Vibration or Stretch? Distinct Mechanoelectrical Signatures Govern Osteogenic Programming in PVDF

A promising method for directing cell behavior and tissue regeneration is the use of smart materials that can transform physical inputs into bioelectrical signals. In this study, the mechanoelectrical control of preosteoblast activity was investigated using a piezoelectric smart biointerface based on positively poled poly(vinylidene fluoride) (PVDF). Distinct mechanical regimes, including vibrational and cyclic stretching, were applied through customized bioreactors, enabling controlled mechanoelectrical inputs ranging from 63 to 227 μVpp mm^-2. The biological response of MC3T3-E1 cells was evaluated in terms of metabolic activity, intracellular calcium signaling, alkaline phosphatase (ALP) activity, matrix mineralization, and gene expression (RUNX2, ALP, OPN, and OCN). The results demonstrated that stretching stimulation combined with higher mechano electric inputs (113-227 μVpp mm^-2) enhanced calcium influx and enhanced osteogenic differentiation, while lower impulses (∼63 μVpp mm^-2) under vibrational circumstances increased cell proliferation. These findings highlight the intensity- and mode-dependent nature of mechanoelectrical signaling in regulating osteogenic commitment. All things considered, this study shows how piezoelectric smart materials can be used as bioresponsive platforms to precisely control cell proliferation and differentiation, creating avenues for bone tissue engineering's next-generation regenerative techniques.