In vivo electrical stimulation (ES) has shown great promise in promoting tissue repair for various tissue engineering applications. However, a significant limitation of current long-term ES technique is that the existing postoperative protocols with transcutaneous leads have great risk of infection and need second operation to remove the tethered electrical-interface. Herein, we explored an ultrasound-driven in vivo ES technique based on the biodegradable piezoelectric nanogenerator (PENG) without any transcutaneous leads for the repair of peripheral nerve injuries. The piezoelectric nanogenerator contains biodegradable piezoelectric materials, including potassium sodium niobate (KNN) nanowires, poly (L-lactic acid) (PLLA), and poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV), biodegradable encapsulation layers, such as Poly (lactic acid) (PLA) or poly-ɛ-caprolactone (PCL) films, as well as biodegradable magnesium (Mg) electrodes and molybdenum (Mo) wires. Owing to the merits of ultrasound (US) in biomedical engineering, such as deep tissue penetration and predominant clinical security, US was selected as an exterior wireless energy source to drive the implantable nanogenerators which were fabricated with dissolvable piezoelectric films. With mechanical excitation remotely activated by programmable US pulses, the implanted piezoelectric nanogenerator can deliver adjustable ES to the biodegradable conductive conduits of peripheral nerves beyond the intraoperative period. Moreover, upon in-situ ES of the recovered nerves by the implanted nanogenerator, the nerve repairing process can be monitored in real-time with recorded muscle electrophysiology response. With a sciatic nerve injury model, our comprehensive investigation on neurologic function recovery analysis, histological assessment and microstructure analysis confirmed the great enhancement in nerve regeneration by the ultrasound-driven in vivo ES. This work provides a novel strategy with ultrasound-responsive biodegradable piezoelectric nanogenerator to deliver in vivo ES for tissue engineering applications.

体内电刺激 (ES) 在促进各种组织工程应用的组织修复方面显示出巨大的希望。然而，目前长期 ES 技术的一个显着限制是现有的经皮导联术后方案具有很大的感染风险，需要二次手术以去除系留的电接口。在此，我们探索了一种基于可生物降解压电纳米发电机 (PENG)的超声驱动的体内ES 技术，该技术无需任何经皮导线来修复周围神经损伤。压电纳米发电机包含可生物降解的压电材料，包括铌酸钾钠 (KNN) 纳米线、聚 ( L-乳酸）（PLLA）和聚（3-羟基丁酸酯-co-3-羟基戊酸酯）（PHBV），可生物降解的封装层，例如聚（乳酸）（PLA）或聚-ε-己内酯（PCL）薄膜，以及可生物降解的镁 (Mg) 电极和钼 (Mo) 线。由于超声（US）在生物医学工程中的优点，如深层组织穿透和主要的临床安全性，选择超声作为外部无线能源来驱动可溶解压电薄膜制造的植入式纳米发电机。通过可编程的 US 脉冲远程激活机械激励，植入的压电纳米发电机可以在术中结束后将可调节的 ES 输送到周围神经的可生物降解导电导管。此外，在现场通过植入的纳米发电机对恢复的神经进行 ES，可以通过记录的肌肉电生理反应实时监测神经修复过程。通过坐骨神经损伤模型，我们对神经功能恢复分析、组织学评估和微观结构分析的综合研究证实了超声驱动的体内ES 对神经再生的极大促进作用。这项工作提供了一种新的策略，即利用超声响应的可生物降解压电纳米发电机为组织工程应用提供体内ES。