IV EPITHELIALIZATION 675 



epidermal edge; (b) Detachment of the epidermis from the basement membrane; 

 {c) Migrationof epithelium over the wound surface; (d) Cessation of cell movement; 

 (e) Reattachment; and (/) Remodeling of the wound. 



(a) Retraction of the epidermal edge 



Retraction of the epidermal edge occurs at the time of injury. It is distinct from 

 that of the dermis and plays little role in mammalian skin, where epithelium is 

 bound firmly to the underlying dermis. In amphibia, where the epidermis is loosely 

 attached, it is quite marked, being 2 to 5°o of the wound diameter (Lash, 1955). 



{b) Detachment of the epidermis fro^n the basement membrane 



The nature of the dermo-epidermal junction in mammals is not clearly under- 

 stood, as has been pointed out in recent reviews by Montagna (1952), Medawar 

 (1953), and Allen (1954). There is even some question as to whether a true base- 

 ment membrane exists. Studies with the electron microscope have shed much 

 light on this subject. In the adult human, human embryo, and rodent skin a sub- 

 microscopical membrane separates dermal connective tissue from the overlying 

 epidermis (Selby, 1955). This argyrophilic membrane is 300 to 400 A thick and 

 is separated from the epidermis by 300 A. It does not correspond to the classic 

 basement membrane but possibly consists of a layer of reticulin fibers. The work 

 of Bear (1952) and Gross (1950) suggests strongly that these reticulin filaments 

 fuse to form the wider collagen fibers of the deeper dermal layers. This theory 

 is in part substantiated by the fact that they possess the same periodicity and are 

 considerably narrower in character than those of the upper layers. 



The mechanism of attachment seems to be as follows: electron-dense areas 

 composed of small, rod-shaped granules are spaced along the basal cell edge 

 facing the connective tissue. They are converged upon by cytoplasmic filaments. 

 Thus the junction consists of filaments from the dermal membrane which are 

 attached to rod-shaped granules on the epithelial cell. Examination of a wound 

 edge with the light microscope does not always show a separation between the 

 epithelium and the basement membrane, as one would expect, if the epithelium is 

 to migrate during wound healing. A study of this area with the electron microscope 

 during the phase of migration should prove of interest. 



Detachment in amphibia has been demonstrated by Lash (1955, 1956). Here 

 the epidermal surface adjacent to the basement lamella consists of a series of 

 bobbin-shaped bodies. Weiss and Ferris (1954a) have postulated that these 

 bodies play a role either in attachment or fibrogenesis. The adjacent base- 

 ment membrane is a complex structure consisting of 20 (± 2) layers of straight 

 collagen fibers stacked crosswise (Porter, 1954). The same pattern occurs in Anura 

 and Urodela (Weiss and Ferris, 1954b). Following injury, detachment begins at 

 the edge of the denuded surface and proceeds in a wave-like fashion, and migration 

 does not begin until this stage is accomplished (Lash, 1955). 



{c) Migration of epithelium over the wound surface 



(i) Stimulus. After a lag phase of several hours epithelium begins to wander out 

 over the wound surface. Although it was previously proposed that this movement 



Literature p. 703 



