Ultrashort wave therapy promotes the repair of jaw defect by regulating the function of jaw bone marrow mesenchymal stromal cells

The mandible is essential for facial structure and oral function. Jaw bone marrow mesenchymal stromal cells (JBMMSCs) exhibit self-renewal and multi-lineage potential for bone regeneration, but are compromised by post-injury inflammation, poor vascularization, and osteogenic microenvironment disruption. This study evaluated the effect of ultrashort wave (USW) therapy on enhancing JBMMSCs function and promoting mandibular repair. In a murine bone defect model, 3 min USW treatment significantly improved bone regeneration (35.2 ± 3.8% increase in BV/TV, P < 0.01) and induced a 42% reduction in fibrosis versus controls. In vitro, USW enhanced JBMMSCs proliferation (2.1-fold increase in Ki67 + cells) and osteogenesis (3.5-fold higher ALP activity; 4.2- and 3.8-fold upregulation of RUNX2 and OCN expression). RNA-seq identified 141 differentially expressed genes, with phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling as the most enriched pathway (FDR < 0.01). Functional annotation of these transcriptomic alterations highlighted significant enrichment in cytokine responses and GTPase activity, suggesting that USW drives JBMMSC osteogenesis through the transcriptional modulation of the PI3K/Akt and JAK-STAT signaling networks These findings demonstrate USW therapy possibly promotes mandibular repair through JBMMSCs activity increase by regulating the gene expressions involved in the PI3K/Akt signaling pathway, with 3 min exposure being optimal. This study offers both theoretical insights and clinical rationale for USW-based maxillofacial bone regeneration strategies.