Magnetoelectric/piezoelectric-based materials for coupled electrical and mechanical stimulation for bone repair: an <i>in silico</i> study

Bone repair is a complex process that requires the simultaneous presence of mechanical and electrical signals to replicate the physiological communication between acting forces, bone, and nerve cells. In this work, a new approach for bone repair is proposed that combines the properties of magnetoelectric nanoparticles (MENPs) and the piezoelectric properties of hydroxyapatite (HAP) particle to provide coupled mechanical and electrical stimulation. Although HAP is widely used in biological applications, its piezoelectric properties have never been modelled within a multiphysics framework. The modelling herewith proposed focuses on the magnetoelectric response of MENPs embedded within an alginate hydrogel matrix subjected to a DC magnetic field, on the effect of MENP concentration on the resulting electric field distribution, and on the mechanical stress generated by a single HAP particle in response to the electric field elicited by MENPs. A final 3D model is developed to investigate the coupled effects of electrical and mechanical stimulation on a human cell. The results show that the electric field generated throughout the alginate hydrogel matrix reaches values known to upregulate key markers associated with extracellular matrix mineralization. Moreover, a single MENP-activated HAP particle induces a localized von Mises stress of up to 4.91 N m^-2, able to trigger osteogenic processes, such as osteoblast proliferation and differentiation.