口腔纳米材料种植体局部微环境通过调节巨噬细胞M1/M2极化影响间充质干细胞成骨功能及其分子机制

The oral immune system has the characteristics of both oral mucosal immunology and osteoimmunology, and maintains the distinct characteristics of the regional immune tissues and organs. In 1980s, oral immunology, including oral immunological characteristics and related oral diseases, has become an important branch of immunology. Dental implant has become an important approch to restore tooth missing and dentition defect. Although the effect of dental implants is closely related to bone immune response, the innate immune response against implanted materials, especially the M1/M2 polarization and inflammatory secretion of macrophages, has been recognized to play the key role of regulating the homeostasis of osteoblasts/osteoclasts and to determine the prognosis of implants. This project firstly intends to compare the effect of different tube size nanostructured TiO2 surfaces on the macrophage polarization and cytokine secreation profile in vitro/vivo, then to figure out the signal pathway of macrophage polarization modulated by activation of integrin β1/2/3, which expressed on macrophage surface. Further work will aim to deplore how to promote the osteogenic differentiation of MSCs through the modulation of macrophage polarization and cytokine secretion profile manipulated by the nanotopography of implant surfaces. Our work will not only help to illustrate the impact of implant microenvironment on the macrophages referring to the M1/M2 polarization and the related molecular mechanisms, but also provide a new theoretical and experimental basis to overcome implant failure induced by the delayed bone formation around implant and impaired bone-implant interface.

口腔免疫系统兼顾黏膜免疫和骨免疫的双重特征，具有鲜明的组织器官区域免疫特性。 以口腔免疫特性和相关口腔疾病为主要内容的“口腔免疫学”在上世纪90年代已成为免疫学中一个重要分支。口腔种植技术是牙齿缺失的重要修复方法，口腔种植体植入修复不仅与骨免疫学密切相关，目前认为种植体植入引发的局部固有免疫应答，尤其是巨噬细胞的M1/M2极化状态和炎性分泌功能，将直接影响成骨和破骨平衡，是决定种植体预后的关键性调节因素。鉴于此，本项目拟在探讨不同管径种植体微纳米形貌体内外对巨噬细胞M1/M2极化影响的基础上；搞清其通过活化整合素分子调节巨噬细胞极化的信号通路；最后，探索通过改良种植体表面微纳米形貌影响巨噬细胞极化进而促进间充质干细胞成骨的可行性。本项目的完成不仅有助于阐明口腔种植体局部微环境对巨噬细胞M1/M2极化的影响和分子机制，还将为临床解决种植体植入后骨结合不良所导致的种植体失败提供理论和实验依据。

种植体植入引发的局部固有免疫应答，尤其是巨噬细胞的M1/M2极化状态和炎性分泌功能，将直接影响成骨和破骨平衡，是决定种植体预后的关键性调节因素。本项目探讨了不同管径种植体微纳米形貌体内外对巨噬细胞M1/M2极化的影响，发现NT20促进巨噬细胞M1极化而NT5促进巨噬细胞M2极化；明确了通过改良种植体表面微纳米形貌影响巨噬细胞极化进而促进间充质干细胞成骨的可行性和分子机制；在此基础上，发现不同管径微纳米形貌种植体微环境可通过影响间充质干细胞的sRANKL等细胞因子的分泌功能调节巨噬细胞破骨生成能力，进而影响种植体体内植入后的骨形成能力。本项目的完成不仅阐明了种植体表面形貌对巨噬细胞M1/M2极化的影响和分子机制，还明确了种植体微环境中巨噬细胞和间充质干细胞的相互调节及其对骨形成的影响和机制，一方面为临床解决种植体植入后骨形成不良所导致的种植体失败提供理论和实验依据，另一方面也为研发旨在提高种植体骨形成能力的新型材料提供了理论指导。