外周神经离断是临床常见的致残性疾病。实现离断神经（尤其是长距离神经缺损）的功能和结构修复是世界性医学难题。优良的组织工程导管可提供良好的机械支持和微环境，桥联断端并引导神经再生，然而外周神经自身相对不足的再生能力限制了修复效果。PTEN和SOCS3是两个关键的神经再生内源性抑制分子；电刺激是促神经再生的强烈外源性信号。我们前期研究表明PTEN/SOCS3沉默和电刺激有明显的协同效应，显著促进神经再生。本项目拟合成一种导电丝胶神经导管，介导电刺激；同时运用dCas9-CRISPRi基因编辑技术高效沉默外周神经细胞内PTEN和SOCS3基因；以此将外源刺激激发出的再生能力与内源性释放出的再生能力巧妙结合，提高外周神经再生效率。本项目的成功实施将为外周神经损伤的组织工程修复提供新策略。

Peripheral nerve transection is a common and disabling injury in clinical practice. Functional and structural recovery of transected peripheral nerves (particularly with large peripheral nerve defects) remains challenging.Tissue engineered nerve guidance conduitscan provide mechanical support and nerve-favorable microenvironment for bridging and guiding transected nerves’regeneration. However, the poorregenerative ability of peripheral nerves limits repairing efficacy. PTEN and SOCS3 are two key inhibitory moleculesinnerve regeneration, while electric stimulation is a strong exogenous signal for promoting nerve regeneration.Our data have shown that PTEN/SOCS3 silencing in conjunction with electric stimulation have significant synergistic effectsin enhancing nerveregeneration. In this project, we aim to fabricate a conductive sericin nerve guidance conduit to mediate electric stimulation to stimulate nerve regeneration. Meanwhile, we will employ dCas9-CRISPRi genome editing techniqueto silence the expression of PTEN and SOCS3 genes in order to release neurons’intrinsic regeneration capability. Thus, the combination of exogenous electric stimulation with intrinsic gene expression regulation would be expected to drastically promote peripheral nerve regeneration. We hope that the successful implementation of this project will offer a new strategy for effective repair of transected peripheral nerves.