IV EPITHELIALIZATION 677 



planimeter determinations of the wound area (Carrel, 1910; Addison and Loeb, 

 1 9 1 3 ; Spain, 1 9 1 5 ; Carrel and Hartmann, 1 9 1 6 ; Du Noliy, 1 9 1 6 ; Spain and Loeb, 

 19 16; De Beaujeu, 191 7; Amar, 1918; Taffier and Desmarres, 191 8; Du Noiiy, 

 1919; Faure-Fremiet and Vies, 1919; Brownlee, 1924; Dann et al., 1941). It has 

 been concluded from numerous experiments by Carrel, Du Noiiy and others that 

 a greater area heals per unit time during the early phase of repair and that the 

 rate is more rapid in large wounds. Lumiere (191 7, 1918a, b), on the other hand, 

 measured epithelialization in terms of decrease in length and breadth of the 

 wound and concluded that the healing rate is essentially constant. More recently 

 Henshaw et al. (Henshaw and Meyer, 1944) compared both methods using the 

 rabbit's ear as a test object. They found that results are similar and that length and 

 breadth measurements are much easier to perform. These studies as well as those by 

 Howes ( 1 943) and Van den Brenk ( 1 956) show that the growth curve for epithelium 

 is essentially linear although three phases can be detected: (i) lag phase, (2) main 

 growth phase, and (3) reduced growth phase at the end of the healing process. 



The lag phase which persists from 0-3 days is less than half the lag phase required 

 for contraction. During this time lateral migration is proceeding slowly and cannot 

 be detected grossly. Microscopic sections of early wounds do reveal, however, 

 that cell movement commences within a few hours after injury. 



During the main growth phase the rate of lateral extension is essentially constant 

 and the perimeter decreases as epithelialization occurs. Thus the area covered 

 per unit of time is smaller. This observation verifies the seemingly conflicting 

 statements of those who have measured the wound in terms of area: namely, that 

 the rate of area coverage is greater in large wounds and during the early period of 

 wound healing. 



The reduced growth phase commences when epithelial elements from either side 

 of the wound contact one another and continues until epithelialization is com- 

 plete. Initially the new epithelium is considerably thicker than the surrounding 

 normal skin, there are more cellular layers and an absence o{ rete pegs. Eventually 

 it returns to normal thickness but without rete peg formation. 



All wounds do not ultimately epithelialize. There appears to be a critical area 

 beyond which healing fails to take place. The size of this area is variable and is 

 affected by a number of factors. Gravity, for example, almost certainly exerts an 

 influence on human wounds, probably by producing stasis. The lower leg ulcer is a 

 classic example of this phenomenon. When individuals with such ulcers are put at bed 

 rest and the involved extremity is elevated, partial healing occurs although the edge 

 of the migrating epithelium becomes thickened and fails to advance beyond a certain 

 stage. Full-thickness burns involving extensive areas also fail to become covered, 

 although the epithelium begins to migrate under the periphery of the eschar 

 within a few hours after injury. Such burns will not epithelialize even after pro- 

 longed periods and must ultimately be covered with skin grafts. The same phe- 

 nomenon has also been observed in rabbit ear wounds with a diameter larger 

 than 1.5 cm (Van den Brenk, 1956). 



The reasons for this failure of complete epithelialization are not known and 

 represent one of the most vexing problems in the study of wound healing. One can 

 assume that somehow changes in either the cellular or chemical constituents of the 



Literature p. 703 



