Jong Keun Song

Novel Effect of Biphasic Electric Current on In Vitro Osteogenesis and Cytokine Production in Human Mesenchymal Stromal Cells

Electrical stimulation (ES) can activate diverse biostimulatory responses in a range of tissues. Of various forms of ES, the application of biphasic electric current (BEC) is a new approach to bone formation. This study is to investigate the effects and mechanism of action of BEC in osteoblast differentiation and cytokine production in human mesenchymal stromal cells (hMSCs). Using an in vitro culture system with a modified version of the BEC stimulator chip used in our previous study, we exposed hMSCs to a 100 Hz ES with a magnitude of 1.5/15 muA/cm(2) for 250/25 mus. hMSCs showed increased proliferation during static BEC stimulation for 5 days. However, alkaline phosphatase activity and calcium deposition were enhanced in hMSCs 7 days after the stimulation, rather than during the period of ES. BEC induced vascular endothelial growth factor (VEGF) and BMP-2 production; the former can enhance the proliferation of human umbilical vein endothelial cells in culture using conditioned media from BEC cultures. Treatment with selective inhibitors of p38 MAPK (SB203580) or Erk (PD98059), as well as calcium channel blockers (verapamil and nifedipine), reduced the BEC-mediated increase of VEGF expression and cell proliferation. These findings reveal that BEC is involved in the osteoblast differentiation of hMSCs through enhancement of cell proliferation and modulation of the local endocrine environment through VEGF and BMP-2 induction through the activation of MAPK (Erk and p38) and the calcium channel. Thus, local stimulation using BEC might be most beneficial in promoting osteogenic differentiation of hMSCs, resulting in enhanced bone formation for bone tissue engineering.

An electronic device for accelerating bone formation in tissues surrounding a dental implant

A dental implant is a unique structure which can be used with a noninvasive method because it is inserted into the bone in part and extended extracorporally. This study presents an electronic device that is temporarily connected with the dental implant, and reports its effect on accelerating bone formation in the surrounding tissues in a canine mandibular model. A small sized and low power consumption biphasic electrical current (BEC) stimulator ASIC was developed and the surrounding tissue was exposed to continuous BEC stimulation for 7 days with the parameters of 20 microA/cm(2), 125 micros duration, and 100 pulses/s. After 2 (n = 5) and 5 weeks (n = 5), animals were sacrificed and the specimens were histomorphometrically evaluated. The newly formed bone area (BA) was 1.30 times (3 weeks, P < 0.05) and 1.35 times (5 weeks, P < 0.05) higher in the experimental group compared to the control group, respectively. Bone-implant contact (BIC) in 3-week specimens was 1.62 times (P < 0.05) greater in the experimental group, while there was no statistically significant difference in 5-week specimens. Based on these results showing accelerated bone formation on and around the dental implant, it could be suggested that the latent time for osseointegration in dental implants can be reduced, and the success rate of implants in poor quality bone can be increased by using our device with BEC.

Enhanced bone formation around dental implant using electrical stimulation

It has been known that electrical stimulation promotes osteogenesis. Electrical stimulation using direct current can be applied to dental implant without invasive technique. The purpose of study was to evaluate the effect of biphasic direct current (BDC) on osteoblast in vitro and on early bone formation around implant. Human mesenchymal stem cells were exposed to BDC (1.5 A/cm2, 1,000 Hz), which was compared to control without stimulation regarding to cell proliferation and cytokine production in vitro. For animal test, a micro-current stimulator chip was developed (120ldrs, 100 Hz 20ldrA/cm2). BDC was applied to the implant 7 days in beagle dog (n=10). No stimulation was applied to control group (n=10). The animals were sacrificed at 2 and 4 weeks after stimulation. Histological specimens was histomorphometrically analyzed. The number of osteoblasts was increased (31%, p<0.05) and VEGF was increased in the stimulated group (p<0.01). The bone volume (BV) and bone implant contact (BIC) in 2 weeks and BV in 4 weeks were significantly (p<0.05) increased in the test group compared to the control. BCS can contribute to enhanced osteogenesis, it could be applied clinically to the early bone formation around implants.