Development of Biomaterials which Induce Tissue and Organ

阐明了HAP-BMP复合材料作为支架材料和人工膜-BMP复合材料诱导新骨和软骨的作用，是一种组织器官诱导的生物材料。而以BMP为骨架构建的种植体外形要求表面光滑，无锐缘。因此，对HAP表面进行润滑，去除锋利的刃口是非常重要的。HAP的管状结构内的空隙很难诱导新骨形成。这说明BMP不仅是骨诱导因子，而且是影响成骨的另一个未知因子。血管内皮生长因子（vascular endothelial growth factor，VEGF）或其他因子可能是新骨形成的辅助因子，这一信息对下一步的研究有重要意义。所有人工膜-BMP复合材料均显示新骨形成，适用于临床应用，如GTR法。当使用生物可降解膜时，在体外诱导新的软骨非常困难。更多的基础研究工作是必要的，这种材料的应用到临床使用。在人工膜上进行软骨诱导的研究，以前只有一篇报道。在本项目中成功地在醋酸膜上形成新的软骨。这种诱导仅停留在软骨阶段，没有进展到骨诱导，但通过将该系统移植到体内，新骨形成是可能的。因此，通过这些实验，研制出了HAP-BMP复合材料和人工膜-BMP复合材料两种组织器官生物材料，为该材料的临床应用积累了重要的资料。

It is elucidated that both HAP-BMP composite material, which was used as a frame works, and artificial membrane - BMP composite material induced new bone and cartilage , those are useful as tissue organ inducible biomaterials. However, outer shape of implant, which was constructed with BMP as a framework, should have smooth surface and no sharp edge. Therefore, lubricating the surface of HAP and delete of the sharp edge is remarkably important. It is very hard to induce new bone inside of the inner vacant space of tubules shape of HAP. It demonstrates that not only the BMP is a factor of bone induction but also another unknown factor influence the osteogenesity. VEGF(vascular endothelial growth factor) or some other factors could be a cofactor for the new bone formation.It is considered that this information contributes largely to the next project. All artificial membrane -BMP composite showed new bone formation, and those are applicable for the clinical usage, such as GTR method. When biodegradable membrane is used, induction of new cartilage in vitro was very hard. More basic research work is necessary on this material for the application to clinical usage. There was only one research report for the cartilage induction on the artificial membrane previously. New cartilage formation on acetate membrane was successfully performed in this project. This induction remained only cartilage stage and not progress to osteoinduction but new bone formation could be possible by transplanting this system in vivo. Consequently, two kinds of tissue organ biomaterials, which are HAP-BMP composite and artificial membrane - BMP composite, are developed through these experiments, and important information for the application of this material for the clinical usage was accumulated.