Abstract：
A regenerative peripheral nerve interface (RPNI) offers a therapeutic solution for nerve injury through reconstruction of the target muscle. However, implanting a transected peripheral nerve into an autologous skeletal muscle graft in RPNI causes donor-site morbidity, highlighting the need for tissue-engineered skeletal muscle constructs. Here, an engineered regenerative isolated peripheral nerve interface (eRIPEN) is developed using 3D skeletal cell printing combined with direct electrospinning to create a nanofiber membrane envelop for host nerve implantation. In this in vivo study, after over 8 months of RPNI surgery, the eRIPEN exhibits a minimum Feret diameter of 15-20 µm with a cross-sectional area of 100-500 µm2, representing the largest distribution of myofibers. Furthermore, neuromuscular junction formation and muscle contraction with a force of ≈28 N are observed. Notably, the decreased hypersensitivity to mechanical/thermal stimuli and an improved tibial functional index from -77 to -56 are found in the eRIPEN group. The present novel concept of eRIPEN paves the way for the utilization and application of tissue-engineered constructs in RPNI, ultimately realizing neuroprosthesis control through synaptic connections.
摘要：
再生周围神经界面（RPNI）通过重建目标肌肉为神经损伤提供了治疗解决方案。然而,将横切的周围神经植入RPNI中的自体骨骼肌移植物会导致供体部位的发病率，突出了对组织工程骨骼肌构建体的需求。这里,使用3D骨骼细胞打印结合直接静电纺丝开发了工程化的再生孤立周围神经界面（eRIPEN），以创建用于宿主神经植入的纳米纤维膜包裹。在这项体内研究中，经过8个月的RPNI手术，eRIPEN的最小Feret直径为15-20µm，横截面积为100-500µm2，代表肌纤维的最大分布。此外，观察到神经肌肉接头形成和肌肉收缩，力≈28N。值得注意的是,在eRIPEN组中发现对机械/热刺激的超敏反应降低,胫骨功能指数从-77提高到-56.eRIPEN的新概念为组织工程构建体在RPNI中的利用和应用铺平了道路。最终通过突触连接实现神经假体控制。
