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

Authors Bariana M, Kaidonis JA, Losic D, Ranjitkar S, Anderson PJ

Received 18 January 2019

Accepted for publication 27 June 2019

Published 6 August 2019 Volume 2019:14 Pages 6313—6324

DOI https://doi.org/10.2147/IJN.S202090

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Ms Justinn Cochran

Peer reviewer comments 3

Editor who approved publication: Prof. Dr. Anderson Oliveira Lobo


Manpreet Bariana,1 John A Kaidonis,1 Dusan Losic,2 Sarbin Ranjitkar,1,* Peter J Anderson1,3,*

1Adelaide Dental School, The University of Adelaide, Adelaide, SA 5005, Australia; 2School of Chemical Engineering, The University of Adelaide, Adelaide, SA 5005, Australia; 3Australian Craniofacial Unit, Adelaide, SA 5006, Australia

*These authors contributed equally to this work

Background: 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.

Keywords: craniosynostosis, protein delivery, glypican, titania nanotube, murine

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