基于3D打印技术构建负载microRNA的凝胶支架对骨修复的影响及机制研究

The clinical repair of bone demands that the structure, composition and drug release of the therapeutic implant are suitable for the bone regeneration. Moreover, the implant should be able to positively direct the cell behaviors related to bone regeneration. However, current implants are not qualified for this multifunction requirement since they somehow have their own defects. To solve this problem, this project attempted to develop a 3D porous scaffold loaded miRNA through bioplotting technology for both precisely controlled structure and regulated the behavior of the cell. We will also investigate the regulation of scaffold’s degradability dressing on bone repair process and explore the associated mechanisms comprehensively and systematically in vitro and in vivo. This project is promising in providing valuable insights into the mechanism of miRNA applied in the bone repair and offering a new idea for the design of next-generation implant. This project was proposed according to the need in theoretical exploring and clinical application, which had both high academic value and social economic value.

骨的临床修复要求修复体不仅在结构、组成、药物释放等方面有利于新骨形成，还能积极介导成骨相关细胞功能的发挥，最终实现新骨再生。然而传统的修复体存在各自不足，难以同时满足上述要求。本项目拟基于快速成型技术，利用microRNA的基因调控作用，构建负载miRNA的三维凝胶支架材料，既能保证空间结构上支架的精确可控，同时能实现生物活性分子在分子水平上对细胞的调控；通过精确控制凝胶支架的结构特征，研究不同理化性能凝胶支架的药物释放动力学，为凝胶支架的最优选择提供理论依据；研究在细胞水平和动物水平上负载miRNA的三维凝胶支架材料对骨修复作用的影响及分子机制，全面深入探讨支架材料的降解性能与miRNA的释放性能的匹配度对骨修复行为的影响及关系，为miRNA在骨修复领域的应用及新一代骨修复材料的设计制备提供理论依据和新思路。本项目从理论探索和实际需求出发具有很高的理论意义和学术价值及广阔的临床应用前景。

骨的临床修复要求修复体不仅在结构、组成、药物释放等方面有利于新骨形成，还能积极介导成骨相关细胞功能的发挥，最终实现新骨再生。然而传统的修复体存在各自不足，难以同时满足上述要求。本项目成功建立打印不同理化性能包载miRNA的三维凝胶支架的实验方法和表征手段，获得不同理化性能的三维凝胶支架；凝胶支架的交联度越高，其硬度越高，细胞的铺展面积越大，凝胶支架表面可沉积矿化形成钙磷纳米团簇，该过程有利于干细胞向成骨分化和矿化基质形成；动物实验证明负载miRNA的高交联度支架更有利于骨生成及血管长入，支架的交联度和miRNA的释放分别为hMSCs的分化提供了物理微环境和化学微环境，在二者的协调下共同影响hMSCs向成骨分化，为miRNA在骨修复领域的研究应用及新一代骨修复材料的设计制备提供理论依据和新思路；在SCI期刊上发表论文5篇，另有1篇文章正在投稿中，申请发明专利2项，授权1项发明专利，并获得拥有自主知识产权、具有应用价值的新型骨组织工程支架。