Scarless Wound Healing: Looking for a Single Remedy With Multiple Targets

Abstract Context: Scars result from prolonged inflammatory phases and abnormal fibroproliferative responses in wounds. Regardless of beauty considerations that have profound psychological and social effects, scars can also have physical effects, such as growth constraints in children. Applying molecular and cellular mechanisms imitating the fetal scarless wound healing, brings about new and effective therapeutic strategies for alleviating scars. This review concentrated on innovative approaches, which simultaneously target multiple effective pathways in reducing scars. Evidence Acquisition: The most outstanding products for reducing scars, were TGF-β3 and IL-10, which failed in phase III clinical trial on their way to reach the market. In this review, multi-targeting remedies for reducing scars and their effective in vitro and in vivo mechanisms are discussed in details. There is also evidence in translation of these investigations to clinical trials. Results: MiRNAs are unique molecular components with pleiotropic actions, which target multiple signaling pathways in scars at the same time. Fetal cells, mesenchymal stem cells, and oral mucosal cells secrete a natural relevant concentration of growth factors and cytokines that are effective in scar reduction. Fat grafting is a promising treatment for scars, providing an appropriate extra cellular matrix with homing mesenchymal stem cells. Conclusions: Increasing the concentration of one growth factor or cytokine overexpressed in fetal scarless wound healing is not sufficient individually in scar reduction. Despite the profound effects of cells in scars, using biomimetic materials, which mimic the fetal cell microenviroment, should also be taken into account