Preparation Of Injectable Thermosensitive Magnetic Hydrogel And Its Mediated Improvement Of Cardiac Function In Rats With Vagus Nerve Magnetic Stimulation

Imbalance of the sympathetic and parasympathetic nervous systems is closely associated with the onset and progression of myocardial infarction.Vagus nerve electrical stimulation has been shown to be potentially beneficial in patients with myocardial infarction by enhancing parasympathetic drive to restore autonomic balance.However,electrode implantation may lead to vagus nerve injury and surgical infection.In this thesis,a magnetic vagus nerve stimulation(m VNS)system consisting of an injectable chitosan/sodium β-glycerophosphate hydrogel(SPIO-CS/GP)loaded with superparamagnetic iron oxide nanodrugs and a gentle magnetic pulse sequence was developed.It is noteworthy that this iron oxide nanodrug has been approved by the CFDA for clinical use.In this paper,SPIO-CS/GP hydrogel was injected and wrapped around the vagus nerve of rats and a magnetic field was applied for magnetic stimulation.The SPIO-CS/GP hydrogel was able to gel under the effect of body temperature.Among other things,the SPIO in the hydrogel makes the magnetic effect more precise.After magnetic stimulation of the vagus nerve,cardiac function was improved in rats with myocardial infarction and the area of cardiac fibrosis was reduced.In addition to this,magnetic stimulation was able to reduce the myocardial infarction-induced inflammatory response and significantly reduced the number and duration of ventricular arrhythmias in a rat ischaemia/reperfusion model.This was done as follows.Firstly,SPIO-CS/GP hydrogels with different composition contents were prepared by loading SPIO into injectable CS/GP hydrogels.SPIO-CS/GP hydrogels could be injected by syringe and underwent sol-gel phase transition at 37°C.The basic materialistic properties of SPIO-CS/GP were tested by scanning electron microscopy,Fourier infrared spectroscopy and vibrating sample magnetometer.The gelation time as well as the rheological properties such as viscosity and modulus of SPIO-CS/GP hydrogels were regulated by modulating the concentration of chitosan and nanoparticles.In addition,chain-like structures were assembled inside the SPIO-CS/GP hydrogels using static magnetic field assembly to obtain hydrogel materials that better mimic biological tissues in terms of morphology and mechanical properties,and the length of the nano-chains was regulated by controlling the magnetic field strength and assembly time.Then,the SPIO-CS/GP hydrogel was injected and wrapped around the right vagus nerve of rats and a magnetic pulse sequence was applied to verify the stimulation effect of the m VNS system on the vagus nerve by electrophysiological tests.Afterwards,a rat myocardial infarction model was successfully established by ligating the left anterior descending branch of the coronary artery.After the magnetic stimulation treatment,the improvement of cardiac function by the m VNS system was assessed by echocardiography,Masson staining and cardiac function marker levels.In addition,the effect of different single magnetic stimulation times on cardiac function was compared and the magnetic stimulation treatment parameters were optimised.Further,the in vivo metabolism of SPIO-CS/GP hydrogel was tracked using magnetic resonance imaging simultaneously during the treatment phase,and it was found that SPIOCS/GP hydrogel could be retained in rats for at least 10 weeks with a good safety profile.Finally,this thesis preliminarily explores the mechanisms by which magnetic stimulation improves post-infarction cardiac function.The ion channel results suggest that the magnetic effect may be the mechanism by which the vagus nerve is stimulated.Furthermore,magnetic stimulation of the vagus nerve reduced serum levels of inflammatory factors in rats with myocardial infarction,and immunohistochemical staining images also showed that magnetic stimulation inhibited inflammatory infiltration and cardiomyocyte apoptosis.In addition,we found that the number and duration of ventricular arrhythmias decreased after magnetic stimulation.These may be the mechanisms by which magnetic stimulation improves cardiac function.