新型骨仿生材料引导牙槽骨垂直向骨再生的研究

Vertical bone augmentation remains a clinical challenge due to the difficulty of migration of bone-forming cells and vascularization. Conventional strategies for bone repair mainly focus on the use of bone grafts from autologous, allogeneic and xenogeneic sources. However, complications such as donor-site morbidity, host immune rejection and compromised new bone formation limited graft application. Therefore, it is important to find a new biomimetic material suitable for vertical bone augmentation, which can regenerate new bone with higher quality, and at the same time can induce vertical migration of bone-forming cells. Previous studies showed that intrafibrillarly-mineralized collagen (IMC), with its biomimetic features and bone-like hierarchy nanostructure, could significantly stimulate neo-bone regeneration in defect areas. At the same time, hyaluronic acid modified mussel foot proteins (HA/Mfps), as a good candidate of adhesive proteins, could promote proliferation, adhesion and migration of bone-forming cells. This project aims to synthesize a novel IMC+HA/Mfps biomaterial to promote vertical bone augmentation. The properties of IMC+HA/Mfps, as well as the effect of IMC+HA/Mfps on proliferation, adhesion, migration and osteogenic differentiation of bone marrow stem cells were tested. Moreover, IMC+HA/Mfps were used to guide vertical bone augmentation in rat and Beagle dog vertical bone defect models, and the mechanism of vertical bone augmentation was investigated. This study is targeted to develop a novel bone biomimetic material to promote vertical bone augmentation, which provides us a new way to repair clinical vertical bone defects.

牙槽骨垂直向骨缺损因修复细胞及血供不足，修复难度较大。传统自体骨移植手术创伤大，技术敏感性高；传统植骨材料成骨时间长，新生骨比例低。因此，急需探索操作更简单，成骨质量更高，能够诱导细胞垂直向上迁移的新型支架材料。以往研究表明，纤维内矿化胶原（IMC）具有良好的理化性能及成骨效果，但缺乏诱导细胞垂直向上迁移的能力。而透明质酸修饰后的贻贝足丝蛋白（HA/Mfps）具有良好的粘附特性，可促进细胞粘附及迁移。本项目拟合成新型的IMC+HA/Mfps支架材料，检测其理化性质，探讨其对骨髓间充质干细胞的诱导作用。同时，探讨IMC+HA/Mfps引导牙槽骨垂直向骨再生的效果及其机制。本项目有望探索出适用于牙槽骨垂直向骨再生的新型修复材料，并为提高临床骨增量手术的效果提供新思路。

牙槽骨垂直向骨缺损因修复细胞及血供不足，修复难度较大。传统自体骨移植手术创伤大，技术敏感性高；传统植骨材料成骨时间长，新生骨比例低。因此，急需探索成骨质量更高，同时能够诱导细胞垂直向上迁移的新型支架材料。以往研究表明，纤维内矿化胶原（IMC）具有良好的理化性能及成骨效果，同时透明质酸修饰后的贻贝足丝蛋白（HA/Mfps）具有良好的粘附特性，因此，本项目结合了IMC支架材料的良好成骨性能以及HA/Mfps的促细胞粘附迁移的特性，通过氢键结合的方式合成了新型的IMC+HA/Mfps支架材料，研究结果表明，新型IMC+HA/Mfps支架材料具有良好的理化性能，体外实验显示IMC+HA/Mfps能够促进rBMSCs的粘附，增殖及迁移，体内实验显示，IMC+HA/Mfps修复下颌骨垂直骨缺损的能力显著高于IMC组以及单纯对照组，进一步免疫荧光染色显示IMC+HA/Mfps组的成骨相关因子，成血管相关因子以及干细胞标记物均高于IMC及对照组。本项目创新性的研发了具备良好的成骨性能以及促细胞粘附迁移的新型支架材料，为提高临床骨增量手术的效果提供新思路。在本项目的后续实验中，本项目组还发现将纳米Ag线与IMC组装合成的新型IMC/Nano-Ag材料具备良好的抗菌性能和成骨作用，未来将进一步探讨该支架材料在感染性骨缺损中的作用及机制，为解决临床重度牙槽骨缺损修复，尤其是与种植体周围炎相关感染性骨缺损修复的难题提供新的思路。