Recent Advances in Scar Biology

Scars develop in the final stage of wound healing. The biological pathways that underlie wound healing and scarring are complex. In particular, the exact mechanisms that initiate and regulate them and lead to their progression remain to be fully elucidated. A major goal of medical science is scar-less wound healing. To achieve this goal, it is necessary to elucidate the relevant clinical, histopathological, and molecular manifestations of scars, and to understand how these manifestations relate to each other. The purpose of the Special Issue “Recent Advances in Scar Biology” that was published recently in the International Journal of Molecular Sciences was to illustrate the biological mechanisms that underpin scarring and effective clinical treatments. This Special Issue included a selection of recent research topics and current review articles in the field of scar research for all kinds of tissues and organs. Normally, the cutaneous wound healing process closes skin gaps by inducing the formation of granulation tissue and epithelialization, which re-establishes an effective epidermal barrier. The complex biochemical events that underlie wound closure can be categorized into four overlapping processes: coagulation, inflammation, proliferation and remodeling. Coagulation and the inflammatory process begin immediately after injury, while the proliferative phases start within a few days. The remodeling phase commences within a week of injury and continues for months. If the inflammatory and proliferative phases are feeble, wound healing may be delayed and chronic wounds may develop. In relation to this, Horng et al. [1] showed in the Special Issue that estrogen deficiency, such as that in postmenopausal women, has detrimental effects on wound-healing processes, particularly inflammation and re-granulation, and that exogenous estrogen treatment may reverse these effects [1]. Conversely, if the inflammatory and proliferative phases are excessively vigorous and prolonged due, for example, to infection or burn, heavy scars can develop. Clinical interventions that target these phases can, therefore, improve wound healing. For example, Jeong et al. [2] showed in a rat incisional wound-healing model that injections with polydeoxyribonucleotide (a mixture of nucleotides from trout sperm) have anti-inflammatory effects and, therefore, reduce the size of the scar [2]. After full-thickness burning, necrotized tissues (eschars) develop. These eschars delay wound healing, thereby promoting the formation of hypertrophic scars. Monsuur et al. [3] showed in the Special Issue that, while acellular extracts of burn eschars stimulate the proliferation and migration of adipose mesenchymal stromal cells and fibroblasts, they also inhibit the basic fibroblast growth factor-induced proliferation and sprouting of endothelial cells. This inhibitory effect may explain why the presence of an eschar blocks the formation of excessive granulation tissue by full-thickness burn wounds [3]. Akita et al. also showed that proper epithelialization plays an important role in the healing of burn wounds: when patients with extensive burns received cultured epithelial autografts (CEA) along with either highly expanded (over 1:6 ratio) or less expanded (gap 1:6) mesh, the former combination was associated with accelerated wound healing. Moreover, scoring by experts using the Vancouver and Manchester Scar Scales showed that CEA with the highly expanded mesh led to better scar formation [4]. The exhaustive review of Mostaço-Guidolin et al. also showed that proper formation of the extracellular matrix plays a key role in the epithelialization and other wound-healing events that lead to a smooth wound-healing course: studies that used second harmonic generation