Abstract
Stem cells from human exfoliated deciduous teeth (SHED) uniquely exhibit high proliferative and neurogenic potential. Charged biomaterials have been demonstrated to promote neural differentiation of stem cells, but the dose-response effect of electrical stimuli from these materials on neural differentiation of SHED remains to be elucidated. Here, by utilizing different annealing temperatures prior to corona poling treatment, BaTiO3/P(VDF-TrFE) ferroelectric nanocomposite membranes with varying charge polarization intensity (d 33 ≈ 0, 4, 12 and 19 pC N-1) were fabricated. Enhanced expression of neural markers, increased cell elongation and more prominent neurite outgrowths were observed with increasing surface charge of the nanocomposite membrane indicating a dose-response effect of surface electrical charge on SHED neural differentiation. Further investigations of the underlying molecular mechanisms revealed that intracellular calcium influx, focal adhesion formation, FAK-ERK mechanosensing pathway and neurogenic-related ErbB signaling pathway were implicated in the enhancement of SHED neural differentiation by surface electrical charge. Hence, this study confirms the dose-response effect of biomaterial surface charge on SHED neural differentiation and provides preliminary insights into the molecular mechanisms and signaling pathways involved.