The role of macrophages in foetal and adult wound healing in the mouse.

The study of embryonic wound healing is of great interest because of the fundamental observation that early in gestation, cutaneous wounds in embryos heal rapidly, and without scar formation. By contrast, the inevitable end result of wound healing in the adult is scarring. However, a transition point is reached, within gestation itself when wound healing no longer results in scar-free healing. This gestational transition point is of key interest in trying to understand the mechanisms which initiate the scarring process - important events occurring at this stage in the wound healing environment give clues as to what the principal contributory factors involved in promotion of the scarring response might be. I have studied this transitional phase in the foetal mouse and have found that coincident with the onset of scarring is the recruitment of macrophages to wound sites - prior to this change-over phase in younger embryos when healing is scar-free, wounds are devoid of an inflammatory response. The tight correlation between the recruitment of macrophages to wound sites and the onset of scar formation has led to the hypothesis that macrophages might play a central role in the scarring process. In order to test this hypothesis, experiments have been carried out in an adult mouse wounding model, to modify the macrophage profile at wound sites to see if scarring can be altered. Strategies to attract macrophages have resulted in worse scarring, but most significantly, where macrophage numbers have been reduced there has been a reduction in scarring and in scar contracture. Both the foetal and the adult experiments support the hypothesis that in the mouse the macrophage is central to the scaning process, and that beneficial manipulation of macrophage numbers at wound sites is an attainable goal, with important possible therapeutic implications for the control of scarring.