Metabolic Mechanism of Osteogenic Differentiation of Bone Marrow Mesenchymal Stem Cell Regulated by Magnetoelectric Microenvironment

Conventional methods to stimulate the metabolism of bone marrow mesenchymal stem cells (BMSCs) for osteogenic differentiation typically involve systemic mobilization, which faces challenges including limited in vivo half‐life, lack of selectivity, and potential side‐effects. Therefore, localized modulation of BMSCs represents a more efficient and safer alternative. However, few studies have explored the regulation of a localized stimuli‐responsive microenvironment to activate osteogenic differentiation via mitochondrial pathways and clarified its underlying mechanisms. Herein, a novel strategy to accelerate the metabolic switch of BMSCs in tissue defects through targeted modulation using built‐in magnetoelectric biomaterials is proposed. BMSCs cultured in the magnetoelectric microenvironment exhibited an increased mitochondrial membrane potential, the highest oxygen consumption rate and enhanced adenosine triphosphate production. Furthermore, BMSCs in the magnetoelectric microenvironment demonstrated a successful metabolic switch of energy resource from glycolysis to oxidative phosphorylation, indicating a strong tendency toward osteogenic differentiation. The highest multiclass metabolite profile, indicating the most active metabolic state, was shown in rats cranial defect model treated with magnetoelectric microenvironment. This research introduces a novel approach to accelerate bone defect repair by targeted modulation of BMSC mitochondria with magnetoelectric microenvironment and provides a promising direction for exploring the intrinsic mechanisms through which the magnetoelectric microenvironment promotes bone regeneration.