Titania nanotube-based protein delivery system to inhibit cranial bone regeneration in Crouzon model of craniosynostosis
Titania nanotube-based protein delivery system to inhibit cranial bone regeneration in Crouzon model of craniosynostosis
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DOI：
10.2147/ijn.s202090
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发表时间：
2019-01-01
影响因子：
8
通讯作者：
Anderson, Peter J.
中科院分区：
文献类型：
--
作者：
Bariana, Manpreet;Kaidonis, John A.;Anderson, Peter J.
背景：颅缝融合是一种发育障碍，其特征是颅缝过早融合，需要在整个婴儿期进行重复的、高风险的神经外科干预。为了解决Crouzon综合征小鼠颅骨临界大小缺损区(CSDs)中的一个关键问题，本研究将携带GPC3的蛋白释放二氧化钛纳米管种植体(TNT/Ti)植入Crouzon小鼠模型(FGFR2(c342y/+)敲入突变)。材料和方法：在两种Crouzon综合征小鼠模型中建立3 mm宽的圆形CSD：(I)手术对照组(CSDs不含TNT/Ti或任何蛋白质，n=6)和(Ii)TNT/Ti负载GPC3的实验组，进一步细分为有或没有壳聚糖涂层(在纳米管上)(每组n=12)。结果：植入90d后回收的纳米种植体具有良好的粘附性、六角形排列和致密排列，平均直径为120+/-10 nm。纳米管结构总体上保存完好。与对照组(不含GPC3)相比，未涂覆GPC3的TNT/Ti骨体积百分比显著降低(P
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 postoperative 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