Enhanced Proliferation and Differentiation of Human Osteoblasts by Remotely Controlled Magnetic-Field-Induced Electric Stimulation Using Flexible Substrates.

Abstract

With the progressive aging of the population, bone fractures are an increasing major health concern. Diverse strategies are being studied to reduce the recovery times using nonaggressive treatments. Electrical stimulation (either endogenous or externally applied electric pulses) has been found to be effective in accelerating bone cell proliferation and differentiation. However, the direct insertion of electrodes into tissues can cause undesirable inflammation or infection reactions. As an alternative, magnetoelectric heterostructures (wherein magnetic fields are applied to induce electric polarization) could be used to achieve electric stimulation without the need for implanted electrodes. Here, we develop a magnetoelectric platform based on flexible kapton/FeGa/P(VDF-TrFE) (flexible substrate/magnetostrictive layer/ferroelectric layer) heterostructures for remote magnetic-field-induced electric field stimulation of human osteoblast cells. We show that the use of flexible supports overcomes the clamping effects that typically occur when analogous magnetoelectric structures are grown onto rigid substrates (which preclude strain transfer from the magnetostrictive to the ferroelectric layers). The study of the diverse proliferation and differentiation markers evidence that in all the stages of bone formation (cell proliferation, extracellular matrix maturation, and mineralization), the electrical stimulation of the cells results in a remarkably better performance. The results pave the way for novel strategies for remote cell stimulation based on flexible platforms not only in bone regeneration but also in many other applications where electrical cell stimulation may be beneficial (e.g., neurological diseases or skin regeneration).