Effects of activated macrophages and fibroblast growth factor on random skin flap survival in swine

Objective: To examine the effect of application of activated autologous macrophages and basic fibroblast growth factor (FGF) on random skin nap survival in swine, Design: A randomized nonblinded controlled trial. According to a standard design, six dorsally based, random-pattern skin flaps were raised in each of 12 Yorkshire pigs. Methods: Twenty-five milliliters of blood is harvested from each animal 20 to 24 hours prior to flap creation. Monocytes are isolated, placed in culture medium, and then activated, by the addition of platelet-derived growth factor (PDGF) and tissue growth factor beta (TGF-P). Following an 18-hour incubation period, the monocytes are decanted and quantified, and their viability confirmed. These cells are then infused into the wound bed of the treatment flaps immediately following nap creation, and FGF is added prior to nap closure, The position of treatment and control naps is systematically varied with regard to anterior-to-posterior and side-to-side flap positions within each animal. The area of superficial nap necrosis is evaluated on postoperative day 7, digitally scanned, and analyzed using graphics software. Control naps are elevated similarly, but receive no placebo treatment. Results: Two-way analysis of variance (ANOVA) demonstrated nonsignificant differences between pig side and anterior, middle, and posterior flap positions within treatment and control nap groups. Using side and position pooled data a one-way ANOVA showed no statistically significant differences between treatment and control flaps. Conclusions: The cellular and biochemical events following creation of a surgical wound are complex and incompletely understood. Our attempt to augment the natural role of the macrophage in wound healing by employing cytokines to activate these cells and to accelerate their arrival by implanting them into the wound bed failed to enhance nap survival. Further study is warranted to ascertain the details of wound healing, particularly with respect to cytokine concentrations and the timing of their roles, if we are to find a clinically applicable means of enhancing flap survival.