Dynamically-Driven Osteoblast Attachment and Stress Fiber Formation on 4D Nanoarchitected Scaffold-on-Chip

Decades of studies on 2D surfaces show mechanical stimulation of bone cells results in osteogenesis however the underlying mechanisms behind mechanically induced bone regeneration in 3D are still now fully understood. How dynamic mechanical stimulation of the ECM transfers deformations to cells in 3D and the cell response remains difficult quantify in vitro. Here, we fabricate and dynamically compress periodic, nano-architected scaffolds seeded with SAOS osteoblast like cells. Experimentally increasing frequency of dynamic loading up to 3 Hz results an increase in adhesion and f-actin, indicating a biphasic response in cytoskeletal organization and based load magnitude. Theory and finite element calculations showed that fluid shear stresses increase with frequency and develop a spatial gradient within a scaffold. The platform enables decoupling aspects of 3D cell-matrix interactions by controlling time-dependent solid and fluid stresses in an engineered ECM.