Antagonistic Effects Between Co-Delivered Bfgf And Bmp9

Investigate the interactions between basic fibroblast growth factor (bFGF) and bone morphogenetic protein 9 (BMP9) to develop optimal growth factor delivery strategies from a bone tissue engineering perspective for accelerated bone healing in osseous defects. BMSCs from 3-4 week-old Sprague-Dawley rats were cultured with bFGF (10, 100ng/ml) and/or BMP9 (10, 200ng/ml). Proliferation was assessed by CCK8 assay (days 1, 4, 7) and osteogenic differentiation by ALP activity/staining (days 4, 7) and Alizarin Red staining (days 14, 21), with statistical analysis using ANOVA (p<0.05). bFGF and BMP9 demonstrated initial synergistic effects (day 1) followed by strong antagonism when co-delivered, particularly at high concentrations. BMP9 transitioned from proliferation promotion to differentiation induction between days 4-7, evidenced by decreased proliferation and increased ALP activity. Simultaneous delivery resulted in reduced mineralization compared to BMP9 alone, confirmed by Alizarin Red staining. bFGF and BMP9 exhibit time-dependent antagonistic interactions when co-delivered, despite their individual abilities to promote proliferation and differentiation respectively. The critical time point for functional transition appears to be between days 4-7, when BMP9 shifts from proliferation support to differentiation induction. These findings provide a robust scientific basis for designing sequential delivery systems with precise timing: bFGF should dominate during days 0-7 to efficiently expand the progenitor cell pool, followed by BMP9 during days 7-21 to promote osteogenic differentiation and matrix mineralization, thus achieving accelerated bone regeneration critical for successful orthognathic and maxillofacial surgical outcomes.