Rapid improvement of heart repair in rats after myocardial infarction by precise magnetic stimulation on the vagus nerve with an injectable magnetic hydrogel

The imbalance between the sympathetic and the parasympathetic nervous system is one of the main pathogeneses of myocardial infarction (MI). Vagus nerve stimulation (VNS), which restores autonomic nervous balance by enhancing the parasympathetic drive, is shown to have benefits for patients with MI. As a clinically safe and effective remote neuromodulation method, magnetic stimulation is expected to overcome the problems of infection and nerve injury caused by electrode implantation. However, it is difficult to achieve precise stimulation on a single vagus nerve due to the poor focus of the magnetic field. Here, we described a novel magnetic vagus nerve stimulation (mVNS) system, which consisted of an injectable chitosan/β-glycerophosphate (CS/GP) hydrogel loaded with superparamagnetic iron oxide (SPIO) nanoparticles and a mild magnetic pulse sequence. The injectable hydrogel prepared from clinically safe materials ensured minimally invasive implantation, and the SPIO nanoparticles in the hydrogel mediated the precise magnetic stimulation of a single vagus nerve. Under a mild magnetic field (∼100 mT), a decrease in heart rate and a change in vagus nerve potential were found in rats under in situ injection of a magnetic CS/GP hydrogel. Magnetic stimulation on the vagus nerve for 4 weeks (20 Hz, three times daily, 5 minutes each time) significantly improved the cardiac function and reduced the infarct size of the rats subjected to myocardial infarction, accompanied by suppression of inflammatory cell infiltration and inflammation factor expression. Taken together, these results demonstrated that the mVNS exhibited promising potential for treating myocardial infarction in the clinic.