An extensive research field in regenerative medicine is electrical stimulation (ES) and its impact on tissue and cells. The mechanism of action of ES, particularly the role of electrical parameters like intensity, frequency, and duration of the electric field, is not yet fully understood. Human MG-63 osteoblasts were electrically stimulated for 10 min with a commercially available multi-channel system (IonOptix). We generated alternating current (AC) electrical fields with a voltage of 1 or 5 V and frequencies of 7.9 or 20 Hz, respectively. To exclude liquid-mediated effects, we characterized the AC-stimulated culture medium. AC stimulation did not change the medium’s pH, temperature, and oxygen content. The H2O2 level was comparable with the unstimulated samples except at 5 V_7.9 Hz, where a significant increase in H2O2 was found within the first 30 min. Pulsed electrical stimulation was beneficial for the process of attachment and initial adhesion of suspended osteoblasts. At the same time, the intracellular Ca2+ level was enhanced and highest for 20 Hz stimulated cells with 1 and 5 V, respectively. In addition, increased Ca2+ mobilization after an additional trigger (ATP) was detected at these parameters. New knowledge was provided on why electrical stimulation contributes to cell activation in bone tissue regeneration.

The development of new biomaterials and medical devices has become a growing field of interdisciplinary research. The medical devices for tissue and cell treatments are being constructed for the application in regenerative medicine. There are many different approaches to improve cellular functions and it is known that physical stimuli affect cell physiology such as proliferation and differentiation. In this review we focus on electrical and mechanical stimulation as well as cold atmospheric pressure plasma treatment and photobiomodulation. Bone forming cells show improved proliferation and migration after electrical stimulation, which is used as treatment in bone fracture healing and to enhance osseointegration. Especially mechanical forces have direct effects on central cell signalling pathways and cell adhesion to biomaterial surfaces. Physical plasma promotes tissue regeneration and exhibits anti-carcinogenic effects, while light of different wavelengths also improves wound healing and tissue repair by influencing stem cell fate. Although the treatment approaches are different, all these physical factors lead to the activation of cell signalling via calcium and reactive oxygen species. A better understanding of the cellular response to the applied stimuli will help develop efficient treatment strategies and optimised device settings.