Periodic-Mechanical-Stimulus Enhanced Osteogenic Differentiation of Mesenchymal Stem Cells on Fe3O4/Mineralized Collagen Coatings

Mechanical stimulus has been demonstrated to be critical to stem cell fate commitment and tissue repair. However, it still remains a challenge to remote control of the mechanical stimulus acting on cells. Here, we designed a magnetic Fe3O4/mineralized collagen coating on titanium substrate to regulate the osteogenic differentiation of mesenchymal stem cells (MSCs). The mode and intensity of the mechanical stimulus acting on cells could be controlled by adjusting the remote applied magnetic field. We demonstrated that the adhesion, proliferation, and differentiation of MSCs were strongly dependent on the mode and intensity of the mechanical stimuli. Strikingly, the periodic mechanical stimulus (12 h every other day, PMS) showed the significantly up-regulated expression of osteogenesis-related markers, ALP, compared to that of the static mechanical stimulus mode. The reason is proposed as (1) initially, PMS mode enables the coatings to have appropriate surface mechanical properties for promoting focal adhesion, integrin expression, and cytoskeleton development of MSCs, letting MSCs have good capability of accepting as well as transferring mechanical stimuli; (2) during MSCs growth, PMS mode may effectively manipulate MSCs cytoskeleton development and movement, and mechanotranduction mechanism could be well activated; thus, MSCs osteogenic differentiation is enhanced. This work therefore provides a novel strategy to engineer bioactive coatings with remote control over the intensity and mode of the mechanical stimulus acting on cells, and would have an impact on the design of smart biomaterial surfaces for orthopedic applications.