Axon-like aligned conductive CNT/GelMA hydrogel fibers combined with electrical stimulation for spinal cord injury recovery

Shenglian Yao; Yongdong Yang; Chenyu Li; Kaitan Yang; Xin Song; Chuanhong Li; Zheng Cao; He Zhao; Xing Yu; Xiumei Wang; Lu-Ning Wang

doi:10.1016/j.bioactmat.2024.01.021

Axon-like aligned conductive CNT/GelMA hydrogel fibers combined with electrical stimulation for spinal cord injury recovery

Bioact Mater. 2024 Feb 22:35:534-548. doi: 10.1016/j.bioactmat.2024.01.021. eCollection 2024 May.

Authors

Shenglian Yao¹, Yongdong Yang^{2

3}, Chenyu Li¹, Kaitan Yang³, Xin Song¹, Chuanhong Li³, Zheng Cao², He Zhao^{2

3}, Xing Yu³, Xiumei Wang², Lu-Ning Wang¹

Affiliations

¹ School of Materials Science and Engineering, University of Science and Technology Beijing, Beijing, 100083, China.
² Key Laboratory of Advanced Materials of Ministry of Education, School of Materials Science and Engineering, Tsinghua University, Beijing, 100084, China.
³ Department of Orthopedics, Dongzhimen Hospital, Beijing University of Chinese Medicine, 5 Hai Yun Cang, Beijing, 100700, China.

Abstract

Rehabilitation and regenerative medicine are two promising approaches for spinal cord injury (SCI) recovery, but their combination has been limited. Conductive biomaterials could bridge regenerative scaffolds with electrical stimulation by inducing axon regeneration and supporting physiological electrical signal transmission. Here, we developed aligned conductive hydrogel fibers by incorporating carbon nanotubes (CNTs) into methacrylate acylated gelatin (GelMA) hydrogel via rotating liquid bath electrospinning. The electrospun CNT/GelMA hydrogel fibers mimicked the micro-scale aligned structure, conductivity, and soft mechanical properties of neural axons. For in vitro studies, CNT/GelMA hydrogel fibers supported PC12 cell proliferation and aligned adhesion, which was enhanced by electrical stimulation (ES). Similarly, the combination of aligned CNT/GelMA hydrogel fibers and ES promoted neuronal differentiation and axon-like neurite sprouting in neural stem cells (NSCs). Furthermore, CNT/GelMA hydrogel fibers were transplanted into a T9 transection rat spinal cord injury model for in vivo studies. The results showed that the incorporating CNTs could remain at the injury site with the GelMA fibers biodegraded and improve the conductivity of regenerative tissue. The aligned structure of the hydrogel could induce the neural fibers regeneration, and the ES enhanced the remyelination and axonal regeneration. Behavioral assessments and electrophysiological results suggest that the combination of aligned CNT/GelMA hydrogel fibers and ES could significantly restore motor function in rats. This study demonstrates that conductive aligned CNT/GelMA hydrogel fibers can not only induce neural regeneration as a scaffold but also support ESto promote spinal cord injury recovery. The conductive hydrogel fibers enable merging regenerative medicine and rehabilitation, showing great potential for satisfactory locomotor recovery after SCI.

Keywords: CNT/GelMA; Conductive hydrogel fibers; Electrical stimulation; NSCs differentiation; Spinal cord injury.