Development of regenerative therapy for jaw bone using scaffold with carbon nanotubes.

本研究通过碳纳米管（carbon nanotubes, CNTs）的生物相容性研究、碳纳米管支架上的细胞培养和块状碳纳米管的制备，目的是利用碳纳米管重建颌骨。将CNTs植入大鼠皮下组织2年，对CNTs进行组织学和超微结构观察。在巨噬细胞的溶酶体中观察到一些CNTs，并且在2年时CNTs周围仅识别到轻微的肉芽肿性炎症反应，尽管在植入后早期CNTs周围可见有吞噬细胞的肉芽组织。随着时间的推移，CNTs的聚集程度逐渐减弱。通过透射电镜观察，2年后大多数CNTs样管的典型结构未发生变化。这些结果表明，CNTs不是强前兆物质，CNTs晶体结构在体内是稳定的。将分散的碳纳米管浆液真空过滤到聚碳酸酯（PC）膜上制备碳纳米管支架。在支架上培养人成骨样细胞Saos-2。CNTs支架上培养的Saos-2细胞增殖能力和碱性磷酸酶活性均高于PC膜。与PC膜相比，将引导骨再生膜CNTs支架应用于大鼠顶骨骨缺损的成骨效果明显。采用火花等离子烧结法制备了块状碳纳米管材料。块状碳纳米管的物理力学性能与骨相似，具有良好的生物相容性。结果表明，SPS法制备的块状碳纳米管适合作为骨替代材料。从这些结果来看，使用碳纳米管对颌骨进行再生治疗是可能的。

In this study, investigation of biocompatibility of carbon nanotubes (CNTs), cell culture on the scaffold using with CNTs and fabrication of bulk CNTs were carried out for the purpose of reconstruction of jaw bone using with CNTs.CNTs were implanted in the subcutaneous tissue in rats for 2 years, and histological and ultramicrostructural investigation to CNTs were done. Some CNTs were observed in lysosome in macrophages and only slight granulomatous inflammatory response was recognized around CNTs at 2 years, although granulation tissue with phagocytes was seen around CNTs at early stage after implant. The degree of aggregation of CNTs became to slight with time. Most of typical structure of CNTs like tubes was not changed after 2 years by observation using TEM. These results suggested that CNTs was not strong prophlogistic substance and structure of crystal of CNTs was stable in vivo.Scaffolds with CNTs were made by vacuum filtration of the dispersed CNTs slurry onto polycarbonate (PC) membrane. Saos-2 (human osteoblast-like cell) was cultured on the scaffolds. Proliferation and alkaline phosphatase activity of Saos-2 cultured on the CNTs scaffolds were higher than those of PC membrane. Application of the CNTs scaffold for guided bone regeneration membrane to bone defects made on rat parietal bone was effective in osteogenesis compared to PC membrane.Bulk CNTs materials were fabricated by spark plasma sintering (SPS). Physical and mechanical properties of bulk CNTs were close to those of bone, and biocompatibility was excellent. These results showed that bulk CNTs made by SPS method was suitable for bone substitute materials.From these results, it was suggested that regenerative therapy for jaw bone using with CNTs would be possible.