Core Viewpoint - Harvard University's research reveals that excessive nerve innervation is a key factor inhibiting perfect healing in mammalian skin, explaining why infants heal without scars while adults often do [2][3][4]. Group 1: Mechanism of Regeneration - The study identifies that during embryonic development, skin injuries can regenerate perfectly, restoring multiple cell types and their connections, but this ability is lost shortly after birth [8]. - Postnatal wounds are characterized by the presence of postnatal wound-specific fibroblasts (PWF), which constitute about 60% of fibroblasts in postnatal wounds and are absent in embryonic wounds [10][19]. - PWF express three key genes: Timp1, Cxcl12, and Ccl7, which, when overexpressed in embryonic wounds, inhibit organ-level regeneration and lead to excessive nerve innervation [11][19]. Group 2: Role of CXCL12 - PWF secrete CXCL12 and other chemokines, attracting an excessive number of nerve fibers to the wound area, creating a "hyperinnervation" environment that blocks the regeneration of multipotent cells [13][19]. - Inhibition of CXCL12 expression in fibroblasts or direct nerve ablation can restore the ability for multipotent regeneration in postnatal wounds [14]. Group 3: Implications for Regenerative Medicine - The findings challenge the traditional view that mammalian organ regeneration is permanently lost, suggesting it can be "unlocked" through specific mechanisms [15]. - The study identifies excessive nerve innervation as a critical barrier to organ regeneration, providing new targets for therapeutic strategies [15]. - This mechanism may have broader applications beyond skin, offering insights for regeneration research in other organs [15].