The biophysical cues from implantable materials, specifically nanotopography, play a pivotal role in directing cellular lineage specification, thereby accelerating tissue healing and regeneration. Despite the recognized impact of these cues, the mechanisms governing mechano-activated signaling pathways between the cytoskeletal and nuclear domains remain largely unexplored. Here, the processes underlying the enhanced osteogenesis of mesenchymal stem cells (MSCs) driven by nanotextured implants are elucidated, focusing on alterations in cytoskeletal mechanosensitive molecules and nuclear chromatin structures. Using green-processed femtosecond laser fabrication, an implant platform featuring nanowave textures is engineered, inducing cellular alignment with oriented cytoskeletons and consequential changes in nuclear shape. Notably, activated and aligned microtubules alongside the nucleus play a key role in shaping nuclear morphology. The nanowave textures induce significant modifications in chromatin structure, characterized by increased histone acetylation, implying a mechano-priming of MSCs for osteogenesis. Mechanically-primed MSCs exhibit enhanced osteogenic transcriptional responsiveness to biochemical cues, with mechanosensitive YAP co-signaling with the RUNX2, facilitated by an opened chromatin structure. In vivo experiments in a rabbit tibia reveal that nanowave-textured implants promote osteogenesis and bone formation. This study underscores the ability of nanowave-textured cues to transmit mechano-signals across the cytoskeletal-to-nuclear space in MSCs, leading to stimulated osteogenesis.

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