Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, 140 Hanzhong Road, Nanjing 210029, China.
Nanjing Children's Hospital, Nanjing Medical University, Nanjing 210093, China.
Biomater Adv. 2022 Jun;137:212853. doi: 10.1016/j.bioadv.2022.212853. Epub 2022 May 13.
Anodic titanium dioxide nanotubes (TNT) have a range of beneficial theranostic properties. However, a lack of effective osseointegration is a problem frequently associated with the titanium dental implant surface. Here, we investigated whether bone-shaped nanotube titanium implants could enhance osseointegration via promoting initial release of vascular endothelial growth factor 165 (VEGF165) and dual release of recombinant human bone morphogenetic protein-2 (rhBMP-2). Thus, we generated cylindrical-shaped nanotubes (TNT1) and bone-shaped nanotubes (TNT2) through voltage-varying and time-varying electrochemical anodization methods, respectively. Additionally, we prepared rhBMP-2-loaded cylindrical-shaped nanotubes/VEGF165-loaded hydrogel (TNT-F1) and rhBMP-2-loaded bone-shaped nanotubes/VEGF165-loaded hydrogel (TNT-F2) drug delivery systems. We evaluated the characteristics and release kinetics of the drug delivery systems, and then analyzed the cytocompatibility and osteogenic differentiation of these specimens with mesenchymal stem cells (MSCs) in vitro. Finally, we utilized a rat femur defect model to test the bone formation capacity of nanotube-hydrogel drug delivery system in vivo. Among these different nanotubes structures, the bone-shaped one was the optimum structure for growth factor release.
阳极氧化钛纳米管（TNT）具有一系列有益的治疗诊断特性。然而，钛牙种植体表面常常存在缺乏有效骨整合的问题。在这里，我们研究了骨状纳米管钛植入物是否可以通过促进血管内皮生长因子 165（VEGF165）的初始释放和重组人骨形态发生蛋白-2（rhBMP-2）的双重释放来增强骨整合。因此，我们分别通过电压变化和时间变化的电化学阳极氧化方法生成了圆柱形纳米管（TNT1）和骨状纳米管（TNT2）。此外，我们制备了负载 rhBMP-2 的圆柱形纳米管/负载 VEGF165 的水凝胶（TNT-F1）和负载 rhBMP-2 的骨状纳米管/负载 VEGF165 的水凝胶（TNT-F2）药物输送系统。我们评估了药物输送系统的特性和释放动力学，然后分析了这些标本与间充质干细胞（MSCs）在体外的细胞相容性和成骨分化。最后，我们利用大鼠股骨缺损模型在体内测试了纳米管-水凝胶药物输送系统的成骨能力。在这些不同的纳米管结构中，骨状结构是生长因子释放的最佳结构。
