基于P3HB4HB静电纺织材料及脂肪干细胞的软骨再生研究

Cartilage defect is common in clinic due to trauma, inflammation or tumor. But it's difficult to heal because of shortage of spontaneous healing ability of the cartilage. Previous methods including autologous and allograft can not reconstruct the structure and function of the cartilage. With the development of regenerative medicine and stem cell biology, the cartilage tissue engineering becomes the most promising method to heal cartilage defect. But the current research about the cartilage scaffolds is not satisfactory, especially the interaction of the seeding cells and the biomimetic scaffolds. In this study, we are trying to identify the micro-structure of the natural cartilage, especially the direction of the collagen fiber which is the most important matrix of the cartilage. Based on the natural structure of the cartilage, Electrostatic spinning technology will be used to make the scaffolds. Radial electrostatic spinning technology can make radial fibers, coaxial electrostatic spinning technology can make the double layer fibers, whose outer layer will be P3HB4HB, and the inner layer will be collagen. Rosary electrostatic spinning technology can make the rosary structure. And the different layer of the coaxial fiber and rosary beads can carry release different growth factors in order to stimulate the cartilage regeneration or maintain the characters of cartilage. The hydrophilic treatment of the scaffolds surface can improve the attachment of the cells and growth factors. With the combination of the CAD/CAM techniques, the 3D scaffold can be made. At the same time, we will study the chondrogenic differentia tion of the induced pluripotent stem cell and mesenchymal stem cells. The interaction between the chondrocytes and stem cells will be explored based on our previous work. Finally, we will load the seeding cell on the biomimetic scaffold to study the interaction of the cells and the scaffold in vitro and in vivo. The in-vivo live observation, Micro-CT, MRI, Morphology, genes analysis, proteins analysis, immunohistochemistry staining, will be applied to study the migration, degradation, reconstruction and regeneration of the cartilage. With de performance of this project, we are going the design and manufacture the biomimetic cartilage scaffolds and study the chondrogenic differentiation mechanism of stem cells, then we are going to regenerate the cartilage from the micro-structure to function..

软骨病损是临床上常见而又难以修复的重要疾病。将干细胞技术与组织工程结合的再生医学为软骨缺损的修复提供了新的思路与方向，然而目前对于干细胞生物学特性及软骨仿生材料的研究尚不深入。本课题拟研究正常软骨的超微结构，并以此为依据采用静电纺织技术，模拟天然纤维结构合成P3HB4HB软骨仿生材料。通过径向静电纺织技术控制纤维的排列方向；通过同轴纺织技术改善材料的物理性能并实现多种生长因子的逐级释放；通过串珠纺织技术实现生长因子的脉冲释放；通过材料表面的亲水化处理改善材料与生长因子和细胞的亲和性。采用计算机辅助设计结合材料打印技术制造特定结构的软骨仿生材料。通过诱导干细胞和脂肪干细胞的分化研究掌握成软骨分化控制体系。研究软骨仿生材料、生长因子对干细胞成软骨分化、基质分泌及软骨表型保持的调控，重建成软骨分化所需的最佳微环境，实现软骨组织形态、结构、功能上的再生，为软骨组织再生提供理

软骨病损是临床上常见而又难以修复的重要疾病。将干细胞技术与组织工程结合的再生医学为软骨缺损的修复提供了新的思路与方向，然而目前对于干细胞生物学特性及软骨仿生材料的研究尚不深入。本课题拟研究正常软骨的超微结构，并以此为依据采用静电纺织技术，模拟天然纤维结构合成P3HB4HB软骨仿生材料。通过径向静电纺织技术控制纤维的排列方向；通过同轴纺织技术改善材料的物理性能并实现多种生长因子的逐级释放；通过串珠纺织技术实现生长因子的脉冲释放；通过材料表面的亲水化处理改善材料与生长因子和细胞的亲和性。采用计算机辅助设计结合材料打印技术制造特定结构的软骨仿生材料。通过诱导干细胞和脂肪干细胞的分化研究掌握成软骨分化控制体系。研究软骨仿生材料、生长因子对干细胞成软骨分化、基质分泌及软骨表型保持的调控，重建成软骨分化所需的最佳微环境，实现软骨组织形态、结构、功能上的再生。.项目按计划进行，超额完成预期任务。发表标注本基金资助的通讯作者SCI论著45篇，包括口腔医学顶级期刊Journal of Dental Research，材料学顶级期刊Materials Today等。最高影响因子24，累积影响因子 288，5篇影响因子大于10，15篇影响因子大于7，40篇影响因子大于3。其中F1000推荐论文1篇，封面（底）论文6篇，ESI热点论文2篇，ESI高被引论文6篇。主编英文专著4部。作为第一发明人授权中国发明专利2项，申请PCT国际专利3项，中国发明专利12项。申请人入选2016年万人计划，2018年天府万人计划，2018年四川省学术与技术带头人。