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

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...

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Bibliographic Details
Published in:International journal of nanomedicine 2019-01, Vol.14, p.6313-6324
Main Authors: Bariana, Manpreet, Kaidonis, John A, Losic, Dusan, Ranjitkar, Sarbin, Anderson, Peter J
Format: Article
Language:English
Subjects:
Airway management
Animals
Biomedical materials
Bone Regeneration
CAT scans
Children
Children & youth
Clinical trials
Craniofacial Dysostosis - diagnostic imaging
Craniofacial Dysostosis - therapy
craniosynostosis
Defects
Disease Models, Animal
Drug Delivery Systems
Female
glypican
Glypicans - administration & dosage
Glypicans - therapeutic use
Male
Mice, Inbred C57BL
murine
Mutation
Nanotubes
Nanotubes - chemistry
Nanotubes - ultrastructure
Original Research
protein delivery
Proteins
Quantum dots
Skull - diagnostic imaging
Skull - pathology
Tissue engineering
Titania nanotube
Titanium
Titanium - chemistry
Tomography
Transplants & implants
X-Ray Microtomography
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Description
Summary: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 ( knock-in mutation) to address a key challenge of delaying post-operative bone regeneration in craniosynostosis. 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. 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 (
ISSN:1178-2013
1176-9114
1178-2013
DOI:10.2147/IJN.S202090