Annals of Biomedical Engineering

, Volume 44, Issue 12, pp 3468–3477 | Cite as

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

  • Brinda Gupta
  • Jason B. Papke
  • Ali Mohammadkhah
  • Delbert E. Day
  • Amy B. Harkins
Article

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.

Keywords

Dorsal root ganglia Nerve regeneration Biocompatibility Glia Fibroblasts 

Notes

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.

References

  1. 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.PubMedGoogle Scholar
  2. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Bellucci, D., A. Sola, and V. Cannillo. Bioactive glass/zro2 composites for orthopaedic applications. Biomed. Mater. 9(1):015005, 2014.CrossRefPubMedGoogle Scholar
  4. 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.CrossRefPubMedGoogle Scholar
  5. 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.CrossRefGoogle Scholar
  6. 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.CrossRefPubMedGoogle Scholar
  7. 7.
    Chitambar, C. R. Gallium and its competing roles with iron in biological systems. Biochim. Biophys. Acta 1863(8):2044–2053, 2016.CrossRefPubMedGoogle Scholar
  8. 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.CrossRefPubMedGoogle Scholar
  9. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 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.CrossRefPubMedGoogle Scholar
  11. 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.CrossRefPubMedGoogle Scholar
  12. 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.CrossRefPubMedGoogle Scholar
  13. 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.CrossRefPubMedGoogle Scholar
  14. 14.
    Hench, L. L., and J. R. Jones. Bioactive glasses: frontiers and challenges. Front. Bioeng. Biotechnol. 3:194, 2015.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 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.Google Scholar
  16. 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. 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.PubMedGoogle Scholar
  18. 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.CrossRefPubMedGoogle Scholar
  19. 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.CrossRefPubMedGoogle Scholar
  20. 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. 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.CrossRefPubMedGoogle Scholar
  22. 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.CrossRefPubMedGoogle Scholar
  23. 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.CrossRefPubMedGoogle Scholar
  24. 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.CrossRefPubMedGoogle Scholar
  25. 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.CrossRefPubMedGoogle Scholar
  26. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 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.CrossRefPubMedGoogle Scholar
  28. 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.CrossRefPubMedGoogle Scholar
  29. 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.CrossRefPubMedGoogle Scholar
  30. 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. 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.CrossRefGoogle Scholar
  32. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  33. 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.CrossRefPubMedGoogle Scholar
  34. 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.CrossRefPubMedGoogle Scholar
  35. 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.CrossRefPubMedGoogle Scholar
  36. 36.
    Witzel, C., C. Rohde, and T. M. Brushart. Pathway sampling by regenerating peripheral axons. J. Comp. Neurol. 485(3):183–190, 2005.CrossRefPubMedGoogle Scholar
  37. 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.CrossRefPubMedGoogle Scholar
  38. 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.CrossRefGoogle Scholar
  39. 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.CrossRefPubMedGoogle Scholar
  40. 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.CrossRefPubMedGoogle Scholar
  41. 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.CrossRefPubMedGoogle Scholar

Copyright information

© Biomedical Engineering Society 2016

Authors and Affiliations

  • Brinda Gupta
    • 1
  • Jason B. Papke
    • 1
  • Ali Mohammadkhah
    • 2
  • Delbert E. Day
    • 2
  • Amy B. Harkins
    • 1
    • 3
  1. 1.Department of Pharmacology and PhysiologySaint Louis UniversitySt. LouisUSA
  2. 2.Graduate Center for Materials Research and Center for Biomedical Science and EngineeringMissouri University of Science and TechnologyRollaUSA
  3. 3.Department of Biomedical EngineeringSaint Louis UniversitySt. LouisUSA

Personalised recommendations