A biomimetic electrical microenvironment is known to facilitate bone defect repair. Nevertheless, precise and non-invasive modulation of the in situ electrical microenvironment poses a formidable challenge. This study develops a poly(vinylidene fluoride-trifluoroethylene) (P(VDF-TrFE)) membrane with a precisely controlled porous structure. Ultrasonic stimulation is applied to induce Acoustic-Mechanic-Electric (AcME) conversion and regulate the membrane’s surface potential to modulate the in situ electrical microenvironment. When the ultrasound frequency aligns with the membrane’s inherent frequency, maximal electrical energy conversion occurs via the resonance effect, which generates the highest possible surface potential. The maximal AcME conversion is achieved by a 12 μm pore-sized P(VDF-TrFE) membrane with a resonance frequency of 40 kHz, resulting in the highest surface potential of -65.56 mV. Finite element modeling indicates that the deformation and stress of porous membranes are higher than that of non-porous membranes under the stimulation of ultrasound, yielding the highest surface potential. In vitro experiments and sequencing analysis show that the honeycomb sandwich-structured P(VDF-TrFE) membrane under the stimulation of the resonance ultrasound promoted osteogenic differentiation of rBMSCs through the PI3K-Akt signaling pathway. When the porous membranes are implanted to cover cranial defects, the bone defect repair is significantly enhanced under the stimulation of ultrasound compared with the non-porous membranes. This study establishes a new strategy for efficient AcME conversion on piezoelectric membranes and offers new insights into the applications of ultrasound-responsive piezoelectric materials for bone defect repair.

Dentine hypersensitivity is an annoying worldwide disease, yet its mechanism remains unclear. The long-used hydrodynamic theory, a stimuli-induced fluid-flow process, describes the pain processes. However, no experimental evidence supports the statements. Here, we demonstrate that stimuli-induced directional cation transport, rather than fluid-flow, through dentinal tubules actually leads to dentine hypersensitivity. The in vitro/in vivo electro-chemical and electro-neurophysiological approaches reveal the cation current through the nanoconfined negatively charged dentinal tubules coming from external stimuli (pressure, pH, and temperature) on dentin surface and further triggering the nerve impulses causing the dentine hypersensitivity. Furthermore, the cationic-hydrogels blocked dentinal tubules could significantly reduce the stimuli-triggered nerve action potentials and the anion-hydrogels counterpart enhances those, supporting the cation-flow transducing dentine hypersensitivity. Therefore, the inspired ion-blocking desensitizing therapies have achieved remarkable pain relief in clinical applications. The proposed mechanism would enrich the basic knowledge of dentistry and further foster breakthrough initiatives in hypersensitivity mitigation and cure.

The high neurogenic potential of dental and oral-derived stem cells due to their embryonic neural crest origin, coupled with their ready accessibility and easy isolation from clinical waste, make these ideal cell sources for neuroregeneration therapy. Nevertheless, these cells also have high propensity to differentiate into the osteo-odontogenic lineage. One strategy to enhance neurogenesis of these cells may be to recapitulate the natural physiological electrical microenvironment of neural tissues via electroactive or electroconductive tissue engineering scaffolds. Nevertheless, to date, there had been hardly any such studies on these cells. Most relevant scientific information comes from neurogenesis of other mesenchymal stem/stromal cell lineages (particularly bone marrow and adipose tissue) cultured on electroactive and electroconductive scaffolds, which will therefore be the focus of this review. Although there are larger number of similar studies on neural cell lines (i.e. PC12), neural stem/progenitor cells, and pluripotent stem cells, the scientific data from such studies are much less relevant and less translatable to dental and oral-derived stem cells, which are of the mesenchymal lineage. Much extrapolation work is needed to validate that electroactive and electroconductive scaffolds can indeed promote neurogenesis of dental and oral-derived stem cells, which would thus facilitate clinical applications in neuroregeneration therapy.