Transition from fetal to adult repair occurring in mouse forelimbs maintained in organ culture.
In previous wound healing experiments with the use of midgestation murine fetal forelimb explants, wounds were made before or immediately after amputation from the fetus. This experimental technique allows one to ask the question: do circulatory elements initiate or sustain the repair process in vitro? The hypotheses tested in the current study were that repair occurs in organ culture in the absence of systemic influences and that the in vivo transition from fetal-like to adult-type repair persists in an unperfused in vitro system. Gestational day-14 mouse forelimbs were harvested and placed in serum-free culture medium. Before amputation, control forelimbs received linear full-incision microscalpel wounds that were closed primarily. The animals in the other group were not immediately wounded but cultured for 4 days and then wounded with primary wound closure. All limbs were cultured for 7 days after wounding and then processed for histologic analysis. In the immediately wounded limbs, scarless healing occurred with collagen fibers deposited in a reticular form. In contrast, the delay-wounded limbs had collagen organized in parallel arrays (disordered), constituting repair by scarring. Wound repair proceeded as a local phenomenon in the absence of systemic mediators. We conclude that day-14 gestation forelimbs undergo maturation in culture, causing a transition from scarless to adult scar repair.