Skip to main content

Advertisement

Log in

Effects of Chemically Doped Bioactive Borate Glass on Neuron Regrowth and Regeneration

  • Published:
Annals of Biomedical Engineering Aims and scope Submit manuscript

Abstract

Peripheral nerve injuries present challenges to regeneration. Currently, the gold standard for nerve repair is an autograft that results in another region of the body suffering nerve damage. Previously, bioactive borate glass (BBG) has been studied in clinical trials to treat patients with non-healing wounds, and we have reported that BBG is conducive for soft tissue repair. BBG provides structural support, degrades in a non-cytotoxic manner, and can be chemically doped. Here, we tested a wide range of chemical compounds that are reported to have neuroprotective characteristics to promote regeneration of peripheral neurons after traumatic injury. We hypothesized that chemical dopants added in trace amounts to BBG would improve neuronal survival and neurite outgrowth from dorsal root ganglion (DRG) explants. We measured neurite outgrowth from whole DRG explants, and survival rates of dissociated neurons and support cells that comprise the DRG. Results show that chemically doped BBGs have differentially variable effects on neuronal survival and outgrowth, with iron, gallium, and zinc improving outgrowth of neurons, and iodine causing the most detriment to neurons. Because chemically doped BBGs support increased nerve regrowth and survival, they show promise for use in peripheral nerve regeneration.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Figure 1
Figure 2
Figure 3
Figure 4

Similar content being viewed by others

References

  1. Archibald, S. J., J. Shefner, C. Krarup, and R. D. Madison. Monkey median nerve repaired by nerve graft or collagen nerve guide tube. J. Neurosci. 15(5 Pt 2):4109–4123, 1995.

    CAS  PubMed  Google Scholar 

  2. Bellantone, M., H. D. Williams, and L. L. Hench. Broad-spectrum bactericidal activity of ag(2)o-doped bioactive glass. Antimicrob. Agents Chemother. 46(6):1940–1945, 2002.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Bellucci, D., A. Sola, and V. Cannillo. Bioactive glass/zro2 composites for orthopaedic applications. Biomed. Mater. 9(1):015005, 2014.

    Article  CAS  PubMed  Google Scholar 

  4. Blaker, J. J., S. N. Nazhat, and A. R. Boccaccini. Development and characterisation of silver-doped bioactive glasscoated sutures for tissue engineering and wound healing applications. Biomaterials 25(7–8):1319–1329, 2004.

    Article  CAS  PubMed  Google Scholar 

  5. Bunting, S., L. Di Silvio, S. Deb, and S. Hall. Bioresorbable glass fibres facilitate peripheral nerve regeneration. J. Hand. Surg. 30(3):242–247, 2005.

    Article  CAS  Google Scholar 

  6. Chiono, V., and C. Tonda-Turo. Trends in the design of nerve guidance channels in peripheral nerve tissue engineering. Prog. Neurobiol. 131:87–104, 2015.

    Article  PubMed  Google Scholar 

  7. Chitambar, C. R. Gallium and its competing roles with iron in biological systems. Biochim. Biophys. Acta 1863(8):2044–2053, 2016.

    Article  CAS  PubMed  Google Scholar 

  8. Deliormanli, A. M. Synthesis and characterization of cerium- and gallium-containing borate bioactive glass scaffolds for bone tissue engineering. J. Mater. Sci. Mater. Med. 26(2):67, 2015.

    Article  CAS  PubMed  Google Scholar 

  9. Dowding, J. M., W. Song, K. Bossy, A. Karakoti, A. Kumar, A. Kim, B. Bossy, S. Seal, M. H. Ellisman, G. Perkins, W. T. Self, and E. Bossy-Wetzel. Cerium oxide nanoparticles protect against abeta-induced mitochondrial fragmentation and neuronal cell death. Cell Death Differ. 21(10):1622–1632, 2014.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Erol, M. M., V. Mourino, P. Newby, X. Chatzistavrou, J. A. Roether, L. Hupa, and A. R. Boccaccini. Copper-releasing, boron-containing bioactive glass-based scaffolds coated with alginate for bone tissue engineering. Acta Biomater. 8(2):792–801, 2012.

    Article  CAS  PubMed  Google Scholar 

  11. Estevez, A. Y., S. Pritchard, K. Harper, J. W. Aston, A. Lynch, J. J. Lucky, J. S. Ludington, P. Chatani, W. P. Mosenthal, J. C. Leiter, S. Andreescu, and J. S. Erlichman. Neuroprotective mechanisms of cerium oxide nanoparticles in a mouse hippocampal brain slice model of ischemia. Free Radic. Biol. Med. 51(6):1155–1163, 2011.

    Article  CAS  PubMed  Google Scholar 

  12. Franchini, M., G. Lusvardi, G. Malavasi, and L. Menabue. Gallium-containing phospho-silicate glasses: synthesis and in vitro bioactivity. Mater Sci. Eng. C Mater. Biol. Appl. 32(6):1401–1406, 2012.

    Article  CAS  PubMed  Google Scholar 

  13. Fu, Q., M. N. Rahaman, B. S. Bal, K. Kuroki, and R. F. Brown. In vivo evaluation of 13-93 bioactive glass scaffolds with trabecular and oriented microstructures in a subcutaneous rat implantation model. J. Biomed. Mater. Res. A 95(1):235–244, 2010.

    Article  CAS  PubMed  Google Scholar 

  14. Hench, L. L., and J. R. Jones. Bioactive glasses: frontiers and challenges. Front. Bioeng. Biotechnol. 3:194, 2015.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Huang, W. H., M. N. Rahaman, D. E. Day, and Y. D. Li. Mechanisms for converting bioactive silicate, borate, and borosilicate glasses to hydroxyapatite in dilute phosphate solution. Phys. Chem. Glasses B 47(6):647–658, 2006.

    CAS  Google Scholar 

  16. Jung, S. B. Bioactive borate glasses. In: Bio-Glasses: An introduction, edited by J. R. Jones, and A. G. Clare. Chichester: Wiley, 2012.

    Google Scholar 

  17. Lin, Y., R. F. Brown, S. B. Jung, and D. E. Day. Angiogenic effects of borate glass microfibers in a rodent model. J. Biomed. Mater. Res. A 102(12):4491–4499, 2014.

    PubMed  Google Scholar 

  18. Looney, M., H. O’Shea, and D. Boyd. Preliminary evaluation of therapeutic ion release from sr-doped zinc-silicate glass ceramics. J. Biomater. Appl. 27(5):511–524, 2013.

    Article  CAS  PubMed  Google Scholar 

  19. Mackinnon, S. E., V. B. Doolabh, C. B. Novak, and E. P. Trulock. Clinical outcome following nerve allograft transplantation. Plast. Reconstr. Surg. 107(6):1419–1429, 2001.

    Article  CAS  PubMed  Google Scholar 

  20. Madison, R. D., S. Archibald, and C. Krarup. Peripheral nerve injury. In: Wound Healing: Biochemical and Clinical Aspects, edited by I. K. Cohen, R. Diegelmann, and W. J. Lindblad. Philadelphia: W.B Saunders, 1992, pp. 450–487.

    Google Scholar 

  21. Marquardt, L. M., D. Day, S. E. Sakiyama-Elbert, and A. B. Harkins. Effects of borate-based bioactive glass on neuron viability and neurite extension. J. Biomed. Mater. Res. A 102(8):2767–2775, 2014.

    Article  CAS  PubMed  Google Scholar 

  22. Modglin, V. C., R. F. Brown, S. B. Jung, and D. E. Day. Cytotoxicity assessment of modified bioactive glasses with mlo-a5 osteogenic cells in vitro. J. Mater. Sci. Mater. Med. 24(5):1191–1199, 2013.

    Article  CAS  PubMed  Google Scholar 

  23. Mohammadkhah, A., L. M. Marquardt, S. E. Sakiyama-Elbert, D. E. Day, and A. B. Harkins. Fabrication and characterization of poly-(epsilon)-caprolactone and bioactive glass composites for tissue engineering applications. Mater. Sci. Eng. C Mater. Biol. Appl. 49:632–639, 2015.

    Article  CAS  PubMed  Google Scholar 

  24. Morais, D. S., S. Fernandes, P. S. Gomes, M. H. Fernandes, P. Sampaio, M. P. Ferraz, J. D. Santos, M. A. Lopes, and N. Sooraj. Hussain. Novel cerium doped glass-reinforced hydroxyapatite with antibacterial and osteoconductive properties for bone tissue regeneration. Biomed. Mater. 10(5):055008, 2015.

    Article  CAS  PubMed  Google Scholar 

  25. Palza, H., B. Escobar, J. Bejarano, D. Bravo, M. Diaz-Dosque, and J. Perez. Designing antimicrobial bioactive glass materials with embedded metal ions synthesized by the sol-gel method. Mater. Sci. Eng. C Mater. Biol. Appl. 33(7):3795–3801, 2013.

    Article  CAS  PubMed  Google Scholar 

  26. Rahaman, M. N., D. E. Day, B. S. Bal, Q. Fu, S. B. Jung, L. F. Bonewald, and A. P. Tomsia. Bioactive glass in tissue engineering. Acta Biomater. 7(6):2355–2373, 2011.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Schindelin, J., I. Arganda-Carreras, E. Frise, V. Kaynig, M. Longair, T. Pietzsch, S. Preibisch, C. Rueden, S. Saalfeld, B. Schmid, J. Y. Tinevez, D. J. White, V. Hartenstein, K. Eliceiri, P. Tomancak, and A. Cardona. Fiji: an open-source platform for biological-image analysis. Nat. Methods 9(7):676–682, 2012.

    Article  CAS  PubMed  Google Scholar 

  28. Schubert, D., R. Dargusch, J. Raitano, and S. W. Chan. Cerium and yttrium oxide nanoparticles are neuroprotective. Biochem. Biophys. Res. Commun. 342(1):86–91, 2006.

    Article  CAS  PubMed  Google Scholar 

  29. Shruti, S., A. J. Salinas, G. Lusvardi, G. Malavasi, L. Menabue, and M. Vallet-Regi. Mesoporous bioactive scaffolds prepared with cerium-, gallium- and zinc-containing glasses. Acta Biomater. 9(1):4836–4844, 2013.

    Article  CAS  PubMed  Google Scholar 

  30. Smith, C. Cultures from chick peripheral ganglia. In: Culturing Nerve Cells, edited by G. Banker, and K. Goslin. Cambridge: A Bradford Book, 1998, pp. 261–287.

    Google Scholar 

  31. Takadama, H., M. Hashimoto, M. Mizuno, and T. Kokubo. Round-robin test of sbf for in vitro measurement of apatite-forming ability of synthetic materials. Phosphorus Res. Bull. 17:119–125, 2004.

    Article  CAS  Google Scholar 

  32. Ulery, B. D., L. S. Nair, and C. T. Laurencin. Biomedical applications of biodegradable polymers. J. Polym. Sci. B Polym. Phys. 49(12):832–864, 2011.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Vulpoi, A., C. Gruian, E. Vanea, L. Baia, S. Simon, H. J. Steinhoff, G. Goller, and V. Simon. Bioactivity and protein attachment onto bioactive glasses containing silver nanoparticles. J. Biomed. Mater. Res. A 100(5):1179–1186, 2012.

    Article  CAS  PubMed  Google Scholar 

  34. Whitlock, E. L., S. H. Tuffaha, J. P. Luciano, Y. Yan, D. A. Hunter, C. K. Magill, A. M. Moore, A. Y. Tong, S. E. Mackinnon, and G. H. Borschel. Processed allografts and type i collagen conduits for repair of peripheral nerve gaps. Muscle Nerve 39(6):787–799, 2009.

    Article  CAS  PubMed  Google Scholar 

  35. Wiederhorn, S. M., Y. H. Chae, C. G. Simon, Jr, J. Cahn, Y. Deng, and D. Day. Cell adhesion to borate glasses by colloidal probe microscopy. Acta Biomater. 7(5):2256–2263, 2011.

    Article  CAS  PubMed  Google Scholar 

  36. Witzel, C., C. Rohde, and T. M. Brushart. Pathway sampling by regenerating peripheral axons. J. Comp. Neurol. 485(3):183–190, 2005.

    Article  PubMed  Google Scholar 

  37. Wu, C., W. Fan, Y. Zhu, M. Gelinsky, J. Chang, G. Cuniberti, V. Albrecht, T. Friis, and Y. Xiao. Multifunctional magnetic mesoporous bioactive glass scaffolds with a hierarchical pore structure. Acta Biomater. 7(10):3563–3572, 2011.

    Article  CAS  PubMed  Google Scholar 

  38. Yao, A. H., D. P. Wang, W. H. Huang, Q. Fu, M. N. Rahaman, and D. E. Day. In vitro bioactive characteristics of borate-based glasses with controllable degradation behavior. J. Am. Ceram. Soc. 90(1):303–306, 2007.

    Article  CAS  Google Scholar 

  39. Zhao, S., L. Li, H. Wang, Y. Zhang, X. Cheng, N. Zhou, M. N. Rahaman, Z. Liu, W. Huang, and C. Zhang. Wound dressings composed of copper-doped borate bioactive glass microfibers stimulate angiogenesis and heal full-thickness skin defects in a rodent model. Biomaterials 53:379–391, 2015.

    Article  CAS  PubMed  Google Scholar 

  40. Zhao, D., N. Moritz, E. Vedel, L. Hupa, and H. T. Aro. Mechanical verification of soft-tissue attachment on bioactive glasses and titanium implants. Acta Biomater. 4(4):1118–1122, 2008.

    Article  CAS  PubMed  Google Scholar 

  41. Zhou, J., H. Wang, S. Zhao, N. Zhou, L. Li, W. Huang, D. Wang, and C. Zhang. In vivo and in vitro studies of borate based glass micro-fibers for dermal repairing. Mater. Sci. Eng. C Mater. Biol. Appl. 60:437–445, 2016.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was funded in part by the Saint Louis University Investigative Learning and Experience Grant (awarded to BG) and a Presidential Research Fund from Saint Louis University (awarded to ABH). We thank Julianna Schneider, Jake Lee, and Claire Ji for assistance with viability counting. We thank Laura Marquardt for helpful discussions in experimental design. We thank Houston Linder and Blake Latty for their assistance in preparation of the glass forms used in this work.

Conflict of interest

None.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Amy B. Harkins.

Additional information

Associate Editor Debra T. Auguste oversaw the review of this article.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Gupta, B., Papke, J.B., Mohammadkhah, A. et al. Effects of Chemically Doped Bioactive Borate Glass on Neuron Regrowth and Regeneration. Ann Biomed Eng 44, 3468–3477 (2016). https://doi.org/10.1007/s10439-016-1689-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10439-016-1689-0

Keywords

Navigation