Split Thickness Grafts Grow From Bottom Up in Large Skin Injuries

Autologous split thickness skin graft is necessary for the survival of patients with large burns and skin defects. It is not clear how a thin split thickness skin graft becomes remarkably thicker within a few weeks following transplantation. Here, we hypothesized that growth of split thickness graft should be from bottom up probably through conversion of immune cells into collagen producing skin cells. We tested this hypothesis in a preclinical porcine model by grafting split thickness meshed skin (0.508 mm thickness, meshed at 3:1 ratio) on full thickness wounds in pigs. New tissue formation was evaluated on days 10 and 20 postoperation through histological analysis and co-staining for immune cell markers (CD45) and type I collagen. The findings revealed that a split thickness graft grew from bottom up and reached to almost the same level as uninjured skin within 60 days postoperation. The result of immune-staining identified a large number of cells, which co-expressed immune cell marker (CD45) and collagen on day 10 postoperation. Interestingly, as the number of these cells reduced on day 20, most of these cells became positive for collagen production. In another set of experiments, we tested whether immune cells can convert to collagen producing cells in vitro. The results showed that mouse adherent immune cells started to express type 1 procollagen and α-smooth muscle actin when cultured in the presence of fibroblast conditioned media. In conclusion, the early thickening of split thickness graft is likely happening through a major contribution of infiltrated immune cells that convert into mainly collagen producing fibroblasts in large skin injuries.