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

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...

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Autores principales: Bariana, Manpreet, Kaidonis, John A, Losic, Dusan, Ranjitkar, Sarbin, Anderson, Peter J
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6690047/
https://www.ncbi.nlm.nih.gov/pubmed/31496688
http://dx.doi.org/10.2147/IJN.S202090
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author Bariana, Manpreet
Kaidonis, John A
Losic, Dusan
Ranjitkar, Sarbin
Anderson, Peter J
author_facet Bariana, Manpreet
Kaidonis, John A
Losic, Dusan
Ranjitkar, Sarbin
Anderson, Peter J
author_sort Bariana, Manpreet
collection PubMed
description 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 (Fgfr2(c342y/+) 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.
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spelling pubmed-66900472019-09-06 Titania nanotube-based protein delivery system to inhibit cranial bone regeneration in Crouzon model of craniosynostosis Bariana, Manpreet Kaidonis, John A Losic, Dusan Ranjitkar, Sarbin Anderson, Peter J Int J Nanomedicine Original Research 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 (Fgfr2(c342y/+) 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. Dove 2019-08-06 /pmc/articles/PMC6690047/ /pubmed/31496688 http://dx.doi.org/10.2147/IJN.S202090 Text en © 2019 Bariana et al. http://creativecommons.org/licenses/by-nc/3.0/ 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).
spellingShingle Original Research
Bariana, Manpreet
Kaidonis, John A
Losic, Dusan
Ranjitkar, Sarbin
Anderson, Peter J
Titania nanotube-based protein delivery system to inhibit cranial bone regeneration in Crouzon model of craniosynostosis
title 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_short 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
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6690047/
https://www.ncbi.nlm.nih.gov/pubmed/31496688
http://dx.doi.org/10.2147/IJN.S202090
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