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

本研究通过对碳纳米管的生物相容性研究、碳纳米管支架上的细胞培养和块状碳纳米管的制备，将碳纳米管植入大鼠皮下组织2年，并对其组织学和超微结构进行观察。植入后2年，巨噬细胞内溶酶体内可见少量的碳纳米管，其周围仅见轻度肉芽肿性炎症反应，但植入后早期可见肉芽组织，周围可见吞噬细胞。随着时间的延长，碳纳米管的聚集程度逐渐减弱。经透射电子显微镜观察，大部分碳纳米管的典型结构在2年后并未发生改变。这些结果表明，碳纳米管不是很强的前体物质，其晶体结构在体内是稳定的。将分散的碳纳米管悬浮液真空过滤到聚碳酸酯(PC)膜上，制成碳纳米管支架。在支架上培养人成骨样细胞SAOS-2。在碳纳米管支架上培养的Saos-2细胞的增殖能力和碱性磷酸酶活力均高于PC膜。将碳纳米管支架用于引导骨再生膜修复大鼠顶骨缺损，与聚碳酸酯膜相比具有更好的成骨效果。采用放电等离子烧结法制备碳纳米管材料。块状碳纳米管的物理力学性能与骨相近，具有良好的生物相容性。这些结果表明，SPS法制备的块状碳纳米管适合作为骨替代材料，提示将碳纳米管应用于颌骨再生治疗是可能的。

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.