Figure 3.
Summary of the tissue-regeneration phase of healing. In this phase, re-epithelialization and the formation of collagen-based ECM occur. Keratinocytes and fibroblasts can migrate to the wound in response to releasing H2O2, exposed Ca2+, and serum from damaged tissue. Fibroblasts are provided to the injured tissue either from the healthy dermis, BM-derived fibrocytes, or multipotent precursor cells. Both fibrocytes and multipotent cells can differentiate into fibroblasts before they are recruited to the wound. Reparative macrophages (green-colored in the wound) play an essential role in this phase by producing several growth factors, including FGF, TGF-β, IGF, and VEGF. TGF-β promotes the differentiation of fibroblasts into myofibroblasts, a type of contractile cell that can re-approximate the wound edges. Additionally, it can negatively regulate the re-epithelialization process. FGF and HGF are associated with keratinocyte migration to the wound edge to perform re-epithelialization. BM, bone marrow; FGF, fibroblast growth factor; IGF, insulin-like growth factor; PMN, polymorphonuclear neutrophil; TGF-β, transforming growth factor beta; VEGF, vascular endothelial growth factor; FGF, fibroblast growth factor; HGF, hepatocytes growth factor.