Noninvasive electrical stimulation enhances the diabetic osseointegration via alleviating mitochondrial damage

Abstract A high‐glucose environment induces an imbalance in mitochondrial homeostasis, and further results in decreased autophagic capacity and energy metabolism in mitochondria. This mitochondrial dysfunction inhibits the regeneration of bone tissue. Electrical stimulation (ES) is an efficient strategy to rebalance the mitochondrial homeostasis to further accelerate the bone regeneration process. However, traditional ES strategies are invasive and easily cause secondary trauma, limiting their medical application. Here, we designed a new noninvasive direct‐current electric field (DCEF) strategy. This strategy can provide ES in situ without implantation. The results show that this strategy can target and regulate mitochondrial homeostasis through the PI3K–AKT signaling pathway, activate mitochondrial autophagy, alleviate high‐glucose‐induced mitochondrial damage, and further promote the osteogenic differentiation of bone marrow mesenchymal stem cells. Consequently, this exogenous noninvasive ES strategy can effectively accelerate the repair of bone defects in a high‐glucose environment through alleviating mitochondrial damage.