Carboxymethyl Chitosan Promotes Osteogenesis Via p38/VEGFR2 and Shows Translational Potential in Sinus Floor Elevation.

BACKGROUND: To explore the osteogenic promotion of carboxymethyl chitosan (CMCS), clarify the signalling pathways involved and preliminarily evaluate the translational potential of CMCS in transcrestal sinus floor elevation. METHODS: Overlapping targets were identified by integrating potential CMCS targets and bone regeneration-related genes, and protein-protein interaction and GO/KEGG enrichment analyses were conducted. The GEO dataset GSE50743 was externally validated. Bone marrow-derived mesenchymal stem cells from mice were induced to osteogenic differentiation in vitro and treated with CMCS alone or in combination with the p38 inhibitor SB203580 or the VEGFR2 inhibitor SU5416. The osteogenic phenotypes and mechanism-related changes were determined by ALP, Alizarin Red S staining, RUNX2 immunofluorescence, qPCR and Western blotting. A retrospective comparative clinical study further evaluated radiographic, functional and patient-reported outcomes after transcrestal sinus floor elevation. RESULTS: We identified 187 common targets of CMCS-bone regeneration. Enrichment analyses revealed that these targets were primarily involved in cell adhesion, inflammatory and immune regulation, extracellular matrix remodelling, and osteogenesis-related pathways, including MAPK and VEGF signalling. Validation with GSE50743 confirmed significant positive enrichment of candidate gene set under osteogenic conditions. In vitro, CMCS increased ALP activity, mineralised nodule formation and the expression of RUNX2, ALP and OPN, whereas inhibition of p38 or VEGFR2 partially reduced these effects. Clinical findings showed that the two groups were generally similar in terms of safety, implant stability and patient-reported outcomes, whereas the CMCS group had better volume maintenance. CONCLUSIONS: CMCS promotes osteogenesis and mineralisation, at least partly via p38 MAPK and VEGF-VEGFR2 signalling. Retrospective clinical findings also indicate its potential utility in transcrestal sinus floor elevation.