可持续高效募集宿主细胞的新型骨生物复合材料在骨修复中的作用及其分子机制

Biomaterials treat for bone regeneration and repair in bone defects is in the increasingly wide application, but the material of high bionic, complete bone integration and in vivo degradation and other issues to be solved. My group has developed the rapid self-curing, biodegradable and high mechanical strength materials based on calcium phosphate at first time in the world. Recently, the animal model of bone defect was successfully reconstructed by introducing stem cells and alginate-releasing carrier, which confirmed that the composite material had good bone-induced and bone regeneration. Based on preliminary research data, the current project will develop a completely novel type of bone biomaterials that promote host cells recruitment, the osteogenic differentiation and vascularization by bioactivation technology. The novel material not only has the biodegradable and absorbable and good mechanical properties of the material. At the same time, the biomechanical properties and organizational structure of the new bone, the new bone and the natural bone are in accordance with the material design scheme of the natural bone. Host cell recruitment, promote blood vessels and promote bone regeneration and other functions, revealing its recruitment of host cells, vascularization and repair of bone defects in the mechanism. The successful implementation of this project will provide complete materials and new ideas for bone tissue regeneration and clinical research, also provide important theoretical basis and experimental basis for clinical application.

骨修复替代材料在骨缺损治疗中的应用日益广泛，但材料的高仿生性、完全骨整合能力及体内降解等问题仍亟待解决。课题组既往首次合成了基于磷酸钙的自固化、可降解、高力学强度材料。新近又通过引入干细胞和藻酸盐释放载体复合该材料，成功修复骨缺损动物模型，证实该材料具有良好骨再生作用。据此，本项目将在前期研究基础上通过生物活化技术方法进一步构建可持续高效募集宿主细胞的新型骨生物复合材料，并深入研究新材料对宿主细胞的募集作用及效率，促血管化及促骨再生等功能，揭示其招募宿主细胞，血管化和对骨缺损修复作用的机制。预期新材料不但具有可降解可吸收和良好的材料力学性能，而且其可持续高效募集宿主细胞的特性使得新生骨、新生骨与天然骨连接处的生物力学性能和血管化等组织结构符合天然骨特征。本项目的顺利实施将为骨组织再生基础与临床研究领域提供新材料、新的设计思路和观点，为临床开发应用新型骨生物材料提供重要的理论基础和实验依据。

骨修复替代材料在骨缺损治疗中的应用日益广泛，但材料的高仿生性、完全骨整合能力及体内降解等问题仍亟待解决。本项目在课题组前期研究基础上设计了增加生物活性组份的可持续高效募集宿主细胞的新型骨生物复合材料，计划深入的研究新材料对宿主细胞的募集作用及效率，促血管化及促骨再生等功能，揭示其招募宿主细胞，血管化和对骨缺损修复作用的机制。项目执行期内，成功构建并优化了可注射新型骨生物复合材料（CPC/PVP/Alginate），完成了BMP2、VEGF等生物活性组份的搭载与缓释检测，在体外细胞实验、大鼠极限颅骨缺损模型中验证了载因子的新型复合材料对干细胞的募集、促成骨、促血管化功能，并初步探明相关分子机制。除利用经典的趋化、促分化细胞因子作为生物活性组份外，本项目检验了自体来源的生物因子复合制剂，血小板裂解液（Platelet Lysate，PL），作为复合材料中的生物活性组份对干细胞成骨分化的影响。基于上述新型复合材料诱导干细胞成骨分化的分子机制研究，本项目还构建了搭载ALK5-smad2/3通路特异性小分子抑制剂SB431542的CPC复合材料，在体外实验中验证了其促干细胞成骨分化作用。本项目的实施为骨组织再生基础与临床研究提供新材料和新的构建思路与方法，为临床开发应用新型骨生物材料提供重要的理论基础和实验依据。