Titania nanotube-based protein delivery system to inhibit cranial bone regeneration in Crouzon model of craniosynostosis

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dc.contributor.authorBariana, M.
dc.contributor.authorKaidonis, J.A.
dc.contributor.authorLosic, D.
dc.contributor.authorRanjitkar, S.
dc.contributor.authorAnderson, P.J.
dc.date.issued2019
dc.description.abstractBackground: Craniosynostosis is a developmental disorder characterized by the premature fusion of skull sutures, necessitating repetitive, high-risk neurosurgical interventions throughout infancy. This study used protein-releasing Titania nanotubular implant (TNT/Ti) loaded with glypican 3 (GPC3) in the cranial critical-sized defects (CSDs) in Crouzon murine model (Fgfr2c342y/+ knock-in mutation) to address a key challenge of delaying post-operative bone regeneration in craniosynostosis. Materials and Methods: A 3 mm wide circular CSD was created in two murine models of Crouzon syndrome: (i) surgical control (CSDs without TNT/Ti or any protein, n=6) and (ii) experimental groups with TNT/Ti loaded with GPC3, further subdivided into the presence or absence of chitosan coating (on nanotubes) (n=12 in each group). The bone volume percentage in CSDs was assessed 90 days post-implantation using micro-computed tomography (micro-CT) and histological analysis. Results: Nano-implants retrieved after 90 days post-operatively depicted well-adhered, hexagonally arranged, and densely packed nanotubes with average diameter of 120±10 nm. The nanotubular architecture was generally well-preserved. Compared with the control bone volume percentage data (without GPC3), GPC3-loaded TNT/Ti without chitosan coating displayed a significantly lower volume percent in cranial CSDs (P<0.001). Histological assessment showed relatively less bone regeneration (healing) in GPC3-loaded CSDs than control CSDs. Conclusion: The finding of inhibition of cranial bone regeneration by GPC3-loaded TNT/Ti in vivo is an important advance in the novel field of minimally-invasive craniosynostosis therapy and holds the prospect of altering the whole paradigm of treatment for affected children. Future animal studies on a larger sample are indicated to refine the dosage and duration of drug delivery across different ages and both sexes with the view to undertake human clinical trials.
dc.description.statementofresponsibilityManpreet Bariana, John A Kaidonis, Dusan Losic, Sarbin Ranjitkar, Peter J Anderson
dc.identifier.citationInternational Journal of Nanomedicine, 2019; 14:6313-6324
dc.identifier.doi10.2147/IJN.S202090
dc.identifier.issn1176-9114
dc.identifier.issn1178-2013
dc.identifier.orcidKaidonis, J.A. [0000-0003-0415-5272]
dc.identifier.orcidLosic, D. [0000-0002-1930-072X]
dc.identifier.orcidRanjitkar, S. [0000-0003-1957-0719]
dc.identifier.orcidAnderson, P.J. [0000-0002-3730-4652]
dc.identifier.urihttp://hdl.handle.net/2440/121192
dc.language.isoen
dc.publisherDove Medical Press
dc.relation.granthttp://purl.org/au-research/grants/arc/FT110100711
dc.relation.granthttp://purl.org/au-research/grants/arc/IH150100003
dc.rights© 2019 Bariana et al. This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php).
dc.source.urihttps://doi.org/10.2147/ijn.s202090
dc.subjectCraniosynostosis; protein delivery; glypican; titania nanotube; murine
dc.titleTitania nanotube-based protein delivery system to inhibit cranial bone regeneration in Crouzon model of craniosynostosis
dc.typeJournal article
pubs.publication-statusPublished

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