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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Autores principales:	Bariana M, Kaidonis JA, Losic D, Ranjitkar S, Anderson PJ
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2019
Materias:	craniosynostosis protein delivery glypican Titania nanotube murine Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/04fa68cb68614427aecc0e95d137334f
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spelling	oai:doaj.org-article:04fa68cb68614427aecc0e95d137334f2021-12-02T11:05:08ZTitania nanotube-based protein delivery system to inhibit cranial bone regeneration in Crouzon model of craniosynostosis1178-2013https://doaj.org/article/04fa68cb68614427aecc0e95d137334f2019-08-01T00:00:00Zhttps://www.dovepress.com/titania-nanotube-based-protein-delivery-system-to-inhibit-cranial-bone-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Manpreet 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, AustraliaThese 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, murineBariana MKaidonis JALosic DRanjitkar SAnderson PJDove Medical Pressarticlecraniosynostosisprotein deliveryglypicanTitania nanotubemurineMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 14, Pp 6313-6324 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	craniosynostosis protein delivery glypican Titania nanotube murine Medicine (General) R5-920
spellingShingle	craniosynostosis protein delivery glypican Titania nanotube murine Medicine (General) R5-920 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
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, AustraliaThese 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
format	article
author	Bariana M Kaidonis JA Losic D Ranjitkar S Anderson PJ
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
publishDate	2019
url	https://doaj.org/article/04fa68cb68614427aecc0e95d137334f
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Titania nanotube-based protein delivery system to inhibit cranial bone regeneration in Crouzon model of craniosynostosis

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