CS-胶原改性的PCL/脱细胞髓核基质仿生支架联合人脐带间充质干细胞构建组织工程椎间盘

项目名称： CS-胶原改性的PCL/脱细胞髓核基质仿生支架联合人脐带间充质干细胞构建组织工程椎间盘

项目编号： No.31500781

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 生物科学

项目作者： 许海委

作者单位： 天津市天津医院

项目金额： 20万元

中文摘要： 组织工程有望成为椎间盘疾病的理想治疗措施，但目前尚无公认的理想支架材料，亟需寻求一种理想的椎间盘支架。前期研究中我们以聚己内酯（PCL）为材料通过湿纺-成形技术制备具有取向性的纤维环支架，以脱细胞髓核基质为材料制备胶冻样的髓核支架。本课题以PCL、脱细胞髓核基质为材料研制硫酸软骨素（CS）-胶原改性的一体化纤维环-髓核双相支架；通过与纤维环细胞/髓核细胞共培养，诱导人脐带间充质干细胞向椎间盘样细胞分化；利用向椎间盘样细胞诱导分化的人脐带间充质干细胞与双相支架复合构建纤维环-髓核复合组织；将构建的纤维环-髓核复合组织移植到动物体内修复椎间盘退变，并评估修复效果，包括椎间盘高度指数变化，不同部位（纤维环、髓核、交界区）的细胞增殖、分布、分化及基因表达，细胞外基质分泌及排列，力学特性等。此研究国内外未见报道，研究成果将为椎间盘的修复与重建提供新的技术和方向，促进组织工程修复椎间盘的临床应用。

中文关键词： 支架材料；复合材料；脱细胞基质；仿生设计；生物相容性

英文摘要： Tissue engineering is expected to the ideal method for the treatment of disc disease, however, there is lack of ideal scaffold materials, which need to be explored in the further study. In our prior study, oriented anulus fibrosus (AF) scaffold has been fabricated with polycaprolactone (PCL) through a wet spinning-forming technique, and gelatinous nucleus pulposus (NP) scaffold has been fabricated with acellular NP matrix. In this project, integrative AF-NP biphasic scaffolds will be developed with PCL and acellular NP matrix, and modified with chondroitin sulfate (CS)-collagen. Human umbilical cord mesenchymal stem cells (HUCMSCs) will be differentiated into intervertebral disc (IVD) like-cells by co-culturing with AF/NP cells. Integrative AF-NP composites will be engineered with AF-NP biphasic scaffolds and IVD-like cells induced from HUCMSCs. The engineered AF-NP composites will be transplanted into the animals to repair degenerative disc, with the result being evaluated, including the changes of disc height index (DHI), cell proliferation, distribution, differentiation and gene expression, extracellular matrix secretion and arrangement, and mechanical properties in different portion of the composites (AF, NP, junctional zone). As far as we know, there is no literature that reported the construction of tissue-engineered IVD with the integrative AF-NP biphasic scaffolds fabricated with PCL and acellular NP matrix. This project will not only provide novel technology and direction for the reparation and reconstruction of IVD, but also promote the clinical application of tissue engineering for the reparation of IVD.

英文关键词： scaffold materials;composite materials;acellular matrix;biomimetic design;biocompatibility