Hybrid nanogenerator based closed-loop self-powered low-level vagus nerve stimulation system for atrial fibrillation treatment

基于复合式纳米发电机的闭环自供电低水平迷走神经刺激系统用于心房颤动治疗

Atrial fibrillation is an “invisible killer” of human health. It often induces high-risk diseases, such as myocardial infarction, stroke, and heart failure. Fortunately, atrial fibrillation can be diagnosed and treated early. Low-level vagus nerve stimulation(LL-VNS) is a promising therapeutic method for atrial fibrillation. However, some fundamental challenges still need to be overcome in terms of flexibility,miniaturization, and long-term service of bioelectric stimulation devices. Here, we designed a closedloop self-powered LL-VNS system that can monitor the patient’s pulse wave status in real time and conduct stimulation impulses automatically during the development of atrial fibrillation. The implant is a hybrid nanogenerator(H-NG), which is flexible, light weight, and simple, even without electronic circuits,components, and batteries. The maximum output of the H-NG was 14.8 V and 17.8 μA(peak to peak). In the in vivo effect verification study, the atrial fibrillation duration significantly decreased by 90% after LLVNS therapy, and myocardial fibrosis and atrial connexin levels were effectively improved. Notably, the anti-inflammatory effect triggered by mediating the NF-κB and AP-1 pathways in our therapeutic system is observed. Overall, this implantable bioelectronic device is expected to be used for self-powerability,intelligentization, portability for management, and therapy of chronic diseases.

房颤是人类健康的“隐形杀手”,常诱发心肌梗塞、中风、心力衰竭等高危疾病.幸运的是,房颤可以早期诊断和治疗.低水平迷走神经刺激(LL-VNS)是一种很有前途的房颤治疗方法.然而,其在生物电刺激装置的灵活性、小型化和长期服务方面仍需要克服很多问题.为此,本文设计了一个闭环自供电LL-VNS系统,可以实时监测患者的脉搏波,并在房颤发生时自动传输刺激的脉冲.该植入物是一种复合式纳米发电机(H-NG),其特点是柔性、便携且不需要电路元件和电池.H-NG的最大输出为14.8 V和17.8μA(峰-峰值).体内的效果验证结果表明,LL-VNS治疗后房颤持续时间显著降低90%,而且心肌纤维化和心房连接蛋白水平得到有效改善.值得注意的是,在该治疗系统中观察到通过介导NF-κB和AP-1途径而触发的抗炎作用.总体而言,这种植入式生物电子设备有望用于慢性病的自供电、智能化、便携式的管理和治疗.