Stimulation of cell cultures with physical and electrical cues has potential to modulate multiple cellular functions including migration, differentiation and survival. Despite the great potential shown by in-vitro models, these are generally based on sophisticated systems with compromised potential to be exploited in-vivo, being the main short-coming the incapability to apply the stimuli “remotely” and on a controlled manner. Here, we report on the fabrication and exploitation of dynamic 3D printed scaffolds that are activated on-command via external application of ultrasounds, resulting in a mechanical nanovibration and a electrical signal that is transmitted to the surrounding cells. Scaffolds were produced via 3D printing from pre-formed polymer blends that spontaneously phasesegregated into well-defined structures, including Janus and particles, following the traditional nucleation and spinoidal decomposition model. 3D printed structures of biodegradable polycaprolactone (PCL) and polylactide (PLA) blends behave as ultrasound transducers (acoustic to mechanical) where the PLA and PCL phases represent the active and backing materials, respectively. To introduce piezoelectricity, biorewable and biocompatible cellulose nanocrystals were added to the PLA phase, at different loading ratios. Remote stimulation of scaffolds led to a nanovibration and/or electrical signal generated by piezoelectric cellulose nanocrystals. Control over the material composition (polymer blend ratio and loading of nanoparticles) and structure formation allowed us to control the amplitude of the deflection, the pulse of this one and the instensity of the electrical signal. Culture of hBMSCs on dynamic scaffolds resulted in enhanced cell proliferation, matrix deposition and osteogenic differentiation as measured by PCR and release and deposition of characteristic markers and matrix proteins. Further, we evidenced that the hBMSC response is a consequence of the formation and activation of voltage-gated calcium ion channels.

3D printed dynamic scaffolds for nanovibration-driven tissue regeneration

ACS Fall 2021

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.