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Directional axonal regrowth induced by an aligned fibrin nanofiber hydrogel contributes to improved motor function recovery in canine L2 spinal cord injury

  • Special Issue: CESB 2019
  • Original Research
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Abstract

Spinal cord injuries (SCI) normally disrupt the long axonal tracts of the spinal cord and cause permanent neurological deficits, for which there is currently a lack of effective therapeutic methods. Biomaterial-based regenerative medicine is a pivotal strategy to induce axonal regeneration through delivery of biophysical and/or biochemical regulatory cues by biomaterials. We previously fabricated a hierarchically aligned fibrin hydrogel (AFG) that could promote neurogenic differentiation of stem cells in vitro and has been successfully applied for peripheral nerve and spinal cord regeneration in rats. In this study, AFG was used to repair a canine lumbar segment 2 hemisection spinal cord injury, and the consistency of histological, imageological and behavioral results was compared. AFG was used to construct an aligned fiber bridge that supported cell adhesion in vitro and rapidly facilitated tissue invasion along the long axis of fibers in vivo, Moreover, in vivo results demonstrated regrowth of axons in an oriented pattern connecting the rostral and caudal stumps. Consistent results were confirmed by diffusion tensor imaging, which allowed successful tracing of reconnected nerve fibers across the defect. As a result, directional axonal regrowth contributed to significantly improved recovery of motor functional behavior of SCI canines with AFG implantation. Our results suggest that AFG has great promise for rapidly directing axonal regrowth for nerve regeneration.

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Funding

This work was supported by funds provided by National Natural Science Foundation of China (No. 31771056), National Key R&D Program of China (2018YFB0704304-1) and Tsinghua University Initiative Scientific Research Program (20161080091).

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Author notes

  1. These authors contributed equally: Zheng Cao, Shenglian Yao

Authors and Affiliations

  1. State Key Laboratory of New Ceramics and Fine Processing, Key Laboratory of Advanced Materials, School of Materials Science and Engineering, Tsinghua University, 100084, Beijing, China

    Zheng Cao, Yongdong Yang & Xiumei Wang

  2. School of Materials Science and Engineering, University of Science and Technology Beijing, 100083, Beijing, China

    Shenglian Yao

  3. Center for Biomedical Imaging Research, Tsinghua University, 100084, Beijing, China

    Yuhui Xiong & Hua Guo

  4. Department of Radiology, China–Japan Friendship Hospital, 100029, Beijing, China

    Zhenxia Zhang & Sheng Xie

  5. Department of Orthopedics, Dongzhimen Hospital, 100007, Beijing, China

    Yongdong Yang, Feng He & He Zhao

  6. Beijing Tsinghua Chang Gung Hospital, School of Clinical Medicine, Tsinghua University, 102218, Beijing, China

    Yi Guo & Guihuai Wang

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  1. Zheng Cao
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Correspondence to Sheng Xie, Hua Guo or Xiumei Wang.

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Cao, Z., Yao, S., Xiong, Y. et al. Directional axonal regrowth induced by an aligned fibrin nanofiber hydrogel contributes to improved motor function recovery in canine L2 spinal cord injury. J Mater Sci: Mater Med 31, 40 (2020). https://doi.org/10.1007/s10856-020-06375-9

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