Harnessing electromagnetic fields to assist bone tissue engineering

Abstract

Bone tissue engineering (BTE) emerged as one of the exceptional means for bone defects owing to it providing mechanical supports to guide bone tissue regeneration. Great advances have been made to facilitate the success of BTE in regenerating bone within defects. The use of externally applied fields has been regarded as an alternative strategy for BTE. Electromagnetic fields (EMFs), known as a simple and non-invasive therapy, can remotely provide electric and magnetic stimulation to cells and biomaterials, thus applying EMFs to assist BTE would be a promising strategy for bone regeneration. When combined with BTE, EMFs improve cell adhesion to the material surface by promoting protein adsorption. Additionally, EMFs have positive effects on mesenchymal stem cells and show capabilities of pro-angiogenesis and macrophage polarization manipulation. These advantages of EMFs indicate that it is perfectly suitable for representing the adjuvant treatment of BTE. We also summarize studies concerning combinations of EMFs and diverse biomaterial types. The strategy of combining EMFs and BTE receives encouraging outcomes and holds a promising future for effectively treating bone defects.

Keywords: Bone regeneration; Bone tissue engineering; Electromagnetic fields; Osteogenesis.

Fig. 1

Harnessing electromagnetic fields to assist bone tissue engineering. Electromagnetic fields can be applied to stimulate loaded cell before and/or after implantation. This image was drawn by the authors. Created with BioRender.com

Fig. 2

Scheme of electromagnetic fields generation system. An electromagnetic field generation system typically composed of a waveform generator, amplifier, oscilloscope, and Helmholtz coils. Two commonly used electromagnetic fields are presented: (1) pulsed electromagnetic field signal refers to the periodically repeated bursts composed of a certain amount of pulses [37]; (2) the non-pulsed sinusoidal electromagnetic field with continuous sinusoidal waveform. B refers to the magnetic flux density, t represents time. This image was drawn by the authors. Created with BioRender.com

Fig. 3

PEMF improves cell adhesion to Ti implant surface by promoting protein adsorption [42]. PEMF induces a negatively charged surface of Ti implant by making dipoles alignment. Cations mainly Ca²⁺ and proteins with positive charges adsorb onto negatively charged Ti surface. Cell adhesion-mediated motifs such as RGD embedded in adsorbed proteins mediate material-cell adhesion by binding to integrins located on cell membrane. PEMF pulsed electromagnetic field, Ti titanium, RGD Arg-Gly-Asp. This image was drawn by the authors. Created with BioRender.com

Fig. 4

Advantages of electromagnetic fields in assisting bone tissue engineering. Advantages of electromagnetic fields including positive effects on stem cells, pro-angiogenesis, and preference of M2 macrophage polarization. This image was drawn by the authors. Created with BioRender.com

Fig. 5

Interactions of MNC and cells under EMFs’ exposure. (1) Vibrations of MNPs induced by the presence of EMF provide mechanical cues for cells load on MNC [180]. (2, 3) Vibrations and generated heat of MNPs in the presence of EMFs affect the release of biological factors such as BMP-2 which would subsequently exert biological effects on adjacent cells [139, 181]. (4) Mild heat generated by MNC under high-frequency EMFs contributes to enhanced osteogenesis [186]. MNC magnetic nanocomposites, EMFs electromagnetic fields, MNPs magnetic nanoparticles, BMP-2 bone morphogenetic protein-2, HSP 90 heat shock protein 90. This image was drawn by the authors. Created with BioRender.com