Biphasic electric current stimulates proliferation and induces VEGF production in osteoblasts

Abstract

This study investigated biphasic electric current (BEC) functions as a new type of electrical stimulation to induce rat calvarial osteoblasts to proliferate, differentiate and synthesize cytokines. The culture system was designed so that biphasic current flowed between upper and lower gold plates. BEC helps to minimize the net charge accumulation during cell exposure to the electrical stimulation. Osteoblasts were exposed to electrical stimulation of 1.5 microA/cm2 at 3000 Hz, and the effect of BEC was assessed in the interrupted mode (6 h daily) and in the continuous mode (24 h daily), depending on the interval of stimulation. Whereas proliferation increased by 31% after stimulation in the continuous mode for 2 days, it was unaffected in the interrupted mode. The transcriptional expression of osteogenesis-related genes such as alkaline phosphatase (ALP), osteopontin, and type I collagen was unchanged 4 days after stimulation in both modes, while cbfa1 was decreased under the same conditions. There was no detectable change in mRNA expression of growth factors (BMP-2, -4, IGF-2 and TGF-beta1) that promote osteoblast differentiation. However, real-time RT-PCR and ELISA demonstrated that vascular endothelial growth factor (VEGF) was markedly up-regulated by BEC. Induction of VEGF by BEC was not hypoxia driven. In conclusion, the present in vitro study demonstrates that BEC increases cell proliferation and induces the production of VEGF. The BEC was more effective with continuous stimulation than with interrupted stimulation. To confirm whether BEC can enhance osteogenesis, further in vivo studies are needed.

Electrical Stimulation in Tissue Regeneration

“…Experiments investigating the response of bone cells to ES based on metallic electrodes are rare. Kim et al (Kim et al, 2006) found that the proliferation of rat calvarial osteoblasts on an Au anode increased 31% after 2 days under an ES of 1.5μA/cm 2 . When electrodes are used as implants in the clinical setting, reliability is crucial.…”

A 16-channel Neural Stimulator IC with DAC Sharing Scheme for Artificial Retinal Prostheses

“…Fig. 4 shows the biphasic current driver circuit, which is widely used because the biphasic current stimulation is easy to control the net charge accumulation [1,6]. The biphasic diver generates the biphasic currents, i CH , and, i REF when STIM_EN is "H".…”

“…Many neural stimulator ICs were reported for the retinal prostheses [4][5][6][7][8][9][10]. In the previous stimulator IC, the each stimulator pixel generally includes digital to analog converter (DAC) and the biphasic current driver.…”

Effects of Micro-Electrical Stimulation on Regulation of Behavior of Electro-Active Stem Cells

“…To determine optimal mES parameters, such as current (µA), stimulation time (ST_TIME; sec), and rest time (ST_INTV; sec) (Berg 1995;Kim et al 2006), a central composite design and a response surface analysis were used (Li et al 2008). The central composite design with five coded levels was applied for optimization.…”