Retinoids in Scarless Skin Regeneration: From Molecular Mechanisms to Therapeutic Strategies

September 2025 in “ Frontiers in Cell and Developmental Biology ”

Kang Wang, Zhongqing Yang, Yunqi Ma, Wenhui Liu, Guangshuai Li, Xuewen Xu, Qingfeng Li

retinoids retinoic acid RA TGF-β signaling myofibroblast differentiation extracellular matrix degradation fibrotic scarring skin appendage regeneration hair follicle formation Wnt/β-catenin signaling Shh signaling

TLDR Retinoic acid may help heal skin without scars by reducing fibrosis and supporting skin regeneration.

This review discusses the potential of retinoids, particularly retinoic acid (RA), in promoting scarless skin regeneration by modulating wound repair processes and reducing fibrosis. RA inhibits TGF-β signaling, suppresses myofibroblast differentiation, and enhances extracellular matrix degradation, which are crucial for minimizing fibrotic scarring. It also supports skin appendage regeneration, including hair follicle formation, by interacting with developmental pathways like Wnt/β-catenin and Shh signaling. Despite challenges such as poor solubility and systemic toxicity, advancements in delivery systems and combination therapies could enhance RA's therapeutic potential, making it a promising agent for scarless wound healing and functional skin regeneration. Further research is needed to optimize its clinical use.

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