Mediation of cellular osteogenic differentiation through daily stimulation time based on polypyrrole planar electrodes

Abstract

In electrical stimulation (ES), daily stimulation time means the interacting duration with cells per day, and is a vital factor for mediating cellular function. In the present study, the effect of stimulation time on osteogenic differentiation of MC3T3-E1 cells was investigated under ES on polypyrrole (Ppy) planar interdigitated electrodes (IDE). The results demonstrated that only a suitable daily stimulation time supported to obviously upregulate the expression of ALP protein and osteogenesis-related genes (ALP, Col-I, Runx2 and OCN), while a short or long daily stimulation time showed no significant outcomes. These might be attributed to the mechanism that an ES induced transient change in intracellular calcium ion concentration, which was responsible for activating calcium ion signaling pathway to enhance cellular osteogenic differentiation. A shorter daily time could lead to insufficient duration for the transient change in intracellular calcium ion concentration, and a longer daily time could give rise to cellular fatigue with no transient change. This work therefore provides new insights into the fundamental understanding of cell responses to ES and will have an impact on further designing materials to mediate cell behaviors.

Electrical stimulation-induced osteogenesis of human adipose derived stem cells using a conductive graphene-cellulose scaffold

“…ALP activity for ADSCs+DIF+ES at Day 14 was 3.6 fold and 2.7 fold higher than the peak value of ADSCs+GRO+ES and ADSCs+DIF, respectively. Not surprisingly, ALP expression for ADSCs+GRO+ES was similar to that for ADSCs+DIF, indicating an inductive effect of ES and graphene on osteogenic differentiation, independent of other inducers, which is consistent with previous reports [7,15]. Statistical analysis revealed that both ES (F (2, 60) = 75.08, P < 0.0001) and day (F (3, 60) = 43.13, P < 0.0001) significantly affected ALP activity within ADSCs, as well as the interaction between ES and day (Overall two-way ANOVA, F (6, 60) = 24.12, P < 0.0001).…”

“…The following day, the devices with cells were subjected to 1 h symmetric biphasic square pulses at 0 V/cm, 1 V/cm, 10 V/cm and 20 V/cm with phase duration of 1 s and interphase interval of 200 ms, respectively. The ES settings were based on previously published research [14,15], with biphasic stimulation chosen to prevent excessive charge accumulation at the electrodecell/tissue interface that could result in cell/tissue damage [26,27]. In addition, excessive charge accumulation at the electrodes can hinder the flow of current from the stimulating electrodes [28].…”

“…Electrical stimulation (ES) has been shown to promote migration, proliferation and differentiation of stem cells, including neural stem cells, bone marrow stromal cells, and ADSCs through modulation of intracellular signalling [7][8][9][10][11][12]. Previous studies have shown that intracellular calcium/calmodulin pathway, downstream calcineurin/NFAT signalling pathway, and master osteogenic transcription factor runt-related transcription factor 2 can be activated by ES, resulting in enhanced osteogenic differentiation of stem cells [13][14][15]. Notwithstanding the putative benefits of ES, there is a need for advanced biocompatible ES devices that omit the use of conventional electrodes such as metal electrodes for more optimal cell-compatibility, avoiding, for example, unwanted biochemical effects of corrosion and poor physical integration with cells and tissues [7].…”

A Mussel‐Inspired Persistent ROS‐Scavenging, Electroactive, and Osteoinductive Scaffold Based on Electrochemical‐Driven In Situ Nanoassembly

“…Several extracellular factors are also activated and enter cells with Ca 2+ through a switch on the cell membrane. Moreover, Ca 2+ further binds to calmodulin and activates the Ca 2+ signaling transduction pathway to regulate the expression of osteogenesis‐related genes, consequently inducing osteogenic differentiation . However, the low Ca 2+ concentration difference between the intracellular and extracellular environment makes an electrical signal alone insufficient to produce significant bone regeneration in vivo.…”

Electroactive 3D Printed Scaffolds Based on Percolated Composites of Polycaprolactone with Thermally Reduced Graphene Oxide for Antibacterial and Tissue Engineering Applications

“…In particular, these biomaterials take advantage of the effect of a direct current (DC) or an electrical field on both cell proliferation and differentiation, stimulating, for instance, the regeneration of muscles, organs, and/or bones [3][4][5][6][7][8]. Moreover, ES has been studied as a potential tool in tissue regeneration to increase the proliferation and differentiation of human stem cells [5,[9][10][11][12][13]. There are several reports in the literature on the use of ES for fracture treatments and tissue repairs using electrical stimulation methodologies, particularly DC or electromagnetic fields [14].…”