bFGF-Loaded Mesoporous Silica Nanoparticles Promote Bone Regeneration Through the Wnt/β-Catenin Signalling Pathway

负载bFGF的介孔二氧化硅纳米颗粒通过Wnt/β-catenin信号通路促进骨再生

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Abstract

BACKGROUND: Bone defects remain an unsolved clinical problem due to the lack of effective osteogenic induction protocols. Nanomaterials play an important role in bone defect repair by stimulating osteogenesis. However, constructing an effective bioactive nanomaterial remains a substantial challenge. METHODS: In this study, mesoporous silica nanoparticles (MSNs) were prepared and used as nanocarriers for basic fibroblast growth factor (bFGF). The characteristics and biological properties of the synthetic bFGF@MSNs were tested. The osteogenic effects of the particles on the behavior of MC3T3-E1 cells were investigated in vitro. In addition, the differentially expressed genes during induction of osteogenesis were analyzed by transcriptomic sequencing. Radiological and histological observations were carried out to determine bone regeneration capability in a distal femur defect model. RESULTS: Achieving bFGF sustained release, bFGF@MSNs had uniform spherical morphology and good biocompatibility. In vitro osteogenesis induction experiments showed that bFGF@MSNs exhibited excellent osteogenesis performance, with upregulation of osteogenesis-related genes (RUNX2, OCN, Osterix, ALP). Transcriptomic sequencing revealed that the Wnt/β-catenin signalling pathway could be activated in regulation of biological processes. In vivo, bone defect repair experiments showed enhanced bone regeneration, as indicated by radiological and histological analysis, after the application of bFGF@MSNs. CONCLUSION: bFGF@MSNs can promote bone regeneration by activating the Wnt/β-catenin signalling pathway. These particles are expected to become a potential therapeutic bioactive material for clinical application in repairing bone defects in the future.

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