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

Abstract

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.

• Authors: Manpreet Bariana, John A Kaidonis, Dusan Losic, Sarbin Ranjitkar, Peter J Anderson
• Journal: International journal of nanomedicine (Int J Nanomedicine) Vol. 14 Pg. 6313-6324 ( 2019) ISSN: 1178-2013 [Electronic] New Zealand
• PMID: 31496688 (Publication Type: Journal Article)

Chemical References

• Glypicans
• titanium dioxide
• Titanium

Topics

• Animals
• Bone Regeneration
• Craniofacial Dysostosis (diagnostic imaging, therapy)
• Disease Models, Animal
• Drug Delivery Systems
• Female
• Glypicans (administration & dosage, therapeutic use)
• Male
• Mice, Inbred C57BL
• Nanotubes (chemistry, ultrastructure)
• Skull (diagnostic imaging, pathology)
• Titanium (chemistry)
• X-Ray Microtomography