Remote Tuning of Built-In Magnetoelectric Microenvironment to Promote Bone Regeneration by Modulating Cellular Exposure to Arginylglycylaspartic Acid Peptide

Mimicking the endogenous physical microenvironment is a promising strategy for biomaterial-mediated tissue regeneration. However, precise control of physical cues such as electric/magnetic fields within extracellular environments 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. The magnetoelectric microenvironment from the nanocomposite membranes promotes osteogenic differentiation of bone marrow mesenchymal stem cells (BM-MSCs) and enhances bone defect regeneration by increasing cellular exposure and integrin binding to arginylglycylaspartic acid peptide, as predicted by molecular dynamics simulations. Moreover, BM-MSCs are directed to the osteogenic lineage by osteoimmuomodulation which involves accelerating transition from an initial inflammatory immune response to a pro-healing regenerative immune response. This work offers a strategy to mimic the magnetoelectric microenvironment for achieving precise and effective tissue regenerative therapies, as well as provides fundamental insights into the biological effects driven by the built-in magnetoelectric membrane, which can be remotely tuned to precisely modulate osteogenesis in situ.