Janus 3D printed dynamic scaffolds for nanodeflection-driven bone regeneration

Abstract The application of physical stimuli to cell cultures has shown potential to modulate multiple cellular functions including migration, differentiation and survival. However, the relevance of these in-vitro models to future potential extrapolation in-vivo depends on whether stimuli can be applied “externally”, without invasive procedures. Here, we report on the fabrication and exploitation of dynamic additive-manufactured Janus scaffolds that are activated “on-command” via external application of ultrasounds, resulting in a mechanical nanodeflection that is transmitted to the surrounding cells. Janus scaffolds were spontaneously formed via phase-segregation of biodegradable polycapolactone (PCL) and polylactide (PLA) blends during the manufacturing process and behave as ultrasound transducers (acoustic to mechanical) where the PLA and PCL phases represent the active and backing materials, respectively. Remote stimulation of Janus scaffolds led to enhanced cell proliferation, matrix deposition and osteogenic differentiation of seeded bone marrow derived stromal cells (BMSCs) via formation and activation of voltage-gated calcium ion channels.