CAR细胞在骨-植入材料界面形成过程中的调控机制研究

Osteointegration and fibrous capsule are two possible outcomes when the artificial materials were implanted into the bone tissue. The exact mechanism of the different bone responses at bone-implant interface remains unclear. Recently, it was found in the field of osteoimmunology that the CXCL-12 abundant reticular cells (CAR cells) in the bone marrow could differentiate into osteoblasts and maintain the quiescence and undifferentiated state of hematopoietic stem cell (HSCs). Besides, CXCL-12 secreted by CAR cells could recruit the mesenchymal stem cells and enhance the osteogenesis. Therefore, it is hypothesized that CAR cells may play an important role in the cross-regulation between the immune and skeletal systems during the bone healing process, which lead to different bone responses at bone-implant interface. This research is focused on the effects of different materials on CAR cells and to explore the cellular and molecular mechanisms of the immune response. By means of experiments in vivo and in vitro, the correlations among CAR cells、HSCs and the bone responses of different implant materials could be clarified. In the end, based on the characteristic molecules of CAR cells under osteointegration and inflammatory, a method is to be established to evaluate the bioactivity of bone implant materials in vitro.

骨内植入体与骨组织可形成以成骨细胞成骨为特征的骨结合或以巨噬细胞融合为主的纤维包膜两种不同形式。有关骨内植入体不同界面形成的细胞分子机制尚不清楚。近年来骨免疫学研究发现，骨基质中的CXCL-12富集网状细胞（CAR细胞）可向成骨细胞分化；其分泌的CXCL-12可调控间充质干细胞（MSC）迁移促进成骨；同时，CAR细胞可维持造血干细胞（HSCs）的未分化状态，抑制HSCs向巨噬细胞等分化。因此，我们提出科学假设，骨髓中CAR细胞对成骨和免疫细胞的交叉调控可能是种植体周形成不同结合形式的关键。基于此，本项目以CAR细胞为切入点，以植入材料对CAR细胞及HSCs细胞的影响为主线，探索不同材料植入骨组织后，局部产生免疫响应的细胞和分子机制，验证CAR细胞、HSCs细胞与骨植入材料转归的相关性。最终，基于植入材料骨结合和炎症时CAR细胞分子表达特征，建立体外评价骨植入材料生物活性新方法。

骨内植入体与骨组织可形成以成骨细胞成骨为特征的骨结合或以巨噬细胞融合为主的纤维包膜两种不同形式。有关骨内植入体不同界面形成的细胞分子机制尚不清楚。近年来骨免疫学研究发现，骨基质中的CXCL-12富集网状细胞（CAR细胞）可向成骨细胞分化；其分泌的CXCL-12可调控间充质干细胞（MSC）迁移促进成骨。因此，我们以巨噬细胞表面CXCL12(SDF1α) -CXCR4/CXCR7信号轴为切入点，探索了该信号轴在植入材料转归中的作用，已经机制，并且制备了载有小分子RNA和tuftsin的酸响应PMMA纳米微球，靶向调控巨噬细胞表面的CXCL12(SDF1α) -CXCR4/CXCR7信号轴，来影响材料植入体内后形成骨结合或者纤维包绕。此外，我们还在钛表面制备京尼平交联的壳聚糖明胶双层纳米生物涂层，并且研究了模式识别受体和NOD2介导的树突状细胞对不同种植体材料的识别效应。为种植体周围骨免疫学研究打下坚实的理论和实验基础，同时为提高种植体骨结合成功率，预防和治疗种植体周围炎提供新思路和新方法。