Department of Oral & Cranio-Maxillofacial Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai, 200011, China.
Research Center for Nano-Biomaterials, Analytical and Testing Center, Sichuan University, Chengdu, 610064, China.
J Nanobiotechnology. 2024 May 12;22(1):244. doi: 10.1186/s12951-024-02507-3.
Biomaterials can modulate the local immune microenvironments to promote peripheral nerve regeneration. Inspired by the spatial orderly distribution and endogenous electric field of nerve fibers, we aimed to investigate the synergistic effects of electrical and topological cues on immune microenvironments of peripheral nerve regeneration. Nerve guidance conduits (NGCs) with aligned electrospun nanofibers were fabricated using a polyurethane copolymer containing a conductive aniline trimer and degradable L-lysine (PUAT). In vitro experiments showed that the aligned PUAT (A-PUAT) membranes promoted the recruitment of macrophages and induced their polarization towards the pro-healing M2 phenotype, which subsequently facilitated the migration and myelination of Schwann cells. Furthermore, NGCs fabricated from A-PUAT increased the proportion of pro-healing macrophages and improved peripheral nerve regeneration in a rat model of sciatic nerve injury. In conclusion, this study demonstrated the potential application of NGCs in peripheral nerve regeneration from an immunomodulatory perspective and revealed A-PUAT as a clinically-actionable strategy for peripheral nerve injury.
生物材料可以调节局部免疫微环境，促进周围神经再生。受神经纤维空间有序分布和内源性电场的启发，我们旨在研究电和拓扑线索对周围神经再生免疫微环境的协同作用。使用含有导电苯胺三聚体和可降解 L-赖氨酸的聚氨酯共聚物（PUAT）制备具有取向电纺纳米纤维的神经引导导管（NGC）。体外实验表明，取向的 PUAT（A-PUAT）膜促进了巨噬细胞的募集，并诱导其向有利于修复的 M2 表型极化，从而促进施万细胞的迁移和髓鞘形成。此外，由 A-PUAT 制成的 NGC 增加了有利于修复的巨噬细胞的比例，并改善了坐骨神经损伤大鼠模型中的周围神经再生。总之，这项研究从免疫调节的角度展示了 NGC 在周围神经再生中的潜在应用，并揭示了 A-PUAT 作为周围神经损伤的临床可行策略。
