Abstract:

Significance Currently, peripheral nerve injury causes great distress to patients, and artificial nerve conduits are used to replace autologous nerve grafting as an ideal treatment option. In the process of peripheral nerve injury and repair, the synergistic effect of conductive nerve conduits and electrical stimulation can greatly accelerate the regeneration and recovery of injured nerves, but polymers suitable for conduit formation are largely nonconductive. Thus, many studies prepare conductive artificial nerve conduits by adding conductive materials, such as carbon nanotubes (CNT), polypyrrole (PPy), and polyaniline (PANI), to the natural or synthetic polymers. Among the conductive materials, CNT has attracted much attention because of their better biocompatibility and excellent electrical conductivity. This review focuses on the physiochemical properties of CNT, their mechanisms for nerve repair and regeneration, the chemical modification of CNT and the formation methods of conductive nerve conduits, to better understand the nerve regeneration mechanism of CNT and clarifies the key progress and difficulties in preparing CNT-composited nerve conduits, hoping provide a beneficial reference for the preparation and application of carbon nanotubes in conductive nerve conduits.

Progress The use of CNT for conductive nerve conduits has been mainly achieved by the doping of CNT with various types of natural or synthetic polymers. Current research mainly focuses on four aspects. The first is the exploration of the role and mechanism of the physiochemical properties of CNT in nerve regeneration. The morphological structure of CNT resembles that of neurites, and the microenvironment constructed by its nanotopography provides structural guidance for the adhesion and extension of neurons. Its anisotropic conductivity is also like that of neurons, and electrical coupling between CNT and neurons facilitates neural signal transmission. The second is the study of various modification methods of CNT to improve its biocompatibility and processability. The modified CNT, with improved water solubility, shows better biocompatibility. Researchers adopted positively and negatively charged particles, polymers, growth factors, etc., to biofunctionalize CNT by covalent and noncovalent methods. Through functionalization, it is easier to interact with nerve cells and avoid agglomeration in vivo, which is beneficial for cellular uptake and internalization and in vivo degradation of nerve conduits. The third is the study of the forming methods of nerve conduits from CNT-doped polymers. The textile processing methods commonly used for conductive artificial nerve conduits include electrospinning techniques, 3D printing techniques, solution casting and braiding. In addition, polymers and CNT can be combined by coating, crosslinking, and so on. The fourth is the investigation on the biological characteristics and applications of conductive nerve conduits. It is believed that nerve repair is better with conductivity of 10^-4~10^-3 S/m, and this range, higher conductivity results in better nerve regeneration because the conductive film can improve functional recovery and myelination of the regenerated nerve fibers.

Conclusion and Prospect Through the analysis and review of the relevant research on the preparation of conductive artificial nerve conduits from CNT-composited polymers, the following conclusions can be drawn. 1) CNT has unique advantages in nerve repair and regeneration by virtue of its unique nanomorphology and excellent conductivity. The nanotopography of CNT facilitates its creation of an extracellular matrix-like environment when compositing with polymer materials, thereby promoting neuronal adherent growth and inducing nerve regeneration. Its excellent electrical conductivity significantly improves the efficiency of nerve signal transmission, and paired with external electrical stimulation, it can better repair and regenerate the injured nerve. 2) The functionalization modification of CNT can significantly improve its water solubility, which makes the fabrication and processing of composite conductive artificial neural conduits more convenient, and its biological toxicity is further reduced. 3) CNT and polymers can be combined by blending, coating, or crosslinking in many different ways, and the fabricated conductive artificial nerve conduits have achieved better nerve regeneration effects in animal experiments. At present, the use of CNT for conductive artificial nerve catheters has become a hotspot, but the possible biological metabolic toxicity and long-term toxicity caused by the added amount of CNT as well as the degradation speed of the nerve conduits are less studied. The mechanisms, methods, and influences of synergistic effects between CNT and electrical stimulation in vitro require further study, especially in addition to the nanotopography, electrical conductivity of CNT in catheter preparation, the structure of the catheter, and polymer characteristics, etc., which should be comprehensively considered to achieve the final product with excellent neurorestorative effects in animal experiments or clinical applications.

Key words: high polymer, carbon nanotube, conductivity, artificial nerve conduit, nanomorphology