Magnetic Fe3O4 Nanoparticles Modified Hydroxyapatite Whisker: A Novel Framework with Superior Osteogenic Efficacy

Abstract The valid repair of bone defects requires considering precise elements mirroring native tissue and the efficiency of treatment reality. Magnetic biomaterial‐mediated mechanotransduction emerges as a critical mechanism for enhancing osteogenic differentiation and bone regeneration. Here, enhancement of osteogenic capacity is achieved in a hydroxyapatite whisker (HAw) by integrating with magnetic Fe 3 O 4 nanoparticles (HAw/Fe 3 O 4 ). The HAw/Fe 3 O 4 exhibited excellent magnetic responsiveness and controllable alignment along magnetic field (MF) vectors enabled precise delivery of programmed mechanical stimuli. In vitro and in vivo experiments showed that Fe 3 O 4 nanoparticles modified HAw has satisfactory biocompatibility and osteoinductivity, while the synergistic efficacy of magnetic biomaterial with external MF stimulation significantly accelerated bone matrix mineralization. The magnetic HAw/Fe 3 O 4 with a MF significantly increased the expression of osteogenic markers and improved bone repair. The mechanosensitive ion channel of Piezo1 enabled efficient transcellular mechanotransduction through the MAPK pathway in response to the magnetic HAw/Fe 3 O 4 with MF stimulation. The current study demonstrates that the HAw/Fe 3 O 4 magnetic framework ‐ developed through Fe 3 O 4 nanoparticle integration to enhance HAw osteoinductivity via coordinated MF application and mechanobiological modulation ‐ served as an optimal therapeutic platform for delivering programmed mechanical cues to activate Piezo1‐mediated mechanotransduction cascades, ultimately accelerating bone tissue regeneration.