Conductive Nerve Conduits With Orientated Topological Structures From Ice-Templating Technology

Abstract

Artificial nerve conduits hold significant promise for treating nerve injuries, with researchers focusing on simplifying techniques to harness microstructures and functions to improve their therapeutic outcomes. Here, a type of conductive nerve guidance conduit (NGC) with orientated topological structures from ice-templating technology is presented for promoting peripheral nerve regeneration. Based on a temperature gradient generated by a thermoelectric cooling platform, conductive carbon nanotubes (CNTs) and methacrylated gelatin are introduced into the ice crystal template to create conductive conduits with unique oriented structures. Ascribed to such structures, together with the great conductivity of CNTs and the loaded nerve growth factors, the obtained conduits can direct the neurite extension and facilitate the differentiation and growth of nerve cells. By constructing rat models with long-segment sciatic nerve defects, it was confirmed that such conductive NGCs can effectively improve injured nerve regeneration and motor function recovery. These features reveal the practical application value and broad prospect of our prepared NGCs in improving peripheral nerve regeneration.

Keywords

conductivity / ice-templating / nerve guidance conduits / nerve regeneration / topological structure

References

[1] (a) Z. Kurtovic, C. I. Svensson, and E. Krock, “Bugs Improve Nerve Regeneration: Fasting-Induced, Microbiome-Derived Metabolite Enhances Peripheral Nerve Regeneration,” Signal Transduction and Targeted Therapy 7 (2022): 351. (b) F. De Virgiliis, F. Mueller, I. Palmisano, et al., “The Circadian Clock Time Tunes Axonal Regeneration,” Cell Metabolism 35 (2023): 2153.

[2] (a) E. Serger, L. Luengo-Gutierrez, J. S. Chadwick, et al., “The Gut Metabolite Indole-3 Propionate Promotes Nerve Regeneration and Repair,” Nature 607 (2022): 585. (b) N. P. B. Au, T. Wu, X. Chen, et al., “Genome-Wide Study Reveals Novel Roles for Formin-2 in Axon Regeneration as a Microtubule Dynamics Regulator and Therapeutic Target for Nerve Repair,” Neuron 111 (2023): 3970. (c) X. Wang, Q. Xu, Y. Xu, et al., “Portable Absorbable Electrical Stimulation System for Enhanced Peripheral Nerve Repair,” Advanced Functional Materials 35 (2025): 2417839.

[3] (a) T. Wan, F.-S. Zhang, M.-Y. Qin, et al., “Growth Factors: Bioactive Macromolecular Drugs for Peripheral Nerve Injury Treatment – Molecular Mechanisms and Delivery Platforms,” Biomedicine & Pharmacotherapy 170 (2024): 116024. (b) R. Li, D. Li, C. Wu, et al., “Nerve Growth Factor Activates Autophagy in Schwann Cells to Enhance Myelin Debris Clearance and to Expedite Nerve Regeneration,” Theranostics 10 (2020): 1649. (c) H. Zhang, J. Guo, Y. Wang, L. Shang, R. Chai, and Y. Zhao, “Natural Polymer-Derived Bioscaffolds for Peripheral Nerve Regeneration,” Advanced Functional Materials 32 (2022): 2203829. (d) O. S. Manoukian, M. R. Arul, S. Rudraiah, I. Kalajzic, and S. G. Kumbar, “Aligned Microchannel Polymer-Nanotube Composites for Peripheral Nerve Regeneration: Small Molecule Drug Delivery,” Journal of Controlled Release 296 (2019): 54. (e) G. Li, Q. Han, P. Lu, et al., “Construction of Dual-Biofunctionalized Chitosan/Collagen Scaffolds for Simultaneous Neovascularization and Nerve Regeneration,” Research 2020 (2020): 2603048. (f) X. Lin, L. Cai, X. Cao, and Y. Zhao, “Stimuli-Responsive Silk Fibroin for On-Demand Drug Delivery,” Smart Medicine 2 (2023): e20220019.

[4] (a) S. Han, L. Gao, X. Dou, et al., “Chiral Hydrogel Nerve Conduit Boosts Peripheral Nerve Regeneration via Regulation of Schwann Cell Reprogramming,” ACS Nano 18 (2024): 28358. (b) W. Zhou, M. S. U. Rahman, C. Sun, et al., “Perspectives on the Novel Multifunctional Nerve Guidance Conduits: From Specific Regenerative Procedures to Motor Function Rebuilding,” Advanced Materials 36 (2024): 2307805. (c) M. Zhang, H. An, Z. Gu, et al., “Mimosa-Inspired Stimuli-Responsive Curling Bioadhesive Tape Promotes Peripheral Nerve Regeneration,” Advanced Materials 35 (2023): 2212015. (d) Z. Yao, Z. Chen, X. He, et al., “Bioactive MgO/MgCO3/Polycaprolactone Multi-Gradient Fibers Facilitate Peripheral Nerve Regeneration by Regulating Schwann Cell Function and Activating Wingless/Integrase-1 Signaling,” Advanced Fiber Materials 7 (2025): 315. (e) X. Wang, S. Chen, X. Chen, et al., “Biomimetic Multi-Channel Nerve Conduits With Micro/Nanostructures for Rapid Nerve Repair,” Bioactive Materials 41 (2024): 577. (f) S. S. Srinivasan, L. Gfrerer, P. Karandikar, et al., “Adaptive Conductive Electrotherapeutic Scaffolds for Enhanced Peripheral Nerve Regeneration and Stimulation,” Med 4 (2023): 541.

[5] (a) L. Zhu, S. Jia, T. Liu, et al., “Aligned PCL Fiber Conduits Immobilized With Nerve Growth Factor Gradients Enhance and Direct Sciatic Nerve Regeneration,” Advanced Functional Materials 30 (2020): 2002610. (b) H. Xu, Y. Yu, L. Zhang, et al., “Sustainable Release of Nerve Growth Factor for Peripheral Nerve Regeneration Using Nerve Conduits Laden With Bioconjugated Hyaluronic Acid-Chitosan Hydrogel,” Composites Part B: Engineering 230 (2022): 109509. (c) B. Xia, X. Gao, J. Qian, et al., “A Novel Superparamagnetic Multifunctional Nerve Scaffold: A Remote Actuation Strategy to Boost In Situ Extracellular Vesicles Production for Enhanced Peripheral Nerve Repair,” Advanced Materials 36 (2024): 2305374. (d) J. Jiao, F. Wang, J.-J. Huang, et al., “Microfluidic Hollow Fiber With Improved Stiffness Repairs Peripheral Nerve Injury Through Non-Invasive Electromagnetic Induction and Controlled Release of NGF,” Chemical Engineering Journal 426 (2021): 131826. (e) W.-C. Huang, C.-C. Lin, T.-W. Chiu, and S.-Y. Chen, “3D Gradient and Linearly Aligned Magnetic Microcapsules in Nerve Guidance Conduits With Remotely Spatiotemporally Controlled Release to Enhance Peripheral Nerve Repair,” ACS Applied Materials & Interfaces 14 (2022): 46188. (f) Y. Qian, H. Lin, Z. Yan, J. Shi, and C. Fan, “Functional Nanomaterials in Peripheral Nerve Regeneration: Scaffold Design, Chemical Principles and Microenvironmental Remodeling,” Materials Today 51 (2021): 165. (g) Y. Qian, X. Zhao, Q. Han, W. Chen, H. Li, and W. Yuan, “An Integrated Multi-Layer 3D-Fabrication of PDA/RGD Coated Graphene Loaded PCL Nanoscaffold for Peripheral Nerve Restoration,” Nature Communications 9 (2018): 323.

[6] (a) H. Zhang and A. I. Cooper, “Aligned Porous Structures by Directional Freezing,” Advanced Materials 19 (2007): 1529. (b) S. Miao, Y. Wang, L. Sun, and Y. Zhao, “Freeze-Derived Heterogeneous Structural Color Films,” Nature Communications 13 (2022): 4044. (c) Y. Cheng, X. Li, P. Gu, et al., “Hierarchical Scaffold With Directional Microchannels Promotes Cell Ingrowth for Bone Regeneration,” Advanced Healthcare Materials 13 (2024): 2303600. (d) X. Zhou, L. Yin, B. Yang, et al., “Programmable Local Orientation of Micropores by Mold-Assisted Ice Templating,” Small Methods 5 (2021): 2000963. (e) H. Joukhdar, A. Seifert, T. Jungst, J. Groll, M. S. Lord, and J. Rnjak-Kovacina, “Ice Templating Soft Matter: Fundamental Principles and Fabrication Approaches to Tailor Pore Structure and Morphology and Their Biomedical Applications,” Advanced Materials 33 (2021): 2100091.

[7] (a) J. Guo, Y. Yu, L. Cai, et al., “Microfluidics for Flexible Electronics,” Materials Today 44 (2021): 105. (b) Y. Wang, J. Guo, X. Cao, and Y. Zhao, “Developing Conductive Hydrogels for Biomedical Applications,” Smart Medicine 3 (2024): e20230023.

RIGHTS & PERMISSIONS

2025 The Author(s). Smart Medicine published by Wiley-VCH GmbH on behalf of Wenzhou Institute, University of Chinese Academy of Sciences.