Britanin-loaded mesoporous silica nanoparticles: a novel approach for enhanced bone regeneration

Bone regeneration requires coordinated regulation of osteogenesis, immunity, and angiogenesis, which remains challenging for traditional strategies. In this study, britanin-loaded mesoporous silica nanoparticles (britanin@MSNs) are synthesized via surface conjugation and drug encapsulation. Their effects and mechanisms are evaluated using bone marrow mesenchymal stem cells (BMSCs), macrophages, and human umbilical vein endothelial cells, and further validated in a rat femoral defect model. Low-dose britanin significantly enhances BMSCs proliferation and osteogenic differentiation, increasing ALP activity, mineralization, and the expression of RUNX2, OPN, and OCN. Mechanistically, britanin activates NPY1R, upregulates the PI3K/AKT/mTOR pathway, and promotes S6K1 phosphorylation, thereby enhancing autophagy and osteogenic protein synthesis. Britanin@MSNs provide efficient delivery and sustained release, maintaining cell viability and promoting osteogenesis and migration. In macrophages, britanin@MSNs improve mitochondrial function, reduce ROS, increase ATP levels, and promote M2 polarization by activating the TGF-β1/SMAD3 pathway. Moreover, britanin@MSNs upregulate angiogenic markers such as CD31 and VEGF, facilitating tube formation by endothelial cells. In vivo studies demonstrate that britanin@MSNs significantly promote new bone formation, increase bone mineral density, and enhance collagen deposition and tissue remodeling, while supporting angiogenesis and osteogenic signaling. This multifunctional platform offers a promising translational strategy for bone tissue engineering by integrating osteoinductive capability and microenvironment modulation