Is the future scarless? – Fibroblasts as targets for scarless wound healing: a narrative review

Abstract

Introduction: Scarless healing is the ideal outcome of wound healing and is exhibited in some species. This narrative review assembles the current understanding of fibroblast heterogenicity along with the latest fibroblast-related targets for scar reduction therapies. Human regenerative wound healing is deemed possible due to the wound regeneration already seen in the early gestation foetus. Methods: This literature narrative review was undertaken by searching PubMed and Web of Science databases and Google Scholar to find articles concerning the fibroblast involvement in wound healing. We evaluated and collated these articles to form a consensus of the current understanding of the field. Discussion: This article describes current understanding of fibroblast heterogenicity and involvement in wound healing, focusing on the role of fibroblasts during physiological scarring. We also present the current most promising targets involving fibroblasts in the reduction of scarring and how we can manipulate the behaviour of fibroblasts to mimic the wound regeneration models in the human foetus. These targets include the pro-fibrotic EN1 positive fibroblast lineage, TGFβ1 inhibition, and genetic therapies utilising miRNAs and siRNAs. Conclusion: No therapies are currently available to eradicate scarring; however, treatment options are available to reduce the appearance of scarring. Further research into the heterogenicity and interactions of fibroblasts in both the foetus and adult is needed, and this may lead to the development of novel treatments against scarring.