676 WOUND HEALING 8 



resulted from an increased mitotic rate at the wound edge which forced the cells 

 across the denuded surface (Eberth, 1891 ; Von Bardeleben, 1901), Barfurth (1891) 

 demonstrated conclusively that such was not the case, and his work has been sub- 

 stantiated in numerous classes, including mammals. The stimulus which sets into 

 motion active migration has not been elucidated, and attempts to explain it on 

 the basis of a wound hormone have thus far failed. Weiss (1950) proposed that 

 creation of a defect disturbs an existing equilibrium and permits cells to resume 

 their inherent propensity of movement. The mechanism of such an equilibrium 

 must rest on a molecular level and remains obscvire at present. Furthermore, the 

 manner in which such a stimulus is communicated to the cell and subsequently 

 motion initiated, is unknown. 



(ii) Source of energy for migration. Interesting findings are now available concerning 

 the metabolic reactions of epithelium which ultimately result in cell movement. 

 Thei-e is considerable evidence to indicate that basic reactions involving motility 

 are similar in all cell types, and this subject has been thoroughly discussed by 

 Weber (1955). Two different mechanisms, contraction and lengthening, are 

 known to occur. Cell models have shown contraction to be a complex reaction 

 involving contractile fibrillar proteins with ATP or ITP. Lengthening appears to 

 be a reaction between a protein and ATP, but in this case inorganic polyphos- 

 phate can replace ATP. ATP or ITP, when bound to contractile proteins, makes 

 them extensible. The splitting of ATP by contractile proteins and the subsequent 

 contraction are dependent upon the presence of magnesium ions and free sulf- 

 hydryl groups on the protein. This requirement suggests that the energy is trans- 

 ferred to the protein by transphosphorylation and changed into mechanical 

 energy by a conversion of the high energy phosphate bonds to low energy bonds 

 as in muscle contraction (Weber, 1955). 



(m) Rate of migration. Epithelialization of a wound produces a gradual decrease 

 in the perimeter and area of the defect. It continues until the wound is completely 

 healed, at which time lateral growth ceases. The lateral growth rate is influenced 

 by many factors, such as the nutritional status of the animal, infection, presence of 

 an eschar, etc. Attempts to elict information concerning this rate have yielded 

 confusing data. It is difficult to separate the effects of contracture from those of 

 epithelial migration, and in many early studies the differences were not recog- 

 nized. Most investigators studied epithelialization using areas of non-mobile skin, 

 e.g. the ear of rabbits and guinea pigs, assuming that contraction would be negli- 

 gible. Another factor which hinders such a study is the presence of an overlying 

 eschar. The migrating epidermal sheet is capable of undermining this eschar and 

 indeed continues to do so until it is completely detached and sloughs. Unfortunately 

 this process can be followed only with fixed histological sections since the new 

 epithelium is hidden under the eschar. The properties of epidermis which permit 

 this extensive undermining rec|uire further investigation. Clark and Clark (1953) 

 reported that advancing sheets of epithelium were able to dissolve fibrin in trans- 

 parent chambers, indicating the presence of an epithelial fibrinolytic enzyme. The 

 majority of measurements concerning healing rates have been based on successive 



