同轴打印多孔管道掺锶陶瓷支架负载干细胞促进大块颌骨再生的作用及其机制研究

Tissue engineering based on stem cells-loaded scaffolds can significantly promote regeneration of the mandible, however, for large tissue regeneration, vascularization restriction will not only slow down tissue regeneration, but also seriously affect the survival of the carrying stem cells and reduce the regeneration effect. Our preliminary results suggest that the hollow channels can induce blood vessels grow into the scaffolds. The strontium ion also has some osteogenic and angiogenic effects. Therefore, the present study intends to modulate the strontium-incorporated hardystonite (Sr-HT) ceramic material paste containing porogen, and then, the porous pipes stacked scaffold is prepared using a coaxial printing technology. On the one hand, the porous/hollow channel structure could increase the porosity of the scaffold, which might be beneficial to the loading and growth of the stem cells. On the other hand, it could induce the rapid vascularization of the scaffold and promote the survival of the loaded stem cells. We will focus on the study of the vascularization and stem cell survival of the Sr-HT scaffolds. We will detect the molecular mechanism of vascularization induced by the structure and strontium ion. Finally, we will evaluate the effects of the porous pipes stacked Sr-HT scaffold carrying bone marrow stem cells for the vasularied bone regeneration in large animals, looking forward providing a new treatment strategy for clinical application of large jaw bone repair.

以支架材料负载干细胞为基础的组织工程技术可显著促进颌骨再生；然而针对大块组织再生，由于血管化限制，不仅会减缓组织再生速度，还将严重影响负载干细胞体内存活而降低再生效果。我们前期研究结果提示大块支架辅以管道结构设计可以诱导血管快速长入支架内部，锶离子同样具有一定的成骨成血管诱导作用。为此，本研究拟调制添加致孔剂的掺锶-锌黄长石（Sr-HT）陶瓷材料浆体，借助同轴打印技术制备具有中空管道／多孔管壁复合结构的多孔管道支架；该结构一方面明显增加了支架的孔隙率，可能更利于干细胞的负载与生长，另一方面还可能与锶离子协同诱导大块支架的整体快速血管化，进而促进所负载干细胞的体内存活。我们将围绕多孔管道Sr-HT支架促进血管化及干细胞存活而展开研究，并重点探讨管道结构及锶离子调控血管化的相关机制，最终在大动物体内综合评估多孔管道支架负载骨髓干细胞的血管化骨再生效果，期待为临床大块颌骨修复提供新的治疗方案。

血管化问题一直是限制大块骨组织再生的关键因素，支架结构整体快速血管化的实现，可加快骨再生速度，提高骨再生质量。本项目围绕大块支架血管化及负载干细胞存活等问题展开研究，从管道结构设计、离子成分、药物使用等方面开展研究，优化组合，加快再生速度和质量。探索管道/多孔结构设计，优化适宜组织和血管长入的支架结构参数，筛选镁离子、锶离子诱导血管化骨再生最佳浓度，并探索了多孔/管道结构协同镁离子、锶离子等生物活性离子成分改性支架以诱导快速血管化骨再生的机制，并最终成功修复犬下颌骨大块骨缺损。本项目的顺利实施可望为大块颌骨再生提供优化方案，并为其他大块组织或器官再生血管化的问题提供新思路。期间共发表SCI论文10篇，其中IF>5的8篇，IF>10的3篇。获国家自然基金优秀青年基金项目、面上项目和上海市青年科技启明星计划等课题资助。获授权国家发明专利1项，另新申请国家发明专利5项。