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A neurotrophic peptide-functionalized self-assembling peptide nanofiber hydrogel enhances rat sciatic nerve regeneration

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Abstract

Nerve guidance conduit (NGC) is a potential alternative to autologous nerve for peripheral nerve regeneration. A promising therapeutic strategy is to modify the nerve guidance conduit intraluminal microenvironment using physical and/or chemical guidance cues. In this study, a neurotrophic peptide-functionalized self-assembling peptide nanofiber hydrogel that could promote PC12 cell adhesion, proliferation, and neuronal differentiation in vitro was prefilled in the lumen of a hollow chitosan tube (hCST) to accelerate axonal regeneration in a rat sciatic nerve defect model. The functionalized self-assembling peptide was developed by introducing a neurotrophic peptide (RGI, RGIDKRHWNSQ) derived from brain-derived neurotrophic factor (BDNF) to the C-terminus of the self-assembling peptide RADA16-I (Ac-(RADA)4-CONH2). Morphological, histological, electrophysiological, and functional analyses demonstrated that the RGI-functionalized, self-assembling, peptide nanofiber hydrogel RAD/RGI could produce a neurotrophic microenvironment that markedly improved axonal regeneration with enhanced re-myelination and motor functional recovery.

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Acknowledgements

This research was supported by the National Natural Science Foundation of China (Nos. 31771056 and 31771052), the Tsinghua University Initiative Scientific Research Program (No. 20161080091) and the 111 Project (No. B17026). We would like to thank Dr. Yueteng Wei at Bruker (Beijing, China) for help in AFM. We thank to Xiaodan Mu at Harbin Medical University and Yifan Liu at Tsinghua University for the helpful suggestion of experiments.

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Authors and Affiliations

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

    Jiaju Lu, Shuhui Yang, Lingyun Zhao, Xiaodan Sun & Xiumei Wang

  2. Institute of Orthopedics, Chinese PLA General Hospital, Beijing, 100853, China

    Xun Sun, Xuezhen Shen, Yu Wang, Shibi Lu & Jiang Peng

  3. School of Medicine, Nankai University, Tianjin, 300071, China

    Xun Sun & Xuezhen Shen

  4. Experimental Surgery and Regenerative Medicine, Department of Surgery, Ludwig-Maximilians-University, Munich, 80336, Germany

    Heyong Yin

  5. Department of Ultrasound, Beijing Hospital, Beijing, 100730, China

    Wenli Jiang

  6. Center of Biomedical Analysis, Tsinghua University, Beijing, 100084, China

    Yue Sun

  7. Department of Bioengineering, Bioscience Research Collaborative, Rice University, Texas, 77030, USA

    Antonios G. Mikos

  8. Co-innovation Center of Neuroregeneration, Nantong University, Nantong, 226007, China

    Jiang Peng

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  1. Jiaju Lu
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  11. Shibi Lu
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  12. Antonios G. Mikos
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  13. Jiang Peng
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Correspondence to Jiang Peng or Xiumei Wang.

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A neurotrophic peptide-functionalized self-assembling peptide nanofiber hydrogel enhances rat sciatic nerve regeneration

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Lu, J., Sun, X., Yin, H. et al. A neurotrophic peptide-functionalized self-assembling peptide nanofiber hydrogel enhances rat sciatic nerve regeneration. Nano Res. 11, 4599–4613 (2018). https://doi.org/10.1007/s12274-018-2041-9

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