Experimental-numerical analysis of cell adhesion-mediated electromechanical stimulation on piezoelectric nanofiber scaffolds

Electrospun nanofibers exhibiting piezoelectricity are a specific class of smart materials which could provide electric stimulation to cells in a noninvasive way and contribute to tissue regeneration. During cell-material interaction, the materials display electromechanical behavior by transforming cell adhesion force into surface charge. In the process, how the cell adhesion states and the electromechanical properties of scaffolds determine the actual piezoelectric potential implemented on a cell is still unclear. Herein, we fabricated piezoelectric poly(vinylidene fluoride) (PVDF) nanofiber scaffolds with different topographies, and investigated their influences on cell morphology and cell adhesion-mediated electromechanical stimulation of mesenchymal stem cell (MSC). Our results demonstrated that MSC seeded on aligned piezoelectric nanofibers exhibited elongated morphology combined with higher intracellular calcium activity than those adhered on random nanofibers with rounded shape. The underlying mechanism was further quantitatively analyzed using a three-dimensional (3D) finite element method with respect to cell adhesion states and architecture parameters of nanofiber scaffolds. The results suggested that cell morphology and cell adhesion force influenced the piezoelectric output through modulating the location and magnification of force implemented on the scaffolds. In addition, the change of alignment, pore size and diameter of the nanofiber network could alter the mechanical property of the scaffolds, and then bias the actual piezoelectric output experienced by a cell. These findings provide new insights for probing the mechanism of cell self-stimulation on piezoelectric scaffolds, and pave the way for rational design of piezoelectric scaffolds for cell regulation and tissue regeneration.