VII FIBROBLASTIC PROLIFERATION 693 



1945). The mechanical force within the clot cannot act directly upon the cell 

 but only upon the clotted medium. If no tension existed, cells would assume a 

 rounded shape due to normally prevailing surface tension forces (Thompson, 

 1942), as demonstrated with fibroblasts in the absence of fibrin (Huzella, 1929). 

 It is most probable that tension within the clot acts upon the colloidal milieu of the 

 cell substance and controls not only the rate and direction of movement but also 

 the shape and direction of cell division (Weiss, 1949a). 



The contraction phase of healing which is both prolonged and relatively con- 

 stant produces a significant effect upon cellular orientation. Unlike the initial 

 expansion phase, forces producing contraction are derived from within the wound 

 (Abercrombie et al., 1954; Abercrombie et al., 1956) and produce radial lines of 

 tension extending into the adjacent normal tissue. Mature fibrocytes in these 

 surrounding areas respond by re-orienting in the direction of the granulation 

 tissue. This strong contraction force subsides when healing is completed and the 

 entire area re-adjusts to the greater forces exerted by the surrounding parts. 



VIII. THE CHEMISTRY OF GRANULATION TISSUE 



The relationship between the appearance of fibroblasts in a wound area and the 

 subsequent formation of collagen has been noted for years but only recently 

 partially explained with the aid of electron microscope studies. In the past it has 

 been thought that collagen was derived extracellularly from fibrin (Baitsell, 1915, 

 1 92 1, 1925; Nageotte and Guyon, 1934) ; however, this is unlikely since the protein 

 complex of collagen is of an entirely different nature (Astbury, 1947). Careful 

 observations of various tissue fibroblasts in culture suggests an extracellular 

 origin of the fine fibrils which seem to form adjacent to those cells (Lewis, 191 7; 

 Maximow, 1928a, 1929; McKinney, 1929; Maximow and Bloom. 1929; Doljanski 

 and Roulet, 1933; Bloom and Sandstrom, 1935). Hass and McDonald (1940) 

 noted that collagen production, in cultures of fibroblasts, follows a pattern similar 

 to that of in vivo wound healing. The period of active fibroblastic proliferation is 

 followed by one of relatively slow cell division during which collagen is formed. 

 Once a certain level of collagen mass is reached, no more is laid down even though 

 the fibroblasts are still viable. This impression has been substantiated in vivo with 

 the transparent ear chamber (Stearns, 1940a, b). Another view, first proposed by 

 Mallory (1903), is that extracellular fibers originate from within the cell. 



Porter (1951) has suggested that the gelated layer beneath the cell membrane 

 either forms collagen or else diffuses through the cell membrane and becomes 

 polymerized into collagen fibrils extracellularly. Jackson's work (1953, 1954, 

 1956) indicates that fibroblasts play a double role in collagen formation, first in 

 connection with formation of the collagen fiber, and second, with elaboration of 

 the ground substance. She observed that fibrogenic cells (fibroblasts, osteoblasts, 

 osteocytes, and chondroblasts) contain intracellular cytoplasmic filaments 

 and lamellae. In tendons these fibrils appear to be formed both intra- and 

 extracellularly, although the method of extrusion is unknown. At first they are 

 80 A in diameter and later develop into typical collagen fibrils of about 750 A 



Literature j), yoj 



