Facial Skin Regenerates with Less Scarring, and the Underlying Mechanism Could Be Applied Elsewhere in the Body
Relative to skin elsewhere on the body, facial skin is less prone to scarring following regeneration from injury. Researchers have identified how this difference is regulated, and here demonstrate that they can influence the relevant mechanisms in order to reduce scarring during regeneration of skin injuries elsewhere on the body. It is also possible that further investigation of this biochemistry may yield approaches to reduce scarring more generally. This is of interest in the context of aging, as tissue maintenance becomes dysfunctional in many organs in ways that lead to excessive formation of disruptive small-scale scar-like structures.
Surgeons have known for decades that facial wounds heal with less scarring than injuries on other parts of the body. This phenomenon makes evolutionary sense: Rapid healing of body wounds prevents death from blood loss, infection or impaired mobility, but healing of the face requires that the skin maintain its ability to function well. Exactly how this discrepancy happens has remained a mystery, although there were some clues.
The face and scalp are developmentally unique. Tissue from the neck up is derived from a type of cell in the early embryo called a neural crest cell. Researchers identified changes in gene expression between facial fibroblasts and those from other parts of the body and followed these clues to identify a signaling pathway involving a protein called ROBO2 that maintains facial fibroblasts in a less-fibrotic state. They also saw something interesting in the genomes of fibroblasts making ROBO2. These fibroblasts more closely resemble their progenitors, the neural crest cells, and they might be more able to become the many cell types required for skin regeneration.
ROBO2 doesn't act alone. It triggers a signaling pathway that results in the inhibition of another protein called EP300 that facilitates gene expression. EP300 plays an important role in some cancers, and clinical trials of a small molecule drug that can inhibit its activity are underway. Researchers found that using this small molecule to block EP300 activity in fibroblasts prone to scarring caused back wounds in mice to heal like facial wounds.
Link: https://med.stanford.edu/news/all-news/2026/01/why-the-face-scars-less-than-the-body.html