Titania nanotube-based protein delivery system to inhibit cranial bone regeneration in Crouzon model of craniosynostosis
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, Ad...
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doaj-04fa68cb68614427aecc0e95d137334f2020-11-25T02:11:47ZengDove Medical PressInternational Journal of Nanomedicine1178-20132019-08-01Volume 146313632447662Titania nanotube-based protein delivery system to inhibit cranial bone regeneration in Crouzon model of craniosynostosisBariana MKaidonis JALosic DRanjitkar SAnderson PJManpreet 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 workBackground: 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, murinehttps://www.dovepress.com/titania-nanotube-based-protein-delivery-system-to-inhibit-cranial-bone-peer-reviewed-article-IJNcraniosynostosisprotein deliveryglypicanTitania nanotubemurine |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Bariana M Kaidonis JA Losic D Ranjitkar S Anderson PJ |
spellingShingle |
Bariana M Kaidonis JA Losic D Ranjitkar S Anderson PJ Titania nanotube-based protein delivery system to inhibit cranial bone regeneration in Crouzon model of craniosynostosis International Journal of Nanomedicine craniosynostosis protein delivery glypican Titania nanotube murine |
author_facet |
Bariana M Kaidonis JA Losic D Ranjitkar S Anderson PJ |
author_sort |
Bariana M |
title |
Titania nanotube-based protein delivery system to inhibit cranial bone regeneration in Crouzon model of craniosynostosis |
title_short |
Titania nanotube-based protein delivery system to inhibit cranial bone regeneration in Crouzon model of craniosynostosis |
title_full |
Titania nanotube-based protein delivery system to inhibit cranial bone regeneration in Crouzon model of craniosynostosis |
title_fullStr |
Titania nanotube-based protein delivery system to inhibit cranial bone regeneration in Crouzon model of craniosynostosis |
title_full_unstemmed |
Titania nanotube-based protein delivery system to inhibit cranial bone regeneration in Crouzon model of craniosynostosis |
title_sort |
titania nanotube-based protein delivery system to inhibit cranial bone regeneration in crouzon model of craniosynostosis |
publisher |
Dove Medical Press |
series |
International Journal of Nanomedicine |
issn |
1178-2013 |
publishDate |
2019-08-01 |
description |
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 workBackground: 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 |
topic |
craniosynostosis protein delivery glypican Titania nanotube murine |
url |
https://www.dovepress.com/titania-nanotube-based-protein-delivery-system-to-inhibit-cranial-bone-peer-reviewed-article-IJN |
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