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Axonal Regeneration and Remyelination Evaluation of Chitosan/Gelatin-Based Nerve Guide Combined with Transforming Growth Factor-β1 and Schwann Cells

  • Translational Biomedical Research
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Abstract

Despite efforts in peripheral nerve injury and regeneration, it is difficult to achieve a functional recovery following extended peripheral nerve lesions. Even if artificial nerve conduit, cell components and growth factors can enhance nerve regeneration, integration in peripheral nerve repair and regeneration remains yet to be explored. For this study, we used chitosan/gelatin nerve graft constructed with collagenous matrices as a vehicle for Schwann cells and transforming growth factor-β1 to bridge a 10-mm gap of the sciatic nerve and explored the feasibility of improving regeneration and reinnervation in rats. The nerve regeneration was assessed with functional recovery, electrophysiological test, retrograde labeling, and immunohistochemistry analysis during the post-operative period of 16 weeks. The results showed that the internal sides of the conduits were compact enough to prevent the connective tissues from ingrowth. Nerve conduction velocity, average regenerated myelin area, and myelinated axon count were similar to those treated with autograft (p > 0.05) but significantly higher than those bridged with chitosan/gelatin nerve graft alone (p < 0.05). Evidences from retrograde labeling and immunohistochemistry analysis are further provided in support of improving axonal regeneration and remyelination. A designed graft incorporating all of the tissue-engineering strategies for peripheral nerve regeneration may provide great progress in tissue engineering for nerve repair.

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References

  1. Fu, S. Y., & Gordon, T. (1997). The cellular and molecular basis of peripheral nerve regeneration. Molecular Neurobiology, 14, 67–116.

    Article  CAS  PubMed  Google Scholar 

  2. Nie, X., Zhang, Y. J., Tian, W. D., et al. (2007). Improvement of peripheral nerve regeneration by a tissue-engineered nerve filled with ectomesenchymal stem cells. International Journal of Oral and Maxillofacial Surgery, 36, 32–38.

    Article  CAS  PubMed  Google Scholar 

  3. Bellamkonda, R. V. (2006). Peripheral nerve regeneration: An opinion on channels, scaffolds and anisotropy. Biomaterials, 27, 3515–3518.

    CAS  PubMed  Google Scholar 

  4. Johnson, E. O., Zoubos, A. B., & Soucacos, P. N. (2005). Regeneration and repair of peripheral nerves. Injury, 36, 24–29.

    Article  Google Scholar 

  5. Evans, G. R. (2003). Approaches to tissue engineered peripheral nerve. Clinics in Plastic Surgery, 30, 559–563.

    Article  PubMed  Google Scholar 

  6. Midha, R., Munro, C., Dalton, P. D., Tator, C. H., & Shoichet, M. S. (2003). Growth factor enhancement of peripheral nerve regeneration through a novel synthetic hydrogel tube. Journal of Neurosurgery, 99, 555–565.

    Article  PubMed  Google Scholar 

  7. Wei, Y., Gong, K., Zheng, Z., Wang, A., Ao, Q., Gong, Y., et al. (2011). Chitosan/silk fibroin-based tissue-engineered graft seeded with adipose-derived stem cells enhances nerve regeneration in a rat model. Journal of Materials Science: Materials in Medicine, 22, 1947–1964.

    CAS  PubMed  Google Scholar 

  8. Chalfoun, C. T., Wirth, G. A., & Evans, G. R. (2006). Tissue engineered nerve constructs: Where do we stand? Journal of Cellular and Molecular Medicine, 10, 309–317.

    Article  CAS  PubMed  Google Scholar 

  9. VandeVord, P. J., Matthew, H. W., DeSilva, S. P., Mayton, L., Wu, B., & Wooley, P. H. (2002). Evaluation of the biocompatibility of a chitosan scaffold in mice. Journal of Biomedical Materials Research, 59, 585–590.

    Article  CAS  PubMed  Google Scholar 

  10. Kim, S. M., Lee, S. K., & Lee, J. H. (2007). Peripheral nerve regeneration using a three dimensionally cultured Schwann cell conduit. Journal of Craniofacial Surgery, 18, 475–488.

    Article  PubMed  Google Scholar 

  11. Lohmeyer, J. A., Shen, Z. L., Walter, G. F., & Berger, A. (2007). Bridging extended nerve defects with an artificial nerve graft containing SC pre-seeded on polyglactin filaments. International Journal of Artificial Organs, 30, 64–74.

    CAS  PubMed  Google Scholar 

  12. Walsh, S., & Midha, R. (2009). Use of stem cells to augment nerve injury repair. Neurosurgery, 65, A80–A86.

    Article  PubMed  Google Scholar 

  13. Neumann, H. (2000). The immunological microenvironment in the CNS: Implications on neuronal cell death and survival. Journal of Neural Transmission. Supplementum, 59, 59–68.

    CAS  PubMed  Google Scholar 

  14. Gantus, M. A., Nasciutti, L. E., Cruz, C. M., Persechini, P. M., & Martinez, A. M. (2006). Modulation of extracellular matrix components by metalloproteinases and their tissue inhibitors during degeneration and regeneration of rat sural nerve. Brain Research, 1122, 36–46.

    Article  CAS  PubMed  Google Scholar 

  15. Nie, X., Tian, W. D., Zhang, Y. J., Chen, X. Z., Dong, R., Jiang, M., et al. (2006). Induction of transforming growth factor-beta 1 on dentine pulp cells in different culture patterns. Cell Biology International, 30, 295–300.

    Article  CAS  PubMed  Google Scholar 

  16. Day, W. A., Koishi, K., & McLennan, I. S. (2003). Transforming growth factor beta 1 may regulate the stability of mature myelin sheaths. Experimental Neurology, 184, 857–864.

    Article  CAS  PubMed  Google Scholar 

  17. Baghdassarian, D., Delbauffe, D. T., Gavaret, J. M., & Pierre, M. (1993). Effects of transforming growth factor-beta1 on the extracellular matrix and cytoskeleton of cultured astrocytes. Glia, 7, 193–202.

    Article  CAS  PubMed  Google Scholar 

  18. Moldovan, M., Sorensen, J., & Krarup, C. (2006). Comparison of the fastest regenerating motor and sensory myelinated axons in the same peripheral nerve. Brain, 129, 2471–2483.

    Article  PubMed  Google Scholar 

  19. Fu, S. Y., & Gordon, T. (1997). The cellular and molecular basis of peripheral nerve regeneration. Molecular Neurobiology, 14, 67–116.

    Article  CAS  PubMed  Google Scholar 

  20. Tabata, Y. (2003). Tissue regeneration based on growth factor release. Tissue Engineering, 9, s5–s15.

    Article  CAS  PubMed  Google Scholar 

  21. Thein-Han, W. W., Saikhun, J., Pholpramoo, C., Misra, R. D., & Kitiyanant, Y. (2009). Chitosan-gelatin scaffolds for tissue engineering: Physico-chemical properties and biological response of buffalo embryonic stem cells and transfectant of GFP-buffalo embryonic stem cells. Acta Biomaterialia, 5, 3453–3466.

    Article  CAS  PubMed  Google Scholar 

  22. Yuan, Y., Zhang, P., Yang, Y., Wang, X., & Gu, X. (2004). The interaction of Schwann cells with chitosan membranes and fibers in vitro. Biomaterials, 25, 4273–4278.

    Article  CAS  PubMed  Google Scholar 

  23. Pulieri, E., Chiono, V., Ciardelli, G., Vozzi, G., Ahluwalia, A., Domenici, C., et al. (2008). Chitosan/gelatin blends for biomedical applications. Journal of Biomedical Materials Research Part A, 86, 311–322.

    Article  PubMed  Google Scholar 

  24. Cao, W., Cheng, M., Ao, Q., Gong, Y., Zhao, N., & Zhang, X. (2005). Physical, mechanical and degradation properties, and Schwann cell affinity of cross-linked chitosan films. Journal of Biomaterials Science, Polymer Edition, 16, 791–807.

    Article  CAS  Google Scholar 

  25. Mao, J. S., Liu, H. F., Yin, Y. J., & Yao, K. D. (2003). The properties of chitosan-gelatin membranes and scaffolds modified with hyaluronic acid by different methods. Biomaterials, 24, 1621–1629.

    Article  CAS  PubMed  Google Scholar 

  26. Madduri, S., & Gander, B. (2010). Schwann cell delivery of neurotrophic factors for peripheral nerve regeneration. Journal of the Peripheral Nervous System, 15, 93–103.

    Article  CAS  PubMed  Google Scholar 

  27. Ruiter, G. C., Malessy, M. J., Yaszemski, M. J., Windebank, A. J., & Spinner, R. J. (2009). Designing ideal conduits for peripheral nerve repair. Neurosurgical Focus, 26, E5.

    Article  PubMed Central  PubMed  Google Scholar 

  28. Scherer, S. S., Kamholz, J., & Jakowlew, S. B. (1993). Axons modulate the expression of transforming growth factor-betas in Schwann cells. Glia, 8, 265–276.

    Article  CAS  PubMed  Google Scholar 

  29. Frostick, S. P., Yin, Q., & Kemp, G. J. (1998). Schwann cells, neurotrophic factors, and peripheral nerve regeneration. Microsurgery, 18, 397–405.

    Article  CAS  PubMed  Google Scholar 

  30. Summa, P. G., Kalbermatten, D. F., Pralong, E., Raffoul, W., Kingham, P. J., & Terenghi, G. (2011). Long-term in vivo regeneration of peripheral nerves through bioengineered nerve grafts. Neuroscience, 181, 278–291.

    Article  PubMed  Google Scholar 

  31. Rosner, B. I., Hang, T., & Tranquillo, R. T. (2005). Schwann cell behavior in three-dimensional collagen gels: Evidence for differential mechano-transduction and the influence of TGF-beta 1 in morphological polarization and differentiation. Experimental Neurology, 195, 81–91.

    Article  CAS  PubMed  Google Scholar 

  32. Ao, Q., Fung, C. K., Tsui, A. Y., Cai, S., Zuo, H. C., Chan, Y. S., et al. (2011). The regeneration of transected sciatic nerves of adult rats using chitosan nerve conduits seeded with bone marrow stromal cell-derived Schwann cells. Biomaterials, 32, 787–796.

    Article  CAS  PubMed  Google Scholar 

  33. Hayashi, A., Moradzadeh, A., Tong, A., Wei, C., Tuffaha, S. H., Hunter, D. A., et al. (2008). Treatment modality affects allograft-derived Schwann cell phenotype and myelinating capacity. Experimental Neurology, 212, 324–336.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

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Acknowledgments

This study was supported by the National Natural Science Foundation of China (No. 31070863) and the Natural Science Foundation Projects of Chongqing, China (Grant nos. CSTC2010BB5161 and CSTC2011BA5013).

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Authors and Affiliations

  1. Department of Maxillofacial Surgery, Daping Hospital & Research Institute of Surgery, The Third Military Medical University, Chongqing, China

    Xin Nie & Maojin Yang

  2. Department of Stomatology, Daping Hospital & Research Institute of Surgery, The Third Military Medical University, Chongqing, China

    Manjing Deng, Luchuan Liu, Yongjie Zhang & Xiujie Wen

  3. Research and Development Center for Tissue Engineering, Fourth Military Medical University, Xi’an, China

    Yongjie Zhang

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  1. Xin Nie
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  2. Manjing Deng
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  3. Maojin Yang
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  4. Luchuan Liu
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Correspondence to Yongjie Zhang or Xiujie Wen.

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Nie, X., Deng, M., Yang, M. et al. Axonal Regeneration and Remyelination Evaluation of Chitosan/Gelatin-Based Nerve Guide Combined with Transforming Growth Factor-β1 and Schwann Cells. Cell Biochem Biophys 68, 163–172 (2014). https://doi.org/10.1007/s12013-013-9683-8

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  • DOI: https://doi.org/10.1007/s12013-013-9683-8

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