Remote Tuning of Builtin Magnetoelectric Microenvironment to Promote Bone Regeneration

Objectives: Precise control of endogenous magnetoelectric microenvironment to facilitate tissue regeneration remains a formidable challenge. Here, remote tuning of the magnetoelectric microenvironment is achieved by a built-in CoFe₂O₄/poly(vinylidene fluoridetrifluoroethylene) [P(VDF-TrFE)] magnetoelectric membrane for effective bone regeneration.
Methods: Firstly, the CoFe₂O₄/P (VDF-TrFE) magnetoelectric nanocomposite with different proportion of CoFe₂O₄ nanoparticles were prepared by the casting process. The external magnetic field was employed for remote tuning of the magnetoelectric microenvironment constructed by the magnetoelectric nanocomposite. Next, molecular dynamics was used to simulate the adsorption of fibronectin on magnetoelectric nanocomposites. The osteoinductive ability of materials was predicted according to the results of molecular dynamics. These predictions were validated by in vitro experiments. Finally, the rat calvarial defects were employed for evaluating the osteoimmunomodulatory and bone regeneration in vivo.
Results: CoFe₂O₄/P(VDF-TrFE) magnetoelectric nanocomposite was prepared by solution casting method. By loading an external magnetic field, the remote tuning of the magnetoelectric microenvironment was realized. According to molecular dynamics simulation, it is predicted that the 10 wt% CoFe₂O₄/P(VDF-TrFE) magnetoelectric nanocomposite has the optimal osteoinductive ability. The magnetoelectric microenvironment constructed by the 10 wt% CoFe₂O₄/P(VDF-TrFE) magnetoelectric nanocomposite and the external magnetic field could promote BMSCs osteogenic differentiation by activating mechanical transduction related signaling pathways, and activate the initial immune response and accelerate the transition from M1 to M2 phenotype to further promote bone regeneration in vivo.
Conclusions: By regulating the CoFe₂O₄/P(VDF-TrFE) magnetoelectric nanocomposite with an external magnetic field, the remote tuning of the build-in magnetoelectric microenvironment was realized, which could directly induce the osteogenic differentiation of BMSCs and promote bone regeneration by regulating the osteoimmunomodulatory. This study offers a novel perspective and direction of regulation of the microenvironment in bone regeneration area by biomimetic materials for promoting bone regeneration.