Modulation of Macrophage Activity by Pulsed Electromagnetic Fields in the Context of Fracture Healing

Author: Yangmengfan Chen1, Maximilian M Menger1, Benedikt J Braun1, Sara Schweizer1, Caren Linnemann1, Karsten Falldorf2, Michael Ronniger2, Hongbo Wang3, Tina Histing1, Andreas K Nussler1, Sabrina Ehnert1
1 Siegfried Weller Research Institute, BG Trauma Center Tübingen, Department of Trauma and Reconstructive Surgery, University of Tübingen, Schnarrenbergstr. 95, D-72076 Tübingen, Germany.
2 Sachtleben GmbH, Haus Spectrum am UKE, Martinistraße 64, D-20251 Hamburg, Germany.
3 Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Ave., Wuhan 430022, China.
Conference/Journal: Bioengineering (Basel)
Date published: 2021 Oct 29
Other: Volume ID: 8 , Issue ID: 11 , Pages: 167 , Special Notes: doi: 10.3390/bioengineering8110167. , Word Count: 316

Delayed fracture healing and fracture non-unions impose an enormous burden on individuals and society. Successful healing requires tight communication between immune cells and bone cells. Macrophages can be found in all healing phases. Due to their high plasticity and long life span, they represent good target cells for modulation. In the past, extremely low frequency pulsed electromagnet fields (ELF-PEMFs) have been shown to exert cell-specific effects depending on the field conditions. Thus, the aim was to identify the specific ELF-PEMFs able to modulate macrophage activity to indirectly promote mesenchymal stem/stromal cell (SCP-1 cells) function. After a blinded screening of 22 different ELF-PEMF, two fields (termed A and B) were further characterized as they diversely affected macrophage function. These two fields have similar fundamental frequencies (51.8 Hz and 52.3 Hz) but are emitted in different groups of pulses or rather send-pause intervals. Macrophages exposed to field A showed a pro-inflammatory function, represented by increased levels of phospho-Stat1 and CD86, the accumulation of ROS, and increased secretion of pro-inflammatory cytokines. In contrast, macrophages exposed to field B showed anti-inflammatory and pro-healing functions, represented by increased levels of Arginase I, increased secretion of anti-inflammatory cytokines, and growth factors are known to induce healing processes. The conditioned medium from macrophages exposed to both ELF-PEMFs favored the migration of SCP-1 cells, but the effect was stronger for field B. Furthermore, the conditioned medium from macrophages exposed to field B, but not to field A, stimulated the expression of extracellular matrix genes in SCP-1 cells, i.e., COL1A1, FN1, and BGN. In summary, our data show that specific ELF-PEMFs may affect immune cell function. Thus, knowing the specific ELF-PEMFs conditions and the underlying mechanisms bears great potential as an adjuvant treatment to modulate immune responses during pathologies, e.g., fracture healing.

Keywords: extracellular matrix; extremely low frequency pulsed electromagnetic fields (ELF-PEMFs); fracture healing; macrophages; mesenchymal stem/stromal cells.

PMID: 34821733 PMCID: PMC8615107 DOI: 10.3390/bioengineering8110167