Diverse effects of pulsed electrical stimulation on cells - with a focus on chondrocytes and cartilage regeneration

Biological effects of pulsed electrical stimulation (PES) on cells and tissues have been intensively studied with the aim of advancing their biomedical applications. These effects vary significantly depending on PES parameters, cell and tissue types, which can be attributed to the diverse variety of signaling pathways, ion channels, and epigenetic mechanisms involved. The development of new technology platforms, such as nanosecond pulsed electric fields (nsPEFs) with finely tuned parameters, have added further complexity. The present review systematically examines current research progress in various aspects of PES, from physical models to biological effects on cells and tissues, including voltage-sensing domains of voltage-gated channels, pore formation, intracellular components/organelles, and signaling pathways. Emphasis is placed on the complexity of PES parameters and inconsistency of induced biological effects, with the aim of exploring the underlying physical and cellular mechanisms of the physiological effects of electrical stimulation on cells. With chondrogenic differentiation of stem cells and cartilage regeneration as examples, the underlying mechanisms involved were reviewed and analyzed, hoping to move forward towards potential biomedical applications. Hopefully, the present review will inspire more interest in the wider clinical applications of PES and lay the basis for further comprehensive studies in this field.