Gradient galectin-1 coating technology: bionic multichannel nerve guidance conduits promote neural cell migration

Liu, Na1,#; Ning, Xuchao2,#; Zhang, Xiaopei1,2,3; Zhou, Ziyi1,2; Fu, Manfei4; Wang, Yuanfei5,*; Wu, Tong1,2,3,*

1 Institute of Neuroregeneration & Neurorehabilitation, Department of Pathophysiology, School of Basic Medicine, Qingdao University, Qingdao, Shandong Province, China

2 The Affiliated Hospital of Qingdao University, Qingdao Medical College, Qingdao University, Qingdao, Shandong Province, China

3 Shandong Key Laboratory of Medical and Health Textile Materials, Collaborative Innovation Center for Eco-textiles of Shandong Province and the Ministry of Education, College of Textiles & Clothing, Qingdao University, Qingdao, Shandong Province, China

4 School of Pharmacy, University of Reading, Whiteknights, UK

5 Qingdao Stomatological Hospital Affiliated to Qingdao University, Qingdao, Shandong Province, China

*Correspondence to: Yuanfei Wang, PhD, zhizunbao19@163.com; Tong Wu, PhD, twu@qdu.edu.cn.

#These authors contributed equally to this work.

Funding: This study was supported by the Special Funds for Taishan Scholars Project of Shandong Province, No. tsqn202211125; the Natural Science Foundation of Shandong Province, No. ZR2021YQ17; and the Young Elite Scientists Sponsorship Program by CAST, No. YESS20200097.

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Advanced Technology in Neuroscience 1(2):p 276-289, December 2024. | DOI: 10.4103/ATN.ATN-D-24-00010

Abstract

Engineered nerve guidance conduits have been widely used to repair peripheral nerve injuries. Galectin-1 is an important biological cue that promotes axon regeneration and Schwann cell migration. In this study, a series of polycaprolactone-based nerve guidance conduits were prepared. First, we determined the concentration of galectin-1 (a member of the galactose lectin family) via the proliferation and morphology of Schwann cells and the viability, morphology, and axon length of PC12 cells. On this basis, nanofiber yarns coated with a uniform or unidirectionally linear gradient coating layer of galectin-1 were prepared by electrospinning to investigate the viability and migration of Schwann cells and neural stem cells on the surfaces. The unidirectional linear gradient coating with increasing galectin-1 content was found to promote the migration of both Schwann cells and neural stem cells. To construct nerve guidance conduits with encapsulated nanofiber yarns, we fabricated nerve guidance conduit walls composed of conjugately electrospun nanofiber yarns and random polycaprolactone nanofibers as the inner and outer layers. With a biocompatible light-absorbing dye, the nanofibers can be sealed via light welding to obtain a hollow polycaprolactone conduit. Finally, we prepared nerve guidance conduits containing nanofiber yarns coated with graded galectin-1 as well as hyaluronic acid methacryloyl hydrogel in the lumen. We found that the topology (nanofiber yarns and hyaluronic acid methacryloyl) and biological cues (gradient galectin-1 coating) synergistically accelerated the migration of Schwann cells and neural stem cells along multiple channels of nerve guidance conduits.

摘要

工程化神经导管已被广泛用于修复周围神经损伤。半乳糖凝集素1是促进轴突再生和许旺细胞迁移的重要生物线索。实验制备了一系列基于聚己内酯的神经导管。实验首先通过观察许旺细胞的增殖和形态以及 PC12 细胞的活力、形态和轴突长度确定纳米纤维纱涂层半乳糖凝集素1的浓度。在此基础上，用静电纺丝法制备了涂有均匀或单向线性梯度半乳糖凝集素1 涂层的纳米纤维纱，以研究许旺细胞和神经干细胞在其表面的存活率和迁移情况。研究发现，随着半乳糖凝集素1浓度的增加，单向线性梯度涂层可促进许旺细胞和神经干细胞的迁移。为了构建封装了这种纳米纤维纱的神经导管，实验制作了由共轭电纺纳米纤维纱和随机聚己内酯纳米纤维组成的神经导管壁作为内层和外层。使用生物相容性光吸收染料，纳米纤维可通过光焊接密封，从而获得中空聚己内酯导管。最后，实验制备了纳米纤维纱线，纱线上涂覆了梯度半乳糖凝集素1，并在管腔中涂覆了透明质酸甲基丙烯酰水凝胶制备工程化神经导管。实验发现，生物线索梯度半乳糖凝集素1涂层技术结合拓扑结构的纳米纤维纱和透明质酸甲基丙烯酰协同加速了许旺细胞和神经干细胞沿神经导管的多通道迁移。