Polydopamine-Decorated PLCL Conduit to Induce Synergetic Effect of Electrical Stimulation and Topological Morphology for Peripheral Nerve Regeneration

聚多巴胺修饰的PLCL导管诱导电刺激和拓扑形态的协同效应促进周围神经再生

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作者:Shunyi Lu, Wen Chen, Jiayi Wang, Zilong Guo, Lan Xiao, Lingyu Wei, Jieqin Yu, Ya Yuan, Weisin Chen, Mengxuan Bian, Lei Huang, Yuanyuan Liu, Jian Zhang, Yu-Lin Li, Li-Bo Jiang

Abstract

Due to the limited self-repairing capacity after peripheral nerve injuries (PNI), artificial nerve conduits are widely applied to facilitate neural regeneration. Exogenous electrical stimulation (ES) that is carried out by the conductive conduit regulates the biological behavior of Schwann cells (SCs). Meanwhile, a longitudinal surface structure counts to guide axonal growth to accelerate the end-to-end connection. Currently, there are no conduits equipped with both electrical conduction and axon-guiding surface structure. Herein, a biodegradable, conductive poly(l-lactide-co-caprolactone)/graphene (PLCL/GN) composite conduit is designed. The conduit with 20.96 ± 1.26 MPa tensile strength has a micropatterned surface of 20 µm groove fabricated by microimprint technology and self-assembled polydopamine (PDA). In vitro evaluation shows that the conduits with ES effectively stimulate the directional cell migration, adhesion, and elongation, and enhance neuronal expression of SCs. The rat sciatic nerve crush model demonstrates that the conductive micropatterned conduit with ES promotes the growth of myelin sheath, faster nerve regeneration, and 20-fold functional recovery in vivo. These discoveries prove that the PLCL(G)/PDA/GN composite conduit is a promising tool for PNI treatment by providing the functional integration of physical guidance, biomimetic biological regulation, and bioelectrical stimulation, which inspires a novel therapeutic approach for nerve regeneration in the future.

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