双相磷酸钙调控T细胞分泌IL-17A的机制及其在材料骨再生中的作用

当骨替代材料植入机体后，在愈合早期会引发机体的免疫反应，所产生的微环境直接影响后续的骨再生过程。近期研究认为，生物材料会影响T细胞的活性，T细胞免疫在生物材料-组织界面愈合发挥重要调控作用。本课题组前期研究发现：将双相磷酸钙（BCP）材料植入肌袋内，材料周围见大量T细胞浸润，并见类骨质形成，而在清除T细胞的模型里，BCP就不能发挥异位形成类骨质的效应。本课题组预实验初步发现，BCP可以调控T细胞对IL-17A的表达。而有研究表明，IL-17A可促进间充质干细胞的分化和矿化基因的表达。因此，本项目提出研究假设：双相磷酸钙调控T细胞分泌的IL-17A，很可能影响界面间充质干细胞的分化和成骨效应，这可能是T细胞骨免疫在生物材料骨再生过程中发挥重要作用的新信号机制。本项目拟通过体内动物实验和体外实验来验证研究假设。本项目对T细胞免疫作用机制的探索，将为具有免疫调控成骨活性的材料研发提供新的科学思路。

When bone substitutes are implanted in the body, it will trigger the body's immune response in the early stage of healing, resulting microenvironment directly affects the subsequent bone regeneration process. Recent studies have found that biomaterials can affect the activity of T cells, and T cell immunity plays an important regulatory role in the healing of biomaterial-tissue interfaces. Our previous research found that when biphasic calcium phosphate (BCP) was implanted into the muscle bag of normal mice, there were a large number of T cells in the tissue surrounding the material. Besides, it could form osteoid. On the contrary, in the T cell defect model, there was no heterotopic osteogenesis in the implant site. The pre-experiment of our research group also found that BCP can regulate the secretion of IL-17A by T cells. Studies have shown that IL-17A can promote the differentiation of mesenchymal stem cells and the expression of mineralization genes. Therefore, this project assumes that BCP regulates the secretion of IL-17A by T cells, which may affect the differentiation and osteogenic effects of mesenchymal stem cells around biomaterial-tissue interfaces. This may be one of the signaling mechanisms by which T cell plays an important role in the osteogenesis using biomaterials. This project intends to verify this hypothesis through in vivo and in vitro experiments. The exploration of the specific mechanism of T cell immunity will provide new scientific thoughts to improve the biological activity of biomaterial.