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Immunophilin FK506 loaded in chitosan guide promotes peripheral nerve regeneration

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Abstract

Immunophilin ligand FK506 has been treated as adjunct therapy for nerve repair due to its potent neurotrophic and neuroprotective actions. It was hypothesized that FK506 releasing from biodegradable chitosan guide provided better nerve regenerative response than the guide with no FK506. The drug was entrapped in the semi-permeable wall of chitosan guide with the drug-loading of 647 μg/g. Rat sciatic nerve defect model treated with FK506-releasing chitosan guide showed more mature appearance of myelinated fibers 8 weeks after surgery; furthermore, the motor functional reinnervation occurred, the amplitude and velocity of compound muscle action potentials reached 60% and 73% with respect to the normal. Thus, FK506-releasing chitosan guide should be acted as a long-lasting delivery device of immunosuppressive and neuroregenerative agent for peripheral nerve repair.

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Acknowledgments

We are grateful to Aihua Xu for assistance in manuscript preparation and Fujisawa Pharmaceuticals, Inc. (Osaka, Japan) for the generous gift of FK506. This study was supported by Knowledge Innovation Project of The Chinese Academy of Sciences (KJCX2-YW-210-02) and the National Natural Science Foundation of China (Grant No. 20736006).

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Authors and Affiliations

  1. Lab of Biomedical Material Engineering, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457 Zhongshan Road, Dalian, 116023, China

    Xiaoxia Li, Wei Wang & Xiaojun Ma

  2. Graduate School of the Chinese Academy of Sciences, 19 Yuquan Road, Beijing, 100049, China

    Xiaoxia Li, Wei Wang & Xiaojun Ma

  3. Department of Orthopedics, The First Affiliated Hospital of Dalian Medical University, Dalian, 116011, China

    Guoqiang Wei & Weiguo Zhang

  4. School of Chemical Engineering, Beijing University of Chemical Technology, Beijing, 100029, China

    Guanxiong Wang

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  1. Xiaoxia Li
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  2. Wei Wang
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  3. Guoqiang Wei
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  4. Guanxiong Wang
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  5. Weiguo Zhang
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Correspondence to Xiaojun Ma.

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10529_2010_287_MOESM1_ESM.docx

Supplementary material 1 (DOCX 25 kb) Supplementary Figure Fourier transformation infrared spectra of (a) FK506, (b) chitosan guide and (c) FK506-loaded chitosan guide; chitosan showed characteristic band of amide-I (1655 cm−1) and amino (1599 cm−1) in the spectra of (b) and (c), and there was no shift for other bands such as 1159 cm−1 for C–O–C stretch and C–N stretch, 1026 cm−1 for C–O skeletal vibration. It could be presented that the structure of chitosan guide does not change significantly with or without FK506

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Li, X., Wang, W., Wei, G. et al. Immunophilin FK506 loaded in chitosan guide promotes peripheral nerve regeneration. Biotechnol Lett 32, 1333–1337 (2010). https://doi.org/10.1007/s10529-010-0287-8

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  • DOI: https://doi.org/10.1007/s10529-010-0287-8

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