biostudies-literatureLin ZFujian Provincial Natural Science Foundation of ChinaInvestigator Initiation Fund project of Fujian Medical University Union HospitalNational Natural Science Foundation of China4https://www.ebi.ac.uk/biostudies/studies/S-EPMC12847925biostudies-literatureUnknown11(1)Trans-sutural distraction osteogenesis (TSDO) is an effective treatment of midfacial hypoplasia, a craniofacial deformity frequently associated with cleft lip and palate. Though extracellular matrix (ECM) remodeling plays a pivotal role in craniofacial correction, the characteristics and mechanisms underlying collagen reorganization and cellular morphological adaptations during TSDO remain poorly understood. This study quantitatively delineates the spatiotemporal changes of sutural cells and ECM morphology, revealing a polarized alignment parallel to the direction of mechanical force. Multi-omics analysis demonstrates that macrophages regulate collagen remodeling in suture mesenchymal stem cells (SuSCs) via the PDGF signaling pathway. Subsequent in vitro stretch loading models confirmed PDGF pathway activation enhances SuSCs migration, collagen synthesis, and cellular morphological reorganization. Validation in macrophage-elimination murine models further corroborated this regulatory axis. Collectively, our work maps the dynamic microenvironmental changes during TSDO and elucidates cell-cell interaction-driven ECM collagen remodeling. These insights advance the understanding of TSDO-mediated osteogenesis and provide a foundation for developing optimized therapeutic strategies.NPJ Regenerative medicineSpatiotemporal dynamics and regulation of suture morphology and collagen remodeling during trans-sutural distraction osteogenesis.PMC128479252024XH0552025J0817982402945Jin MZha YChen YLin ZZhao ZZhang PfalseSpatiotemporal dynamics and regulation of suture morphology and collagen remodeling during trans-sutural distraction osteogenesis.Trans-sutural distraction osteogenesis (TSDO) is an effective treatment of midfacial hypoplasia, a craniofacial deformity frequently associated with cleft lip and palate. Though extracellular matrix (ECM) remodeling plays a pivotal role in craniofacial correction, the characteristics and mechanisms underlying collagen reorganization and cellular morphological adaptations during TSDO remain poorly understood. This study quantitatively delineates the spatiotemporal changes of sutural cells and ECM morphology, revealing a polarized alignment parallel to the direction of mechanical force. Multi-omics analysis demonstrates that macrophages regulate collagen remodeling in suture mesenchymal stem cells (SuSCs) via the PDGF signaling pathway. Subsequent in vitro stretch loading models confirmed PDGF pathway activation enhances SuSCs migration, collagen synthesis, and cellular morphological reorganization. Validation in macrophage-elimination murine models further corroborated this regulatory axis. Collectively, our work maps the dynamic microenvironmental changes during TSDO and elucidates cell-cell interaction-driven ECM collagen remodeling. These insights advance the understanding of TSDO-mediated osteogenesis and provide a foundation for developing optimized therapeutic strategies.2026-01-01T00:00:00Z2026 Jan2026-06-09T07:28:41.774Z2026-06-09T03:12:20.935ZS-EPMC128479254149088910.1038/s41536-025-00448-5