A Wireless 3D Magneto‐Mechanical Stimulation Platform Drives In Situ Chondrogenic Commitment of Endogenous MSCs

ABSTRACT Mechanical signals play a fundamental role in regulating stem cell fate. However, due to the lack of spatiotemporal mechanical tools, directing the in situ chondrogenic differentiation of endogenous bone marrow mesenchymal stem cells (BMSCs) remains a formidable challenge in articular cartilage repair. Here, we develop a magneto‐mechanical stimulation platform with unique 3D actuation to orchestrate chondrogenic commitment of endogenous BMSCs. The BMSC‐targeted antioxidative magnetic nanomotors are designed to perform trans‐planar rotational‐bouncing motions in lysosomes under a self‐developed 3D rotating fluctuating magnetic field, generating amplified dynamic mechanical stimulation. They potentiate chondrogenic differentiation of BMSCs by lysosomal mechanically‐gated actin cytoskeletal remodeling. After intra‐articular delivery of nanomotors via an injectable hydrogel, they can target endogenous BMSCs and be wirelessly controlled to apply the dynamic mechanical stimulation in vivo for hyaline cartilage regeneration. Beyond cartilage repair, this platform offers a generalized methodology to remotely regulate the mechanical signals of cell fate for regenerative medicine.