Peripheral nerve regeneration and functional recovery remain a major clinical challenge. Nerve guidance conduit (NGC) that can regulate biological behavior of Schwann cells (SCs) and facilitate axonal regeneration through microenvironmental remodeling is beneficial for nerve regeneration and functional recovery. Gastrodin, a main constituent of a Chinese traditional herbal medicine, has been known to display several biological and pharmacological properties, especially antioxidative, anti‐inflammatory and nerve regeneration. Herein, polyurethane (PU) NGCs modified by different weight ratio of Gastrodin (0, 1 and 5 wt%) were designed for sequential and sustainable drug release, that created a favorable microenvironment for nerve regeneration. The scaffold showed suitable pore structure and biocompatibility in vitro, and evidently promoted morphological and functional recovery of regenerated sciatic nerves in vivo. Compared to the PU and 1%Gastrodin/PU scaffolds, the 5%Gastrodin/PU significantly enhanced the proliferation, migration and myelination of SCs and up-regulated expression of neurotrophic factors, as well as induction of the differentiation of PC12 cells. Interestingly, the obvious anti-inflammatory response was observed in 5%Gastrodin/PU by reduced expression of TNF-α and iNOS, which also evidenced by the few fibrous capsule formation in the subcutaneous implantation. Such a construct presented a similarity to autograft in vivo repairing a 10 mm sciatic nerve defects. It was able to not only boost the regenerated area of nerve and microvascular network, but also facilitate functional axons growth and remyelination, leading to highly improved functional restoration. These findings demonstrate that the 5%Gastrodin/PU NGC efficiently promotes nerve regeneration, indicating their potential for use in peripheral nerve regeneration applications.

周围神经再生和功能恢复仍然是主要的临床挑战。神经引导导管 (NGC) 可以调节雪旺细胞 (SC) 的生物学行为，并通过微环境重塑促进轴突再生，有利于神经再生和功能恢复。天麻素是中草药的主要成分，具有多种生物学和药理特性，尤其是抗氧化、抗炎和神经再生。在此，由不同重量比的天麻素（0、1 和 5 wt%）改性的聚氨酯 (PU) NGC 设计用于顺序和可持续的药物释放，为神经再生创造了有利的微环境。该支架在体外表现出合适的孔结构和生物相容性，并明显促进体内再生坐骨神经的形态和功能恢复。与 PU 和 1%Gastrodin/PU 支架相比，5%Gastrodin/PU 显着增强 SCs 的增殖、迁移和髓鞘形成，上调神经营养因子的表达，以及诱导 PC12 细胞的分化。有趣的是，通过降低 TNF-α 和 iNOS 的表达，在 5% 天麻素/PU 中观察到明显的抗炎反应，这也可以通过皮下植入中很少的纤维囊形成来证明。这种构建体表现出与体内自体移植的相似性修复 10 毫米坐骨神经缺损。它不仅能够促进神经和微血管网络的再生区域，还能够促进功能性轴突的生长和髓鞘再生，从而大大改善功能恢复。这些发现表明 5% 天麻素/PU NGC 有效促进神经再生，表明它们在周围神经再生应用中的潜力。