A BMP6 supply system based on PBVHx nanoparticles promotes the osteogenic differentiation of human stem cells in...

To continuously stimulate osteogenic differentiation of stem cells under microgravity, we developed an effective bone morphogenetic protein 6 (BMP6) sustained-release system based on nanoparticles (NPs) based on medical poly (3-hydroxybutyrate-3-hydroxyvalerate-3-hydroxyhexanoate) (PBVHx), which promotes osteogenic differentiation in human bone marrow-derived stem cells (hBMSCs). The system involves the loading of hydrophobically modified BMP6 onto PBVHx nanoparticles via soybean lecithin (sB6), followed by modification with positively charged poly-l-lysine (PLL) to enhance cellular uptake, thereby forming sB6/PBVHx@PLL-NPs. These NPs have a uniform size ranging from 90 to 200 nm, a surface charge of -5 to -6 mV, and exhibit a sustained BMP6 release for over 25 days. Under simulated microgravity, compared to the untreated control group (NT), sB6/PBVHx@PLL-NPs can effectively stimulate stem cell growth, significantly enhance alkaline phosphatase secretion, calcium deposition, and upregulate osteogenic-related genes. The results are comparable to the effects of sustained free BMP6 supply. This innovative approach offers a potential strategy for mitigating bone loss during long-term space missions.