牙髓炎进程中，持续激活的炎性巨噬细胞反应抑制牙髓修复再生，尚无有效调控手段。外泌体是细胞分泌的包裹miRNAs等信号分子的纳米囊泡，间充质干细胞外泌体具有显著的免疫调节功能。我们前期发现牙囊干细胞条件培养基促进巨噬细胞M2型极化，减轻LPS诱导的大鼠肺部炎症，推测外泌体可能从中起主要作用。能否利用牙囊干细胞外泌体的免疫调节特性，诱导巨噬细胞极化转换，调控炎症微环境，重建组织稳态，促进牙髓修复与保存？本项目以探索牙髓炎的干预靶点和手段为目标，评估牙囊干细胞外泌体能否促进大鼠实验性牙髓炎中巨噬细胞M2型极化，缓解炎症促进修复；明确外泌体传递的效应miRNA及下游信号通路，揭示外泌体－巨噬细胞的信息传递与作用机制；研发自主知识产权、智能递释外泌体的ROS响应型凝胶体系，评价用于大鼠实验性牙髓炎直接盖髓的效果。旨在揭示牙囊干细胞外泌体对牙髓免疫的调节作用及机制，为牙髓炎的微创生物治疗策略提供依据。

In the process of pulpitis, the inflammatory cascades evoked by activated macrophages may inhibit pulp repair and regeneration. There has not yet been any effective way to modulate the inflammatory progress. Exosomes are nanovesicles secreted by cells and contain a variety of signal molecules including miRNAs. Exosomes derived from mesenchymal stem cells have been shown significant immunomodulatory potential. Our findings showed that the conditioned medium of rat dental follicle stem cells (rDFSCs-CM) induced the M2 polarization of macrophages and alleviated LPS-induced lung inflammation in rats, among which the exosomes in rDFSCs-CM might underlie these immunomodulatory functions. We hereby hypothesize that the immunomodulatory properties of rDFSCs derived exosomes (rDFSCs-exo) could induce M2 macrophage polarization, optimize the inflammatory microenvironment, reconstruct tissue homeostasis, thus promoting pulp repair and regeneration. To explore the potential regulatory targets and interventions for pulpitis, firstly we will evaluate, both in vitro and in vivo, whether rDFSCs-exo could promote the M2 macrophage polarization, relieve inflammation and promote tissue repair in rat experimental pulpitis. Secondly, the key miRNAs in rDFSCs-exo and its downstream signaling pathways will be identified to reveal the mechanism by which rDFSCs-exo exerts immunomodulatory effects on activated macrophages. Thirdly, we will prepare ROS-responsive intelligent hydrogels for rDFSCs-exo delivery, and assess its effects on rat experimental pulpitis as the pulp-capping agents. Taken together, this study may help us to gain insight into the immunomodulatory role of rDFSCs-exo in dental pulp inflammation and immunity, and lay basis for developing minimally invasive bio-therapeutic endodontic strategy.