The interaction between nanoscale MIL-53(Fe) and Fzd6 protein drives enhanced bone regeneration

The interaction between nanomaterials and biomolecules is pivotal in advancing biomedical applications, especially in bone tissue regeneration. While metal–organic framework (MOF) nanomaterials are widely used in bone tissue engineering, their interactions with biomolecules remain underexplored. This study utilized MIL-53(Fe), a MOF known for its structural stability and biocompatibility, to investigate its impact on osteogenesis through biomolecular interactions. Results indicated that MIL-53(Fe) significantly promoted osteogenesis in human bone marrow stromal cells (hBMSCs) by activating the Wnt/β-catenin signaling pathway. Molecular docking and dynamics simulations revealed that MIL-53(Fe) had the highest binding affinity for the Fzd6 receptor, a key component of the Wnt/β-catenin pathway. This binding stabilized the Fzd6 protein, enhancing its structural dynamics and reducing conformational flexibility. These findings suggest that MIL-53(Fe)’s interaction with Fzd6 is crucial to its osteogenic effects. Additionally, MIL-53(Fe) promoted bone regeneration in a rat calvarial bone defect model, as confirmed by micro-CT and histological analyses. These results indicate the potential of MIL-53(Fe) as a novel nanomaterial for bone regeneration and provide new insights into nanomaterial-biomolecule interactions in osteogenesis.