Sinusoidal electromagnetic fields accelerate bone regeneration by boosting the multifunctionality of bone marrow mesenchymal stem cells

Abstract

Background The repair of critical-sized bone defects is always a challenging problem. Electromagnetic fields (EMFs), used as a physiotherapy for bone defects, have been suspected to cause potential hazards to human health due to the long-term exposure. To optimize the application of EMF while avoiding its adverse effects, a combination of EMF and tissue engineering techniques is critical. Furthermore, a deeper understanding of the mechanism of action of EMF will lead to better applications in the future. Methods In this research, bone marrow mesenchymal stem cells (BMSCs) seeded on 3D-printed scaffolds were treated with sinusoidal EMFs in vitro. Then, 5.5 mm critical-sized calvarial defects were created in rats, and the cell scaffolds were implanted into the defects. In addition, the molecular and cellular mechanisms by which EMFs regulate BMSCs were explored with various approaches to gain deeper insight into the effects of EMFs. Results The cell scaffolds treated with EMF successfully accelerated the repair of critical-sized calvarial defects. Further studies revealed that EMF could not directly induce the differentiation of BMSCs but improved the sensitivity of BMSCs to BMP signals by upregulating the quantity of specific BMP (bone morphogenetic protein) receptors. Once these receptors receive BMP signals from the surrounding milieu, a cascade of reactions is initiated to promote osteogenic differentiation via the BMP/Smad signalling pathway. Moreover, the cytokines secreted by BMSCs treated with EMF can better facilitate angiogenesis and osteoimmunomodulation which play fundamental roles in bone regeneration. Conclusion In summary, EMF can promote the osteogenic potential of BMSCs and enhance the paracrine function of BMSCs to facilitate bone regeneration. These findings highlight the profound impact of EMF on tissue engineering and provide a new strategy for the clinical treatment of bone defects.

Harnessing electromagnetic fields to assist bone tissue engineering

“…And such crosstalk can be affected by EMFs [ 78 ]. Our group demonstrated that conditioned medium of BMSCs stimulated by EMFs showed prominent pro-angiogenetic capacity and osteoimmunomodulation effect [ 79 ]. And we further confirmed that it was the secreted cytokines within the conditioned medium that promote angiogenesis and M2 macrophage polarization (will be introduced later) [ 79 ].…”

“…Our group demonstrated that conditioned medium of BMSCs stimulated by EMFs showed prominent pro-angiogenetic capacity and osteoimmunomodulation effect [ 79 ]. And we further confirmed that it was the secreted cytokines within the conditioned medium that promote angiogenesis and M2 macrophage polarization (will be introduced later) [ 79 ]. A recent study similarly indicated that EMFs augmented the pro-angiogenetic capacity of MSCs by promoting the expression of miRNAs with intrinsic pro-angiogenic effect [ 80 ].…”

“…Besides PLLA, PCL is another commonly used synthetic polymer to overcome the brittleness of HA owing to its high mechanical properties and approved safety. Our work showed that the combination of EMFs and PCL/HAp scaffold also obtained pleasing outcomes in treating rat bone defects [ 79 , 94 ]. In the study carried out by Li et al, rat BMSCs-laden-PCL/HAp scaffolds were pre-treated with osteogenic medium and SEMF for 7 days (4 h/d) before in vivo implantation.…”

“…In the study carried out by Li et al, rat BMSCs-laden-PCL/HAp scaffolds were pre-treated with osteogenic medium and SEMF for 7 days (4 h/d) before in vivo implantation. And 8 weeks later, calvarial defect implanted with such scaffolds had more new bone area ( P < 0.01) than rats received BMSCs-laden-PCL/HAp scaffolds pre-treated with osteogenic medium only [ 79 ]. Another example of composites composed of synthetic polymers and natural polymers is PCL/carboxymethyl chitosan (CMC).…”

Carbon-based electrically conductive materials for bone repair and regeneration

“…In the alternative, inductive coupling uses non-invasive electromagnetic field stimulation. [51][52][53] In this method, one or two current-carrying coils are placed onto the skin, through which pulsed or sinusoidal electromagnetic fields are delivered that subsequently induce an electrical field in the damaged area. 54 Amongst these three techniques, inductive coupling best mimics the natural strain-generated potentials found in bone for its repair.…”