The pursuit of perfect healing: deciphering the code of scarless healing in regenerative medicine

Abstract

Scarless wound healing represents the ideal regenerative process, restoring normal tissue architecture and function without fibrosis, a phenomenon predominantly observed in fetal development. This stands in stark contrast to the fibrotic scarring typical of adult wound healing, which can lead to significant functional and aesthetic impairments. This review provides a comprehensive analysis of the cellular, molecular, and genetic mechanisms that underpin scarless healing, highlighting key differences across the hemostasis, inflammatory, proliferative, and remodeling phases compared to scar-forming pathways. The critical roles of immune-regulatory cells, mesenchymal stem cells, and fibroblasts, which are governed by a distinct molecular environment characterized by modulated transforming growth factor-beta (TGF-β) signaling and organized extracellular matrix remodeling, are detailed here. Furthermore, the review explores emerging therapeutic strategies including regenerative medicine approaches like stem cell-derived exosomes, targeted molecular therapies, and advanced drug delivery systems inspired by these mechanisms to promote scarless repair in adult tissues. Finally, this work discusses the significant challenges in clinical translation, such as the limitations of animal models and patient heterogeneity, and outlines future directions for research aimed at achieving scar-free wound care.

Graphical abstract

Keywords

scarless wound healing / ECM remodeling / TGF-β / tissue regeneration / fibrosis / regenerative medicine

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Higher Education Press