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Thermosensitive polymer-based hydrogel mixed with the anti-inflammatory agent minocycline induces axonal regeneration in hemisected spinal cord

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Abstract

Bridging lesion cavities with bioengineered scaffolds is a promising strategie for spinal cord repair. In a rat model of spinal cord hemisection, the present study utilized an injectable hydrogel Tetronic-oligolactide (TL) copolymer, which is a liquid solution at room temperature and gels at 37 °C. The implantation of the TL hydrogel allowed the growth of laminin-laden connective tissue matrix and the formation of blood vessels in the lesion cavities. However, TL implantation alone did not significantly increase the level of axonal growth through the lesion areas. It was hypothesized that macrophage infiltration into the lesion areas reduced the growth promoting effect of the TL hydrogel. Implanting TL mixed with an anti-inflammatory agent, minocycline, decreased the extent of macrophage infiltration and the deposition of chondroitin sulfate proteoglycans, which can potently inhibit axonal regeneration. Finally, TL plus minocycline increased the length of the axon growth through the lesion areas in a dose-dependent manner. These results suggest that controlling inflammation improves the functionality of an injectable hydrogel used as a bridging strategy.

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References

  1. A. Sandvig, et al., Glia, 46, 225 (2004).

    Article  Google Scholar 

  2. R. P. Bunge, et al., Adv. Neurol., 59, 75 (1993).

    CAS  Google Scholar 

  3. J. W. McDonald and C. Sadowsky, Lancet, 359, 417 (2002).

    Article  Google Scholar 

  4. M. H. Tuszynski, et al., J. Neurotrauma, 16, 523 (1999).

    Article  CAS  Google Scholar 

  5. M. B. Bunge, Neuroscientist, 7, 325 (2001).

    Article  CAS  Google Scholar 

  6. H. M. Geller and J. W. Fawcett, Exp. Neurol., 174, 125 (2002).

    Article  Google Scholar 

  7. C. E. Schmidt and J. B. Leach, Annu. Rev. Biomed. Eng., 5, 293 (2003).

    Article  CAS  Google Scholar 

  8. H. Nomura, C. H. Tator, and M. S. Shoichet, J. Neurotrauma, 23, 496 (2006).

    Article  Google Scholar 

  9. A. Hejcl, et al., Physiol. Res., 57Suppl 3, S121–132 (2008).

    CAS  Google Scholar 

  10. L. N. Novikova, L. N. Novikov, and J. O. Kellerth, Curr. Opin. Neurol., 16, 711 (2003).

    Article  CAS  Google Scholar 

  11. K. S. Straley, C. Wong Po Foo, and S. C. Heilshorn, J. Neurotrauma, 27, 1 (2010).

    Article  Google Scholar 

  12. D. H. Go, et al., Macromol. Biosci., 8, 1152 (2008).

    Article  CAS  Google Scholar 

  13. B. Jeong, et al., Nature, 388, 860 (1997).

    Article  CAS  Google Scholar 

  14. S. A. Busch, et al., J. Neurosci., 29, 9967 (2009).

    Article  CAS  Google Scholar 

  15. M. T. Fitch and J. Silver, Exp. Neurol., 148, 587 (1997).

    Article  CAS  Google Scholar 

  16. E. J. Bradbury, et al., Nature, 416, 636 (2002).

    Article  CAS  Google Scholar 

  17. M. T. Fitch, et al., J. Neurosci., 19, 8182 (1999).

    CAS  Google Scholar 

  18. A. Jain, et al., Biomaterials, 27, 497 (2006).

    Article  CAS  Google Scholar 

  19. Y. J. Jun, et al., Macromol. Res., 16, 704 (2008).

    CAS  Google Scholar 

  20. J. Piantino, et al., Exp. Neurol., 201, 359 (2006).

    Article  CAS  Google Scholar 

  21. B. Grimpe and J. Silver, Prog. Brain. Res., 137, 333 (2002).

    Article  CAS  Google Scholar 

  22. R. Hallmann, et al., Physiol. Rev., 85, 979 (2005).

    Article  CAS  Google Scholar 

  23. L. L. Jones, et al., J. Neurosci., 22, 2792 (2002).

    CAS  Google Scholar 

  24. L. L. Jones, D. Sajed, and M. H. Tuszynski, J. Neurosci., 23, 9276 (2003).

    CAS  Google Scholar 

  25. S. G. Kremlev, R. L. Roberts, and C. Palmer, J. Neurosci. Res., 85, 2450 (2007).

    Article  CAS  Google Scholar 

  26. D. P. Stirling, et al., J. Neurosci., 24, 2182 (2004).

    Article  CAS  Google Scholar 

  27. K. P. Horn, et al., J. Neurosci., 28, 9330 (2008).

    Article  CAS  Google Scholar 

  28. M. S. Beattie, Trends Mol. Med., 10, 580 (2004).

    Article  CAS  Google Scholar 

  29. D. R. Nisbet, et al., Biomaterials, 30, 4573 (2009).

    Article  CAS  Google Scholar 

  30. D. T. Luttikhuizen, M. C. Harmsen, and M. J. Van Luyn, Tissue Eng., 12, 1955 (2006).

    Article  CAS  Google Scholar 

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Correspondence to Byung Gon Kim.

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Kang, Y.M., Hwang, D.H., Kim, B.G. et al. Thermosensitive polymer-based hydrogel mixed with the anti-inflammatory agent minocycline induces axonal regeneration in hemisected spinal cord. Macromol. Res. 18, 399–403 (2010). https://doi.org/10.1007/s13233-010-0412-5

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  • DOI: https://doi.org/10.1007/s13233-010-0412-5

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