22 DEVELOPMENT AND FUNCTION OF MACROPHAGES IN BONE-REPAIR. 



scar tissue, in which but few macro phages may be descried. Surrounding this 

 scar, and bordering the bone edges, there remain macrophages in considerable 

 numbers. Callus in this specimen is well advanced, and in the spaces of this, which 

 are now quite large, considerable numbers of large-sized macrophages may easily 

 be seen with the higher power of the binocular. 



The sections of the skull show marked scarring, but nothing of note as to vital 

 staining. In the long-bone sections no blue-staining debris was noted. In the vicinity 

 of the fracture the muscle fibers are scattered, and between them there is a great 

 deal of scar tissue. Here, too, there is some excess in the number of macrophages, 

 but these cells are numerically insignificant as compared with earlier stages. Tran- 

 sitionals and degenerate forms are very rare. It is evident that little or no tissue 

 destruction is going on. The synchronism between proteolysis on the one hand 

 and heightened efficiency of the macrophagic tissue on the other is thus consis- 

 tently maintained to the end, both phenomena ceasing practically at the same 

 time. As will be seen by the subsequent stages, there is no further evidence, beyond 

 the twelfth day, that extraosseous tissue destruction is going on, and the macro- 

 phages which remain in places where tissue resorption has once taken place soon 

 disappear. 



The callus is of greater dimensions than before, and is evidently still growing 

 in places, as the outer layer of deeply basophilic osteoblasts is often seen to be quite 

 thick. It is very obvious that erosion of the callus is proceeding rapidly at this 

 stage, for not only do the spaces in the vicinity of the original bone show increase 

 in size, but the spaces throughout the callus almost as far as the periphery are 

 enlarged. These spaces are occupied by large, very brilliantly stained reticulum 

 macrophages. The cells are very numerous and crowded, some fields being quite 

 blue with them, so that they present an exceedingly striking appearance in the 

 cleared section (fig. 15, b). They are even more marked than in the last stage, and 

 have evidently developed an intense avidity for the blue dye, for the cytoplasm is 

 literally packed with granules in most of the cells. There are degrees of staining, 

 however, and some cells are found with but a sprinkling of dye-granules, so that 

 it may be assumed that as time goes on more and more reticulum cells are developed 

 as phagocytes. Again, some of the cells have a few very large, rounded granules, 

 looking as though they were produced by a concentration of dye from the rest of 

 the cytoplasm, as was noted in the last stage. 



The distribution of the macrophages is more widespread than before and goes 

 hand in hand with erosion of the callus, for they inhabit the expanding spaces 

 almost as far out as the periphery. In size they show a slight increase over those 

 of the tenth day, the average long diameter of ten of the largest cells being 9.15 

 microns. These are fairly uniform in dimensions. As before, they are found in the 

 loose reticulum of the spaces (fig. 16), or are crowded between the plates of bone 

 and the walls of the sinuses. They are not in actual contact with the bone. The 

 blood sinuses are very large at this stage, pointing to a sluggish blood flow. Their 

 walls are formed by a single layer of endothelium. 



