Suture stem cells in pediatric craniosynostosis: pathophysiological mechanisms, surgical management, and emerging regenerative therapies

Craniosynostosis (CS) is a complex congenital disorder characterized by the premature fusion of one or more cranial sutures resulting from interactions between genetic alterations, environmental influences, and the dysregulated differentiation of cranial suture stem cells (SuSCs).Increasing evidence indicates that SuSC homeo stasis disruption, including alterations in gliomaasso ciated oncogene homolog 1positive, axis inhibition protein 2positive, and other stem/progenitor cell populations, along with aberrant regulation of developmental signaling pathways, plays a central role in the pathogenesis of CS.This review summarizes current advances in SuSC biology and the molecular mechanisms of, diagnostic approaches for, and therapeutic strategies for CS.By integrating evidence from studies published in 2000-2026, we discuss how genetic mutations and signaling pathways, including the fibroblast growth factor, bone morphogenetic pro tein, Wnt, and Hedgehog pathways, influence SuSC main tenance, lineage commitment, and osteogenic differen tiation.We further summarize recent clinical advances, including virtual surgical planning, threedimensional printing, and endoscopeassisted minimally invasive techniques, as well as emerging molecular and stem cell based regenerative strategies aimed at restoring func tional cranial suture structures.By connecting genetic mechanisms, stem cell biology, and translational me dicine, this review provides an integrated framework to increase our understanding of the pathogenesis of CS and highlights potential directions for the development of mechanismbased therapies to improve longterm cranio facial and neurodevelopmental outcomes.