仿生骨膜复合三维支架用于临界尺寸骨缺损修复研究

Periosteum plays an important role in bone repair, for rich of osteogenic growth factors and vessels as well as the surface hierarchical topological.structure capable of harnessing and regulating cell arrangement and differentiation. In order to promote the rapid repair of bone defect, artificial materials simulating the structure and function of natural periosteum will be developed in this study. A combination of PLGA film with microgrooved structure and gelatin hydrogel with 3D net structure is to be introduced to effectively induce and promote osteogenesis. Further based on the characteristics of 2-N,6-O-sulfated chitosan (26SCS) as synergistic to bone morphogenetic protein (BMP-2) and favor to vascularization, BMP-2 loading 26SCS modified PLGA/gelatin composite membrane will be developed to promote its osteogenesis and vascularization abilities. Then the regulation of periosteum-mimic microstructure on biological function of MSC will be further systematically evaluated. Moreover, this BMP-2 loading periosteum-mimic membrane composited with 3D printing PLGA scaffold will be applied to repair the radius critical-size bone defects in rabbits to reveal the regulatory pattern of the sulfated modified nano-structure on the performance of bone repair in vivo. The present study may provide a new bone graft material for bone defect repair, as well as provide an innovative strategy to rapidly enhance the surface biofunction of scaffolds.

骨膜在骨组织修复过程中起重要作用。骨膜中含有利于成骨的生长因子及血管，且具有约束并调控细胞定向和分化的多级拓扑表面。因此，为了实现骨组织缺损的快速修复，本项目拟制备具有仿生天然骨膜结构和功能的人工骨修复材料。利用定向纳米微结构PLGA膜复合三维网络明胶水凝胶，实现复合膜有效诱导并促进成骨功能，进一步基于2-N,6-O-磺化壳聚糖（26SCS）与骨形态发生蛋白（BMP-2）的协同作用及其促血管生成特性，构建载BMP-2的26SCS磺化改性PLGA/明胶仿生骨膜。系统研究载BMP-2的磺化改性仿生骨膜对骨髓间充质干细胞（MSC）生物学功能的调控作用。进而应用该仿生骨膜复合PLGA三维打印支架修复兔桡骨临界尺寸缺损，揭示载BMP-2磺化仿生骨膜调控体内骨修复的性能规律。本研究可望为临界尺寸骨缺损修复提供新型的植骨材料，并为快速提升支架表面的生物功能性提供新的策略。

骨膜在骨组织修复过程中起重要作用。骨膜中含有利于成骨的生长因子及血管，且具有约束并调控细胞定向和分化的多级拓扑表面。因此，为了实现骨组织缺损的快速修复，本项目利用定向纳米微结构PLGA膜可促进骨髓间充质干细胞(BMSCs)成骨分化的特性，并结合2-N,6-O-磺化壳聚糖(26SCS)与骨形态发生蛋白(BMP-2)的协同作用及其促血管生成功能，将26SCS磺化改性的PLGA定向纳米微结构膜与载BMP-2的光交联明胶水凝胶复合，构建出具有显著成骨/成血管活性的仿生骨膜材料。本项目进一步开展了关于载BMP-2的磺化改性仿生骨膜对BMSCs生物学功能调控作用的系统研究，并验证该仿生骨膜复合PLGA三维打印支架能够在3个月内修复兔桡骨临界尺寸缺损。本项目为临界尺寸骨缺损修复提供了新型的植骨材料，并为快速提升支架表面的生物功能性提供了新的策略。本项目执行期间，共发表SCI论文6篇，其中第一标注本项目论文3篇；项目负责人参编英文专著《Developments and Applications of Calcium Phosphate Bone Cements》1部；申请国家发明专利1项；参与培养硕士研究生1名。已完成计划任务书的各项考核指标。