Using Functionalized Silica Nanoparticles Encapsulating Aspirin/BMP-2 to Promote Bone Formation

Objectives: Regeneration of large bone defects is still challenging for the clinician, since there is little achievement on the regulation of bone material and bone defect niche. In this study, the bone formation ability of silica nanoparticles (SNs) encapsulating aspirin/BMP-2 gene is studied in vitro and in vivo to reveal their potential in bone regeneration.
Methods: The carbon dots (CDs) were prepared by pyrolysis of aspirin and SNs were synthesized by an ethyl ether emulsion approach which covalently grafted PEI on the surface. Drug delivery efficiency and gene binding capability were evaluated by UV-vis spectroscopy measurement and agarose gel electrophoresis. In vitro anti-inflammatory effect of aspirin and CDs was compared by quantitative real-time polymerase chain reaction using RAW264.7 cell line. The bone formation ability of SNs encapsulating aspirin/BMP-2 gene was evaluated by Micro-CT after 12 weeks.
Results: The size of CDs and SNs observed by transmission electron microscopy were 3~5nm and 100~200nm, respectively. Drug loading efficiency of SNs could reach 21.08% and higher gene expression of plasmid DNA was obtained at a weight ratio of 30:1. Anti-inflammatory effect of CDs was more obvious than that of aspirin by measuring pro-inflammatory cytokines (IL-1β, TNF-α and MMP-9) under the stimulation of LPS. Furthermore, we demonstrated that bone formation area of SNs encapsulating aspirin/BMP-2 gene group could reach 69.8±3.5%, which was significantly higher than that of the control group (26.4±1.6%) (P<0.01), SNs/aspirin group (36.9±1.4%) (P<0.01) and SNs/BMP-2 group (50.9±1.7%) (P<0.01).
Conclusions: SNs encapsulating aspirin/BMP-2 gene could efficiently deliver the drug aspirin and functionally express BMP-2 plasmid in vivo, suggesting their potential applications in bone regeneration.