Reactive oxygen species (ROS) can irreversibly damage biological molecules, a process known as oxidative stress. Elevated ROS levels are associated with immune cell activation. Sustained immune system activation can affect many different cells in the environment. One cell type that has been detected in almost all tissues of the body is mesenchymal stem/stromal cells (MSC). MSC possess proliferation and differentiation potential, thus facilitating regeneration processes. However, the regenerative capacity of MSC might be impaired by oxidative stress, and the effects of long-term oxidative stress on MSC functions are sparsely described. The examination of oxidative stress is often performed by exposure to H2O2. Since H2O2 is rapidly degraded, we additionally exposed the cell cultures to glucose oxidase (GOx), resulting in sustained exposure to H2O2. Using these model systems, we have focused on the effects of short- and long-term oxidative stress on viability, migration, differentiation, and signaling. All cellular functions examined were affected by the applied oxidative stress. The differences that occur between pulsed and sustained oxidative stress indicated higher oxidative stress in MSC upon direct H2O2 exposure, whereas the GOx-induced prolonged exposure to H2O2 seems to allow for better cellular adaptation. The mechanisms underlying these different responses are currently unknown.

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.