DEVELOPMENT AND FUNCTION OF MACROPHAGES IN BONE-REPAIR. 



Iii the earlier stages of the reparative process following bone-v. / nds, too, 

 there is a great deal of debris to be eliminated, such as injured bone, blood-clot, 

 damaged muscle, and other devitalized tissue, and it is plain from the writings of 

 other workers that the potentialities of the macrophages eminently fit them for 

 the performance of this duty. That they play a part in the healing of wounds of 

 soft tissues, such as skin, kidney, and liver, may be inferred from the work of Gold- 

 mann (1912), who demonstrated by the aid of vital-dyes that they were increased 

 in the regions where repair was proceeding. Indeed, the evidence of numerous 

 investigators points to the macrophages being concerned in all inflammatory con- 

 ditions. Maximow (1902, 1909 2 ), notably, has made a special study of these cells in 

 inflammatory areas, where he finds them increased in number and size, and speaks 

 of them as "polyblasts" ; and Tschaschin (1913) has recorded similar findings. 



The problem of the healing of wounds of bone, therefore, seemed to offer a 

 particularly favorable field for the application of the vital-staining method, for 

 it was expected that in the early stages of bone-repair, where damaged soft parts 

 must be cleared away, as well as in the later stages, where provisional bone has to 

 be eroded, the trypanophil cells ?'. e., the macrophages in the pursuance of 

 their physiological vocation as phagocytes, would become locally very numerous 

 and would show hypertrophy and intensified phagocytic power. These expecta- 

 tions, as will be seen, were realized, and the following pages are devoted to the 

 discussion of the gross and microscopic appearances presented in the progressive 

 stages of healing of fractures and trephine wounds in rats in whose tissues the 

 macrophages were made visible by the introduction of the dyestuff (trypan-blue) 

 into the circulating fluids shortly before death. 



MATERIAL AND METHOD. 



For the most part, the experiments were carried out on the albino rat, though 

 the black and crossed breeds were also used. The material was collected at the 

 admirable rat colony of the Wistar Institute of Anatomy and Biology, Philadel- 

 phia,* and this insures that the rats were all perfectly healthy and were kept under 

 the most favorable conditions during the time of experimentation. A complete 

 series of stages was secured, covering the entire period of repair. 



The operations were conducted as follows : The animal having been anesthet- 

 ized with ether, the top of the head was carefiu.y shaved and sterilized; a median 

 incision was then made and the skin reflected over the parietal areas. The parietal 

 bone having been laid bare, a small trephine of 5 mm. diameter was used to per- 

 forate it. In some cases the piece was removed altogether; in others it was replaced, 

 sometimes upside down; and in still other cases a piece of living or dead bone from 

 another rat, or even dead bone from an animal of a different species, was inserted. 

 As a rule two areas were trephined, one in each parietal bone. The wounds were 



*I wish to thank Drs. Greenman and Donaldson, of the Wistar Institute, fur laboratory facilities ami access to the rat 

 roll my; also Dr. McClung, of the University of Pennsylvania, for placing his laboratory at my disposal for the operations. 

 Finally, I wish to express to Miss Madge DeG. Thurlow my most cordial thanks for the invaluable assistance rendered by 

 her in carrying on this investigation. 



