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.

Background Magnetofection-mediated gene delivery shows great therapeutic potential through the regulation of the direction and degree of differentiation. Lumbar degenerative disc disease (DDD) is a serious global orthopaedic problem. However, even though intervertebral fusion is the gold standard for the treatment of DDD, its therapeutic effect is unsatisfactory. Here, we described a novel magnetofection system for delivering therapeutic miRNAs to promote osteogenesis and angiogenesis in patients with lumbar DDD. Results Co-stimulation with electromagnetic field (EMF) and iron oxide nanoparticles (IONPs) enhanced magnetofection efficiency significantly. Moreover, in vitro, magnetofection of miR-21 into bone marrow mesenchymal stem cells (BMSCs) and human umbilical endothelial cells (HUVECs) influenced their cellular behaviour and promoted osteogenesis and angiogenesis. Then, gene-edited seed cells were planted onto polycaprolactone (PCL) and hydroxyapatite (HA) scaffolds (PCL/HA scaffolds) and evolved into the ideal tissue-engineered bone to promote intervertebral fusion. Finally, our results showed that EMF and polyethyleneimine (PEI)@IONPs were enhancing transfection efficiency by activating the p38 MAPK pathway. Conclusion Our findings illustrate that a magnetofection system for delivering miR-21 into BMSCs and HUVECs promoted osteogenesis and angiogenesis in vitro and in vivo and that magnetofection transfection efficiency improved significantly under the co-stimulation of EMF and IONPs. Moreover, it relied on the activation of p38 MAPK pathway. This magnetofection system could be a promising therapeutic approach for various orthopaedic diseases. Graphical Abstract

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