Skin wound healing is a process tha

Skin wound healing is a process that consists of three sequential phases: inflammation, proliferation and regeneration. HS formation can occur as a result of an abnormality in these processes. When skin is deeply injured, the early inflammatory cascade will be activated, in which numerous inflammatory cells infiltrate the damaged area and release cytokines [14]. The cytokines stimulate the migration of keratinocytes and fibroblasts to the wound site, and subsequent proliferation of these cells begins 4–5 days later. Fibroblasts secrete extracellular matrix (ECM) proteins such as fibronectin, collagen and hyaluronic acid, resulting in the formation of granulation tissue [1]. During the proliferation phase, abundant vascularization and angiogenesis play a key role in supplying the inflammatory cells and fibroblasts for the formation of an occasional granulation matrix [15]. It is well known that increased vascular density is present in hypertrophic scars compared with normal scars [16]. Approximately 1 week after sustaining the wound, some fibroblasts differentiate into myofibroblasts that also secrete ECM proteins, including collagen 1 and 3. Myofibroblasts are alpha-smooth muscle actin (α-SMA)-positive cells which are activated by transforming growth factor-β1 (TGF-β1). They play a key role in contracting the edges of the wound and reducing wound size [17, 18]. Simultaneously, re-epithelization begins as keratinocytes proliferate at the wound margin. When the re-epithelization is initiated, the number of blood vessels is decreased, which induces apoptosis in both fibroblasts and myofibroblasts. As a result, wound contraction is discontinued [17]. Therefore, there are few fibroblasts in mature scar tissue (Fig. 1).