; Madden 1972; Peacock and Van Winkle
1976; Goss 1992). In studies of vertebrate skin regeneration distinctions have been
drawn between reepithelialization processes that regenerate skin appendages and
inflammatory processes that affect deposition of ECM (Seifert and Maden 2014;
a detailed review of healing mode of tissues in skin appears later in this volume).
Corneal epithelium provides another example where the precise depth of injury
determines the outcome. After a superficial injury, resulting in complete removal
of the epithelial layer, the surface becomes covered by conjunctival cells and the
latter are transformed eventually into typical corneal epithelium. However, some-
what deeper injury, extending into the underlying supporting tissue (stroma), causes
formation of scar and opacity of the eye (McMinn 1969).
A further example of injury that goes deeper than the cell lining at the surface
of an organ is afforded by studies with the intima, the endothelial lining of blood
vessels with large diameter. Superficial scraping of the endothelium by balloon an-
gioplasty is followed by proliferation of cells in the intact lining adjacent to the de-
nuded area and by resurfacing of the lumenal surface. However, an injury extending
deeply into the tissue layer underneath (media) leads to accumulation of scar-like
connective tissue (Stemerman and Ross 1972). Deep vein injury leading to scar
formation has been studied with emphasis on the role of matrix metalloproteinases
which degrade collagen (Henke et al. 2007).
The gut provides another contrast in healing mode between a superficial vs. a
deep injury in a hollow organ. Gastric epithelium responds to superficial injury
(erosion) by rapid reepithelialization. A much deeper wound that has penetrated
through the thin basement membrane into the underlying layers (submucosa and
muscularis propria) leads to scar formation (ulcers; Graham et al. 1992). Similarly,
while the surface epithelia or endothelia of the gall bladder and the urinary blad-
der readily regenerate, the stroma underneath does not (Goss 1964). Deep injury to
the deep (longitudinal) muscle layer of the gut following use of different types of
cautery instruments, acting as models of heat sources, were assessed to appreciate
outcomes from differences in depth of injury (Norton et al. 2002).
The outcome of injury to lung ranges from a mild and reversible response to light
injury, caused by exposure to 100 % oxygen for a few hours, to a lethal process in
which the tiny hollow sacs responsible for gas exchange processes (alveoli) under-
go irreversible changes leading to massive fibrosis. As with other organs, the early
stage of acute lung injury is characterized by an inflammatory process. Depending
on a variety of conditions, this initial stage leads either to limited formation of fi-
brotic tissue with subsequent resumption of lung function or to massive fibrosis that
causes the lung to become nonfunctional (Hertz et al. 1992). In studies of dog lung,
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