Impact of Alternating Electric Fields on Musculoskeletal Tissue Regeneration

In regenerative medicine, electrical stimulation is an interesting approach to promote the growth of heart and nerve tissue, wound healing, or musculoskeletal regeneration. Electrical fields can be applied directly, capacitively, or inductively, and the effects of electrical stimulation on various cell types are the subject of a controversial discussion in the literature. Generally, electrical stimulation influences cell behavior in terms of cell survival, proliferation, and differentiation, as well as the formation of the extracellular matrix. In our working group, we have been investigating the influence of alternating electric fields on human bone, cartilage, and skeletal muscle cells for several years. Hereby, we developed various in vitro stimulation systems to this end, either coupling the fields directly (DC) or capacitively (CC). The spectrum of the thus applied electric fields ranges from 5.2 × 10 −6 µV/m (for CC) to 150 V/m (for DC). In addition to cell biological studies on cellular viability, our work focuses on the modulation of tissue-specific gene expression profiles and the release of defined extracellular matrix and signaling molecules. In the in vitro studies, we were able to show that alternating electric fields up to a maximum of 100 V/m are effective in stimulating bone and cartilage cells. In particular, the induction of osteoblast maturation, osteogenic differentiation, and mineralization capacity is dependent on the applied electric field strength and stimulation time. Further, the synthesis of cartilage-specific matrix proteins by chondrocytes also appears to be modulated in a field strength-dependent manner, whereby the cellular response appears to be strongly dependent on the donor tissue, i.e., cells from degeneratively altered cartilage are more sensitive to applied electric fields than cells from undamaged cartilage. Previous studies with human skeletal muscle cells resulted in the induction of differentiation-associated genes after treatment with low alternating electric fields in the µV/m range. Research on the effects of alternating electric fields on musculoskeletal tissue focuses on increasing the differentiation capacity of cells and thus improving the regeneration of the target tissue. The in vitro experiments serve as the basis for identifying suitable stimulation parameters for future clinical applications, e.g. for use of electrically active implant systems. This work is supported by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)-JO 1483/1-1 and SFB 1270/1,2 – 299150580) and the Bundesministerium für Ernährung und Landwirtschaft (BMEL-281A819B21).