Research progress on scar-free healing.

INTRODUCTION: Pathological scars resulting from wound healing can cause functional impairment, cosmetic disfigurement, and psychological distress, highlighting the urgent need for regenerative solutions. Scar-free healing observed in embryonic development and some adult mammalian models have achieved complete tissue repair without fibrosis. METHODS: This article reviews literature on wound healing and scarless healing published over the past 25 years. The databases searched were PubMed/MEDLINE, Embase, Web of Science, CNKI, Wanfang, and ChiCTR (used to supplement research from Chinese scholars). Search terms included 'wound healing,' 'scarless healing,' 'scar-free healing,' 'embryo,' 'immunotherapy' and 'tissue engineering therapy,' among others. Additionally, the reference lists of key articles were examined to identify further relevant studies. DISCUSSION: In this article, we reviewed the influencing factors of scarless healing, covering both macroscopic and microscopic factors-including fibroblasts, collagen, matrix metalloproteinases, neurological influences, and cytokines-which are key therapeutic targets in clinical practice. It details four critical signalling pathways: (1) the SDF-1/CXCR4 axis, (2) the Wnt signalling pathway, (3) the [Ca2+]i and Rho/ROCK pathways, and (4) the Hippo signalling pathway and integrin-linked kinase, along with newly identified genes like YAP and En1. The analysis highlights the promise of combined targeted therapies. Additionally, it reviews advanced treatments and animal models for scarless healing and introduces an innovative immune-targeted strategy to optimize wound healing outcomes. CONCLUSION: The formation of scars is influenced by multiple internal and external factors. To achieve scar-free healing, a combination of multiple effective treatment methods is required, such as targeting related signalling pathways or genes. Furthermore, immunotherapy-related approaches hold great potential and require further research to clarify the relevant reaction processes in order to develop new and effective treatment methods.