Macrophages significantly enhance wound healing in a vascularized skin model

Tissue‐engineered dermo‐epidermal skin grafts could be applied for the treatment of large skin wounds or used as an in vitro wound‐healing model. However, there is currently no skin replacement model that includes both, endothelial cells to simulate vascularization, and macrophages to regulate wound healing and tissue regeneration. Here, we describe for the first time a tissue‐engineered, fully vascularized dermo‐epidermal skin graft based on a fibrin hydrogel scaffold, using exclusively human primary cells. We show that endothelial cells and human dermal fibroblasts form capillary‐like structures within the dermis whereas keratinocytes form the epithelial cell layer. Macrophages played a key role in controlling the number of epithelial cells and their morphology after skin injury induced with a CO2 laser. The activation of selected cell types was confirmed by mRNA analysis. Our data underline the important role of macrophages in vascularized skin models for application as in vitro wound healing models or for skin replacement therapy. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1340–1350, 2019.