Ti3c2tx/Ppy Coated Pla/ Oleanic Acid Multi-Layered Nerve Conduit Promotes Peripheral Nerve Regeneration Through Anti-Inflammatory Effects and Electrical Stimulation

Traditional nerve conduits normally perform unsatisfactory therapeutic effects for peripheral nerve injury (PNI) because of lacking biomimetic structural design and functional modification. Recent researches demonstrated that balanced immune response and electrical stimulation were the two essential factors that could alter the microenvironment to boost neuronal regeneration. Here, a novel and potential kind of conductive nerve conduit with biomimetic structure was designed in which Ti3C2Tx /PPy was coated on the Oleanic acid (OA) loaded Poly-lactic acid (PLA) conduit with an oriented inner layer through electrostatic spraying. Physical evaluation indicated that the neural conduit had moderate hydrophilicity, enhanced tensile strength (2.01 ± 0.24Mpa) and elasticity (96.4 ± 1.1%), as well as excellent conductivity (1.28 × 10-2S/cm). In vitro evaluation showed that the weight loss rate of the conduit within 8 weeks reached 58 ± 1.35% and exhibited no obvious toxicity which was suitable for the adhesion, proliferation and migration of nerve cells in vitro. Importantly, when coupled with electrical stimulation, it might not only dramatically increase PC12 differentiation and proliferation but also quicken nerve cell regeneration. Meanwhile, the OA released by the conduit could help to repolarize pro-inflammatory macrophages into healing promoting macrophages to accelerate peripheral nerve regeneration.