666 WOUND HEALING 8 



(1950, 1955) and his co-workers have emphasized this aspect and formulated the 

 coaptation theory to explain such movements. This theory is not an answer to 

 the problem but rather a scheme that categorizes the subsequent events. Un- 

 doubtedly the mechanism is of a highly complex physico-chemical nature; it 

 occtirs at the cell boimdary, but its explanation is not known. 



There are many questions to be solved in order to understand wound healing 

 completely. These are not merely isolated problems restricted to a particular 

 phase of an animal's biology but are intimately correlated with a basic under- 

 standing of cell populations and their reactions to environment dtiring growth 

 and repair. It is a fallacy to think that advances in our knowledge of wovmd 

 healing, which will ultimately benefit the surgeon, must come from a study of 

 mammals. All evidence strongly indicates that the cell mechanics involved in 

 tissue formation and repair are essentially alike. It is difficult to believe that 

 there are two sets of physico-chemical stimuli : one set regulating initial stages of 

 development and another for repair. 



In this chapter, the present concepts of mammalian wotmd healing and related 

 studies that bear directly on its fundamental aspects are discussed. Particular 

 emphasis has been placed on the recent literature concerning the origin of the 

 cellular components and their chemical reactions during the healing process. 

 An effort has been made to present both sides of the many controversial issues. 



II. THE STIMULUS FOR W^OUND HEALING 



Wiesner, in 1892, was the first to propose that injured cells might liberate sub- 

 stances capable of stimulating growth. In plant tissues this has been verified by 

 English and Bonner (1937; English et al., 1939), who isolated a dibasic acid, 

 "traumatic acid", capable of promoting cell division in the bean mesocarp. 



Marchand, in igoi, and Bier, in 191 7, both suggested that the stimulus for 

 mammalian wound healing might also result from products of cell degradation. 

 Carrel (1922, 1924, 1930), one of the first investigators in this field, believed that 

 growth-activating polypeptides, "trephones," were produced by the action of 

 leukocytic enzymes at the wound site. In the superficial wound, where leukocytes 

 are either absent or present in small numbers, he thought that damaged cells 

 per se could produce stich substances. According to Burrows, (1914, 1924, 1926a, 

 1926b, 1927) acctimulated waste products were the growth-stimulating sub- 

 stances. He noted that adequately nourished embryonic cells in tissue culture 

 failed to thrive unless present in large numbers. Growth could be inhibited by 

 washing the cells with serum or placing them in a large quantity of media. 



Menkin (1940) has focused attention upon substances, e.g. leukotaxine, pro- 

 duced during the inflammatory reaction which invariably accompany healing. 

 He demonstrated that injured cells at the site of a sterile abscess liberate growth- 

 promoting factors into the inflammatory exudate (Menkin, 1941, 1956). Repeated 

 subcuticular injections of sterile difftisible inflammatory exudate into rabbit ears 

 eventually produced proliferative activity of both the epithelium and underlying 

 cartilage. Cameron (1935) had noted previously that cell growth in tisstie 



