Discrimination between the effects of pulsed electrical stimulation and electrochemically conditioned medium on human osteoblasts

脉冲电刺激与电化学条件培养基对人类成骨细胞的影响的鉴别

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作者:Meike Bielfeldt, Kai Budde-Sagert, Nikolai Weis, Maren Buenning, Susanne Staehlke, Julius Zimmermann, Nils Arbeiter, Sahba Mobini, María Ujué González, Henrike Rebl, Adelinde Uhrmacher, Ursula van Rienen, Barbara Nebe

Background

Electrical stimulation is used for enhanced bone fracture healing. Electrochemical processes occur during the electrical stimulation at the electrodes and influence cellular reactions. Our approach aimed to distinguish between electrochemical and electric field effects on osteoblast-like MG-63 cells. We applied 20 Hz biphasic pulses via platinum electrodes for 2 h. The electrical stimulation of the cell culture medium and subsequent application to cells was compared to directly stimulated cells. The electric field distribution was predicted using a digital twin.

Conclusion

The electrochemical by-product hydrogen peroxide is not the main contributor to the cellular effects of electrical stimulation. However, undesired effects like decreased adhesion are mediated through electrochemical products in stimulated medium. Detailed characterisation and monitoring of the stimulation set up and electrochemical reactions are necessary to find safe electrical stimulation protocols.

Results

Cyclic voltammetry and electrochemical impedance spectroscopy revealed partial electrolysis at the electrodes, which was confirmed by increased concentrations of hydrogen peroxide in the medium. While both direct stimulation and AC-conditioned medium decreased cell adhesion and spreading, only the direct stimulation enhanced the intracellular calcium ions and reactive oxygen species.

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